Jacqueline Center

Quantitative ultrasound and fracture risk prediction in non-osteoporotic men and women as defined by WHO criteria

Publisher: Springer Science and Business Media LLC

Date: 10-08-2013

DOI: 10.1007/S00198-012-2001-2

Abstract: This study sought to determine the association between calcaneal quantitative ultrasound (QUS) and fracture risk in in iduals without osteoporosis according to the World Health Organization criteria (i.e., BMD T-score > -2.5). We found that calcaneal QUS is an independent predictor of fracture risk in women with non-osteoporotic bone mineral density (BMD). More than 50 % of women and 70 % of men who sustain a fragility fracture have BMD above the osteoporotic threshold (T-score > -2.5). Calcaneal QUS is associated with fracture risk. This study aimed to test the hypothesis that low calcaneal QUS is associated with increased fracture risk in in iduals with non-osteoporotic BMD. We included 312 women and 390 men aged 62-90 years with BMD T-score > -2.5 at femoral neck. QUS was measured in broadband ultrasound attenuation (BUA) at the calcaneus using a CUBA sonometer. BMD was measured at the femoral neck (FNBMD) by dual energy X-ray absorptiometry using GE Lunar DPX-L densitometer. The incidences of any fragility fracture were ascertained by X-ray reports during the follow-up period from 1994 to 2011. Of the 702 participants, 26 % of women (n = 80/312) and 14 % of men (n = 53/390) experienced at least one fragility fracture during the follow-up period. In women, after adjusting for covariates, increased risk of any fracture was significantly associated with decreased BUA (HR = 1.50 95 % CI, 1.13-1.99). Compared with that of FNBMD, the models with BUA, in women, had greater AUC (0.71, 0.85, 0.71 for any, hip and vertebral fracture, respectively), and yielded a net reclassification improvement of 16.4 % (P = 0.009) when combined with FNBMD. In men, BUA was not significantly associated with fracture risk before and after adjustment. These results suggest that calcaneal BUA is an independent predictor of fracture risk in women with non-osteoporotic BMD.

Osteoglycin, a novel coordinator of bone and glucose homeostasis

Publisher: Elsevier BV

Date: 07-2018

DOI: 10.1016/J.MOLMET.2018.05.004

Clinical fractures cluster in time after initial fracture

Publisher: Elsevier BV

Date: 12-2010

DOI: 10.1016/J.MATURITAS.2010.09.002

Abstract: A history of fractures is a well recognised risk factor for a new clinical fracture. However, this subsequent fracture risk is not constant, but fluctuates over time, with the greatest increase in the years immediately after the initial fracture, followed by a gradual waning of risk toward the population risk. The clustering of fractures occurred regardless of age, gender and initial fracture location. It is therefore likely that fracture risk models, which take into account this fluctuation of fracture risk over time, will be more relevant in predicting an in idual's subsequent fracture risk. Regardless of the cause of this clustering, these studies all strongly support the need for early action after an initial fracture to reduce the preventable risk of subsequent fractures with medical interventions that have been shown to immediately decrease the risk of fractures.

Asymptomatic Vertebral Deformity as a Major Risk Factor for Subsequent Fractures and Mortality: A Long‐Term Prospective Study

Publisher: Wiley

Date: 08-2005

DOI: 10.1359/JBMR.050317

Development of prognostic nomograms for individualizing 5-year and 10-year fracture risks

Publisher: Springer Science and Business Media LLC

Date: 07-03-2008

DOI: 10.1007/S00198-008-0588-0

Abstract: We have developed clinical nomograms for predicting 5-year and 10-year fracture risks for any elderly man or woman. The nomograms used age and information concerning fracture history, fall history, and BMD T-score or body weight. Although many fracture risk factors have been identified, the translation of these risk factors into a prognostic model that can be used in primary care setting has not been well realized. The present study sought to develop a nomogram that incorporates non-invasive risk factors to predict 5-year and 10-year absolute fracture risks for an in idual man and woman. The Dubbo Osteoporosis Epidemiology Study was designed as a community-based prospective study, with 1358 women and 858 men aged 60+ years as at 1989. Baseline measurements included femoral neck bone mineral density (FNBMD), prior fracture, a history of falls and body weight. Between 1989 and 2004, 426 women and 149 men had sustained a low-trauma fracture (not including morphometric vertebral fractures). Two prognostic models based on the Cox's proportional hazards analysis were considered: model I included age, BMD, prior fracture and falls and model II included age, weight, prior fracture and fall. Analysis of the area under the receiver operating characteristic curve (AUC) suggested that model I (AUC = 0.75 for both sexes) performed better than model II (AUC = 0.72 for women and 0.74 for men). Using the models' estimates, we constructed various nomograms for in idualizing the risk of fracture for men and women. If the 5-year risk of 10% or greater is considered "high risk", then virtually all 80-year-old men with BMD T-scores < -1.0 or 80-year-old women with T-scores < -2.0 were predicted to be in the high risk group. A 60-year-old woman's risk was considered high risk only if her BMD T-scores < or = -2.5 and with a prior fracture however, no 60-year-old men would be in the high risk regardless of their BMD and risk profile. These data suggest that the assessment of fracture risk for an in idual cannot be based on BMD alone, since there are clearly various combinations of factors that could substantially elevate an in idual's risk of fracture. The nomograms presented here can be useful for in idualizing the short- and intermediate-term risk of fracture and identifying high-risk in iduals for intervention to reduce the burden of fracture in the general population.

Sequence variants in the PTCH1 gene associate with spine bone mineral density and osteoporotic fractures

Publisher: Springer Science and Business Media LLC

Date: 06-01-2016

DOI: 10.1038/NCOMMS10129

Abstract: Bone mineral density (BMD) is a measure of osteoporosis and is useful in evaluating the risk of fracture. In a genome-wide association study of BMD among 20,100 Icelanders, with follow-up in 10,091 subjects of European and East-Asian descent, we found a new BMD locus that harbours the PTCH1 gene, represented by rs28377268 (freq. 11.4–22.6%) that associates with reduced spine BMD ( P =1.0 × 10 −11 , β =−0.09). We also identified a new spine BMD signal in RSPO3 , rs577721086 (freq. 6.8%), that associates with increased spine BMD ( P =6.6 × 10 −10 , β =0.14). Importantly, both variants associate with osteoporotic fractures and affect expression of the PTCH1 and RSPO3 genes that is in line with their influence on BMD and known biological function of these genes. Additional new BMD signals were also found at the AXIN1 and SOST loci and a new lead SNP at the EN1 locus.

Investigation of incidental hypercalcaemia

Publisher: BMJ

Date: 20-11-2009

DOI: 10.1136/BMJ.B4613

Educational Inequalities in Post‐Hip Fracture Mortality: A NOREPOS Studys

Publisher: Wiley

Date: 14-07-2015

DOI: 10.1002/JBMR.2579

Abstract: Hip fractures are associated with high excess mortality. Education is an important determinant of health, but little is known about educational inequalities in post-hip fracture mortality. Our objective was to investigate educational inequalities in post-hip fracture mortality and to examine whether comorbidity or family composition could explain any association. We conducted a register-based population study of Norwegians aged 50 years and older from 2002 to 2010. We measured total mortality according to educational attainment in 56,269 hip fracture patients (NORHip) and in the general Norwegian population. Both absolute and relative educational inequalities in mortality in people with and without hip fracture were compared. There was an educational gradient in post-hip fracture mortality in both sexes. Compared with those with primary education only, the age-adjusted relative risk (RR) of mortality in hip fracture patients with tertiary education was 0.82 (95% confidence interval [CI] 0.77-0.87) in men and 0.79 (95% CI 0.75-0.84) in women. Additional adjustments for Charlson comorbidity index, marital status, and number of children did not materially change the estimates. Regardless of educational attainment, the 1-year age-adjusted mortality was three- to fivefold higher in hip fracture patients compared with peers in the general population without fracture. The absolute differences in 1-year mortality according to educational attainment were considerably larger in hip fracture patients than in the population without hip fracture. Absolute educational inequalities in mortality were higher after hip fracture compared with the general population without hip fracture and were not mediated by comorbidity or family composition. Investigation of other possible mediating factors might help to identify new targets for interventions, based on lower educational attainment, to reduce post-hip fracture mortality.

Reduced mortality and subsequent fracture risk associated with oral bisphosphonate recommendation in a fracture liaison service setting: A prospective cohort study

Publisher: Public Library of Science (PLoS)

Date: 06-2018

DOI: 10.1371/JOURNAL.PONE.0198006

Factors associated with fragility fractures in type 2 diabetes: An analysis of the randomised controlled Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study

Publisher: Wiley

Date: 19-03-2023

DOI: 10.1002/DMRR.3631

Abstract: Fracture risk is elevated in some type 2 diabetes patients. Bone fragility may be associated with more clinically severe type 2 diabetes, although prospective studies are lacking. It is unknown which diabetes‐related characteristics are independently associated with fracture risk. In this post‐hoc analysis of fracture data from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial (ISRCTN#64783481), we hypothesised that diabetic microvascular complications are associated with bone fragility. The FIELD trial randomly assigned 9795 type 2 diabetes participants (aged 50–75 years) to receive oral co‐micronised fenofibrate 200 mg ( n = 4895) or placebo ( n = 4900) daily for a median of 5 years. We used Cox proportional hazards models to identify baseline sex‐specific diabetes‐related parameters independently associated with incident fractures. Over 49,470 person‐years, 137/6138 men experienced 141 fractures and 143/3657 women experienced 145 fractures incidence rates for the first fracture of 4∙4 (95% CI 3∙8–5∙2) and 7∙7 per 1000 person‐years (95% CI 6∙5–9∙1), respectively. Fenofibrate had no effect on fracture outcomes. In men, baseline macrovascular disease (HR 1∙52, 95% CI 1∙05–2∙21, p = 0∙03), insulin use (HR 1∙62, HR 1∙03–2∙55, p = 0∙03), and HDL‐cholesterol (HR 2∙20, 95% CI 1∙11–4∙36, p = 0∙02) were independently associated with fracture. In women, independent risk factors included baseline peripheral neuropathy (HR 2∙04, 95% CI 1∙16–3∙59, p = 0∙01) and insulin use (HR 1∙55, 95% CI 1∙02–2∙33, p = 0∙04). Insulin use and sex‐specific complications (in men, macrovascular disease in women, neuropathy) are independently associated with fragility fractures in adults with type 2 diabetes.

Chapter 42. Genetics of Osteoporosis

Publisher: Wiley

Date: 18-11-2008

DOI: 10.1002/9780470623992.CH42

Ten-year risk of second hip fracture. A NOREPOS study

Publisher: Elsevier BV

Date: 2013

DOI: 10.1016/J.BONE.2012.09.009

Abstract: Second hip fracture risk is elevated after the first, however whether risk differs with age, by sex or over time is not well known. To examine the risk of second hip fracture by sex, age and time after first hip fracture. Data on all hip fractures in subjects 50 years and older and treated in Norwegian hospitals during 1999-2008 were retrieved. Surgical procedure codes and additional diagnosis codes were used to define incident fractures. Survival analyses with and without adjustment for competing risk of death were used to estimate the risk of second hip fracture. Among the 81,867 persons who sustained a first hip fracture, 6161 women and 1782 men suffered a second hip fracture during follow-up. The overall age-adjusted hazard ratio (HR) of a second hip fracture did not differ between the sexes (women versus men, HR=1.03 95% confidence interval (CI): 0.98-1.09). Taking competing risk of death into account, the corresponding age-adjusted HR of a second hip fracture was 1.40 (95% CI: 1.33-1.47) in women compared to men. The greater risk in women was due to a higher mortality in men. Based on competing risk analyses, we estimate that 15% of women and 11% of men will have suffered a second hip fracture within 10 years after the first hip fracture. The ten-year cumulative incidence was above 10% in all age-groups, except in men 90 years and older. Fracture preventive strategies have a large potential in both women and men who suffer their first hip fracture due to the high risk of another hip fracture.

More-than-minimal-trauma fractures are associated with low bone density: an 8-year prospective study

Publisher: Springer Science and Business Media LLC

Date: 09-2017

DOI: 10.1007/S00198-016-3739-8

Abstract: Few studies have examined the relationship between more-than-minimal-trauma fractures and bone density. This study demonstrated that more-than-minimal-trauma fractures are associated with lower bone density similar to that seen in minimal trauma fractures. Men and women over 50 years with a more-than-minimal-trauma fracture should be investigated to exclude low bone density. The aim of this study was to assess the prevalence and predictors of low bone density in men and women with more-than-minimal-trauma fractures. In an Australian hospital, 630 community-dwelling men and women, 20 years of age or older, sustained a fracture due to more-than-minimal-trauma (force greater than a fall from standing height but less than high trauma). We studied 349 in iduals who agreed to have a bone mineral density (BMD) scan. These participants were compared with 472 men and women with minimal trauma fractures. Men and women with more-than-minimal-trauma fractures had significantly lower bone density than expected for their age, gender and weight (Z-score Men and women over 50 years with a more-than-minimal-trauma fracture, especially those with low body weight, prior minimal trauma fracture or an osteoporosis-associated condition, should be investigated to exclude low bone density and its associated risk of subsequent fractures.

Publisher Correction: GWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures

Publisher: Springer Science and Business Media LLC

Date: 24-05-2019

DOI: 10.1038/S41467-019-10425-4

Abstract: The original HTML version of this Article was updated shortly after publication to add links to the Peer Review file. In addition, affiliations 16 and 17 incorrectly read ‘School of Medicine Sydney, University of Notre Dame Australia, Sydney, WA, 6160, Australia’ and ‘St Vincent’s Clinical School, University of New South Wales Medicine, University of New South Wales, Sydney, NSW, 2052, Australia.’ This has now been corrected in both the PDF and HTML versions of the Article.

The epidemiology and pathogenesis of osteoporosis

Publisher: Elsevier BV

Date: 04-1997

DOI: 10.1016/S0950-351X(97)80489-2

Abstract: Osteoporosis is an increasing health care concern as populations age throughout the developed and developing world. The social and economic costs of osteoporosis are due to its clinical outcome of fracture which increases exponentially with age. This review will highlight some of the key epidemiological aspects of osteoporosis incorporating areas of more recent interest. These include the definition the magnitude of the problem encompassing differing incidence and prevalence patterns of both low bone mass and fracture in different cultural groups the social consequences of fracture, including economic costs, morbidity and mortality the evaluation of fracture risk, including the role of bone density, bone quality and the risk of falling as well as an overview of some of the factors involved in determining low bone mass. Bone mineral density (BMD) is the most easily measured and accurate predictor of fracture risk. For any in idual, BMD is the combination of their peak bone density and subsequent bone loss, both of which are influenced by genetic, hormonal and environmental factors. An understanding of key issues relating to this important disease may lead to earlier detection of the in idual at high risk for fracture and rational approach to prevention and management.

Two-Thirds of All Fractures Are Not Attributable to Osteoporosis and Advancing Age: Implications for Fracture Prevention

Publisher: The Endocrine Society

Date: 05-04-2019

DOI: 10.1210/JC.2018-02614

Abstract: Although bone mineral density (BMD) is strongly associated with fracture and postfracture mortality, the burden of fractures attributable to low BMD has not been investigated. We sought to estimate the population attributable fraction of fractures and fracture-related mortality that can be attributed to low BMD. This study is a part of an ongoing population-based prospective cohort study, the Dubbo Osteoporosis Epidemiology study. In total, 3700 participants aged ≥50 years participated in the study. Low-trauma fracture was ascertained by X-ray reports, and mortality was ascertained from the Birth, Death and Marriage Registry. Overall, 21% of women and 11% of men had osteoporotic BMD. In univariable analysis, 21% and 16% of total fractures in women and men, respectively, were attributable to osteoporosis. Osteoporosis combined with advancing age ( years) accounted for 34% and 35% of fractures in women and men, respectively. However, these two factors accounted for ∼60% of hip fractures. About 99% and 66% of postfracture mortality in women and men, respectively, were attributable to advancing age, osteoporosis, and fracture however, most of the attributable proportion was accounted for by advancing age. A substantial health care burden of fracture is on people aged years or nonosteoporosis, suggesting that treatment of people with osteoporosis is unlikely to reduce a large number of fractures in the general population.

Establishing baseline absolute risk of subsequent fracture among adults presenting to hospital with a minimal-trauma-fracture

Publisher: Springer Science and Business Media LLC

Date: 28-02-2020

DOI: 10.1186/S12891-020-3161-4

Abstract: One in three women and one in five men are expected to experience a minimal-trauma-fracture after the age of 50-years, which increases the risk of subsequent fracture. Importantly, timely diagnosis and optimal treatment in the form of a fracture liaison service (FLS), has been shown to reduce this risk of a subsequent fracture. However, baseline risk of subsequent fracture among this group of FLS patients has not been well described. Therefore, this study aims to estimate absolute risk of subsequent fracture, among women and men aged 50-years or more, presenting to hospital with a minimal-trauma-fracture. Women and men aged 50-years or more with a minimal-trauma-fracture, presenting to hospitals across the South Western Sydney Local Health District between January 2003 and December 2017 were followed to identify subsequent fracture presentations to hospital. Absolute risk of subsequent fracture was estimated, by taking into account the competing risk of death. Between January 2003 and December 2017–15,088 patients presented to the emergency departments of the five hospitals in the SWSLHD (11,149, women [74%]), with minimal-trauma-fractures. Subsequent fractures identified during the follow-up period (median = 4.5 years [IQR, 1.6–8.2]), occurred in 2024 (13%) patients. Death during the initial hospital stay, or during a subsequent hospital visit was recorded among 1646 patients (11%). Women were observed to have 7.1% risk of subsequent fracture after 1-year, following an initial fracture and, the risk of subsequent fracture after 1-year was 6.2% for men. After 5-years the rate among women was 13.7, and 11.3% for men, respectively. Cumulative risk of subsequent fracture when initial fractures were classified as being at proximal or distal sites are also presented. This study has estimated the baseline risk of subsequent fracture among women and men presenting to hospital with minimal trauma fractures. Importantly, this information can be used to communicate risk to patients deciding to attend an osteoporosis refracture prevention clinic, and highlight the need for screening, and initial of treatment when indicated, once a minimal-trauma-fracture has occurred.

Incidence and risk factors for low trauma fractures in men with prostate cancer

Publisher: Elsevier BV

Date: 09-2008

DOI: 10.1016/J.BONE.2008.05.003

Abstract: Men with prostate cancer on androgen deprivation therapy (ADT) are at increased risk of bone loss. The present study sought to determine the incidence of low trauma fracture in men with prostate cancer (PC), and to characterize the association between potential risk factors and fracture risk in these men. In the prospective, population-based Dubbo Osteoporosis Epidemiology Study, 43 men aged 60+ years reported a history of prostate cancer among whom, 22 men received ADT, and 21 men did not. Low-trauma fractures were ascertained between 1989 and 2004. Bone mineral density at the femoral neck (FNBMD), postural instability and lifestyle factors were obtained at baseline. Men with prostate cancer had significantly higher lumbar spine BMD than those without cancer (p=0.013). During the follow-up period, 15 men with prostate cancer had sustained a fracture, yielding the age-adjusted incidence of fracture among this group was 31.6 per 1000 person-years, which was greater than those without cancer (22.1 per 1000 person-years). The age-adjusted incidence of fracture was more pronounced among those with prostate cancer on ADT (40.2 per 1000 person-years). After adjusting for age, the increase in fracture risk among prostate cancer patients was associated with lower femoral neck BMD (hazard ratio [HR] per SD=1.8, 95% CI: 1.0-3.4) and increased rate of bone loss (HR 2.3, 1.2-4.6). Men with prostate cancer, particularly those treated with ADT, had an increased fracture risk. Although the average BMD in men with prostate cancer was higher than men without cancer, a low BMD prior to treatment or increased rate of bone loss after initiating ADT treatment was each a significant predictor of fracture in these.

Koreans Do Not Have Higher Percent Body Fat than Australians: Implication for the Diagnosis of Obesity in Asians

Publisher: Wiley

Date: 29-09-2019

DOI: 10.1002/OBY.22610

Abstract: It has been assumed that, for a given BMI, Asians have higher percent body fat (PBF) than Caucasians. As a result, it has been suggested that the BMI threshold for diagnosing obesity in Asians be lowered to less than 30 kg/m Whole-body fat mass and PBF were measured in 1,211 Koreans and 1,006 Australians using dual-energy x-ray absorptiometry (Lunar Prodigy GE Healthcare, Madison, Wisconsin). The two groups were then matched for age and BMI by the propensity score method. For a given age and BMI, Koreans had lower PBF than Australians, and the difference was statistically significant in women (mean difference: -2.13% 95% CI: -2.61% to -1.65%) but not in men (difference: -0.54% 95% CI: -1.22% to 0.14%). Matched-pair analysis (423 pairs of women and 208 pairs of men) also showed that Korean women had statistically lower PBF than their Australian counterparts (P < 0.001). In in iduals aged 60 years and older, Koreans do not have higher PBF than Australians after adjusting for BMI. These results suggest that there is no evidence for lowering the BMI threshold for the diagnosis of obesity in elderly Koreans.

Successful Treatment of Adult Cerebral Salt Wasting With Fludrocortisone

Publisher: American Medical Association (AMA)

Date: 11-02-2008

DOI: 10.1001/ARCHINTERNMED.2007.126

Prognosis of fracture: Evaluation of predictive accuracy of the FRAX algorithm and Garvan nomogram: Rejoinder to comments by Pluskiewicz and Drozdzowska

Publisher: Springer Science and Business Media LLC

Date: 29-01-2011

DOI: 10.1007/S00198-010-1527-4

Barriers to effective management of osteoporosis in moderate and minimal trauma fractures: A prospective study

Publisher: Springer Science and Business Media LLC

Date: 23-11-2005

DOI: 10.1007/S00198-004-1788-X

Abstract: Osteoporosis management is suboptimal even for high-risk people with a history of prior fracture. There is also evidence that in iduals with moderate trauma fracture have a lower bone density and are at higher risk of subsequent fracture. This study aimed to define factors influencing the management of in iduals at risk for osteoporosis and to examine the risk profiles of in iduals with minimal and moderate trauma fractures. Consecutive fracture patients (n =218) treated in the outpatient fracture clinic in St Vincent's Hospital, Sydney, over a 15-month period (February 2002-July 2003) were interviewed. Fracture risk factors, prior investigation and treatment for osteoporosis were collected and participants were contacted after 3 months to ascertain follow-up. Risk factors for osteoporosis including family history, low dietary calcium and conditions associated with bone loss were similar between low- and moderate-trauma groups and between sexes. Even though half of participants had had a prior fracture, only 34% had a bone density scan and 16% were on anti-resorptive treatment. There was a minimal (6%) increase in the rates of investigation and treatment at the 3-month follow-up, and less in the moderate trauma group and males. Independent predictors for being investigated for osteoporosis were: age over 50, prior fracture and female gender, while predictors for treatment were: age over 50 and having been investigated. This study has confirmed low rates of investigation and treatment even in in iduals who have already suffered a prior fracture, and especially in those <50 and in males. People with moderate and minimal trauma fractures had similar risk factors for osteoporosis, including a similarly high proportion of prior fractures. These findings support the concept that people with moderate trauma fractures are at higher subsequent fracture risk, yet are neither investigated nor treated. This study highlights the need for further exploration of barriers to osteoporosis management.

‘Skeletal Age’ for mapping the impact of fracture on mortality

Publisher: eLife Sciences Publications, Ltd

Date: 16-05-2023

DOI: 10.7554/ELIFE.83888

Abstract: Fragility fracture is associated with an increased risk of mortality, but mortality is not part of doctor-patient communication. Here, we introduce a new concept called ‘Skeletal Age’ as the age of an in idual’s skeleton resulting from a fragility fracture to convey the combined risk of fracture and fracture-associated mortality for an in idual. We used the Danish National Hospital Discharge Register which includes the whole-country data of 1,667,339 adults in Denmark born on or before January 1, 1950, who were followed up to December 31, 2016 for incident low-trauma fracture and mortality. Skeletal age is defined as the sum of chronological age and the number of years of life lost (YLL) associated with a fracture. Cox’s proportional hazards model was employed to determine the hazard of mortality associated with a specific fracture for a given risk profile, and the hazard was then transformed into YLL using the Gompertz law of mortality. During the median follow-up period of 16 years, there had been 307,870 fractures and 122,744 post-fracture deaths. A fracture was associated with between 1 and 7 years of life lost, with the loss being greater in men than women. Hip fractures incurred the greatest loss of life years. For instance, a 60-year-old in idual with a hip fracture is estimated to have a skeletal age of 66 for men and 65 for women. Skeletal Age was estimated for each age and fracture site stratified by gender. We propose ‘Skeletal Age’ as a new metric to assess the impact of a fragility fracture on an in idual’s life expectancy. This approach will enhance doctor-patient risk communication about the risks associated with osteoporosis. National Health and Medical Research Council in Australia and Amgen Competitive Grant Program 2019.

The definition and clinical significance of nonvertebral fractures

Publisher: Springer Science and Business Media LLC

Date: 02-09-2010

DOI: 10.1007/S11914-010-0030-3

Abstract: Nonvertebral fractures form the bulk of osteoporotic fractures and yet, other than hip fractures, are often dismissed, particularly in the younger age groups. Thus, less than 30% of women with osteoporotic fractures and less than 10% of men worldwide are receiving appropriate treatment. This article discusses the incidence, cost, and consequences of nonvertebral fractures. Recent evidence suggests these fractures form the bulk of costs to the community and herald an increased risk of refracture and premature mortality that applies to all types of nonvertebral, and not just hip, fractures.

Microsimulation model for the health economic evaluation of osteoporosis interventions: study protocol

Publisher: BMJ

Date: 02-2019

DOI: 10.1136/BMJOPEN-2018-028365

Abstract: Osteoporosis is a systemic skeletal disease that is characterised by reduced bone strength and increased fracture risk. Osteoporosis-related fractures impose enormous disease and economic burden to the society. Although many treatments and health interventions are proven effective to prevent fractures, health economic evaluation adds evidence to their economic merits. Computer simulation modelling is a useful approach to extrapolate clinical and economic outcomes from clinical trials and it is increasingly used in health economic evaluation. Many osteoporosis health economic models have been developed in the past decades however, they are limited to academic use and there are no publicly accessible health economic models of osteoporosis. We will develop the Australian osteoporosis health economic model based on our previously published microsimulation model of osteoporosis in the Chinese population. The development of the model will follow the recommendations for the conduct of economic evaluations in osteoporosis by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases and the US branch of the International Osteoporosis Foundation. The model will be a state-transition semi-Markov model with memory. Clinical parameters in the model will be mainly obtained from the Dubbo Osteoporosis Epidemiology Study and the health economic parameters will be collected from the Australian arm of the International Costs and Utilities Related to Osteoporotic Fractures Study. Model transparency and validates will be tested using the recommendations from Good Research Practices in Modelling Task Forces. The model will be used in economic evaluations of osteoporosis interventions including pharmaceutical treatments and primary care interventions. A user-friendly graphical user interface will be developed, which will connect the user to the calculation engine and the results will be generated. The user interface will facilitate the use of our model by people in different sectors. No ethical approval is needed for this study. Results of the model validation and future economic evaluation studies will be submitted to journals. The user interface of the health economic model will be publicly available online accompanied with a user manual.

Mortality risk reduction differs according to bisphosphonate class: a 15-year observational study

Publisher: Springer Science and Business Media LLC

Date: 03-01-2019

DOI: 10.1007/S00198-018-4806-0

Abstract: In this prospective cohort of 6120 participants aged 50+, nitrogen-bisphosphonates but not non-nitrogen bisphosphonates were associated with a significant 34% mortality risk reduction compared to non-treated propensity score matched controls. These findings open new avenues for research into mechanistic pathways. Emerging evidence suggests that bisphosphonates (BP), first-line treatment of osteoporosis, are associated with reduced risks for all-cause mortality. This study aimed to determine the association between different BP types and mortality risk in participants with or without a fracture. A prospective cohort study of users of different BPs matched to non-users by propensity score (age, gender, co-morbidities, fragility fracture status) and time to starting the BP medication from the population-based Canadian Multicentre Osteoporosis Study from nine Canadian centres followed from 1995 to 2013. Mortality risk for bisphosphonate users vs matched non-users was assessed using pairwise multivariable Cox proportional hazards models. There were 2048 women and 308 men on BP and 1970 women and 1794 men who did not receive medication for osteoporosis. The relationship between BP and mortality risk was explored in three separate 1:1 propensity score-matched cohorts of BP users and no treatment (etidronate, n = 599, alendronate, n = 498, and risedronate n = 213). Nitrogen BP (n-BP) (alendronate and risedronate) was associated with lower mortality risks [pairwise HR, 0.66 (95% CI, 0.48-0.91)] while the less potent non-n-BP, etidronate, was not [pairwise HR: 0.89 (95% CI, 0.66-1.20)]. A direct comparison between n-BP and etidronate (n = 340 pairs) also suggested a better survival for n-BP [paired HR, 0.47 (95%CI, (95% CI, 031-0.70)] for n-BP vs. etidronate]. Compared to no treatment, nitrogen but not non-nitrogen bisphosphonates appear to be associated with better survival.

A Randomized Study of a Single Dose of Intramuscular Cholecalciferol in Critically Ill Adults

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 11-2015

DOI: 10.1097/CCM.0000000000001201

alpha-Actinin-3 deficiency is associated with reduced bone mass in human and mouse

Publisher: Elsevier BV

Date: 10-2011

DOI: 10.1016/J.BONE.2011.07.009

Abstract: Bone mineral density (BMD) is a complex trait that is the single best predictor of the risk of osteoporotic fractures. Candidate gene and genome-wide association studies have identified genetic variations in approximately 30 genetic loci associated with BMD variation in humans. α-Actinin-3 (ACTN3) is highly expressed in fast skeletal muscle fibres. There is a common null-polymorphism R577X in human ACTN3 that results in complete deficiency of the α-actinin-3 protein in approximately 20% of Eurasians. Absence of α-actinin-3 does not cause any disease phenotypes in muscle because of compensation by α-actinin-2. However, α-actinin-3 deficiency has been shown to be detrimental to athletic sprint ower performance. In this report we reveal additional functions for α-actinin-3 in bone. α-Actinin-3 but not α-actinin-2 is expressed in osteoblasts. The Actn3(-/-) mouse displays significantly reduced bone mass, with reduced cortical bone volume (-14%) and trabecular number (-61%) seen by microCT. Dynamic histomorphometry indicated this was due to a reduction in bone formation. In a cohort of postmenopausal Australian women, ACTN3 577XX genotype was associated with lower BMD in an additive genetic model, with the R577X genotype contributing 1.1% of the variance in BMD. Microarray analysis of cultured osteoprogenitors from Actn3(-/-) mice showed alterations in expression of several genes regulating bone mass and osteoblast/osteoclast activity, including Enpp1, Opg and Wnt7b. Our studies suggest that ACTN3 likely contributes to the regulation of bone mass through alterations in bone turnover. Given the high frequency of R577X in the general population, the potential role of ACTN3 R577X as a factor influencing variations in BMD in elderly humans warrants further study.

Muscle Strength and Physical Performance Are Associated With Risk of Postfracture Mortality But Not Subsequent Fracture in Men

Publisher: Wiley

Date: 06-07-2022

DOI: 10.1002/JBMR.4619

Abstract: Muscle strength and physical performance are associated with incident fractures and mortality. However, their role in the risk of subsequent fracture and postfracture mortality is not clear. We assessed the association between muscle strength (grip strength) and performance (gait speed and chair stands time) and the risk of subsequent fracture and mortality in 830 men with low‐trauma index fracture, who participated in the Osteoporotic Fractures in Men (MrOS) USA Study and had their index measurements assessed within 5 years prior to the index fracture. The annual decline in muscle strength and performance following index fracture, estimated using linear mixed‐effects regression, was also examined in relation to mortality. The associations were assessed using Cox proportional hazards models adjusted for age, femoral neck bone mineral density (FN BMD), prior fractures, falls, body mass index (BMI), index fracture site, lifestyle factors, and comorbidities. Over a median follow‐up of 3.7 (interquartile range [IQR], 1.3–8.1) years from index fracture to subsequent fracture, 201 (24%) men had a subsequent fracture and over 5.1 (IQR, 1.8–9.6) years to death, and 536 (65%) men died. Index measurements were not associated with subsequent fracture (hazard ratios [HRs] ranging from 0.97 to 1.07). However, they were associated with postfracture mortality. HR (95% confidence interval [CI]) per 1 standard deviation (1‐SD) decrement in grip strength: HR 1.12 (95% CI, 1.01–1.25) and gait speed: HR 1.14 (95% CI, 1.02–1.27), and 1‐SD increment in chair stands time: HR 1.08 (95% CI, 0.97–1.21). Greater annual declines in these measurements were associated with higher mortality risk, independent of the index values and other covariates. HR (95% CI) per 1‐SD annual decrement in change in grip strength: HR 1.15 (95% CI, 1.01–1.33) and in gait speed: HR 1.38 (95% CI, 1.13–1.68), and 1‐SD annual increment in chair stands time: HR 1.28 (95% CI, 1.07–1.54). Men who were unable to complete one or multiple tests had greater risk of postfracture mortality (24%–109%) compared to those performed all tests. It remains to be seen whether improvement in these modifiable factors can reduce postfracture mortality. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

A Profiling analysis of contributions of cigarette smoking, dietary calcium intakes, and physical activity to fragility fracture in the elderly

Publisher: Springer Science and Business Media LLC

Date: 10-07-2018

DOI: 10.1038/S41598-018-28660-Y

Abstract: Fragility fracture and bone mineral density (BMD) are influenced by common and modifiable lifestyle factors. In this study, we sought to define the contribution of lifestyle factors to fracture risk by using a profiling approach. The study involved 1683 women and 1010 men (50+ years old, followed up for up to 20 years). The incidence of new fractures was ascertained by X-ray reports. A “lifestyle risk score” (LRS) was derived as the weighted sum of effects of dietary calcium intake, physical activity index, and cigarette smoking. Each in idual had a unique LRS, with higher scores being associated with a healthier lifestyle. Baseline values of lifestyle factors were assessed. In either men or women, in iduals with a fracture had a significantly lower age-adjusted LRS than those without a fracture. In men, each unit lower in LRS was associated with a 66% increase in the risk of total fracture (non-adjusted hazard ratio [HR] 1.66 95% CI, 1.26 to 2.20) and still significant after adjusting for age, weight or BMD. However, in women, the association was uncertain (HR 1.30 95% CI, 1.11 to 1.53). These data suggest that unhealthy lifestyle habits are associated with an increased risk of fracture in men, but not in women, and that the association is mediated by BMD.

Excess mortality attributable to hip-fracture: A relative survival analysis

Publisher: Elsevier BV

Date: 09-2013

DOI: 10.1016/J.BONE.2013.05.006

Abstract: In iduals with hip fracture are at substantially increased risk of mortality. The aim of this study was to estimate the excess mortality attributable to hip fracture in elderly men and women. The Dubbo Osteoporosis Epidemiology Study was designed as a prospective epidemiologic investigation, in which more than 2000 men and women aged 60+ as of 1989 had been followed for 21 years. During the follow-up period, the incidence of atraumatic hip fractures was ascertained by X-ray reports, and mortality was ascertained by the New South Wales Birth, Death and Marriage Registry. Relative survival ratios were estimated by taking into account the age-and-sex specific expected survival in the general Australian population from 1989 to 2010. During the follow-up period 151 women and 55 men sustained a hip fracture. Death occurred in 86 (57%) women and 36 (66%) men. In women, the cumulative relative survival post hip-fracture at 1, 5 and 10 years was 0.83 (95% confidence interval (CI) 0.76-0.89), 0.59 (95% CI 0.48-0.68), and 0.31 (95% CI 0.20-0.43), respectively in men, the corresponding estimates of relative survival were: 0.63 (95% CI 0.48-0.75), 0.48 (95% CI 0.32-0.63), and 0.36 (95% CI 0.18-0.56). On average post hip-fracture women died 4 years earlier (median: 4.1, inter-quartile range (IQR) 1.7-7.8) and men died 5 years earlier (median = 4.8, IQR 2.4-7.0) than expected. For every six women and for every three men with hip fracture one extra death occurred above that expected in the background population. Hip fracture is associated with reduced life expectancy, with men having a greater reduction than women, even after accounting for time-related changes in background mortality in the population. These data underscore that hip fracture is an independent clinical risk factor for mortality.

Challenges associated with recruiting multigenerational, multicultural families into a randomised controlled trial: Balancing feasibility with validity

Publisher: Elsevier BV

Date: 07-2015

DOI: 10.1016/J.CCT.2015.06.004

Abstract: Recruitment of participants into research studies has become an increasingly difficult task with justifiable criticisms of representativeness of s les. The difficulties of recruitment are exacerbated when the study is longitudinal, requires multiple members from one family and incorporates people from non-dominant ethnic backgrounds. This paper describes a complex trial's recruitment process. Family groups were required for a longitudinal randomised controlled trial investigating links between health and dietary behaviours with an aim to improve primary prevention health messages and initiatives. To be representative of the multi-ethnic composition of the South Australian population, families from three of South Australia's largest ethnic backgrounds were invited to participate. Of these, only families with participating members spanning three generations were enrolled, so that links between health and lifestyle behaviours with possible generational ties could be investigated. Immense difficulties were faced during recruitment and significant modifications to the initial recruitment plan were necessary to enable the enrolment of 96 families. Challenges faced included lack of response to recruitment materials displaying complex eligibility criteria and different response outcomes from different communities. Solutions implemented included simplifying materials and tailoring recruitment activities to specific communities' needs. This trial's recruitment journey will be used as a case study to highlight the practicalities of recruiting for complex trials. Recommendations will be provided for future researchers seeking to recruit multigenerational, multi-ethnic families into the same study, along with issues to consider regarding the implications of the recruitment journey on the integrity of a complex trial and the potential threats to internal validity.

Identification of High‐Risk Individuals for Hip Fracture: A 14‐Year Prospective Study

Publisher: Wiley

Date: 11-2005

DOI: 10.1359/JBMR.050520

A Highly Selective Sensor for Cyanide in Organic Media and on Solid Surfaces

Publisher: MDPI AG

Date: 24-02-2016

DOI: 10.3390/S16030271

Relationship between Serum Testosterone and Fracture Risk in Men: A Comparison of RIA and LC-MS/MS.

Publisher: Oxford University Press (OUP)

Date: 09-2015

DOI: 10.1373/CLINCHEM.2015.242339

Abstract: Serum testosterone can be measured by LC-MS/MS and RIA. We investigated whether the testosterone–fracture relationship was affected by the method of measurement. We measured total testosterone (TT) by LC-MS/MS (TTLC-MS/MS) and RIA (TTRIA) in serum s les collected from 602 men whose incident fractures had been continuously ascertained by x-ray reports from 1989 to 2010. We measured bone mineral density (BMD) by dual-energy x-ray absorptiometry. The association between TT and fracture risk was assessed by the Cox proportional hazards model, taking into account the effect of age and BMD. Mean TTLC-MS/MS was higher than TTRIA by 27 ng/dL (95% CI 13–41). The concordance correlation coefficient between TTLC-MS/MS and TTRIA was 0.72 (95% CI 0.68–0.76). The Deming regression equation linking the 2 measurements was ln(TTLC-MS/MS + 10) = 0.87 + 0.87 × ln(TTRIA + 10). The hazard ratio of fracture per SD decrease in TT was 1.32 (95% CI 1.12–1.54) for TTLC-MS/MS and 1.23 (1.06–1.43) for TTRIA. The correlation between predicted probabilities of fracture by TTLC-MS/MS and TTRIA was r = 0.96, with the mean difference being 0.01% (95% CI −6.1% to 6.2%). Slightly more patients were classified as having hypogonadism if TTRIA was used (29% vs 26%). The concordance between LC-MS/MS and RIA in the measurement of serum TT was moderate. Moreover, the magnitude of association between testosterone and fracture risk in older men was largely unaffected by the method of measurement.

Population-Wide Impact of Non-Hip Non-Vertebral Fractures on Mortality

Publisher: Wiley

Date: 15-05-2017

DOI: 10.1002/JBMR.3118

Abstract: Data on long-term consequences of non-hip non-vertebral (NHNV) fractures, accounting for approximately two-thirds of all fragility fractures, are scanty. Our study aimed to quantify the population-wide impact of NHNV fractures on mortality. The national population-based prospective cohort study (Canadian Multicentre Osteoporosis Study) included 5526 community dwelling women and 2163 men aged 50 years or older followed from July 1995 to September 2013. Population impact number was used to quantify the average number of people for whom one death would be attributable to fracture and case impact number to quantify the number of deaths out of which one would be attributable to a fracture. There were 1370 fragility fractures followed by 296 deaths in women (mortality rate: 3.49 95% CI, 3.11 to 3.91), and 302 fractures with 92 deaths in men (5.05 95% CI, 4.12 to 6.20). NHNV fractures accounted for three-quarters of fractures. In women, the population-wide impact of NHNV fractures on mortality was greater than that of hip and vertebral fractures because of the greater number of NHNV fractures. Out of 800 women, one death was estimated to be attributable to a NHNV fracture, compared with one death in 2000 women attributable to hip or vertebral fracture. Similarly, out of 15 deaths in women, one was estimated to be attributable to a NHNV fracture, compared with one in over 40 deaths for hip or vertebral fracture. The impact of forearm fractures (ie, one death in 2400 women and one out of 42 deaths in women attributable to forearm fracture) was similar to that of hip, vertebral, or rib fractures. Similar, albeit not significant, results were noted for men. The study highlights the important contribution of NHNV fractures on mortality because many NHNV fracture types, except for the most distal fractures, have serious adverse consequences that affect a significant proportion of the population. © 2017 American Society for Bone and Mineral Research.

Bone turnover in elderly men: relationships to change in bone mineral density.

Publisher: Springer Science and Business Media LLC

Date: 22-02-2007

DOI: 10.1186/1471-2474-8-13

Contribution of Hip Strength Indices to Hip Fracture Risk in Elderly Men and Women

Publisher: Wiley

Date: 31-05-2005

DOI: 10.1359/JBMR.050519

Genetic Sharing with Cardiovascular Disease Risk Factors and Diabetes Reveals Novel Bone Mineral Density Loci

Publisher: Public Library of Science (PLoS)

Date: 22-12-2015

DOI: 10.1371/JOURNAL.PONE.0144531

Secondary Fracture Prevention

Publisher: Elsevier

Date: 2019

DOI: 10.1016/C2016-0-04629-6

Nonsense mutation in the LGR4 gene is associated with several human diseases and other traits

Publisher: Springer Science and Business Media LLC

Date: 05-05-2013

DOI: 10.1038/NATURE12124

Abstract: Low bone mineral density (BMD) is used as a parameter of osteoporosis. Genome-wide association studies of BMD have hitherto focused on BMD as a quantitative trait, yielding common variants of small effects that contribute to the population ersity in BMD. Here we use BMD as a dichotomous trait, searching for variants that may have a direct effect on the risk of pathologically low BMD rather than on the regulation of BMD in the healthy population. Through whole-genome sequencing of Icelandic in iduals, we found a rare nonsense mutation within the leucine-rich-repeat-containing G-protein-coupled receptor 4 (LGR4) gene (c.376C>T) that is strongly associated with low BMD, and with osteoporotic fractures. This mutation leads to termination of LGR4 at position 126 and fully disrupts its function. The c.376C>T mutation is also associated with electrolyte imbalance, late onset of menarche and reduced testosterone levels, as well as an increased risk of squamous cell carcinoma of the skin and biliary tract cancer. Interestingly, the phenotype of carriers of the c.376C>T mutation overlaps that of Lgr4 mutant mice.

Worsening of soft tissue dystrophic calcification in an osteoporotic patient treated with teriparatide

Publisher: Springer Science and Business Media LLC

Date: 15-12-2018

DOI: 10.1007/S00198-017-4330-7

Abstract: Teriparatide, used for treatment of osteoporosis in patients at high risk of fracture risk, sometimes results in mild and transient hypercalcemia. There have been two recent reports of worsening dystrophic calcification in patients with autoimmune disorders following teriparatide treatment. We report a patient with severe osteoporosis and without a pre-existing autoimmune disorder, who developed symptomatic worsening of dystrophic calcification 4 months after teriparatide was initiated. Symptoms resolved within 1 week of teriparatide cessation.

Transplant Recipients on the Edge of the Hypocalcemia Abyss

Publisher: Elsevier BV

Date: 2009

DOI: 10.1016/J.HEALUN.2008.09.010

Abstract: Hypovitaminosis D is a risk factor for transplant-related osteoporosis. Its contribution to severe hypocalcemia in transplant recipients is less well recognized. We present 2 cases to illustrate how risk factors specific to transplant recipients significantly increase the risk of development of severe hypocalcemia, on a background of unrecognized vitamin D deficiency. Regular surveillance of calcium homeostasis should be incorporated into routine clinical care of transplant recipients.

Comparison of calcaneal quantitative ultrasound and bone densitometry parameters as fracture risk predictors in type 2 diabetes mellitus

Publisher: Wiley

Date: 06-12-2020

DOI: 10.1111/DME.14183

Abstract: To investigate the utility of calcaneal quantitative ultrasound compared with bone densitometry (DXA) in predicting incident low-trauma fracture in type 2 diabetes. This retrospective cohort study included a subset of participants in the Dubbo Osteoporosis Epidemiology Study who had concurrent calcaneal quantitative ultrasound and DXA measurement, comprising 809 people without type 2 diabetes and 96 with type 2 diabetes. Fracture data had been collected prospectively. Cox proportional hazard models and receiver operating curves (ROC) were used to compare calcaneal quantitative ultrasound and DXA parameters as predictors for any low-trauma fracture. The median age of participants was 71 years (IQR 68-76, 50% men) for those without type 2 diabetes and 70 years (IQR 68-76, 55% men) for those with type 2 diabetes. There was no difference in low-trauma fracture incidence between groups when stratified by sex. In those without type 2 diabetes, the hazard ratio for fracture per 1 sd decrease in broadband ultrasound attenuation and femoral neck bone mineral density (BMD) was 1.47 [95% confidence interval (CI) 1.26-1.71] and 1.39 (95% CI 1.17-1.64), respectively. The corresponding figures in type 2 diabetes were 1.81 (95% CI 1.03-3.19) for broadband ultrasound attenuation and 2.55 (95% CI 1.28-5.08) for femoral neck BMD. Broadband ultrasound attenuation is comparable with femoral neck BMD as a predictor for low trauma incident fracture in type 2 diabetes. Calcaneal quantitative ultrasound offers several advantages over DXA and should be considered in further studies of bone health screening or in clinical practice where DXA is unavailable.

In Memoriam: Philip Neil Sambrook OBITUARY

Publisher: Springer Science and Business Media LLC

Date: 10-05-2012

DOI: 10.1007/S00198-012-2010-1

Glucocorticoid-Induced Osteoporosis

Publisher: Elsevier

Date: 2001

DOI: 10.1016/B978-012470862-4/50045-3

Age-related changes in serum testosterone and sex hormone binding globulin in Australian men: longitudinal analyses of two geographically separate regional cohorts.

Publisher: The Endocrine Society

Date: 09-2007

DOI: 10.1210/JC.2007-0862

Abstract: Background: Cross-sectional studies from different populations show a variable decline in blood testosterone concentrations as men age. Few population representative cohorts have been followed up over time. Objective: The objective of the study was to quantify longitudinally the change in serum testosterone and SHBG concentrations with age in two well-defined, representative but geographically widely separated regional Australian cohorts. Subjects and Setting: The Busselton cohort comprises in iduals aged 18–90 yr residing in Western Australia assessed prospectively since 1981. Sera were assayed from 910 men, from whom further s les were available 14 yr later in 480. The Dubbo cohort involves in iduals aged 61–90 yr living in Eastern Australia. Baseline sera were collected from 610 men and additional sera on a second (n = 370) and third (n = 200) occasion from 1989 to 2004. Men from both cohorts are community dwelling and of predominately European origin. Results: Longitudinal analyses show the following: 1) total testosterone declines comparably (P & 0.9) by 1.3% (Busselton) and 0.9% (Dubbo) per annum with the same rates of decline when analyses were restricted to men older than 60 yr of age 2) annual changes in SHBG were also very similar in age-restricted analyses (2.3% vs. 2.5%, P = 0.48) and 3) the annual increase in SHBG was steeper in middle-aged and older men (P & 10−3vs. young men). These longitudinal changes were all up to 4-fold greater in magnitude, compared with cross-sectional analyses of baseline data. Conclusion: In two separate regional Australian populations, blood testosterone fell and SHBG increased comparably with age. Age-related changes in blood testosterone and SHBG previously described in urban-dwelling men are the same in men who reside in smaller regional cities of another continent.

Important risk factors and attributable risk of vertebral fractures in the population-based Tromsø study

Publisher: Springer Science and Business Media LLC

Date: 31-08-2012

DOI: 10.1186/1471-2474-13-163

Decreased Mortality and Subsequent Fracture Risk in Patients With a Major and Hip Fracture After the Introduction of a Fracture Liaison Service: A 3-Year Follow-Up Survey.

Publisher: Wiley

Date: 10-09-2022

DOI: 10.1002/JBMR.4674

Abstract: Fracture liaison services (FLS) are considered to be the most effective organizational approach for secondary fracture prevention. In this study, we evaluated whether FLS care was associated with reduced subsequent fracture and mortality risk over 3 years of follow-up. In total, 8682 consecutive patients aged 50-90 years with a recent fracture were included. Before FLS introduction, regular fracture treatment procedures were followed (pre-FLS). After FLS introduction, patients were invited to the FLS and FLS attenders were assessed for osteoporosis, prevalent vertebral fractures, metabolic bone disorders, medication use, and fall risk, and treatment for fracture prevention was initiated according to Dutch guidelines. All fractures were radiographically confirmed and categorized into major/hip (pelvis, proximal humerus or tibia, vertebral, multiple rib, distal femur) and non-major/non-hip (all other fractures). Mortality risk was examined using age and sex adjusted Cox proportional hazard models. For subsequent fracture risk, Cox proportional hazard models were adjusted for age, sex, and competing mortality risk (subdistribution hazard [SHR] approach). The pre-FLS group consisted of 2530 patients (72% women), of whom 1188 (46.9%) had major/hip index fractures, the post-FLS group consisted of 6152 patients (69% women), of whom 2973 (48.3%) had major/hip index fractures. In patients with a non-major/non-hip fracture there was no difference in subsequent non-major/non-hip fracture risk or mortality between pre-FLS and post-FLS. In patients with a major/hip index fracture, mortality risk was lower post-FLS (hazard ratio [HR] 0.84 95% confidence interval [CI], 0.73-0.96) and subsequent major/hip fracture risk was lower in the first 360 days after index fracture post-FLS compared to pre-FLS (SHR 0.67 95% CI, 0.52-0.87). In conclusion, FLS care was associated with a lower mortality risk in the first 3 years and a lower subsequent major/hip fracture risk in the first year in patients with a major/hip index fracture but not in patients with a non-major/non-hip fracture. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Outcomes Following Osteoporotic Fractures

Publisher: Elsevier

Date: 2013

DOI: 10.1016/B978-0-12-415853-5.00035-2

Compound risk of high mortality following osteoporotic fracture and refracture in elderly women and men

Publisher: Wiley

Date: 18-10-2013

DOI: 10.1002/JBMR.1968

Abstract: After fracture there is increased risk of refracture and premature mortality. These outcomes, particularly premature mortality following refracture, have not previously been studied together to understand overall mortality risk. This study examined the long-term cumulative incidence of subsequent fracture and total mortality with mortality calculated as a compound risk and separated according to initial and refracture. Community-dwelling participants aged 60+ years from Dubbo Osteoporosis Epidemiology Study with incident fractures, followed prospectively for further fractures and deaths from 1989 to 2010. Subsequent fracture and mortality ascertained using cumulative incidence competing risk models allowing four possible outcomes: death without refracture death following refracture refracture but alive, and event-free. There were 952 women and 343 men with incident fracture. Within 5 years following initial fracture, 24% women and 20% men refractured and 26% women and 37% men died without refracture. Of those who refractured, a further 50% of women and 75% of men died, so that total 5-year mortality was 39% in women and 51% in men. Excess mortality was 24% in women and 27% in men. Although mortality following refracture occurred predominantly in the first 5 years post-initial fracture, total mortality (post-initial and refracture) was elevated for 10 years. Most of the 5-year to 10-year excess mortality was associated with refracture. The long-term (>10 years) refracture rate was reduced, particularly in the elderly as a result of their high mortality rate. The 30% alive beyond 10 years postfracture were at low risk of further adverse outcomes. Refractures contribute substantially to overall mortality associated with fracture. The majority of the mortality and refractures occurred in the first 5 years following the initial fracture. However, excess mortality was observed for up to 10 years postfracture, predominantly related to that after refracture.

Endogenous sex hormones and incident fracture risk in older men: the Dubbo Osteoporosis Epidemiology Study.

Publisher: American Medical Association (AMA)

Date: 14-01-2008

DOI: 10.1001/ARCHINTERNMED.2007.2

Abstract: Data on the influence of gonadal hormones on incident fracture risk in elderly men are limited. We prospectively examined the relationship between serum levels of testosterone and estradiol and future fracture risk in community-dwelling men. A total of 609 men older than 60 years had been observed between January 1989 and December 2005, with the median duration being 5.8 years (up to 13 years). Clinical risk factors, including bone mineral density and lifestyle factors, were assessed at baseline. Serum testosterone and estradiol levels were measured by tandem mass spectrometry. The incidence of a low-trauma fracture was ascertained during follow-up. During follow-up, 113 men had at least 1 low-trauma fracture. The risk of fracture was significantly increased in men with reduced testosterone levels (hazard ratio [HR], 1.33 95% confidence interval [CI], 1.09-1.62). After adjustment for sex hormone-binding globulin, serum testosterone (HR, 1.48 95% CI, 1.22-1.78) and serum estradiol (HR, 1.21 95% CI, 1.00-1.47) levels were associated with overall fracture risk. After further adjustment for major risk factors of fractures (age, weight or bone mineral density, fracture history, smoking status, calcium intake, and sex hormone-binding globulin), lower testosterone was still associated with increased risk of fracture, particularly with hip (HR, 1.88 95% CI, 1.24-2.82) and nonvertebral (HR, 1.32 95% CI, 1.03-1.68) fractures. In community-dwelling men older than 60 years, serum testosterone is independently associated with the risk of osteoporotic fracture and its measurement may provide additional clinical information for the assessment of fracture risk in elderly men.

Significant perturbation of vitamin D-parathyroid-calcium axis and adverse clinical outcomes in critically ill patients

Publisher: Springer Science and Business Media LLC

Date: 13-10-2013

DOI: 10.1007/S00134-012-2713-Y

Abstract: A prospective multicentre cohort study was conducted to determine the prevalence of hypovitaminosis D in adult critically ill patients, to characterize alterations in the parathyroid hormone (PTH)-vitamin D-calcium axis and to explore associations between hypovitaminosis D and adverse clinical outcomes. Demographic, disease severity scores and clinical outcome data were collected in 100 consecutive patients with expected intensive care unit (ICU) admission of at least 2 days. Levels of 25-hydroxyvitamin D (25-OH-D), 1,25-dihydroxyvitamin D (1,25-(OH)(2)-D), PTH and ionized calcium were measured on days 1, 3 and on day 7 or ICU discharge. The prevalence of vitamin D insufficiency (25 nmol/L ≤ 25-OH-D ≤ 50 nmol/L) and deficiency (25-OH-D 7 pmol/L) was observed in 37.5 % of hypocalcaemic and 32.5 % of vitamin D insufficient/deficient patients, and was associated with higher SAPS-II [43 (31.3-60) vs. 36 (30-43), p = 0.03]. Hypovitaminosis D and secondary hyperparathyroidism are highly prevalent in critically ill patients. Low vitamin D status persists during ICU stay and is associated with worse disease severity and fewer hospital-free days.

Preadmission Bisphosphonate and Mortality in Critically Ill Patients

Publisher: The Endocrine Society

Date: 05-2016

DOI: 10.1210/JC.2015-3467

Abstract: Increased bone resorption predicts mortality and bone resorption heightens during critical illness. Bisphosphonates are potent inhibitors of bone resorption. Whether bisphosphonate impacts clinical outcome of intensive care unit (ICU) admission is unknown. We investigated the relationship between preadmission bisphosphonate use and clinical outcome in critically ill patients. This was a retrospective hospital-based analysis. The study was conducted at a tertiary referral hospital ICU. A total of 7830 critically ill patients between 2003 and 2014 participated in the study. The intervention included bisphosphonate treatment. In-hospital mortality in the main study (n = 7830) and bone density loss and biochemical and hematological changes in the mechanistic substudy (n = 111) were measured. A total of 245 patients received preadmission bisphosphonate. Bisphosphonate users were older (66 ± 16 vs 58 ± 18 y, P < .01) and had greater comorbid disease burden (Charlson comorbidity index: 5.7 ± 3.6 vs 4.6 ± 3.8, P < .01), yet bisphosphonate use was associated with a lower in-hospital mortality (mortality rate ratio: 0.41, 95% confidence interval 0.24-0.71, P < .01), which remained significant after adjusting for age, sex, principal diagnosis, admitting unit, comorbidities and admission year. Bisphosphonate-associated survival benefit was independent of vitamin D, but bisphosphonate/vitamin D co-use was associated with additive reduction in mortality (mortality rate ratio 0.38, 95% confidence interval 0.20-0.71, P < .01). Bone density decreased during ICU admission (-13% ± 19% per week, P < .01) but was significantly attenuated among bisphosphonate users compared with nonusers (-3% ± 13% per week v. -15% ± 14% per week, P < .01), despite similar disease severity on admission. All bisphosphonate users in the substudy survived, whereas six nonusers died. Preadmission bisphosphonate use was associated with superior survival among critically ill patients. Prospective studies examining the effects of bisphosphonate in critical illness are required.

Safer medicines To reduce falls and refractures for OsteoPorosis (#STOP): a study protocol for a randomised controlled trial of medical specialist-initiated pharmacist-led medication management review

Publisher: BMJ

Date: 08-2023

DOI: 10.1136/BMJOPEN-2023-072050

Abstract: Minimal trauma fractures (MTFs) often occur in older patients with osteoporosis and may be precipitated by falls risk-increasing drugs. One category of falls risk-increasing drugs of concern are those with sedative/anticholinergic properties. Collaborative medication management services such as Australia’s Home Medicine Review (HMR) can reduce patients’ intake of sedative/anticholinergics and improve continuity of care. This paper describes a protocol for an randomised controlled trial to determine the efficacy of an HMR service for patients who have sustained MTF. Eligible participants are as follows: ≥65 years of age, using ≥5 medicines including at least one falls risk-increasing drug, who have sustained an MTF and under treatment in one of eight Osteoporosis Refracture Prevention clinics in Australia. Consenting participants will be randomised to control (standard care) or intervention groups. For the intervention group, medical specialists will refer to a pharmacist for HMR focused on reducing falls risk predominately through making recommendations to reduce falls risk medicines, and adherence to antiosteoporosis medicines. Twelve months from treatment allocation, comparisons between groups will be made. The main outcome measure is participants’ cumulative exposure to sedative and anticholinergics, using the Drug Burden Index. Secondary outcomes include medication adherence, emergency department visits, hospitalisations, falls and mortality. Economic evaluation will compare the intervention strategy with standard care. Approval was obtained via the New South Wales Research Ethics and Governance Information System (approval number: 2021/ETH12003) with site-specific approvals granted through Human Research Ethics Committees for each research site. Study outcomes will be published in peer-reviewed journals. It will provide robust insight into effectiveness of a pharmacist-based intervention on medicine-related falls risk for patients with osteoporosis. We anticipate that this study will take 2 years to fully accrue including follow-up. ACTRN12622000261718.

Mortality following the first hip fracture in Norwegian women and men (1999–2008). A NOREPOS study

Publisher: Elsevier BV

Date: 06-2014

DOI: 10.1016/J.BONE.2014.02.016

Abstract: Hip fractures are associated with increased mortality and their incidence in Norway is one of the highest worldwide. The aim of this nationwide study was to examine short- and long-term mortality after hip fractures, burden of disease (attributable fraction and potential years of life lost), and time trends in mortality compared to the total Norwegian population. Information on incident hip fractures between 1999 and 2008 in all persons aged 50 years and older was collected from Norwegian hospitals. Death and emigration dates of the hip fracture patients were obtained through 31 December 2010. Standardized mortality ratios (SMRs) were calculated and Poisson regression analyses were used for the estimation of time trends in SMRs. Among the 81,867 patients with a first hip fracture, the 1-year excess mortality was 4.6-fold higher in men, and 2.8-fold higher in women compared to the general population. Although the highest excess mortality was observed during the first two weeks post fracture, the excess risk persisted for twelve years. Mortality rates post hip fracture were higher in men compared to women in all age groups studied. In both genders aged 50 years and older, approximately 5% of the total mortality in the population was related to hip fractures. The largest proportion of the potential life-years lost was in the relatively young-old, i.e. less than 80 years. In men, the 1-year absolute mortality rates post hip fracture declined significantly between 1999 and 2008, by contrast, the mortality in women increased significantly relatively to the population mortality.

U-shaped association of plasma testosterone, and no association of plasma estradiol, with incidence of fractures in men

Publisher: The Endocrine Society

Date: 10-03-2020

DOI: 10.1210/CLINEM/DGAA115

Abstract: Whether androgens, distinct from estrogen, maintain bone health during male aging has implications for understanding osteoporosis. We assessed associations of different sex hormones with incidence of any bone fracture or hip fracture in older men. Analysis of 3307 community-dwelling men aged 76.8 ± 3.5 years, median follow-up period of 10.6 years. Plasma testosterone (T), dihydrotestosterone (DHT), and estradiol (E2) assayed by mass spectrometry, sex hormone-binding globulin (SHBG), and luteinizing hormone (LH) using immunoassay. Incident fractures determined via data linkage. We analyzed probability of fracture and performed Cox regression adjusted for age, medical comorbidities, and frailty. Incident fractures occurred in 330 men, including 144 hip fractures. Probability plots suggested nonlinear relationships between hormones and risk of any fracture and hip fracture, with higher risk at lower and higher plasma T, lower E2, higher SHBG, and higher LH. In fully adjusted models, there was a U-shaped association of plasma T with incidence of any fracture (Quartile 2 [Q2] versus Q1: fully adjusted hazard ratio [HR] = 0.69, 95% confidence interval [CI] 0.51–0.94, P = .020 Q3: HR 0.59, 95% CI 0.42–0.83, P = .002) and hip fracture (Q2 versus Q1: HR 0.60, 95% CI 0.37–0.93, P = .043 Q3: HR 0.52, 95% CI 0.31–0.88, P = .015). DHT, E2, and LH were not associated with fracture. Higher SHBG was associated with hip fracture (Q4 versus Q1: HR 1.76, 95% CI 1.05–2.96, P = .033). Midrange plasma T was associated with lower incidence of any fracture and hip fracture, and higher SHBG with increased risk of hip fracture. Circulating androgen rather than estrogen represents a biomarker for hormone effects on bone driving fracture risk.

The Effect of Changing Scan Mode on Trabecular Bone Score Using Lunar Prodigy

Publisher: Elsevier BV

Date: 10-2016

DOI: 10.1016/J.JOCD.2016.01.002

Abstract: Trabecular bone score (TBS) is a measure of gray scale homogeneity that correlates with trabecular microarchitecture and is an independent predictor of fracture risk. TBS is being increasingly used in the assessment of patients at risk of osteoporosis and has recently been incorporated into FRAX

The role of calcium and non calcium-based phosphate binders in chronic kidney disease

Publisher: Wiley

Date: 03-2017

DOI: 10.1111/NEP.13031

Abstract: Rising levels of serum phosphate occur late in the course of chronic kidney disease (CKD) and have been easy targets for nephrologists to treat using phosphate binding drugs, as well as fertile ground for the pharmaceutical industry, for meta-analysis and for the earnest pontifications of guideline writers. Unfortunately, the evidence does little to support this focus, which might be better applied to earlier, adaptive hormonal changes, and to phosphate balance rather than serum phosphate levels. Nevertheless, phosphate binders are ubiquitously prescribed to patients on dialysis, and often prescribed to patients with earlier stages of CKD for which there is no evidence of benefit and some evidence that calcium-based binders (CBBs) and possibly non-CBBs may cause more harm than placebo. For patients on dialysis, observational studies suggest that phosphate binder use may reduce mortality. Meta-analyses report reduced hypercalcaemia for non-CBBs versus CBBs, and compared with CBBs sevelamer has been reported to significantly reduce vascular calcification progression and, in some but not all studies, overall mortality. However, limitations include study heterogeneity. For patients on dialysis, CBBs appear to have no advantages over the non-CBBs, apart from lower cost. In general, it seems prudent to avoid prescribing calcium-based drugs to patients who are pre-dialysis, and to use non-CBBs preferentially in CKD stage 5D. Current draft Kidney Disease Improving Global Outcomes guidelines suggest that CBB dosage be minimized in CKD stages 3 to 5D.

Absolute fracture-risk prediction by a combination of calcaneal quantitative ultrasound and bone mineral density

Publisher: Springer Science and Business Media LLC

Date: 17-12-2012

DOI: 10.1007/S00223-011-9556-3

Abstract: Quantitative ultrasound measurement (QUS) and bone mineral density (BMD) have each been shown to predict fracture risk in women. The present study examined whether a combination of QUS and BMD could improve the predictive accuracy of fracture risk. This is a population-based prospective study which involved 454 women and 445 men aged 62-89 years. Femoral neck BMD (FNBMD) was measured by DXA and calcaneal QUS was measured as broadband ultrasound attenuation (BUA) by a CUBA sonometer. Fragility fracture was ascertained by X-ray reports during the follow-up period, which took place between mid-1989 and 2009. During the follow-up period (median 13 years, range 11-15), 75 men and 154 women sustained a fragility fracture. In women, the model with FNBMD and BUA had a higher AUC compared to that without BUA (0.73 vs. 0.71 for any fracture, 0.81 vs. 0.77 for hip fracture, and 0.72 vs. 0.70 for vertebral fracture). Reclassification analysis yielded a total net reclassification improvement of 7.3%, 11.1%, and 5.2% for any, hip, and vertebral fractures, respectively. For men, the addition of BUA to FNBMD did not improve the predictive power for any, hip, or vertebral fracture. These results suggest that calcaneal QUS is an independent predictor of fracture risk and that a combination of QUS and BMD measurement could improve the predictive accuracy of fracture risk in elderly women.

Epidemiological transition to mortality and refracture following an initial fracture

Publisher: eLife Sciences Publications, Ltd

Date: 09-02-2021

DOI: 10.7554/ELIFE.61142

Abstract: This study sought to redefine the concept of fracture risk that includes refracture and mortality, and to transform the risk into "skeletal age". We analysed data obtained from 3521 women and men aged 60 years and older, whose fracture incidence, mortality, and bone mineral density (BMD) have been monitored since 1989. During the 20-year follow-up period, among 632 women and 184 men with a first incident fracture, the risk of sustaining a second fracture was higher in women (36%) than in men (22%), but mortality risk was higher in men (41%) than in women (25%). The increased risk of mortality was not only present with an initial fracture, but was accelerated with refractures. Key predictors of post-fracture mortality were male gender (hazard ratio [HR] 2.4 95% CI, 1.79–3.21), advancing age (HR 1.67 1.53–1.83), and lower femoral neck BMD (HR 1.16 1.01–1.33). A 70-year-old man with a fracture is predicted to have a skeletal age of 75. These results were incorporated into a prediction model to aid patient-doctor discussion about fracture vulnerability and treatment decisions.

Impact of osteoporotic fracture type and subsequent fracture on mortality: the Tromsø Study

Publisher: Springer Science and Business Media LLC

Date: 26-10-2019

DOI: 10.1007/S00198-019-05174-5

Abstract: Less is known about the impact of non-hip non-vertebral fractures (NHNV) on early death. This study demonstrated increased risk of dying following hip and NHNV fractures which was further increased by a subsequent fracture. This highlights the importance of early intervention to prevent both initial and subsequent fractures and improve survival. Osteoporotic fractures are a major health concern. Limited evidence exists on their impact on mortality in ageing populations. This study examined the contribution of initial fracture type and subsequent fracture on mortality in a Norwegian population that has one of the highest rates of fractures. The Tromsø Study is a prospective population-based cohort in Norway. Women and men aged 50+ years were followed from 1994 to 2010. All incident hip and non-hip non-vertebral (NHNV) fractures were registered. NHNV fractures were classified as either proximal or distal. Information on self-reported co-morbidities, lifestyle factors, general health and education level was collected. Multivariable Cox models were used to quantify mortality risk with incident and subsequent fractures analysed as time-dependent variables. Of 5214 women and 4620 men, 1549 (30%) and 504 (11%) sustained a fracture, followed by 589 (38%) and 254 (51%) deaths over 10,523 and 2821 person-years, respectively. There were 403 (26%) subsequent fractures in women and 68 (13%) in men. Hip fracture was associated with a two-fold increase in mortality risk (HR 2.05, 95% CI 1.73-2.42 in women and 2.49, 95% CI 2.00-3.11 in men). Proximal NHNV fractures were associated with 49% and 81% increased mortality risk in women and men (HR 1.49, 95% CI 1.21-1.84 and 1.81, 95% CI 1.37-2.41), respectively. Distal NHNV fractures were not associated with mortality. Subsequent fracture was associated with 89% and 77% increased mortality risk in women and men (HR 1.89, 95% CI 1.52-2.35 and 1.77, 95% CI 1.16-2.71), respectively. Hip, proximal NHNV and subsequent fractures were significantly associated with increased mortality risk in the elderly, highlighting the importance of early intervention.

Vitamin D deficiency and supplementation in critical illness—the known knowns and known unknowns

Publisher: Springer Science and Business Media LLC

Date: 29-10-2018

DOI: 10.1186/S13054-018-2185-8

GWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures

Publisher: Springer Science and Business Media LLC

Date: 03-05-2019

DOI: 10.1038/S41467-019-09860-0

Abstract: Bone area is one measure of bone size that is easily derived from dual-energy X-ray absorptiometry (DXA) scans. In a GWA study of DXA bone area of the hip and lumbar spine (N ≥ 28,954), we find thirteen independent association signals at twelve loci that replicate in s les of European and East Asian descent ( N = 13,608 – 21,277). Eight DXA area loci associate with osteoarthritis, including rs143384 in GDF5 and a missense variant in COL11A1 (rs3753841). The strongest DXA area association is with rs11614913[T] in the microRNA MIR196A2 gene that associates with lumbar spine area ( P = 2.3 × 10 −42 , β = −0.090) and confers risk of hip fracture ( P = 1.0 × 10 −8 , OR = 1.11). We demonstrate that the risk allele is less efficient in repressing miR-196a-5p target genes. We also show that the DXA area measure contributes to the risk of hip fracture independent of bone density.

Sex Differences in the Relationship Between Socio-Cultural Norms and Sunbathing

Publisher: Springer Science and Business Media LLC

Date: 31-10-2017

DOI: 10.1007/S12529-016-9606-3

Abstract: The tripartite influence model (Thompson et al. 1999) proposes that internalized appearance ideals mediate the relationship between socio-cultural norms endorsing a tanned appearance and sunbathing. This study examined the extent to which socio-cultural norms lead to an idealization of darker skin, which in turn predicts sunbathing. This study also explored whether the relationship between an internalized muscular physique and sunbathing is moderated by sex. Adult males (N = 124) and females (N = 175) completed an online questionnaire measuring socio-cultural norms endorsing a tanned appearance, internalization of mesomorphic and tanned ideals, and sunbathing. The internalization of a tanned ideal mediated between norms and sunbathing in both sexes, with a greater internalization of a tanned ideal associated with more frequent sunbathing in both sexes. Moderation analysis revealed that increased sunbathing was associated with a greater internalization of a mesomorphic ideal for males but a lesser internalization for females. A positive association was also found between the internalization of mesomorphic and tanned ideals in males. Overall, people who internalize a tanned ideal based on the perceived attitudes of others are more likely to sunbathe. This study extended current literature by suggesting that males internalize a tanned ideal and finding an association between internalized mesomorphic and tanned ideals in males.

Progressively increasing fracture risk with advancing age after initial incident fragility fracture: The Tromsø Study

Publisher: Wiley

Date: 18-09-2013

DOI: 10.1002/JBMR.1952

Abstract: The risk of subsequent fracture is increased after initial fractures however, proper understanding of its magnitude is lacking. This population-based study examines the subsequent fracture risk in women and men by age and type of initial incident fracture. All incident nonvertebral fractures between 1994 and 2009 were registered in 27,158 participants in the Tromsø Study, Norway. The analysis included 3108 subjects with an initial incident fracture after the age of 49 years. Subsequent fracture (n = 664) risk was expressed as rate ratios (RR) and absolute proportions irrespective of death. The rates of both initial and subsequent fractures increased with age, the latter with the steepest curve. Compared with initial incident fracture rate of 30.8 per 1000 in women and 12.9 per 1000 in men, the overall age-adjusted RR of subsequent fracture was 1.3 (95% CI, 1.2-1.5) in women, and 2.0 (95% CI, 1.6-2.4) in men. Although the RRs decreased with age, the absolute proportions of those with initial fracture who suffered a subsequent fracture increased with age from 9% to 30% in women and from 10% to 26% in men, between the age groups 50-59 to 80+ years. The type of subsequent fracture varied by age from mostly minor fractures in the youngest to hip or other major fractures in the oldest age groups, irrespective of type and severity of initial fracture. In women and men, 45% and 38% of the subsequent hip or other major fractures, respectively, were preceded by initial minor fractures. The risk of subsequent fracture is high in all age groups. At older age, severe subsequent fracture types follow both clinically severe and minor initial incident fractures. Any fragility fracture in the elderly reflects the need for specific osteoporosis management to reduce further fracture risk.

Obesity: Bariatric surgery, weight loss and bone

Publisher: Springer Science and Business Media LLC

Date: 10-2013

DOI: 10.1038/NRENDO.2013.189

β3-adrenergic receptor gene, body mass index, bone mineral density and fracture risk in elderly men and women: The Dubbo Osteoporosis Epidemiology Study (DOES)

Publisher: Springer Science and Business Media LLC

Date: 05-07-2006

DOI: 10.1186/1471-2350-7-57

Abstract: Recent studies have suggested that the Arg allele of β3-adrenergic receptor (ADRB3) gene is associated with body mass index (BMI), which is an important predictor of bone mineral density (BMD) and fracture risk. However, whether the ADRB3 gene polymorphism is associated with fracture risk has not been investigated. The aim of study was to examine the inter-relationships between ADRB3 gene polymorphisms, BMI, BMD and fracture risk in elderly Caucasians. Genotypes of the ADRB3 gene were determined in 265 men and 446 women aged 60+ in 1989 at entry into the study, whose BMD were measured by DXA (GE Lunar, WI USA) at baseline. During the follow-up period (between 1989 and 2004), fractures were ascertained by reviewing radiography reports and personal interviews. The allelic frequencies of the Trp and the Arg alleles were 0.925 and 0.075 respectively, and the relative frequencies of genotypes Trp/Trp , Trp/Arg and Arg/Arg 0.857, 0.138 and 0.006 respectively. There was no significant association between BMI and ADRB3 genotypes (p = 0.10 in women and p = 0.68 in men). There was also no significant association between ADRB3 genotypes and lumbar spine or femoral neck BMD in either men and women. Furthermore, there were no significant association between ADRB3 genotypes and fracture risk in both women and men, either before or after adjusting for and, BMD and BMI. The present data suggested that in Caucasian population the contribution of ADRB3 genotypes to the prediction of BMI, BMD and fracture risk is limited.

Musculoskeletal health of Indigenous Australians

Publisher: Springer Science and Business Media LLC

Date: 14-07-2018

DOI: 10.1007/S11657-018-0493-X

Abstract: Research on non-communicable diseases (NCD) in Indigenous Australians has mostly focused on diabetes mellitus and chronic kidney or cardiovascular disease. Osteoporosis, characterised by low bone mass and structural deterioration of bone tissue, and sarcopenia, the age-related loss of muscle mass and strength, often co-exist with these common NCDs-the combination of which will disproportionately increase bone fragility and fracture risk and negatively influence cortical and trabecular bone. Furthermore, the social gradient of NCDs, including osteoporosis and fracture, is well-documented, meaning that specific population groups are likely to be at greater risk of poorer health outcomes: Indigenous Australians are one such group. This review summarises the findings reported in the literature regarding the muscle and bone health of Indigenous Australians. There are limited data regarding the musculoskeletal health of Indigenous Australians however, areal bone mineral density (aBMD) measured by dual-energy X-ray absorptiometry (DXA) is reported to be greater at the hip compared to non-Indigenous Australians. Falls are the leading cause of injury-related hospitalisations in older Australians, particularly Indigenous Australians, with a great proportion suffering from fall-related fractures. Despite sparse data, it appears that Indigenous men and women have a substantially higher risk of hip fracture at a much younger age compared to non-Indigenous Australians. Data on more detailed musculoskeletal health outcomes are required in Indigenous Australians to better understand fracture risk and to formulate evidence-based strategies for fracture prevention and to minimise the risk of falls.

Current status and distribution of hip fractures among older adults in China

Publisher: Springer Science and Business Media LLC

Date: 02-03-2021

DOI: 10.1007/S00198-021-05849-Y

Response to Letter to the Editor: “Two-Thirds of All Fractures Are Not Attributable to Osteoporosis and Advancing Age: Implication for Fracture Prevention”

Publisher: The Endocrine Society

Date: 22-05-2019

DOI: 10.1210/JC.2019-01016

Antiresorptive Medication Use Is not Associated With Acute Cardiovascular Risk: An Observational Study

Publisher: The Endocrine Society

Date: 21-11-2022

DOI: 10.1210/CLINEM/DGAC669

Abstract: Bisphosphonates have been reported to be cardioprotective in some, but not all, studies. It is unknown whether denosumab (Dmab) use protects against cardiovascular events (CVEs). To determine whether oral bisphosphonate (oBP) or Dmab use is associated with CVEs in persons with incident fracture. Participants with an incident minimal trauma fracture from the Sax Institute’s 45 and Up Study, a population-based cohort from NSW, Australia, were followed between 2005/2009 and 2017. Questionnaire data were linked to hospital admissions (Admitted Patients Data Collection [APDC]) by the Centre for Health Record Linkage). Medicare Benefit Schedule (MBS) and Pharmaceutical Benefits Scheme (PBS) data sets were provided by Services Australia. Data was stored in a secure computing environment (Secure Unified Research Environment). Fractures, CVEs, and comorbidities were identified from the APDC and oBP and Dmab medication from the PBS. oBP and Dmab users were matched to never users (NoRx) by propensity scores. The main outcome measures were association between oBP and Dmab with CVE (acute myocardial infarction, unstable angina, cerebrovascular accident, and transient ischemic attack) and were determined using a stratified Cox's proportional hazards model. There were 880 pairs of oBP and NoRx (616 women) and 770 pairs of Dmab and NoRx (615 women) followed for ∼4.3 years. CVE risk was similar for oBP and NoRx Hazard Ratios (HR) women, 0.88 [95% CI 0.65-1.18] men, 1.07 [95% CI 0.72-1.57]). Similar findings were obtained for Dmab (Hazard Ratios (HR) women, 1.08 [95% CI 0.78-1.50] men, 1.55 [95% CI 0.96-2.48]). oBP and Dmab use was not associated with CVEs.

Successful direct intervention for osteoporosis in patients with minimal trauma fractures

Publisher: Springer Science and Business Media LLC

Date: 30-06-2007

DOI: 10.1007/S00198-007-0418-9

Abstract: In this study, we offered osteoporosis investigation and treatment directly to patients at out-patient fracture clinics shortly after they sustained minimal trauma fractures. We achieved long-term compliance to the recommended investigation and treatment in 80% of patients. This approach is much more successful than previous interventions. Osteoporosis remains under-treated in minimal-trauma fracture subjects. The aim of this study was to determine if direct intervention at orthopaedic fracture clinics would improve post-fracture management in these subjects. From March 2004 to March 2006, 155 consecutive minimal-trauma fracture subjects (mean age 64.0 +/- 17.6) attending fracture clinics at St. Vincent's Hospital, Sydney, had a specific medical assessment, following which they were recommended BMD and laboratory testing. Treatment recommendations were given after review of investigations with further follow-up at a median of 8.6 months following therapy. Comparison of outcomes was made with a similar group of patients given written information 2 years prior. At baseline, 47% of patients had prior fractures, but only 26% had had BMD screening. Twenty-one percent were on anti-resorptive therapy, and 15% were on calcium/vitamin D. Following intervention, 83% had a BMD and of these, 68% had a T-score < -1.0. Of treatment naïve patients, 44% were recommended anti-resorptive therapy and 56% were recommended calcium/vitamin D. Compliance was 80% for anti-resorptive and 76% for calcium/vitamin D. Female gender and lower BMD were predictors of compliance. Compared with information-based intervention, direct intervention improved management two to fivefold, maintaining long-term treatment in 90% of osteoporotic and 73% of osteopenic subjects requiring therapy.

Hypogonadism in men with intellectual disabilities: A population study

Publisher: Informa UK Limited

Date: 06-2003

DOI: 10.1080/1366825031000147094

New sequence variants associated with bone mineral density

Publisher: Springer Science and Business Media LLC

Date: 14-12-2008

DOI: 10.1038/NG.284

Abstract: In an extended genome-wide association study of bone mineral density among 6,865 Icelanders and a follow-up in 8,510 subjects of European descent, we identified four new genome-wide significant loci. These are near the SOST gene at 17q21, the MARK3 gene at 14q32, the SP7 gene at 12q13 and the TNFRSF11A (RANK) gene at 18q21. Furthermore, nonsynonymous SNPs in the C17orf53, LRP4, ADAM19 and IBSP genes were suggestively associated with bone density.

Mortality after all major types of osteoporotic fracture in men and women: An observational study

Publisher: Elsevier BV

Date: 03-1999

DOI: 10.1016/S0140-6736(98)09075-8

Risk factors for proximal humerus, forearm, and wrist fractures in elderly men and women: The Dubbo osteoporosis epidemiology study

Publisher: Oxford University Press (OUP)

Date: 15-03-2001

DOI: 10.1093/AJE/153.6.587

Abstract: Fractures of the proximal humerus, forearm, and wrist account for approximately one third of total osteoporotic fractures in the elderly. Several risk factors for these fractures were evaluated in this prospective study of 739 men and 1,105 women aged > or =60 years in Dubbo, Australia. During follow-up (1989-1996), the respective incidences of humerus and of forearm and wrist fractures, per 10,000 person-years, were 22.6 and 33.8 for men and 54.8 and 124.6 for women. Independent predictors of humerus fracture were femoral neck bone mineral density (FNBMD) (relative risk (RR) = 2.3, 95% confidence interval (CI): 1.2, 4.5) in men and FNBMD (RR = 2.4, 95% CI: 1.7, 3.5) and height loss (RR = 1.1, 95% CI: 1.0, 1.2) in women. For forearm and wrist fractures, risk factors were FNBMD (men: RR = 1.5, 95% CI: 1.0, 2.3 women: RR = 1.5, 95% CI: 1.2, 1.9) and height loss (men: RR = 1.2, 95% CI: 1.0, 1.3 women: RR = 1.1, 95% CI: 1.0, 1.2). In addition, dietary calcium (men: RR = 2.0, 95% CI: 1.0, 3.6) and a history of falls (women: RR = 1.9, 95% CI: 1.4, 2.6) were also significant. These data suggest that elderly men and women largely share common risk factors for upper limb fractures and that FNBMD is the primary risk factor.

Adequacy of vitamin D replacement in severe deficiency is dependent on body mass index.

Publisher: Elsevier BV

Date: 11-2009

DOI: 10.1016/J.AMJMED.2009.06.008

Abstract: Obesity is associated with hypovitaminosis D. Whether body mass index (BMI) determines the replacement dose of vitamin D to achieve sufficiency is unclear. To determine the relationship between BMI and serum 25-OH vitamin D concentrations and whether the increase in serum 25-OH vitamin D concentrations with vitamin D replacement is dependent on BMI. Retrospective review of anthropometric data and serum 25-OH vitamin D concentrations in 95 patients attending an outpatient clinic in a tertiary hospital. In a second component of the study, 17 hospital inpatients with severe vitamin D deficiency (serum 25-OH D concentrations<6 ng/mL [15 nmol/L]) were supplemented with 10,000 units vitamin D(3)/day orally for 1 week. Biochemistry and anthropometric measurements were compared before and after vitamin D replacement. Serum 25-OH vitamin D concentrations correlated negatively with BMI in the 95 outpatients (r(2) = 0.11, P <.01). In the longitudinal study, BMI correlated positively with serum intact parathyroid hormone (r(2) = 0.84, P <.01) and negatively with 1.25-(OH)(2) vitamin D (r(2) = 0.19, P=.06) at baseline. Serum 25-OH D concentrations achieved following 1 week of vitamin D(3) replacement correlated negatively with BMI (r(2) = 0.63, P <.01). Efficacy of vitamin D supplementation is dependent on BMI. Overweight and obese patients with hypovitaminosis D might require higher doses of vitamin D to achieve vitamin D repletion compared with in iduals with normal body weight.

Contribution of Quadriceps Weakness to Fragility Fracture: A Prospective Study

Publisher: Wiley

Date: 04-08-2016

DOI: 10.1002/JBMR.2594

Abstract: The association between muscle weakness and fracture is not well understood. This study sought to examine the contribution of muscle strength at baseline and change in muscle strength to the observed risk of fragility fracture in older people. The study involved 595 men and 1066 women aged 60+ years (median 69 years) who had been followed for a median of 11 years (range, 4 to 22 years). Quadriceps isometric muscle strength (MS) measured at baseline and biennially was adjusted for height. Femoral neck bone mineral density (FNBMD) was measured by DXA. Low-trauma fracture was ascertained from X-ray reports and interview. The relationship between baseline MS and serial MS and fracture assessed by time-invariant and time-variant Cox's regression models was expressed as hazard ratio (HR) and 95% confidence interval (CI). During the follow-up period, 282 (26%) women and 89 (15%) men sustained a fragility fracture. From age 60 years, women lost 0.28 kg/m (1.6%) of MS per year, whereas men lost 0.39 kg/m (1.5%) of MS per year. In the time-variant model, using serial MS, each 1 SD (4.7 kg/m) lower MS was associated with a 27% increase in the risk of fracture in women (HR 1.27 95% CI, 1.11 to 1.43) and 46% increase in men (HR 1.46 95% CI, 1.22 to 1.75). After adjusting for FNBMD, age and prior fracture, history of fall and smoking, HR per SD of lower MS was 1.13 (95% CI, 0.99 to 1.28) for women and 1.35 (95% CI, 1.18 to 1.64) for men. These data indicate that muscle weakness is an independent determinant of fracture risk in men, but not in women. This sex difference suggests that apart from mechanical load effect of muscle on bone, there are other muscle-bone interactions that need to be investigated in future studies. The accuracy of fracture risk prediction for men may be improved by incorporating muscle strength.

Imminent fracture risk and disability post fracture

Publisher: Elsevier

Date: 2021

DOI: 10.1016/B978-0-12-813073-5.00028-9

Determinants of mortality risk following osteoporotic fractures

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 07-2016

DOI: 10.1097/BOR.0000000000000300

Abstract: Increased mortality risk is accepted for hip and vertebral fracture. Recent data suggest that other fracture types have also been linked to excess mortality. This article reviews the existing evidence on the pattern and determinants of postfracture mortality. The pattern of mortality over time following hip and vertebral fractures has recently been clarified. Nonhip nonvertebral fractures at major, and even minor sites in older in iduals have also been associated with excess mortality. Studies have revealed the higher excess mortality in men and in younger age groups for all fracture types. Despite the increasing knowledge on the fracture-mortality association, little is known about its cause. The role of co-morbidities is inconsistent across studies. Recent findings suggest low bone mass, bone loss and muscle weakness are linked to both fracture and mortality risk, and thus may play a role in postfracture mortality. Nonhip nonvertebral fractures have recently been associated with mortality risk. Larger studies are needed to better understand which specific fractures and factors contribute to fracture-associated mortality risk. The role of bone loss in postfracture mortality needs to be validated in more studies, because of its potential reversibility with antifracture therapies.

Decline in Muscle Strength and Performance Predicts Fracture Risk in Elderly Women and Men

Publisher: The Endocrine Society

Date: 08-07-2020

DOI: 10.1210/CLINEM/DGAA414

Abstract: Muscle strength and performance are associated with fractures. However, the contribution of their rate of decline is unclear. To assess the independent contribution of the rate of decline in muscle strength and performance to fracture risk. Community-dwelling women (n = 811) and men (n = 440) aged 60 years or older from the prospective Dubbo Osteoporosis Epidemiology Study followed from 2000 to 2018 for incident fracture. Clinical data, appendicular lean mass/height2 (ht)2, bone mineral density, quadricep strength/ht (QS), timed get-up-and-go (TGUG), 5 times repeated sit-to-stand (5xSTS), and gait speed (GS) measured biennially. Rates of decline in muscle parameters were calculated using ordinary least squares regression and fracture risk was assessed using Cox’s models. Incident low-trauma fracture ascertained by x-ray report. Apart from lean mass in women, all muscle parameters declined over time. Greater rates of decline in physical performance were associated with increased fracture risk in women (Hazard ratios [HRs] ranging from 2.1 (95% CI: 1.5–2.9) for GS to 2.7 (95% CI: 1.9–3.6) for 5xSTS, while in men only the decline in GS was associated with fracture risk (HR: 3.4 [95% CI: 1.8–6.3]). Baseline performance and strength were also associated with increased fracture risk in men (HRs ranging from 1.8 (95% CI: 1.1–3.0) for QS to 2.5 (95% CI: 1.5–4.1) for TGUG, but not in women. Rate of decline in physical performance in both genders, and baseline strength and performance in men, contributed independently to fracture risk. Sit-to-stand and GS were the tests most consistently associated with fractures. Further studies are required to determine whether muscle strength and/or performance improve the predictive accuracy of fracture prediction models.

Muscle Strength and Physical Performance Improve Fracture Risk Prediction Beyond Garvan and FRAX: The Osteoporotic Fractures in Men (MrOS) Study

Publisher: Wiley

Date: 08-12-2021

DOI: 10.1002/JBMR.4483

Abstract: Muscle strength and physical performance are associated with fracture risk in men. However, it is not known whether these measurements enhance fracture prediction beyond Garvan and FRAX tools. A total of 5665 community‐dwelling men, aged ≥65 years, from the Osteoporotic Fractures in Men (MrOS) Study, who had data on muscle strength (grip strength) and physical performance (gait speed and chair stand tests), were followed from 2000 to 2019 for any fracture, major osteoporotic fracture (MOF), initial hip, and any hip fracture. The contributions to different fracture outcomes were assessed using Cox's proportional hazard models. Tool‐specific analysis approaches and outcome definitions were used. The added predictive values of muscle strength and physical performance beyond Garvan and FRAX were assessed using categorical net reclassification improvement (NRI) and relative importance analyses. During a median follow‐up of 13 (interquartile range 7–17) years, there were 1014 fractures, 536 MOFs, 215 initial hip, and 274 any hip fractures. Grip strength and chair stand improved prediction of any fracture (NRI for grip strength 3.9% and for chair stand 3.2%) and MOF (5.2% and 6.1%). Gait speed improved prediction of initial hip (5.7%) and any hip (7.0%) fracture. Combining grip strength and the relevant performance test further improved the models (5.7%, 8.9%, 9.4%, and 7.0% for any, MOF, initial, and any hip fractures, respectively). The improvements were predominantly driven by reclassification of those with fracture to higher risk categories. Apart from age and femoral neck bone mineral density, muscle strength and performance were ranked equal to or better than the other risk factors included in fracture models, including prior fractures, falls, smoking, alcohol, and glucocorticoid use. Muscle strength and performance measurements improved fracture risk prediction in men beyond Garvan and FRAX. They were as or more important than other established risk factors. These measures should be considered for inclusion in fracture risk assessment tools. © 2021 American Society for Bone and Mineral Research (ASBMR).

Roux-en-Y gastric bypass and gastric sleeve surgery result in long term bone loss

Publisher: Springer Science and Business Media LLC

Date: 26-08-2021

DOI: 10.1038/S41366-020-00660-X

The utility of absolute risk prediction using FRAX^® and Garvan Fracture Risk Calculator in daily practice

Publisher: Elsevier BV

Date: 02-2014

DOI: 10.1016/J.MATURITAS.2013.10.021

Abstract: There are two commonly used fracture risk prediction tools FRAX(®) and Garvan Fracture Risk Calculator (GARVAN-FRC). The objective of this study was to investigate the utility of these tools in daily practice. A prospective population-based 5-year follow-up study was conducted in ten general practice centres in the Netherlands. For the analyses, the FRAX(®) and GARVAN-FRC 10-year absolute risks (FRAX(®) does not have 5-year risk prediction) for all fractures were used. Among 506 postmenopausal women aged ≥60 years (mean age: 67.8±5.8 years), 48 (9.5%) sustained a fracture during follow-up. Both tools, using BMD values, distinguish between women who did and did not fracture (10.2% vs. 6.8%, respectively for FRAX(®) and 32.4% vs. 39.1%, respectively for GARVAN-FRC, p<0.0001) at group level. However, only 8.9% of those who sustained a fracture had an estimated fracture risk ≥20% using FRAX(®) compared with 53.3% using GARVAN-FRC. Although both underestimated the observed fracture risk, the GARVAN-FRC performed significantly better for women who sustained a fracture (higher sensitivity) and FRAX(®) for women who did not sustain a fracture (higher specificity). Similar results were obtained using age related cut off points. The discriminant value of both models is at least as good as models used in other medical conditions hence they can be used to communicate the fracture risk to patients. However, given differences in the estimated risks between FRAX(®) and GARVAN-FRC, the significance of the absolute risk must be related to country-specific recommended intervention thresholds to inform the patient.

Prevalence of vertebral fractures in women and men in the population-based Tromsø Study

Publisher: Springer Science and Business Media LLC

Date: 17-01-2012

DOI: 10.1186/1471-2474-13-3

Bone resorption and osteoporotic fractures in elderly men: the dubbo osteoporosis epidemiology study.

Publisher: Wiley

Date: 04-2005

DOI: 10.1359/JBMR.041207

Assessing the clinical utility of genetic profiling in fracture risk prediction: a decision curve analysis

Publisher: Springer Science and Business Media LLC

Date: 12-08-2021

DOI: 10.1007/S00198-020-05403-2

Association of Muscle Weakness With Post-Fracture Mortality in Older Men and Women: A 25-Year Prospective Study

Publisher: Wiley

Date: 03-2017

DOI: 10.1002/JBMR.3037

Abstract: Osteoporotic fracture increases the risk of premature mortality. Muscle weakness is associated with both increased fracture risk and low bone mineral density (BMD). However, the role of muscle strength in post-fracture mortality is not well understood. This study examines the change of muscle strength measured at quadriceps (QS) before and after fracture and defines the relationship between muscle strength and post-fracture mortality. The study involved 889 women and 295 men (who were participating in the Dubbo Osteoporosis Study) who had at least one low-trauma fracture (ascertained from X-ray reports) after the age of 50 years. Median follow-up time was 11 years (range 1 to 24). To determine the change in muscle strength before and after a fracture, we selected a subset of 344 women and 99 men who had had at least two muscle strength measurements before the fracture event and a subset of 407 women and 105 men who had had at least two measurements after the fracture. During the follow-up period, 366 (41.2%) women and 150 (50.9%) men died. The annual rate of decrease in height-adjusted muscle strength before fracture was 0.27 kg/m (1.85%) in women and 0.40 kg/m (1.79%) in men. Strength loss after fracture was not significantly different from that before fracture. In women, after adjusting for baseline age and BMD, each SD (5 kg/m) lower height-adjusted pre- and post-fracture quadriceps strength was associated with a 27% (hazard ratio [HR] = 1.27 95% confidence interval [CI] 1.07, 1.50) and 18% (HR = 1.18 95% CI 1.01, 1.38) increase in post-fracture mortality risk, respectively. Similarly, in men, each SD (5 kg/m) lower height-adjusted pre- and post-fracture QS was associated with increased mortality before fracture (HR = 1.33 95% CI 1.09, 1.63) and after fracture (HR = 1.43 95% CI 1.16, 1.78). Muscle weakness accounted for 15% (95% CI 0.05, 0.24) of premature deaths after fracture in women and 23% (95% CI 0.11, 0.35) in men. These results indicate that in the older in iduals, lower muscle strength is an independent risk factor for post-fracture mortality. © 2017 American Society for Bone and Mineral Research.

Association between breast cancer and bone mineral density: The Dubbo Osteoporosis Epidemiology Study

Publisher: Elsevier BV

Date: 07-2000

DOI: 10.1016/S0378-5122(00)00133-X

Abstract: The association between bone mineral density and breast cancer was investigated in a nested case-control study, involving 30 breast cancer cases and 120 controls, aged 68+/-6 (mean +/-S.D.) years, as part of the Dubbo Osteoporosis Epidemiology Study (Australia). Bone mineral density (BMD, g/cm(2)) at the femoral neck and lumbar spine was measured by dual energy X-ray absorptiometry. Anthropometric data and reproductive history were collected by direct interview using a structured questionnaire. In univariate conditional logistic regression analysis, lower age at menarche, longer overall duration of lifetime ovulation and higher bone density were associated with higher risk of breast cancer. Among the breast cancer cases, 20% of subjects had lumbar spine BMD greater than 1.20 g/cm(2) (or 2.5 S.D. above the mean) compared with less than 1% of the controls. After adjusting for the effects of duration of lifetime ovulation and body mass index, each 0.1 g/cm(2) increase in lumbar spine and femoral neck BMD was associated with a 2.1-fold (95% CI: 1.3-3.4) and 1.5-fold (1.0-2.4) respectively, higher risk of breast cancer. Further adjustment for age at menarche, hormone replacement therapy, and parity did not alter the result. Thus, postmenopausal BMD, which is affected by lifetime exposure to estrogen, is also related to risk of breast cancer. Importantly, it is estimated that estrogen therapy in osteoporotic women, even if raising the risk of breast cancer by 70% as suggested by some studies, would not elevate their risk to the level experienced by their non-osteoporotic counterparts. While the mechanism of this relationship remains to be explored, these data support the concept that lifetime exposure to estrogen is an indicator of risk of both breast cancer and osteoporosis. However, the use of estrogen in osteoporosis treatment would not elevate the risk of breast cancer in osteoporotic women up to the level experienced by their non-osteoporotic counterparts.

Effects of bariatric surgery and dietary intervention on insulin resistance and appetite hormones over a 3 year period

Publisher: Springer Science and Business Media LLC

Date: 13-04-2023

DOI: 10.1038/S41598-023-33317-6

Abstract: To examine an impact of three types of bariatric surgery compared with dietary intervention (DIET), on concurrent changes in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and appetite hormones over 3 years. Fifty-five adults were studied during phase of weight loss (0–12 months) and during weight stability (12–36 months) post intervention. Measurements of HOMA-IR, fasting and postprandial PYY and GLP1, adiponectin, CRP, RBP4, FGF21 hormones and dual-Xray absorptiometry were performed throughout the study. All surgical groups achieved significant reductions in HOMA-IR with greatest difference between Roux-en-Y gastric bypass and DIET (− 3.7 95% CI − 5.4, − 2.1 p = 0.001) at 12–36 months. Initial (0–12 months) HOMA-IR values were no different to DIET after adjustment for the lost weight. During 12–36 months, after controlling for treatment procedure and weight, for every twofold increase in postprandial PYY and adiponectin, HOMA-IR decreased by 0.91 (95% CI − 1.71, − 0.11 p = 0.030) and by 0.59 (95% CI − 1.10, − 0.10 p = 0.023) respectively. Initial, non-sustained changes in RBP4 and FGF21 were not associated with HOMA-IR values. While initial rapid weight loss reduces insulin resistance, the enhanced secretions of PYY and adiponectin may contribute to weight-independent improvements in HOMA-IR during weight stability. Clinical trial registration : Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12613000188730.

Prediction of changes in bone mineral density in the elderly: contribution of “osteogenomic profile”

Publisher: Springer Science and Business Media LLC

Date: 21-06-2018

DOI: 10.1007/S11657-018-0480-2

Abstract: The contribution of genetic variants to longitudinal bone loss has not been well documented. We constructed an "osteogenomic profile" based on 62 BMD-associated genetic variants and showed that the profile was significantly associated with bone loss, independently from baseline BMD and age. The osteogenomic profile can help predict bone loss in an in idual. The rate of longitudinal bone loss (ΔBMD) is a risk factor for fracture. The variation in ΔBMD is partly determined by genetic factors. This study sought to define the association between an osteogenomic profile and ΔBMD. The osteogenomic profile was created from 62 BMD-associated SNPs from genome-wide association studies (GWAS) that were genotyped in 1384 elderly men and women aged 60+ years. Weighted genetic risk scores (GRS) were constructed for each in idual by summing the products of the number of risk alleles and the sex-specific regression coefficients [associated with BMD from GWAS]. ΔBMD, expressed as annual percent change-in-BMD, was determined by linear regression analysis for each in idual who had had at least two femoral neck BMD measurements. The mean ΔBMD was - 0.65% (SD 1.64%) for women and - 0.57% (SD 1.40%) for men, and this difference was not statistically significant (P = 0.32). In women, each unit increase in GRS was associated with 0.21% (SE 0.10) higher ΔBMD at the femoral neck (P = 0.036), and this association was independent of baseline BMD and age. In logistic regression analysis, each unit increase of GRS was associated with 41% odds (95%CI: 1.07-1.87) of rapid bone loss (ΔBMD ≤ - 1.2%/year mean of rapid loss group = - 2.2%/year). There was no statistically significant association between ΔBMD and GRS in men. We conclude that the osteogenomic profile constructed from BMD-associated genetic variants is modestly associated with long-term changes in femoral neck BMD in women, but not in men.

Bone Failure in Critical Illness

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 12-2016

DOI: 10.1097/CCM.0000000000001874

Abstract: The origin of systemic inflammatory response syndrome and multiple organ dysfunction syndrome is poorly understood but remains a fundamental concern in the ICU. This paper provides a critical appraisal on whether bone failure may represent an unrecognized component of systemic inflammatory response syndrome/multiple organ dysfunction syndrome. Search of the PubMed database and manual review of selected articles investigating bone pathophysiology in critical illness. Bone hyperresorption is highly prevalent among critically ill patients. Bone breakdown releases numerous systemically active cytokines and bone-sequestered toxins, with the capacity to fuel inflammatory hypercytokinaemia and metabolic toxaemia. Anti-resorptive medication inhibits bone break down and preadmission anti-resorptive use is associated with superior survival among critically ill patients. We propose that hyperresorptive bone failure is an unrecognised component of systemic inflammatory response syndrome/multiple organ dysfunction syndrome that is causal to critical illness progression. If this hypothesis is valid, bone preservative strategies could reduce the risk of osteoporosis/fractures among ICU survivors, as well as decreasing critical illness mortality.

Trigger Warnings: Caring or Coddling

Publisher: Australian and New Zealand Student Services Association Inc.

Date: 08-10-2017

DOI: 10.30688/JANZSSA.2017.20

Osteoporosis management in 2017: still thin and fragmented

Publisher: Wiley

Date: 11-2017

DOI: 10.1111/IMJ.13598

Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture.

Publisher: Springer Science and Business Media LLC

Date: 14-09-2015

DOI: 10.1038/NATURE14878

Increased bone mineral density in Aboriginal and Torres Strait Islander Australians: Impact of body composition differences

Publisher: Elsevier BV

Date: 07-2012

DOI: 10.1016/J.BONE.2012.04.011

Abstract: Bone mineral density (BMD) has been reported to be both higher and lower in Indigenous women from different populations. Body composition data have been reported for Indigenous Australians, but there are few published BMD data in this population. We assessed BMD in 161 Indigenous Australians, identified as Aboriginal (n=70), Torres Strait Islander (n=68) or both (n=23). BMD measurements were made on Norland-XR46 (n=107) and Hologic (n=90) dual-energy X-ray absorptiometry (DXA) machines. Norland BMD and body composition measurements in these in iduals, and also in 36 Caucasian Australians, were converted to equivalent Hologic BMD (BMD(H)) and body composition measurements for comparison. Femoral neck (FN) and lumbar spine Z-scores were high in Indigenous participants (mean FN Z-score: Indigenous men +0.98, p<0.0001 vs. mean zero Indigenous women +0.82, p<0.0001 vs. mean zero). FN BMD(H) was higher in Aboriginal and/or Torres Strait Islander than Caucasian participants, after adjusting for age, gender, diabetes and height and remained higher in men after addition of lean mass to the model. We conclude that FN BMD is higher in Aboriginal and/or Torres Strait Islander Australians than Caucasian Australian reference ranges and these differences still remained significant in men after adjustment for lean mass. It remains to be seen whether these BMD differences translate to differences in fracture rates.

Premature Ovarian Failure and Ovarian Dysgenesis Associated with Balanced and Unbalanced X‐6 Translocations, Respectively: Implications for the Investigation of Ovarian Failure

Publisher: Wiley

Date: 05-1994

DOI: 10.1111/J.1479-828X.1994.TB02687.X

Abstract: This study reports the effect of an inherited (X ) translocation which has not previously been described. The proband was intellectually delayed and had ovarian dysgenesis. Karyotyping revealed an unbalanced karyotype: 46,X,der(X)t(X )(q22 p11.2)*. Her mother was shown to be a carrier of an apparently balanced translocation between the X chromosome and chromosome 6: 46,X,t(X )(q22 11.2). This finding in the mother raises to 7 the number of cases reported which involve a break within the X chromosome 'critical region', at band Xq22, without causing ovarian dysgenesis, although it was associated with premature ovarian failure. These cases aim to highlight to clinical specialists the range of gonadal and other phenotypic anomalies (apart from those associated with Turner syndrome) which can occur due to partial deletions of the X chromosome. These findings have implications for the investigation of both ovarian dysgenesis and premature ovarian failure.

Osteoporotic fracture: Missed opportunity for intervention

Publisher: Springer Science and Business Media LLC

Date: 09-2003

DOI: 10.1007/S00198-003-1452-X

Abstract: As prior fracture is consistently associated with increased risk of subsequent fracture, subjects with a history of prior fracture represent a high risk group which should be targeted for intervention to reduce future fracture rates. The aim of this study was to investigate whether prior osteoporotic fracture affected treatment patterns among subjects admitted with hip fractures. All hip fracture admissions to two major teaching hospitals of the University of New South Wales, Sydney, Australia, over the 12-month period between July 1997 and June 1998 were identified retrospectively from medical records. Patient demographics, frequency and location of prior fractures, and treatment status on admission were recorded. There were a total of 348 atraumatic hip fracture admissions over this 12-month period. Forty five percent of 251 women and 30% of 97 men with an osteoporotic hip fracture had a known prior fracture, including prior hip fracture in 19% of the women and 8% of the men. Among subjects with prior fractures, only 18% of women and 7% of men were on any specific anti-osteoporosis therapy. Even among those with a prior hip fracture, only 21% of women and none of the men were taking optimal appropriate therapy. A high proportion of in iduals suffering hip fractures had sustained prior "signal" fractures. Although more subjects with prior fracture received treatment than those without prior fracture, total treatment levels were low, and the majority of high-risk subjects did not receive therapy shown to reduce the risk of further fractures.

Genetic Prediction of Lifetime Risk of Fracture

Publisher: The Endocrine Society

Date: 11-05-2023

DOI: 10.1210/CLINEM/DGAD254

Abstract: Fragility fracture is a significant public health problem because it is associated with increased mortality. We want to find out whether the risk of fracture can be predicted from the time of birth. To examine the association between a polygenic risk score (PRS) and lifetime fracture risk. This population-based prospective study involved 3515 community-dwelling in iduals aged 60+ years who have been followed for up to 20 years. Femoral neck bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry. A PRS was created by summing the weighted number of risk alleles for each single nucleotide polymorphism using BMD-associated coefficients. Fragility fractures were radiologically ascertained, whereas mortality was ascertained through a state registry. Residual lifetime risk of fracture (RLRF) was estimated by survival analysis. The mortality-adjusted RLRF for women and men was 36% (95% CI, 34%-39%) and 21% (18%-24%), respectively. In iduals with PRS & 4.24 (median) had a greater risk (1.2-fold in women and 1.1-fold in men) than the population average risk. For hip fracture, the average RLRF was 10% (95% CI, 8%-12%) for women and ∼5% (3%-7%) for men however, the risk was significantly increased by 1.5-fold and 1.3-fold for women and men with high PRS, respectively. A genetic profiling of BMD-associated genetic variants is associated with the residual lifetime risk of fracture, suggesting the potential for incorporating the polygenic risk score in personalized fracture risk assessment.

Genetic profiling and individualized prognosis of fracture

Publisher: Wiley

Date: 20-01-2011

DOI: 10.1002/JBMR.219

Abstract: Fragility fracture is a serious public health problem in the world. The risk of fracture is determined by genetic and nongenetic clinical risk factors. This study sought to quantify the contribution of genetic profiling to fracture prognosis. The study was built on the ongoing Dubbo Osteoporosis Epidemiology Study, in which fracture and risk factors of 858 men and 1358 women had been monitored continuously from 1989 and 2008. Fragility fracture was ascertained by radiologic reports. Bone mineral density at the femoral neck was measured by dual-energy X-ray absorptiometry (DXA). Fifty independent genes with allele frequencies ranging from 0.01 to 0.60 and relative risks (RRs) ranging from 1.01 to 3.0 were simulated. Three predictive models were fitted to the data in which fracture was a function of (1) clinical risk factors only, (2) genes only, and (3) clinical risk factors and 50 genes. The area under the curve (AUC) for model 1 was 0.77, which was lower than that of model II (AUC = 0.82). Adding genes into the clinical risk factors model (model 3) increased the AUC to 0.88 and improved the accuracy of fracture classification by 45%, with most (41%) improvement in specificity. In the presence of clinical risk factors, the number of genes required to achieve an AUC of 0.85 was around 25. These results suggest that genetic profiling could enhance the predictive accuracy of fracture prognosis and help to identify high-risk in iduals for appropriate management of osteoporosis or intervention.

Contribution of Lumbar Spine BMD to Fracture Risk in Individuals with T-Score Discordance

Publisher: Wiley

Date: 03-09-2016

DOI: 10.1002/JBMR.2611

Abstract: Fracture risk estimates are usually based on femoral neck (FN) BMD. It is unclear how to address T-score discordance, where lumbar spine (LS) T-score is lower than FN T-score. The objective of this work was to examine the impact of LS BMD on fracture risk, in in iduals with lower LS T-score than FN T-score. Participants aged 60+ years from the Dubbo Osteoporosis Epidemiology Study with LS and FN BMD measured at first visit, and were followed from 1989 to 2014. Five-hundred and seventy-three (573) of 2270 women and 131 of 1373 men had lower LS than FN T-score by ≥ 0.6 standard deviation (SD) (low-LS group based on least significant change). In low-LS women, each 1 SD lower LS T-score than FN was associated with a 30% increase in fracture risk (hazard ratio [HR] 1.30 95% CI, 1.11 to 1.45). For low-LS men there was a 20% nonsignificant increase in fracture risk for each 1 SD lower LS than FN T-score (HR 1.20 95% CI, 0.10 to 1.67). Low-LS women had greater absolute fracture risks than the rest of the women. This increased risk was more apparent for lower levels of FN T-score and in older age groups. At an FN T-score of -2, low-LS women had a 3%, 10%, and 23% higher 5-year absolute fracture risk than non-low LS women in the 60 to 69 year, 70 to 79 year, and 80+ years age-groups, respectively. Furthermore, an osteoporotic LS T-score increased 5-year absolute fracture risk for women with normal or osteopenic FN T-score by 10% to 13%. Men in the low-LS group had very few fractures therefore, a meaningful analyses of fracture risk could not be conducted. This study shows the significant contribution of lower LS BMD to fracture risk over and above FN BMD in women. A LS BMD lower than FN BMD should be incorporated into fracture risk calculators at least for women in older age-groups.

Enhancement of absolute fracture risk prognosis with genetic marker: The collagen i alpha 1 gene

Publisher: Springer Science and Business Media LLC

Date: 30-09-2009

DOI: 10.1007/S00223-009-9296-9

Abstract: An important objective of genetic research in osteoporosis is to translate genotype data into the prognosis of fracture. The present study sought to develop a prognostic model for predicting osteoporotic fracture by using information from a genetic marker and clinical risk factors. It was designed as a prospective epidemiological study which involved 894 women of Caucasian background aged 60+ years who had been followed for a median of 9 years (from 1989 and 2008, range 0.2-18 years). During the follow-up period, fragility fracture was ascertained by X-ray reports for all women. Bone mineral density (BMD) at the femoral neck was measured by dual-energy X-ray absorptiometry. Genotypes of the Sp1 binding site in the first intron of the collagen I alpha 1 (COLIA1) gene polymorphism were determined by polymerase chain reaction, digestion with BalI restriction enzyme, and agarose gel electrophoresis. The relationship between COL1A1 genotype and fracture was assessed by the Cox proportional hazards model, from which nomograms were developed for in idualizing the risk of fracture. The distribution of COL1A1 genotypes was consistent with the Hardy-Weinberg equilibrium law: GG (63.8%), GT (32.6%), and TT (3.6%). During the follow-up period, there were 322 fractures, including 77 hip and 127 vertebral fractures. There was an overrepresentation of the TT genotype in the fracture group (6.2%) compared with the nonfracture group (2.3%). Compared with carriers of GT and GG, women carrying the TT genotype had increased risk of any fracture (relative risk [RR] = 1.91, 95% CI 1.21-3.00), hip fracture (RR = 3.67, 95% CI 1.69-8.00), and vertebral fracture (RR = 3.36, 95% CI 1.81-6.24). The incorporation of COL1A1 genotypes improved the risk reclassification by 2% for any fragility fracture, 4% for hip fracture, and 5% for vertebral fracture, beyond age, BMD, prior fracture, and fall. Three nomograms were constructed for predicting fracture risk in an in idual woman based on age, BMD, and COLIA1 genotypes. These data suggest that the COLIA1 Sp1 polymorphism is associated with the risk of fragility fracture in Caucasian women and that the polymorphism could enhance the predictive accuracy of fracture prognosis. The nonograms presented here can be useful for in idualizing the short- and intermediate-term prognosis of fracture risk and help identify high-risk in iduals for intervention for appropriate management of osteoporosis.

Osteoporosis medication and reduced mortality risk in elderly women and men

Publisher: The Endocrine Society

Date: 04-2011

DOI: 10.1210/JC.2010-2730

Abstract: Osteoporotic fractures are associated with premature mortality. Antiresorptive treatment reduces refracture but mortality reduction is unclear. The objective of the study was to examine the effect of osteoporosis treatment [bisphosphonates (BP), hormone therapy (HT), and calcium ± vitamin D only (CaD)] on mortality risk. This was a prospective cohort study (April 1989 to May 2007). The study was conducted with community-dwelling elderly (aged 60+ yr) subjects in Dubbo, a semiurban city, Australia. Subjects included 1223 and 819 women and men in the Dubbo Osteoporosis Epidemiology Study. Mortality according to treatment group was recorded. There were 325 (BP, n = 106 HT, n = 77 CaD, n = 142) women and 37 men (BP, n = 15 CaD, n = 22) on treatment. In women, mortality rates were lower with BP 0.8/100 person-years (0.4, 1.4) and HT 1.2/100 person-years (0.7, 2.1) but not CaD 3.2/100 person-years (2.5, 4.1) vs. no treatment 3.5/100 person-years (3.1, 3.8). Accounting for age, fracture occurrence, comorbidities, quadriceps strength, and bone mineral density, mortality risk remained lower for women on BP [hazard ratio (HR) 0.3 (0.2, 0.6)] but not HT [HR 0.8 (0.4, 1.8)]. For 429 women with fractures, mortality risk was still reduced in the BP group [adjusted HR 0.3 (0.2, 0.7)], not accounted for by a reduction in subsequent fractures. In men, lower mortality rates were observed with BP but not CaD [BP 1.0/100 person-years (0.3, 3.9) and CaD 3.1/100 person-years (1.5, 6.6) vs. no treatment 4.3/100 person-years (3.9, 4.8)]. After adjustment, mortality was similar, although not significant [HR 0.5 (0.1, 2.0)]. Osteoporosis therapy appears to reduce mortality risk in women and possibly men.

Association between abdominal obesity and fracture risk: A prospective study

Publisher: The Endocrine Society

Date: 06-2013

DOI: 10.1210/JC.2012-2958

Abstract: Higher body weight is associated with greater bone mineral density (BMD) and lower fracture risk. However, the relationship between abdominal fat mass (aFM) and fracture risk is unclear because of limited prospective data. The present study sought to examine the association between aFM, BMD, and fracture risk. The study was designed as a prospective investigation, in which a s le of 1126 participants (360 men and 766 women) aged 50 years or older had been continuously followed up for an average of 5 years. The mean age of participants was 71 years (range, 57–94 years). At baseline, BMD at the femoral neck and lumbar spine and aFM were measured by dual-energy X-ray absorptiometry. The incidence of low-trauma and nonpathological fractures was ascertained prospectively from X-ray reports. During the follow-up period, 19 men and 107 women had sustained a fracture. In women, each 1-kg lower aFM was associated with a 50% higher risk of fracture (hazard ratio [HR], 1.50 95% confidence interval [CI], 1.10–2.05) after adjustment for age, femoral neck BMD, falls, stature, physical activity, and prior fracture. Subgroup analysis by fracture type found that the association was mainly observed in clinical vertebral fracture (HR, 1.96 95% CI, 1.22–3.13). In men, although there was no statistically significant association between aFM and fracture risk (HR, 1.15 95% CI, 0.58–2.25), the strength of this finding is affected negatively by the low number of fractures. Lower abdominal fat was significantly associated with an higher fracture risk in women.

Residual Lifetime Risk of Fractures in Women and Men

Publisher: Wiley

Date: 06-2007

DOI: 10.1359/JBMR.070315

Abstract: In a s le of 1358 women and 858 men, > or = 60 yr of age who have been followed-up for up to 15 yr, it was estimated that the mortality-adjusted residual lifetime risk of fracture was 44% for women and 25% for men. Among those with BMD T-scores or = 60 yr of age as of 1989 of white background from the Dubbo Osteoporosis Epidemiology Study were analyzed. The participants have been followed for up to 15 yr. During the follow-up period, incidence of low-trauma, nonpathological fractures, confirmed by X-ray and personal interview, were recorded. Incidence of mortality was also recorded. BMD at the femoral neck was measured by DXA (GE-LUNAR) at baseline. Residual lifetime risk of fracture from the age of 60 was estimated by the survival analysis taking into account the competing risk of death. After adjusting for competing risk of death, the RLRF for women and men from age 60 was 44% (95% CI, 40-48) and 25% (95% CI, 19-31), respectively. For in iduals with osteoporosis (BMD T-scores < or = -2.5), the mortality-adjusted lifetime risk of any fracture was 65% (95% CI, 58-73) for women and 42% (95% CI, 24-71) for men. For the entire cohort, the lifetime risk of hip fracture was 8.5% (95% CI, 6-11%) for women and 4% (95% CI, 1.3-5.4%) for men risk of symptomatic vertebral fracture was 18% (95% CI, 15-21%) for women and 11% (95% CI, 7-14%) for men. These estimates provide a means to communicate the absolute risk of fracture to an in idual patient and can help promote the identification and targeting of high-risk in iduals for intervention.

Association between beta-blocker use and fracture risk: The Dubbo Osteoporosis Epidemiology Study

Publisher: Elsevier BV

Date: 03-2011

DOI: 10.1016/J.BONE.2010.10.170

Abstract: In animal model, mice treated with beta-blockers (BB) had increased bone mass. In humans, high bone mass is associated with reduce fracture risk. The present study sought to test the hypothesis that BB use is associated with reduced fracture risk. Data from 3488 participants (1285 men) aged 50 years and above in the Dubbo Osteoporosis Epidemiology Study (DOES) were analyzed. Baseline characteristics of participants were obtained at the initial visit which had taken place between 1989 and 1993. Bone mineral density (BMD) at the lumbar spine and femoral neck was measured by dual energy X-ray absorptiometry (GE-LUNAR Corp, Madison, WI). Two hundred and sixty two (20%) men and 411 (19%) women had been on BB, as ascertained by direct interview and verification with medication history. The incidence of fragility fractures was ascertained during the follow-up period (1989-2008). In men, BB use was associated with higher BMD at the femoral neck (0.96 versus 0.92 g/cm², P < 0.01), higher lumbar spine (1.32 versus 1.25 g/cm², P < 0.01), and lower fracture risk than those not on BB (odds ratio [OR]: 0.49 95% CI: 0.32-0.75). In women, BB users also had higher femoral neck BMD (0.83 versus 0.81 g/cm², P < 0.01), higher lumbar spine BMD (1.11 versus 1.06 g/cm², P < 0.01), and lower risk of fracture than non-users (OR 0.68, 95% CI: 0.53-0.87). The associations between BB use and fracture risk were independent of age, BMD, and clinical risk factors. Subgroup analysis suggested that the association was mainly found in selective BB, not in non-selective BB. Beta-blockers use, particularly selective BB, was associated with reduced fracture risk in both men and women, and the association was independent of BMD.

Contribution of the collagen I α1 and vitamin D receptor genes to the risk of hip fracture in elderly women

Publisher: The Endocrine Society

Date: 12-2005

DOI: 10.1210/JC.2005-1153

Abstract: Hip fracture is partially genetically determined. The present study was designed to examine the contributions of vitamin D receptor (VDR) and collagen I alpha1 (COLIA1) genotypes to the liability to hip fracture in postmenopausal women. The study was designed as a prospective population-based cohort investigation. Six hundred seventy-seven postmenopausal women of Caucasian background, aged 70 +/- 7 yr (mean +/- SD), have been followed for up to 14 yr. Sixty-nine women had sustained a hip fracture during the period. Atraumatic hip fractures were prospectively identified through radiologists' reports. Bone mineral density (BMD) at the hip and lumbar spine was measured by dual-energy x-ray absorptiometry. GENOTYPES: The TaqI and SpI COLIA1 polymorphisms of the VDR and COLIA1 genes were determined. Using the Single Nucleotide Polymorphism database, VDR TT, Tt, and tt genotypes were coded as TT, TC, and CC, whereas COLIA1 SS, Ss, and ss were coded as GG, GT, and TT. Women with VDR CC genotype (16% prevalence) and COLIA1 TT genotype (5% prevalence) had an increased risk of hip fracture [odds ratio (OR) associated with CC, 2.6 95% confidence interval (CI), 1.2-5.3 OR associated with TT, 3.8 95% CI, 1.3-10.8] after adjustment for femoral neck BMD (OR, 3.4 per SD 95% CI, 2.3-5.0) and age (OR, 1.4 per 5 yr 95% CI, 1.1-1.7). Approximately 20 and 12% of the liability to hip fracture was attributable to the presence of the CC genotype and TT genotype, respectively. The VDR CC genotype and COLIA1 TT genotype were associated with increased hip fracture risk in Caucasian women, and this association was independent of BMD and age.

Bariatric Surgery and Bone Loss: Do We Need to Be Concerned?

Publisher: Springer Science and Business Media LLC

Date: 13-03-2014

DOI: 10.1007/S12018-014-9162-9

A Risk Assessment Tool for Predicting Fragility Fractures and Mortality in the Elderly

Publisher: Wiley

Date: 30-07-2020

DOI: 10.1002/JBMR.4100

Comorbidities Only Account for a Small Proportion of Excess Mortality After Fracture: A Record Linkage Study of Individual Fracture Types

Publisher: Wiley

Date: 23-03-2018

DOI: 10.1002/JBMR.3374

Abstract: Nonhip, nonvertebral (NHNV) fractures constitute the majority of osteoporotic fractures, but few studies have examined the association between these fractures, comorbidity, and mortality. Our objective was to examine the relationship between in idual nonhip, nonvertebral fractures, comorbidities, and mortality. The prospective population-based cohort of 267,043 subjects (45 and Up Study, Australia) had baseline questionnaires linked to hospital administrative and all-cause mortality data from 2006 to 2013. Associations between fracture and mortality were examined using multivariate, time-dependent Cox models, adjusted for age, prior fracture, body mass index, smoking, and comorbidities (cardiovascular disease, diabetes, stroke, thrombosis, and cancer), and survival function curves. Population attributable fraction was calculated for each level of risk exposure. During 1,490,651 person-years, women and men experienced 7571 and 4571 fractures and 7064 deaths and 11,078 deaths, respectively. In addition to hip and vertebral fractures, pelvis, humerus, clavicle, rib, proximal tibia/fibula, elbow and distal forearm fractures in both sexes, and ankle fractures in men were associated with increased multivariable-adjusted mortality hazard ratios ranging from 1.3 to 3.4. Comorbidity independently added to mortality such that a woman with a humeral fracture and 1 comorbidity had a similarly reduced 5-year survival as that of a woman with a hip fracture and no comorbidities. Population mortality attributable to any fracture without comorbidity was 9.2% in women and 5.3% in men. All proximal nonhip, nonvertebral fractures in women and men were associated with increased mortality risk. Coexistent comorbidities independently further increased mortality. Population attributable risk for mortality for fractures was similar to cardiovascular disease and diabetes, highlighting their importance and potential benefit for early intervention and treatment. © 2018 American Society for Bone and Mineral Research.

Multiple Genetic Loci for Bone Mineral Density and Fractures

Publisher: Massachusetts Medical Society

Date: 29-05-2008

DOI: 10.1056/NEJMOA0801197

Development of a nomogram for individualizing hip fracture risk in men and women

Publisher: Springer Science and Business Media LLC

Date: 17-03-2007

DOI: 10.1007/S00198-007-0362-8

Abstract: Until now there has been no published prognostic tool available for predicting of hip fracture to primary care settings. We have developed a nomogram for predicting the absolute risk of hip fracture for any in idual by using clinical factors, including age, prior fracture and fall, in addition to BMD that was based on a 15-year follow-up cohort study. Bone mineral density or clinical risk factors alone are useful but limited tools for the identification of in iduals with high-risk of hip fracture. It is hypothesized that the combination of clinical risk factors and BMD can improve the accuracy of fracture prediction. This study was aimed at developing a nomogram which combines these factors for predicting 5-year and 10-year risk of hip fracture for an in idual. The study, designed as a epidemiologic, community-based prospective study, included 1,208 women and 740 men aged 60+ years with median duration of follow-up of 13 years (inter-quartile range, IQR: 6-14) for both women and men, yielding 10,523 and 7,586 person-years of observation, respectively. Main outcome measures were incidence of hip fractures and risk factors were femoral neck bone mineral density (FNBMD), prior fracture, history of fall, postural sway and quadriceps strength. Femoral neck BMD was measured by DXA (GE-LUNAR Corp, Madison, Wisconsin, USA). Cox's proportional hazards model was used to estimate the risk of fracture for in iduals, and a nomogram was constructed for predicting hip fracture risk. Between 1989 and 2004, 127 in iduals (96 women) sustained a hip fracture. Advancing age, low femoral neck BMD, prior fracture and history of falls were independent predictors of hip fracture. The area under the receiver operating characteristic curve for the model was 0.85 for both sexes. A nomogram was constructed for predicting hip fracture risk for an in idual. Among those aged 75 or older with BMD T-scores < or = -2.5, the risk of hip fracture in men was comparable to or higher than in women however, in younger age groups, the risk was higher in women than in men. The combination of BMD and non-invasive clinical risk factors in a nomogram could be useful for identifying high-risk in iduals for intervention to reduce the risk of hip fracture.

Bariatric surgery, bone loss, obesity and possible mechanisms

Publisher: Wiley

Date: 25-10-2012

DOI: 10.1111/J.1467-789X.2012.01050.X

Association between hypertension and fragility fracture: A longitudinal study

Publisher: Springer Science and Business Media LLC

Date: 27-07-2014

DOI: 10.1007/S00198-013-2457-8

Abstract: Hypertension is an independent risk factor for osteoporosis and osteoporotic fracture in postmenopausal women. Although hypertension has been suggested to be associated with increased fracture risk, it is not clear whether the association is independent of bone mineral density (BMD). The present study sought to examine the interrelationships between hypertension, BMD, and fracture risk. The study included 1,032 men and 1,701 women aged 50 years and older who were participants in the Dubbo Osteoporosis Epidemiology Study. BMD at the femoral neck and lumbar spine was measured by dual energy X-ray absorptiometry (GE-LUNAR Corp., Madison, WI, USA). The presence of hypertension was ascertained by direct interview and verification through clinical history. The incidence of fragility fractures was ascertained by X-ray report during the follow-up period (1989-2008). The Cox proportional hazards model was used to assess the association between hypertension and fracture risk. Women with hypertension had lower BMD at the femoral neck (0.79 versus 0.82 g/cm(2), P = 0.02) than those without the disease. After adjusting for BMD and covariates, hypertension was an independent risk factor for fragility fracture [hazard ratio (HR), 1.49 95% CI, 1.13-1.96]. In men, hypertension was associated with higher femoral neck BMD (0.94 versus 0.92 g/cm(2), P = 0.02), but the association between hypertension and fracture risk did not reach statistical significance. Hypertension is associated with increased fracture risk in women, and the association is independent of BMD.

Abdominal fat and hip fracture risk in the elderly: The Dubbo Osteoporosis Epidemiology Study

Publisher: Springer Science and Business Media LLC

Date: 23-02-2005

DOI: 10.1186/1471-2474-6-11

Abstract: Fat mass, which is a major component of body weight, is directly related to bone mineral density and reduced fracture risk. It is not known whether abdominal fat is associated with hip fracture. The present study was designed to examine the association between abdominal fat and hip fracture in women and men aged 60+ years. This was a nested case-control study with one fracture case being matched with two controls of the same age. In women 63 cases were matched with 126 controls, and in men 26 cases were matched with 52 controls. Hip fracture was confirmed by X-ray and personal interview. Other measurements included weight, height, body mass index (BMI), abdominal fat, and femoral neck bone density (FNBMD). Conditional logistic regression model was used to analyse data. The odds ratio of hip fracture risk associated with each 10% lower abdominal fat was 1.5 (95% CI, 1.1 to 2.1) in women and 1.2 (95% CI, 0.7 to 2.0) in men. However after adjusting for FNBMD or body weight, the abdominal fat-fracture association was no longer statistically significant. Similarly, body weight and BMI was each significantly associated with hip fracture risk (in women), but after taking with account the effect of FNBMD, the association become statistically non-significant. Lower abdominal fat was associated with an increased risk of hip fracture in elderly women, but the association was not independent of FNBMD or weight. The contribution of abdominal fat to hip fracture risk is likely to be modest.

Prognosis of fracture: Evaluation of predictive accuracy of the FRAX™ algorithm and Garvan nomogram

Publisher: Springer Science and Business Media LLC

Date: 25-07-2010

DOI: 10.1007/S00198-009-1026-7

Abstract: We evaluated the prognostic accuracy of fracture risk assessment tool (FRAX) and Garvan algorithms in an independent Australian cohort. The results suggest comparable performance in women but relatively poor fracture risk discrimination in men by FRAX. These data emphasize the importance of external validation before widespread clinical implementation of prognostic tools in different cohorts. Absolute risk assessment is now recognized as a preferred approach to guide treatment decision. The present study sought to evaluate accuracy of the FRAX and Garvan algorithms for predicting absolute risk of osteoporotic fracture (hip, spine, humerus, or wrist), defined as major in FRAX, in a clinical setting in Australia. A retrospective validation study was conducted in 144 women (69 fractures and 75 controls) and 56 men (31 fractures and 25 controls) aged between 60 and 90 years. Relevant clinical data prior to fracture event were ascertained. Based on these variables, predicted 10-year probabilities of major fracture were calculated from the Garvan and FRAX algorithms, using US (FRAX-US) and UK databases (FRAX-UK). Area under the receiver operating characteristic curves (AUC) was computed for each model. In women, the average 10-year probability of major fracture was consistently higher in the fracture than in the nonfracture group: Garvan (0.33 vs. 0.15), FRAX-US (0.30 vs. 0.19), and FRAX-UK (0.17 vs. 0.10). In men, although the Garvan model yielded higher average probability of major fracture in the fracture group (0.32 vs. 0.14), the FRAX algorithm did not: FRAX-US (0.17 vs. 0.19) and FRAX-UK (0.09 vs. 0.12). In women, AUC for the Garvan, FRAX-US, and FRAX-UK algorithms were 0.84, 0.77, and 0.78, respectively, vs. 0.76, 0.54, and 0.57, respectively, in men. In this analysis, although both approaches were reasonably accurate in women, FRAX discriminated fracture risk poorly in men. These data support the concept that all algorithms need external validation before clinical implementation.

Fracture Burden: What Two and a Half Decades of Dubbo Osteoporosis Epidemiology Study Data Reveal About Clinical Outcomes of Osteoporosis

Publisher: Springer Science and Business Media LLC

Date: 03-03-2017

DOI: 10.1007/S11914-017-0352-5

Abstract: This review aims to highlight important clinical findings from the over 25 year-long Dubbo Osteoporosis Epidemiology Study particularly focusing on outcomes post fracture. Every low trauma fracture in the elderly is associated with an increased risk of a subsequent fracture, with a higher risk in men than women. All major or proximal fractures and even minor fractures in the very elderly or minor fractures that are then followed by re-fracture are associated with premature mortality, greatest in the first 5 years post fracture. Having a subsequent fracture further increases this high mortality risk, but if an in idual survives the high risk period, their risk returns to that of the background population. Non-hip non-vertebral fractures account for a significant proportion of the premature mortality. Despite an improvement in overall health and population mortality over the years, excess mortality post fracture has not changed in the last 2 decades. All low trauma, fractures in the elderly herald a high risk of poor outcomes, particularly in the first few years post fracture. Early intervention should be initiated.

Relationship Between Body Mass Index and Fracture Risk Is Mediated by Bone Mineral Density

Publisher: Wiley

Date: 20-10-2014

DOI: 10.1002/JBMR.2288

Abstract: The relationship between body mass index (BMI) and fracture risk is controversial. We sought to investigate the effect of collinearity between BMI and bone mineral density (BMD) on fracture risk, and to estimate the direct and indirect effect of BMI on fracture with BMD being the mediator. The study involved 2199 women and 1351 men aged 60 years or older. BMI was derived from baseline weight and height. Femoral neck BMD was measured by dual-energy X-ray absorptiometry (DXA GE-LUNAR, Madison, WI, USA). The incidence of fragility fracture was ascertained by X-ray reports from 1991 through 2012. Causal mediation analysis was used to assess the mediated effect of BMD on the BMI-fracture relationship. Overall, 774 women (35% of total women) and 258 men (19%) had sustained a fracture. Approximately 21% of women and 20% of men were considered obese (BMI ≥ 30). In univariate analysis, greater BMI was associated with reduced fracture risk in women (hazard ratio [HR] 0.92 95% confidence interval [CI], 0.85 to 0.99) and in men (HR 0.77 95% CI, 0.67 to 0.88). After adjusting for femoral neck BMD, higher BMI was associated with greater risk of fracture in women (HR 1.21 95% CI, 1.11 to 1.31) but not in men (HR 0.96 95% CI, 0.83 to 1.11). Collinearity had minimal impact on the BMD-adjusted results (variance inflation factor [VIF] = 1.2 for men and women). However, in mediation analysis, it was found that the majority of BMI effect on fracture risk was mediated by femoral neck BMD. The overall mediated effect estimates were -0.048 (95% CI, -0.059 to -0.036 p < 0.001) in women and -0.030 (95% CI, -0.042 to -0.018 p < 0.001) in men. These analyses suggest that there is no significant direct effect of BMI on fracture, and that the observed association between BMI and fracture risk is mediated by femoral neck BMD in both men and women.

Pharmacogenetics of osteoporosis and the prospect of individualized prognosis and individualized therapy

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 12-2008

DOI: 10.1097/MED.0B013E32831A46BE

Prevention of Hip Fractures: Trade‐off between Minor Benefits to Individuals and Large Benefits to the Community

Publisher: Wiley

Date: 26-09-2023

DOI: 10.1002/JBMR.4907

Abstract: Goeffrey Rose postulated that a population‐based measure bringing a small benefit to each in idual can yield large benefits to the community. We aimed to test this axiom by quantifying the relationship between change in bone mineral density (BMD) and hip fracture incidence between two prospective cohorts separated by ~10 years. In this prospective population‐based Dubbo Osteoporosis Epidemiology Study (DOES), the participants aged 60+ were recruited in two waves: the initial cohort (1311 women, 842 men) in 1989‐1992, and the second cohort (974 women, 544 men) in 1999‐2001. The incident hip fracture was radiologically ascertained. Femoral neck BMD was measured biannually. Multivariable‐adjusted Cox's proportional hazards models were adjusted for the predefined covariates such as age, BMI, lifestyle factors, falls, and prior fracture. Compared with the initial cohort, the second cohort had a higher femoral neck BMD by ~ 0.04 g/cm 2 in women and 0.03 g/cm 2 in men. However, the prevalence of osteoporosis in the second cohort was halved (prevalence ratio 0.51, 95% CI 0.36‐0.73 in women 0.45, 0.24‐0.84 in men), and its hip fracture incidence was significantly reduced (hazard ratio 0.54, 95% CI, 0.38‐0.78 in women 0.39, 0.19‐0.80 in men). Sensitivity analyses indicated that the “effect” was unlikely due to unmeasured confounders. These findings suggest that a population‐wide strategy aiming at enhancing BMD across the entire population could lead to a substantial decrease in the incidence of hip fractures. This article is protected by copyright. All rights reserved.

KBG syndrome presenting with brachydactyly type E

Publisher: Elsevier BV

Date: 06-2019

DOI: 10.1016/J.BONE.2019.03.012

Abstract: We report the case of a young woman who presented at age 10 years with height on the tenth centile, brachydactyly type E and mild developmental delay. Biochemistry and hormonal profiles were normal. Differential diagnoses considered included Albright hereditary osteodystrophy without hormone resistance (a.k.a pseudopseudohypoparathyroidism), 2q37 microdeletion syndrome and acrodysostosis. She had a normal karyotype and normal FISH of 2q37. Whole genome sequencing (WGS) identified a mutation in the ANKRD11 gene associated with KBG syndrome. We review the clinical features of the genetic syndromes considered, and suggest KBG syndrome be considered in patients presenting with syndromic brachydactyly type E, especially if short stature and developmental delay are also present.

Reduced Bone Loss Is Associated With Reduced Mortality Risk in Subjects Exposed to Nitrogen Bisphosphonates: A Mediation Analysis

Publisher: Wiley

Date: 12-08-2019

DOI: 10.1002/JBMR.3816

Abstract: Bisphosphonates, potent antiresorptive agents, have been found to be associated with mortality reduction. Accelerated bone loss is, in itself, an independent predictor of mortality risk, but the relationship between bisphosphonates, bone loss, and mortality is unknown. This study aimed to determine whether the association between bisphosphonates and mortality is mediated by a reduction in the rate of bone loss. Participants from the population-based Canadian Multicentre Osteoporosis Study were followed prospectively between1996 and 2011. Comorbidities and lifestyle factors were collected at baseline and bone mineral density (BMD) at baseline and at years 3 (for those aged 40 to 60 years), 5, and 10. Rate of bone loss was calculated using linear regression. Information on medication use was obtained yearly. Bisphosphonate users grouped into nitrogen bisphosphonates (nBP alendronate or risedronate) and etidronate and non-users (NoRx) were matched by propensity score, including all baseline factors as well as time of treatment. Cox's proportional hazards models, unadjusted and adjusted for annual rate of bone loss, were used to determine the association between nBP and etidronate versus NoRx. For the treatment groups with significant mortality risk reduction, the percent of mortality reduction mediated by a reduction in the rate of bone loss was estimated using a causal mediation analysis. There were 271 pairs of nBP and matched NoRx and 327 pairs of etidronate and matched NoRx. nBP but not etidronate use was associated with significant mortality risk reduction (hazard ratios [HR] = 0.61 [95% confidence interval 0.39-0.96] and 1.35 [95% CI 0.86-2.11] for nBP and etidronate, respectively). Rapid bone loss was associated with more than 2-fold increased mortality risk compared with no loss. Mediation analysis indicated that 39% (95% CI 7%-84%) of the nBP association with mortality was related to a reduction in the rate of bone loss. This finding provides an insight into the mechanism of the relationship between nBP and survival benefit in osteoporotic patients. © 2019 American Society for Bone and Mineral Research.

Timing of Repeat BMD Measurements: Development of an Absolute Risk‐Based Prognostic Model

Publisher: Wiley

Date: 11-2009

DOI: 10.1359/JBMR.090514

Abstract: This study attempted to address the following questions: for an in idual who is at present nonosteoporotic, given their current age and BMD level, what is the in idual's risk of fracture and when is the ideal time to repeat a BMD measurement? Nonosteoporotic women (n = 1008) and men (n = 750) over the age of 60 in 1989 from the Dubbo Osteoporosis Epidemiology Study were monitored until one of the following outcomes occurred: (1) BMD reached "osteoporosis" level (i.e., T-scores < or = -2.5) or (2) an incident fragility fracture. During the follow-up period (average, 7 yr), 346 women (34%) and 160 men (21%) developed osteoporosis or sustained a low-trauma fracture. The risk of osteoporosis or fracture increased with advancing age (women: RR/10 yr, 1.3 95% CI, 1.1-1.6 men: RR/10 yr, 2.3 95% CI, 1.7-2.9) and lower BMD levels (women: RR per -0.12 g/cm(2), 3.2 95% CI, 2.6-4.1 RR per -0.12 g/cm(2), 2.6 95% CI, 2.0-3.3). Using the predicted risk (of osteoporosis or fracture) of 10% as a cut-off level for repeating BMD measurement, the estimated time to reach the cut-off level varied from 1.5 (for an 80-yr-old woman with a T-score of -2.2) to 10.6 yr (for a 60-yr-old man with a T-score of 0). These results suggest that, based on an in idual's current age and BMD T-score, it is possible to estimate the optimal time to repeat BMD testing for the in idual. The prognostic model and approach presented in this study may help improve the in idualization and management of osteoporosis.

Two Rare Mutations in the COL1A2 Gene Associate With Low Bone Mineral Density and Fractures in Iceland

Publisher: Wiley

Date: 29-08-2015

DOI: 10.1002/JBMR.2604

Abstract: We conducted a genome-wide association study of low bone mineral density (BMD) at the hip and spine utilizing sequence variants found through whole-genome sequencing of 2636 Icelanders. We found two rare missense mutations, p.Gly496Ala and p.Gly703Ser, in the COL1A2 gene that associate with measures of osteoporosis in Icelanders. Mutations in COL1A2 are known to cause the autosomal dominant disorder osteogenesis imperfecta. Both variants associate with low BMD and with osteoporotic fractures. p.Gly496Ala (frequency of 0.105%) shows the strongest association with low BMD at the spine (p = 1.8 × 10(-7) , odds ratio [OR] = 4.61 [95% confidence interval (CI) 2.59, 8.18]), whereas p.Gly703Ser (frequency of 0.050%) is most strongly associated with low BMD at the hip (p = 1.9 × 10(-8) , OR = 9.34 [95% CI 4.28, 20.3]). Association with fractures was p = 2.2 × 10(-5) , OR = 3.75 (95% CI 2.03, 6.93) and p = 0.0023, OR = 4.32 (95% CI 1.69, 11.1), respectively. The carriers of these variants do not have signs of osteogenesis imperfecta other than low BMD, demonstrating that similar mutations in COL1A2 can affect skeletal phenotypes in more than one way.

Response to Letter to the Editor: “Two-Thirds of All Fractures Are Not Attributable to Osteoporosis and Advancing Age: Implications for Fracture Prevention”

Publisher: The Endocrine Society

Date: 12-07-2019

DOI: 10.1210/JC.2019-01457

Effect of weight loss via severe vs moderate energy restriction on lean mass and body composition among postmenopausal women with obesity: The tempo diet randomized clinical trial

Publisher: American Medical Association (AMA)

Date: 30-10-2019

DOI: 10.1001/JAMANETWORKOPEN.2019.13733

Serum level of under-carboxylated osteocalcin and bone mineral density in early menopausal Norwegian women

Publisher: Springer Science and Business Media LLC

Date: 30-11-2013

DOI: 10.1007/S00394-011-0285-1

Abstract: Serum level of under-carboxylated osteocalcin (ucOC) is considered a sensitive measure of vitamin K status, and ucOC levels are associated with bone mineral density (BMD) and fracture risk in elderly persons. The aim of this study was to assess the relationship between ucOC and BMD in early menopausal women. The data reported here come from the enrollment in a double-blinded placebo-controlled randomized trial comprising 334 healthy Norwegian women between 50 and 60 years, 1-5 years after menopause, not using warfarin or medication known to affect bone metabolism. Total hip, femoral neck, lumbar spine, and total body BMD and serum level of ucOC and total osteocalcin were measured, and information of lifestyle was collected through questionnaires. The association between ucOC and BMD at all measurement sites was assessed by multiple regression analyses adjusting for possible confounding variables. The absolute serum level of ucOC was significantly and negatively associated with BMD at all measurements sites, both in univariate analyses (p < 0.01) and in multivariate analyses adjusting for years since menopause, smoking status and weight (p < 0.01). However, serum ucOC, expressed as percentage of the total osteocalcin level, was not associated with BMD at any site. Achievement of adequate vitamin K nutritional intake is important, but ucOC expressed as percentage of total osteocalcin levels as reflection of vitamin K status does not seem to play a central role in determining BMD levels in early menopausal women.

Plasma insulin concentration is useful to guide glucose supplement in insulin overdose

Publisher: Springer Science and Business Media LLC

Date: 06-08-2009

DOI: 10.1007/S00134-008-1233-2

Risk of subsequent fractures and mortality in elderly women and men with fragility fractures with and without osteoporotic bone density: The dubbo osteoporosis epidemiology study

Publisher: Wiley

Date: 25-03-2015

DOI: 10.1002/JBMR.2393

Abstract: Half of fragility fractures occur in in iduals with nonosteoporotic BMD (BMD T-score > -2.5) however, there is no information on postfracture adverse events of subsequent fracture and mortality for different BMD levels. The objective of this work was to determine the risk and predictors of subsequent fracture and excess mortality following initial fracture according to BMD. The subjects were community-dwelling participants aged 60+ years from the Dubbo Osteoporosis Epidemiology Study with incident fractures followed from 1989 to 2011. The outcome measurements were as follows: risk of subsequent fracture and mortality according to BMD categorized as normal (T-score -2.5), and osteoporosis (T-score ≤ -2.5). There were 528 low-trauma fractures in women and 187 in men. Of these, 12% occurred in in iduals with normal BMD (38 women, 50 men) and 42% in in iduals with osteopenia (221 women, 76 men). The relative risk (RR) of subsequent fracture was >2.0-fold for all levels of BMD (normal BMD: 2.0 [1.2 to 3.3] for women and 2.1 [1.2 to 3.8] for men osteopenia: 2.1 [1.7 to 2.6] for women and 2.5 [1.6 to 4.1] for men and osteoporosis 3.2 [2.7 to 3.9] for women and 2.1 [1.4 to 3.1] for men. The likelihood of falling and reduced quadriceps strength contributed to subsequent fracture risk in women with normal BMD. By contrast with subsequent fracture risk, postfracture mortality was increased particularly in in iduals with low BMD (age-adjusted standardized mortality ratio [SMR] for osteopenia 1.3 [1.1 to 1.7] and 2.2 [1.7 to 2.9] for women and men, respectively, and osteoporosis 1.7 [1.5 to 2.0] and 2.7 [2.0 to 3.6] for women and men, respectively). This study demonstrates the high burden of subsequent fracture in in iduals with normal BMD and osteopenia, and excess mortality particularly for those with osteopenia (and osteoporosis). These findings highlight the importance of these fractures and underscore the gap in evidence for benefit of antiosteoporotic treatment for fragility fracture, in those with only mildly low BMD.

Fractures in type 2 diabetes confer excess mortality: The Dubbo osteoporosis epidemiology study

Publisher: Elsevier BV

Date: 06-2022

DOI: 10.1016/J.BONE.2022.116373

Abstract: Diabetes and fractures are both associated with increased mortality, however the effect of the combination is not well-established. We examined the mortality risk following all types of fractures in type 2 diabetes (T2D). In the Dubbo Osteoporosis Epidemiology Study (1989-2017), participants were grouped according to T2D and/or incident fracture. Study outcome was all-cause mortality. First incident radiological fragility fracture and incident T2D diagnosis were time-dependent variables. Cox's proportional hazards models quantified mortality risk associated with T2D and incident fracture overall, as well as by fracture site, T2D duration and T2D medication type. In 3618 participants (62% women), 272 had baseline and 179 developed T2D over median 13.0 years (IQR 8.2-19.6). 796 women (56 with T2D) and 240 men (25 with T2D) sustained a fracture. Compared to those without T2D or fracture, mortality risk increased progressively, in T2D without fracture, then no T2D with fracture, and was highest in those with T2D with fracture (adjusted hazard ratio (aHR) (95% CI) for women 2.62 (1.75-3.93) and men 2.61 (1.42-4.81)). Within T2D participants, incident fracture was associated with increased mortality (aHR for women 1.87 (1.10-3.16) and men 2.83 (1.41-5.68)), especially following hip/vertebral fractures in men (aHR 2.97 (1.29-6.83)) and non-hip non-vertebral fractures in women (aHR 2.42 (1.24-4.75)), and in T2D duration >5 years. Any fracture in T2D conferred significant excess mortality. In iduals with T2D should be carefully monitored post-fracture, especially if T2D >5 years. Optimising fracture prevention and post-fracture management in T2D is critical and warrants further studies.

Incidence of hip and other osteoporotic fractures in elderly men and women: Dubbo Osteoporosis Epidemiology Study

Publisher: Wiley

Date: 04-2004

DOI: 10.1359/JBMR.040109

Complex interplay among adiposity, insulin resistance and bone health

Publisher: Wiley

Date: 15-01-2018

DOI: 10.1111/COB.12240

Abstract: Obesity and osteoporosis are common public health problems. Paradoxically, while obesity is associated with higher bone density, type 2 diabetic obese in iduals have an increased fracture risk. Although obesity and insulin resistance co-exist, some obese in iduals remain insulin-sensitive. We suggest that the apparent paradox relating obesity, bone density and fracture risk in type 2 diabetes may be at least partly influenced by differences in bone strength and quality between insulin-resistant and insulin-sensitive obese in iduals. In this review, we focus on the complex interplay between, adiposity, insulin resistance and osteoporotic fracture risk and suggest that this is an important area of study that has implications for in idually tailored and targeted treatment to prevent osteoporotic fracture in obese type 2 diabetic in iduals.

Association between fat-mass-And-obesity-Associated (FTO) gene and hip fracture susceptibility

Publisher: Wiley

Date: 25-10-2014

DOI: 10.1111/CEN.12335

Abstract: Common variants in the fat-mass-and-obesity-associated (FTO) gene are related to body mass index (BMI), which is a predictor of hip fracture risk. This study sought to examine the association between variants in the FTO gene and hip fracture risk. This is a prospective study including 934 postmenopausal women aged 60 years and above living in Dubbo, Australia (Dubbo Osteoporosis Epidemiology Study), followed up between 1989 and 2007. Six single nucleotide polymorphisms (SNPs) (rs1421085, rs1558902, rs1121980, rs17817449, rs9939609 and rs9930506) of the FTO gene were genotyped using Taqman assay. Bone mineral density at the lumbar spine and femoral neck was measured by DXA (GE-Lunar) at baseline. Incidence of hip fractures during the follow-up was ascertained by reviewing X-ray reports. We used Cox's models to estimate the association between the genetic variants and hip fracture risk. We also utilized Bayes factor to evaluate the association. One hundred and two women (11%) had sustained a hip fracture. The incidence of hip fracture was greater in women homozygous for the minor allele of all SNPs. Women homozygous for the minor allele (AA) of rs1121980 had significantly higher risk of hip fracture (hazard ratio, 2.06 95% CI 1.17-3.62) than women homozygous for the major allele (TT). The observed data favoured the hypothesis of FTO gene and fracture association over the hypothesis of nonassociation by a factor of nine. Common variations in the FTO gene are associated with hip fracture risk in women and that FTO gene may help improve the predictive value of hip fracture risk.

Low-trauma rib fracture in the elderly: Risk factors and mortality consequence

Publisher: Elsevier BV

Date: 11-2018

DOI: 10.1016/J.BONE.2018.08.016

Abstract: Low trauma rib fracture (hereinafter, rib fracture) is common in the elderly, but its risk factors and mortality consequence are rarely studied. We sought to define the epidemiology of rib fracture and the association between rib fracture and postfracture mortality. The study was part of the Dubbo Osteoporosis Epidemiology Study, which was designed as a population-based prospective study, and consisted of 2041 women and men (aged ≥ 60). The incidence of rib fracture was ascertained from X-ray reports. Bone mineral density (BMD) was measured by DXA (GE-Lunar). The time-dependent Cox model was used to access the relationship between rib fracture and mortality. During the median follow-up of 13 years, 59 men and 78 women had sustained a rib fracture, making the annual incidence of 4.8/1000 person-years. Each SD (0.15 g/cm A rib fracture signifies an increased risk of subsequent fractures and mortality. The increased risk of mortality during the first 2.5 years postfracture suggests a window of opportunity for treatment.

Risk factors for fracture in nonosteoporotic men and women

Publisher: The Endocrine Society

Date: 03-2007

DOI: 10.1210/JC.2006-1476

Abstract: It is not known which factors are associated with fracture in nonosteoporotic elderly. The aim of this study was to assess the association between fall-related risk factors and fracture risk in men and women without osteoporosis. This study was part of the ongoing Dubbo Osteoporosis Epidemiology Study, which was designed as a prospective population-based cohort investigation. At baseline, 924 women and 723 men aged 60+ yr did not have osteoporosis [bone mineral density (BMD) T-scores > -2.5]. The in iduals have been followed for up to 15 yr. Atraumatic fractures were prospectively identified through radiologists' reports. At baseline, femoral neck BMD (FNBMD) was measured by dual energy x-ray absorptiometry (DXA) history of fall, postural stability, and quadriceps strength was obtained. During the follow-up period, among the nonosteoporotic group, 221 women and 105 men had sustained a fracture, accounting for 55 and 74% of total fractures in the entire Dubbo Osteoporosis Epidemiology Study s le, respectively. The following factors were independent risk factors for any fracture: in women, age per sd (hazard ratio, 1.2 95% CI, 1.0-1.3), postural sway per sd (1.1, 1.0-1.2), FNBMD per sd (1.6, 1.3-1.9), fall in the previous 12 months (2.1, 1.6-2.7), and prior fracture (1.8, 1.2-2.7) in men, age (1.4, 1.1-1.6), postural sway (1.2, 1.0-1.3), FNBMD (1.2, 1.0-1.5), and fall in the previous 12 months (1.9, 1.2-3.0). Exposure to at least one of the risk factors could account for 49% (women) and 39% (men) of any fractures in this population. In nonosteoporotic elderly, the combination of low BMD, advancing age, fall during the last 12 months, and prior fracture could identify a subgroup of in iduals with high risk of fracture.

Early changes in bone turnover and inflammatory biomarkers and clinically significant bone mineral density loss over 48 weeks among HIV‐infected patients with virological failure of a standard first‐l

Publisher: Wiley

Date: 23-06-2020

DOI: 10.1111/HIV.12882

Author response: Bisphosphonate drugs have actions in the lung and inhibit the mevalonate pathway in alveolar macrophages

Publisher: eLife Sciences Publications, Ltd

Date: 10-11-2021

DOI: 10.7554/ELIFE.72430.SA2

Limited utility of clinical indicies, for the prediction of symptomatic fracture risk in postmenopausal women

Publisher: Springer Science and Business Media LLC

Date: 2004

DOI: 10.1007/S00198-003-1511-3

Abstract: Bone mineral density (BMD) is the primary predictor of fracture, and is utilised in the definition of osteoporosis. Mass screening for osteoporosis is, however, currently not recommended. The primary objective of this study was to develop, validate and assess a simple, non-invasive scoring system to identify women at high risk of fracture. Using baseline data of the Dubbo Osteoporosis Epidemiology Study, a s le of 1256 women aged 60 or above was randomly ided into a development cohort (n=846) and a validation cohort (n=410). Low BMD was evaluated by DXA, with respect to 2.0 or 2.5 SD below the mean for young normal women at the femoral neck and lumbar spine. A logistic regression model was used to derive a predictive score, "DOEScore", in the development cohort, and the performance of this score was then assessed in the validation cohort. Incident fractures over 9395 person-years (median of follow-up duration: 8.4 years) were identified by X-ray records. Approximately 57% and 40% of women (in both cohorts) had T-scores less than -2.0 and greater than -2.5, respectively. Only age, body weight, and previous fracture were significantly related to BMD at both the femoral neck and lumbar spine. These three variables were used in the development of the DOEScore. When applied to the validation cohort, the sensitivity and specificity of DOEScore were 0.82 and 0.52, respectively, for selecting women with T-scores less than -2.5 the area under the receiver operating characteristic (ROC) curve was 0.75. These goodness-of-fit indices were comparable to, or better than, those obtained by the FOSTA, SOFSURF and ORAI score systems. However, neither the DOEScore nor other score systems reliably identify women with incident fractures for DOEScore, the sensitivity and specificity were 0.52 and 0.49, respectively, with an area under the ROC curve of 0.48. Clinical risk scores can be used to identify women likely to have low BMD (albeit with low specificity), but they are not a useful tool to identify women who will have a fracture.

Bone Loss, Weight Loss, and Weight Fluctuation Predict Mortality Risk in Elderly Men and Women

Publisher: Wiley

Date: 08-2007

DOI: 10.1359/JBMR.070412

Abstract: Low baseline BMD, rate of BMD loss, weight loss, and weight fluctuation are significant predictors of all-cause mortality in elderly men and women, independent of each other and of age, incident fracture, and concomitant diseases. Although low BMD has been shown to be associated with mortality in women, the effect of BMD is affected by weight and weight change and the contribution of these factors to mortality risk, particularly in men, is not known. This study examined the association between baseline BMD, rate of bone loss, weight loss, and weight fluctuation and all-cause mortality risk in elderly men and women. Data from 1059 women and 644 men, >or=60 years of age (as of 1989), of white background who participated in the Dubbo Osteoporosis Epidemiology Study were analyzed. All-cause mortality was recorded annually between 1989 and 2004. BMD at the femoral neck was measured by DXA (GE-LUNAR) at baseline and at approximately every 2 yr afterward. Data on incident osteoporotic fractures and concomitant diseases, including cardiovascular diseases, all types of cancer, and type I/II diabetes mellitus, was also recorded. In the multivariable Cox's proportional hazards model with adjustment for age, incident fractures, and concomitant diseases, the following variables were independent risk factors of all-cause mortality in men: rate of BMD loss of at least 1%/yr, rate of weight loss of at least 1%/yr, and weight fluctuation (defined by the CV) of at least 3%. In women, in addition to the significant factors observed in men, lower baseline BMD was also an independent risk factor of mortality. In both sexes, baseline weight was not an independent and significant predictor of mortality risk. Approximately 36% and 22% of deaths in women and men, respectively, were attributable to the four risk factors. These data suggest that, although low BMD was a risk factor of mortality in women, it was not a risk factor of mortality in men. However, high rates of BMD loss, weight loss, and weight fluctuation were also independent predictors of all-cause mortality in elderly men and women, independent of age, incident fracture, and concomitant diseases.

Individualized fracture risk assessment: Progresses and challenges

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 07-2013

DOI: 10.1097/BOR.0B013E328361FF8C

The relationship between social networking site use and the internalization of a thin ideal in females: A meta-analytic review

Publisher: Frontiers Media SA

Date: 07-08-2017

DOI: 10.3389/FPSYG.2017.01351

Bone mineral density and association of osteoarthritis with fracture risk

Publisher: Elsevier BV

Date: 09-2014

DOI: 10.1016/J.JOCA.2014.07.004

Abstract: High body mass index (BMI) is associated with increased risk of osteoarthritis (OA) and reduced risk of fragility fracture. However, the relationship between fragility fracture and OA remained unclear. This study sought to investigate the effect of bone mineral density (BMD) in the OA-fracture relationship. Data from 2412 women and 1452 men aged >45 years in the Dubbo Osteoporosis Epidemiology Study (DOES) were analyzed. In iduals have been followed for up to 22 years (median: 7.5 years range: 0.1-22 years). Femoral neck BMD (FNBMD) and lumbar spine BMD (LSBMD) was measured by dual energy X-ray absorptiometry (DXA) (GE LUNAR, Madison, WI). The presence of OA was ascertained at baseline by self-reported diagnosis. The incidence of low-trauma fracture was ascertained from X-ray reports. Overall, 29% of women and 26% of men had reported a diagnosis of OA. Fracture risk was significantly higher in women with OA than those without OA (Hazard ratio (HR) = 1.50 95% confidence interval (CI), 1.28-1.76). However, the association was mainly observed in women with osteopenic BMD (HR = 1.74 95% CI, 1.38-2.17) and normal-BMD (HR = 1.50 95% CI, 1.06-2.13) and not in those with osteoporosis. Further analysis revealed that osteopenic women with OA had significant increase in risk of vertebral (HR = 1.85 95% CI, 1.24-2.75) and limb fracture (HR = 2.49 95% CI, 1.77-3.48), but not in hip fracture. In men, no comparable relationship was found before and after adjustment for covariates. Women with OA have an increased risk of fragility fracture, and the risk was mainly observed in non-osteoporotic group.

High prevalence of diabetes before and after lung transplantation: target for improving outcome?

Publisher: Wiley

Date: 08-2018

DOI: 10.1111/IMJ.13963

Abstract: Diabetes increases morbidity and mortality of lung transplantation. However, the reported prevalence of diabetes varies post-transplantation partly due to lack of detection protocols. To determine the prevalence of diabetes in patients (i) waitlisted for lung transplant and (ii) early post-transplantation. We analysed patients on the St Vincent's Heart Lung database from 1 April 2014 to 30 September 2015 on the waitlist (Study 1) and those transplanted (Study 2). Standard of care required all non-diabetic patients to have an oral glucose tolerance test (modified for patients with cystic fibrosis (CF) to screen for CF-related hyperglycaemia (CFRH) (plasma glucose ≥8.2 mmol/L at 60 or 90 min). Study 1 included 114 patients (32 with CF and 82 without CF). Of 30 CF patients with glycaemic data, 27 (90%) had abnormal glucose metabolism: 18 had diabetes and nine had CFRH. In 50 patients without CF, 20 (40%) had abnormal glucose metabolism: eight had diabetes and 12 had impaired fasting glucose and/or impaired glucose tolerance. Study 2 included 78 transplanted patients (25 with CF and 53 without CF). Fourteen CF patients had pre-existing diabetes and seven had pre-existing CFRH. All but one patient were diagnosed with diabetes post-transplantation. Hence, diabetes prevalence in CF patients post-transplantation was 96%. Among 53 transplanted patients without CF, seven (13%) had abnormal glucose metabolism but 30 (57%) were diagnosed with post-transplant diabetes. There is a high prevalence of diabetes in lung transplant patients. Earlier endocrine participation in lung transplant services is likely to lower diabetes-related morbidity and mortality further.

Bone mineral density-independent association of quantitative ultrasound measurements and fracture risk in women

Publisher: Springer Science and Business Media LLC

Date: 07-08-2004

DOI: 10.1007/S00198-004-1717-Z

Abstract: Osteoporotic fracture is considered to result from reduced bone strength and to be related to decreased bone mass and impaired bone architecture. Quantitative ultrasound measurements (QUS) of bone, that may reflect certain architectural aspects of bone, have been shown to be associated with fracture, but it is not clear whether the association is independent of bone mineral density (BMD). This study was designed to examine the contributions of cortical QUS and BMD measurements to the prediction of fracture risk in postmenopausal Caucasian women. Speed of sound (SOS) at the distal radius, tibia, and phalanx (Sunlight Omnisense) and BMD at the lumbar spine and femoral neck (GE Lunar) were measured in 549 women, aged 63.2 +/- 12.3 years (mean +/- SD range, 49-88 years), including 77 fracture cases. Lower SOS at the distal radius, tibia, and phalanx, which were correlated with each other, were associated with increased risk of fracture. Independent predictors of fracture risk (in multivariate analysis) were distal radius SOS (OR per SD = 1.8 95% CI, 1.3-2.4), femoral neck BMD (OR per SD = 1.9 95% CI, 1.4-2.4), and age (OR per 5 years = 1.2 95% CI, 1.0-1.5). Approximately 30% of the women had distal radius SOS T-scores <-2.5 however, only 6.6% of women had both BMD and SOS T-scores <-2.5. Among the 77 fracture cases, only 14 (18.2%) had both BMD and QUS T-scores below -2.5. These data in postmenopausal women suggest that speed of sound at the distal radius was associated with fracture risk, independent of BMD and age. The combination of QUS and BMD measurements may improve the accuracy of identification of women who will sustain a fracture.

The Challenges and Opportunities of Pharmacoepidemiology in Bone Diseases

Publisher: Wiley

Date: 30-04-2018

DOI: 10.1002/JBM4.10051

Acculturation, Skin Tone Preferences, and Tanning Behaviours Among Young Adult Asian Australians

Publisher: Springer Science and Business Media LLC

Date: 30-08-2016

DOI: 10.1007/S10935-016-0442-7

Volumetric bone density at the femoral neck as a common measure of hip fracture risk for men and women

Publisher: The Endocrine Society

Date: 06-2004

DOI: 10.1210/JC.2003-030551

Secular changes in postfracture outcomes over 2 decades in Australia: A time-trend comparison of excess postfracture mortality in two birth controls over two decades

Publisher: The Endocrine Society

Date: 06-2016

DOI: 10.1210/JC.2016-1514

Abstract: Hip fracture incidence has been declining and life expectancy improving. However, trends of postfracture outcomes are unknown. The objective of the study was to compare the refracture risk and excess mortality after osteoporotic fracture between two birth cohorts, over 2 decades. Prospective birth cohorts were followed up over 2 decades (1989–2004 and 2000–2014). The study was conducted in community-dwelling participants in Dubbo, Australia. Women and men aged 60–80 years, participating in Dubbo Osteoporosis Epidemiology Study 1 (DOES 1 born before 1930) and Dubbo Osteoporosis Epidemiology Study 2 (DOES 2 born after 1930) participated in the study. Age-standardized fracture and mortality over two time intervals: (1989–2004 [DOES 1] and 2000–2014 [DOES 2]) were measured. The DOES 2 cohort had higher body mass index and bone mineral density and lower initial fracture rate than DOES 1, but similar refracture rates [age-standardized refracture rates per 1000 person-years: women: 53 (95% confidence interval [CI] 42–63) and 51 (95% CI 41–60) and men: 53 (95% CI 38–69) and 55 (95% CI 40–71) for DOES 2 and DOES 1, respectively). Absolute postfracture mortality rates declined in DOES 2 compared with DOES 1, mirroring the improvement in general-population life expectancy. However, when compared with period-specific general-population mortality, there was a similar 2.1- to 2.6-fold increased mortality risk after a fracture in both cohorts (age-adjusted standardized mortality ratio, women: 2.05 [95% CI 1.43–2.83] and 2.43 [95% CI 1.95–2.99] and men: 2.56 [95% CI 1.78–3.58] and 2.48 [95% CI 1.87–3.22] for DOES 2 and DOES 1, respectively). Over the 2 decades, despite the decline in the prevalence of fracture risk factors, general-population mortality, and initial fracture incidence, there was no improvement in postfracture outcomes. Refracture rates were similar and fracture-associated mortality was 2-fold higher than expected. These data indicate that the low postfracture treatment rates are still a major problem.

Accelerated bone loss and increased post-fracture mortality in elderly women and men

Publisher: Springer Science and Business Media LLC

Date: 20-01-2015

DOI: 10.1007/S00198-014-3014-9

Abstract: Bone loss, a fracture risk factor, may play a role in post-fracture mortality. We found accelerated bone loss (≥1.31 % bone loss/year for women and ≥1.35 % bone loss/year for men) associated with 44-77 % increased mortality. It remains unclear whether bone loss is a marker or plays a role in mortality. Osteoporotic fractures are associated with increased mortality although the cause is unknown. Bone loss, a risk factor for osteoporotic fracture is also associated with increased mortality, but its role in mortality risk post-fracture is unclear. This study aimed to examine post-fracture mortality risk according to levels of bone loss. Community-dwelling participants aged 60+ from Dubbo Osteoporosis Epidemiology Study with incident fractures were followed from 1989 to 2011. Kaplan-Meier survival curves were constructed according to bone loss quartiles. Cox proportional hazard models were used to determine the effect of bone loss on mortality. There were 341 women and 106 men with ≥2 BMD measurements. The rate of bone loss was similar for women and men (women mean -0.79 %/year, highest bone loss quartile -1.31 %/year men mean -0.74 %/year, highest quartile -1.35 %/year). Survival was lowest for the highest quartile of bone loss for women (p < 0.005) and men (p = 0.05). When analysed by fracture type, the association of bone loss with mortality was observed for vertebral (highest vs lower 3 quartiles of bone loss, women p = 0.03 and men p = 0.02) and non-hip non-vertebral fractures in women (p < 0.0001). Bone loss did not play an additional role in mortality risk following hip fractures. Importantly, overall, rapid bone loss was associated with 44-77 % increased mortality risk after multiple variable adjustment. Rapid bone loss was an independent predictor of post-fracture mortality risk in both women and men. The association of bone loss and post-fracture mortality was predominantly observed following vertebral fracture in both women and men and non-hip non-vertebral fracture in women. It remains to be determined whether bone loss is a marker or plays a role in the mortality associated with fractures.

Translational Genetics of Osteoporosis

Publisher: Wiley

Date: 28-09-2018

DOI: 10.1002/9781119266594.CH48

3-Year effect of weight loss via severe versus moderate energy restriction on body composition among postmenopausal women with obesity - the TEMPO Diet Trial

Publisher: Elsevier BV

Date: 06-2020

DOI: 10.1016/J.HELIYON.2020.E04007

Prediction of hip fracture in post-menopausal women using artificial neural network approach

Publisher: IEEE

Date: 07-2017

DOI: 10.1109/EMBC.2017.8037784

Hypocalcaemic cardiac failure post BMT secondary to unrecognized vitamin D deficiency

Publisher: Springer Science and Business Media LLC

Date: 23-06-2008

DOI: 10.1038/BMT.2008.178

Bisphosphonates and lifespan

Publisher: Elsevier BV

Date: 12-2020

DOI: 10.1016/J.BONE.2020.115566

Osteoporose-Update

Publisher: Hogrefe Publishing Group

Date: 2007

DOI: 10.1024/1019-1291.16.1.53

People with mental retardation have an increased prevalence of osteoporosis: A population study

Publisher: American Association on Intellectual and Developmental Disabilities (AAIDD)

Date: 1998

DOI: 10.1352/0895-8017(1998)103<0019:PWMRHA>2.0.CO;2

Discordance of longitudinal changes in bone density between densitometers

Publisher: Elsevier BV

Date: 10-2007

DOI: 10.1016/J.BONE.2007.07.002

Abstract: This study examined the concordance in BMD measurement and longitudinal change in BMD between the GE Lunar Prodigy and GE Lunar DPX. Even though a high concordance between the densitometers was observed on a single measurement occasion, a significant discordance in longitudinal changes in BMD was observed. Measurement of bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) technology plays an important role in the diagnosis and management of osteoporosis. The present study examined the concordance in BMD measurement and longitudinal change in BMD between GE Lunar Prodigy and DPX. BMD at the lumbar spine and femoral neck was measured in 135 in iduals (47 men and 88 women, mean age 73+/-9 years) using both GE Lunar DPX and Prodigy densitometers at baseline. In this group, 56 in iduals (22 men and 34 women) had repeated BMD measurements using the DPX and Prodigy during a subsequent follow-up visit (average duration: 2.2 years). For a single BMD measurement, the coefficient of concordance between the Prodigy and DPX was greater than 0.98 at the lumbar spine and 0.96 at the femoral neck, with the slope of linear regression being approximately 1.0. During the period of follow-up, the lumbar spine BMD decreased by -0.5% (S.D. 1.8%) when measured by DPX, which was significantly different (p=0.002) from the change measured by Prodigy (mean change=0, S.D. 2.0%). However, there was no significant difference (p=0.95) in the rate of change in femoral neck BMD measured by DPX (mean=-1.6%, S.D.=2.9) and Prodigy (mean=-1%, S.D.=1.8%). The correlation in rates of BMD change between Prodigy and DPX was 0.63 at the lumbar spine and 0.52 at the femoral neck. Simulation analysis showed that the theoretical maximum correlation in rates of BMD change between Prodigy and DPX was 0.71. Despite both densitometers being highly concordant in a single BMD measurement, discordance in the assessment of BMD changes between the Prodigy and DPX densitometers was observed. These findings have implications regarding the assessment of response to therapy in a multi-centre setting when different densitometers are used.

Fracture incidence rates in Norwegian children, The Tromsø Study, Fit Futures

Publisher: Springer Science and Business Media LLC

Date: 12-2016

DOI: 10.1007/S11657-016-0294-Z

Abstract: This study describes childhood fracture rates in Norway, a country known for high fracture rates in the adult population. Fracture rates correspond with other reports from Scandinavia, although with a slightly higher proportion in girls. Indications of increased vulnerability during stages of puberty require further exploration. Fractures are common injuries during childhood. Incidence rates and patterns vary, but population-based data are scarce. The aim of this study was to describe the sex-, age- and maturation-specific incidence of fractures in a representative population-based s le from a region in Norway. All fractures in the population based convenient cohort Fit Futures, comprising 961 adolescents under 18 years, were recorded retrospectively from the local hospital. Details on in idual's age and fracture site were recorded. A radiologist confirmed all fractures. In the period from birth to cohort scanning, the register recorded 316 fractures in 253 in iduals. Fractures were more common in boys (35%) than in girls (31%). The overall annual fracture incidence was 204 per 10,000 persons-year under the age of 18 and 205 under the age of 16. The majority of fractures involved the upper extremities and the most common site of fracture was the forearm with 24% of the fractures followed by phalanges with 23% of the fractures. Fractures peaked in girls at sexual maturation stage 3. Boys had a peak in stage 2. Timing of subsequent fractures was also consistent with stages of sexual maturation. The overall incidence of fractures in childhood in Northern Norway corresponds with other reports from Scandinavia, although the proportion of fractures in girls is higher than in other studies. Both sexes seem especially vulnerable at stages related to sexual maturation. Whether this reflects bone vulnerability or other changes related to puberty requires further investigation.

Genetic determination of bone mineral density: Evidence for a major gene

Publisher: The Endocrine Society

Date: 08-2003

DOI: 10.1210/JC.2002-030026

Abstract: This study was designed to test the hypothesis of a major gene influence on the variation in bone mineral density (BMD). BMD and bone mineral content at the lumbar spine and femoral neck were measured in 330 men and 413 women, aged 18-90 yr, from 107 nuclear and complex families (including 5 large pedigrees with 194 in iduals who were identified through an index case with moderately high BMD at the femoral neck (z-score, >or=1.28)). After adjusting for age and body weight, familial factors accounted for up to 72% of the total variation in BMD. In complex segregation analysis, for all variables examined the best-fitting most parsimonious model consistently suggested the Mendelian transmission of a major gene locus with significant residual correlations among siblings. This genetic model suggested that the proportion of a total variance (adjusted for significant covariates) attributable to a putative major gene effect ranged between 0.30 +/- 0.09 for femoral neck BMD and 0.53 +/- 0.07 for the principal component obtained on BMD and corresponding bone mineral content measures. These findings clearly support the hypothesis that a large component of the variance in BMD is under genetic control, with strong evidence for a major gene locus influencing BMD transmission.

Hip fractures in Norway 1999–2008: time trends in total incidence and second hip fracture rates. A NOREPOS study

Publisher: Springer Science and Business Media LLC

Date: 30-06-2012

DOI: 10.1007/S10654-012-9711-9

Abstract: Declining incidences of hip fractures are reported from western countries. Norway has among the highest rates in the world. The aim of this study was to investigate trends in total hip fracture rates in Norway between 1999 and 2008 and risk of second hip fractures. All hospitalizations given a hip fracture diagnosis code (International Classification of Diseases (ICD) 9 or ICD 10) (cervical, trochanteric or subtrochanteric) in Norwegian hospitals were retrieved with accompanying surgical procedure codes and additional diagnoses. A total of 93,123 hip fractures were identified between 1999 and 2008 in persons ≥50 years. Annual incidences of hip fractures were calculated and tested for trends. Rates of first and second hip fractures (2006-2008) were compared. The age-standardized total incidence of hip fracture decreased by 13.4 % (95 % confidence interval (CI): 11.0-15.6) in women and 4.8 % (95 % CI: 0.7, 8.7) in men. Age-adjusted rates of second hip fractures did not change in the observation period. In those with a prior hip fracture, the age-standardized risk of a subsequent hip fracture was 2.5-fold (95 % CI: 2.5, 2.6) in women, and 4.6-fold (95 % CI: 4.5, 4.7) in men. Total hip fracture rates declined in both genders during 1999-2008, whereas rates of second hip fractures did not change.

Erratum to: Association between fat mass, lean mass, and bone loss: the Dubbo osteoporosis epidemiology study, (Osteoporosis International, 10.1007/s00198-014-3009-6)

Publisher: Springer Science and Business Media LLC

Date: 24-03-2015

DOI: 10.1007/S00198-015-3101-6

Vitamin D Status and Supplementation in Adult Patients Receiving Extracorporeal Membrane Oxygenation

Publisher: SAGE Publications

Date: 11-2018

DOI: 10.1177/0310057X1804600609

Abstract: The prevalence of vitamin D deficiency in critical illness is known to be high and associated with adverse clinical outcomes. Patients receiving extracorporeal membrane oxygenation (ECMO) may be at increased risk of vitamin D deficiency due to high severity of acute illness. Challenges with drug dosing in ECMO patients are recognised due to increased volume of distribution and drug absorption to circuit components. To describe the prevalence of vitamin D deficiency in ECMO patients and the effect of intramuscular dosing of cholecalciferol on levels of vitamin D metabolites, and to compare these data with intensive care unit (ICU) patients not receiving ECMO, two prospective studies were performed sequentially: an observational study of 100 consecutive ICU patients and an interventional study assessing effects of intramuscular cholecalciferol in 50 ICU patients. The subgroup of patients who required ECMO support in each of these studies was analysed and compared to patients who did not receive ECMO. Twenty-four ECMO patients, 12 from the observational study and 12 from the interventional study (who received intramuscular cholecalciferol) were studied—21/24 (88%) ECMO patients were vitamin D deficient at baseline compared to 65/126 (52%) of non-ECMO patients (P=0.006). Of the 12 ECMO patients who received cholecalciferol, six patients (50%) achieved correction of deficiency compared to 36/38 (95%) non-ECMO patients (P=0.001). The prevalence of vitamin D deficiency is higher in ECMO patients compared to other critically ill adults. Correction of deficiency with single dose cholecalciferol is not reliable higher or repeated doses should be considered to correct deficiency.

Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism

Publisher: Wiley

Date: 18-11-2008

DOI: 10.1002/9780470623992

Vitamin D deficiency in the intensive care unit: An invisible accomplice to morbidity and mortality?

Publisher: Springer Science and Business Media LLC

Date: 15-09-2009

DOI: 10.1007/S00134-009-1642-X

Abstract: The association between vitamin D deficiency and chronic illness is well-known. Vitamin D deficiency has been associated with increased mortality in the general population. Despite this knowledge, vitamin D insufficiency is seldom considered and rarely replaced adequately, if at all, in critically ill patients in intensive care. We present a hypothetic model demonstrating how vitamin D deficiency may be an unrecognized contributor to adverse outcome in intensive care patients.

Vitamin D C3-epimer levels are proportionally higher with oral vitamin D supplementation compared to ultraviolet irradiation of skin in mice but not humans

Publisher: Elsevier BV

Date: 02-2019

DOI: 10.1016/J.JSBMB.2018.10.002

Abstract: A proportion of circulating 25-hydroxy vitamin D

The impact of nonhip nonvertebral fractures inn elderly women and men

Publisher: The Endocrine Society

Date: 02-2014

DOI: 10.1210/JC.2013-3461

Abstract: Nonhip nonvertebral fractures represent half of all osteoporotic fractures however, their contribution to the burden of refracture and premature mortality is unclear. To examine the risk and burden of subsequent fracture and mortality associated with an initial nonhip nonvertebral fracture. This is a prospective cohort from the Dubbo Osteoporosis Epidemiology Study, 1989-2010 of community dwelling participants aged 60+ with incident fractures. Relative risk of all subsequent fractures and age-adjusted standardized mortality ratios were calculated according to initial fracture type. The total burden of adverse events was assessed using competing risk models with four potential outcomes: mortality after initial fracture, mortality after subsequent fracture, subsequent fracture and alive, or event-free. Of the 952 fractures in women and 343 in men, over half were nonhip nonvertebral fractures (486 in women and 173 in men). Nonhip nonvertebral fractures were associated with increased risk of any subsequent fracture (1.95 [1.67-2.27] for women and 2.47 [1.82-3.35] for men), hip refracture (2.11 [1.04-4.28] for women and 2.63 [1.35-5.13] for men), and vertebral refracture (1.89 [1.43-2.48] for women and 2.13 [1.20-3.79] for men). More importantly, nonhip nonvertebral fractures were associated overall with 20% excess mortality for the first 5 years postfracture, of which approximately half were due to initial fracture and the remaining due to subsequent fractures. Proximal fractures were associated with increased mortality risk per se, whereas distal fractures were associated with increased mortality risk only in the group who sustained subsequent fractures. Nonhip nonvertebral fractures are associated with significant risk of subsequent fracture including hip and vertebral refracture, and premature mortality. Due to their high prevalence, about half of all subsequent fractures and a quarter of all fracture-related excess mortality were attributable to nonhip nonvertebral fracture. Thus nonhip nonvertebral fracture warrants early investigation and appropriate intervention.

Bisphosphonate drugs have actions outside the skeleton and inhibit the mevalonate pathway in alveolar macrophages

Publisher: Cold Spring Harbor Laboratory

Date: 10-08-2021

DOI: 10.1101/2021.08.09.455652

Abstract: Bisphosphonates drugs target the skeleton and are used globally for the treatment of common bone disorders. Nitrogen-containing bisphosphonates act by inhibiting the mevalonate pathway in bone-resorbing osteoclasts but, surprisingly, also appear to reduce the risk of death from pneumonia. We overturn the long-held belief that these drugs act only in the skeleton and show that a fluorescently-labelled bisphosphonate is internalised by alveolar macrophages and peritoneal macrophages in vivo . Furthermore, a single dose of a nitrogen-containing bisphosphonate (zoledronic acid) in mice was sufficient to inhibit the mevalonate pathway in tissue-resident macrophages, causing the build-up of a mevalonate metabolite and preventing protein prenylation. Importantly, one dose of bisphosphonate enhanced the immune response to bacterial endotoxin in the lung and increased the level of cytokines and chemokines in bronchoalveolar fluid. These studies suggest that bisphosphonates, as well as preventing bone loss, may boost immune responses to infection in the lung and provide a mechanistic basis to fully examine the potential of bisphosphonates to help combat respiratory infections that cause pneumonia.

Understanding maternal dietary choices during pregnancy: The role of social norms and mindful eating

Publisher: Elsevier BV

Date: 05-2017

DOI: 10.1016/J.APPET.2017.02.004

Abstract: Serious health complications associated with excessive weight have been documented for pregnant women and their babies during pregnancy, birth and beyond. Whilst research has focused on identifying particular foods that can be either detrimental or essential for the developing baby, pregnant women's food choices are likely determined by broader considerations. This study examined social influences as represented in reports of descriptive and injunctive social norms related to healthy eating during pregnancy, and in idual differences in mindfulness while eating, as important potential correlates of pregnant women's self-reported diet. Pregnant women (N = 139) completed a questionnaire that measured self-reported consumption of healthy and unhealthy foods, descriptive and injunctive norms related to healthy eating during pregnancy and the Mindful Eating Questionnaire (MEQ). Hierarchical multiple regressions were conducted to assess the extent to which norms and mindful eating accounted for variance in consumption of both foods. No significant associations were observed between perceived social norms related to diet during pregnancy and self-reported dietary behaviour. Mindful eating was found to play a role in pregnant women's eating behaviour, with the awareness subscale of the MEQ significantly associated with healthy eating and the emotional subscale associated with unhealthy eating. Age was also associated with consumption of unhealthy foods younger pregnant women reported consuming more unhealthy snacks and fast food meals. The associations between mindful eating and dietary behaviour suggests that improving mindfulness related to food consumption before and during pregnancy may provide a strategy to address excessive gestational weight gain.

Acute hypocalcaemia following denosumab in heart and lung transplant patients with osteoporosis

Publisher: Wiley

Date: 06-2018

DOI: 10.1111/IMJ.13744

Abstract: Osteoporosis is highly prevalent in the heart and lung transplant population. Given high rates of concurrent renal impairment, there is increasing use of denosumab in this population. However, denosumab may be associated with hypocalcaemia, particularly in patients with chronic kidney disease (CKD). To explore the risk of hypocalcaemia in a heart and lung transplant cohort prescribed denosumab for osteoporosis. We performed a retrospective database review of all surviving heart and lung transplant patients who had received denosumab for osteoporosis between January 2012 and November 2015. We assessed the rates of hypocalcaemia in this cohort and collected baseline clinical data to determine associated factors. Ten patients received denosumab and had laboratory results available within 3 months of the dose. Of these, three patients developed severe (grade 4) hypocalcaemia, while two patients developed mild (grade 1) hypocalcaemia. In comparison to the five patients who remained normocalcaemic, patients with hypocalcaemia had significantly lower baseline mean estimated glomerular filtration rate but similar baseline mean corrected serum calcium. Unexpectedly, patients developing hypocalcaemia had non-significantly higher levels of 25-hydroxyvitamin D and lower baseline doses of prednisone. In heart and lung transplant patients, denosumab should be used judiciously in patients with advanced renal disease due to the risk of hypocalcaemia.

Osteoporosis in groups with intellectual disability

Publisher: Informa UK Limited

Date: 1994

DOI: 10.1080/07263869400035291

Independent external validation of nomograms for predicting risk of low-trauma fracture and hip fracture

Publisher: CMA Joule Inc.

Date: 20-12-2010

DOI: 10.1503/CMAJ.100458

Models of care for the secondary prevention of osteoporotic fractures: a systematic review and meta-analysis.

Publisher: Springer Science and Business Media LLC

Date: 25-07-2013

DOI: 10.1007/S00198-012-2090-Y

Abstract: Most people presenting with incident osteoporotic fractures are neither assessed nor treated for osteoporosis to reduce their risk of further fractures, despite the availability of effective treatments. We evaluated the effectiveness of published models of care for the secondary prevention of osteoporotic fractures. We searched eight medical literature databases to identify reports published between 1996 and 2011, describing models of care for secondary fracture prevention. Information extracted from each publication included study design, patient characteristics, identification strategies, assessment and treatment initiation strategies, as well as outcome measures (rates of bone mineral density (BMD) testing, osteoporosis treatment initiation, adherence, re-fractures and cost-effectiveness). Meta-analyses of studies with valid control groups were conducted for two outcome measures: BMD testing and osteoporosis treatment initiation. Out of 574 references, 42 articles were identified as analysable. These studies were grouped into four general models of care-type A: identification, assessment and treatment of patients as part of the service type B: similar to A, without treatment initiation type C: alerting patients plus primary care physicians and type D: patient education only. Meta-regressions revealed a trend towards increased BMD testing (p = 0.06) and treatment initiation (p = 0.03) with increasing intensity of intervention. One type A service with a valid control group showed a significant decrease in re-fractures. Types A and B services were cost-effective, although definition of cost-effectiveness varied between studies. Fully coordinated, intensive models of care for secondary fracture prevention are more effective in improving patient outcomes than approaches involving alerts and/or education only.

Vitamin D metabolites are lower with active Crohn’s disease and spontaneously recover with development of remission

Publisher: SAGE Publications

Date: 2019

DOI: 10.1177/1756284819865144

Abstract: Vitamin D deficiency is associated with active Crohn’s disease (CD). However, it remains unclear if lower 25-hydroxyvitamin D [25(OH)D] concentration is the cause, or consequence, of intestinal inflammation. Existing literature has focused on circulating 25(OH)D rather than the active metabolite 1,25(OH) 2 D, or its breakdown product, 24,25(OH) 2 D. We aimed to characterise vitamin D metabolism in a cohort of patients with active and inactive CD. Fifty-four patients with CD and not on corticosteroids or vitamin D supplements, were enrolled in a 6-month prospective cohort study. Sera were collected on enrolment and at 6 months and tested for 25(OH)D, 1,25(OH) 2 D, 24,25(OH) 2 D using liquid chromatography tandem mass spectroscopy as well as vitamin-D-binding protein. There were no differences in 25(OH)D or 1,25(OH) 2 D levels between participants with active versus inactive disease. Levels of 24,25(OH) 2 D were significantly lower in those with active compared with inactive disease (mean 3.9 versus 6.0 µmol/l p = 0.007) and therefore the ratio of 25(OH)D:24,25(OH) 2 D was higher (mean 17.3 versus 11.1 p = 0.001). In those patients with active disease who achieved remission, there was a mean increase in 25(OH)D of 32.3 nmol/l (i.e. to a level in the sufficient range) and 24,25(OH) 2 D of 2.1 µmol/l. These increases were not seen in patients with persistently active or inactive disease. Levels of 24,25(OH) 2 D, but not 25(OH)D, were lower in patients with active CD, and spontaneously increased with resolution of underlying inflammation. The utility of 24,25(OH) 2 D as a biomarker of disease activity and vitamin D status in CD warrants further exploration.

Nonstandard Lumbar Region in Predicting Fracture Risk

Publisher: Elsevier BV

Date: 04-2018

DOI: 10.1016/J.JOCD.2017.05.014

Abstract: Femoral neck (FN) bone mineral density (BMD) is the most commonly used skeletal site to estimate fracture risk. The role of lumbar spine (LS) BMD in fracture risk prediction is less clear due to osteophytes that spuriously increase LS BMD, particularly at lower levels. The aim of this study was to compare fracture predictive ability of upper L1-L2 BMD with standard L2-L4 BMD and assess whether the addition of either LS site could improve fracture prediction over FN BMD. This study comprised a prospective cohort of 3016 women and men over 60 yr from the Dubbo Osteoporosis Epidemiology Study followed up for occurrence of minimal trauma fractures from 1989 to 2014. Dual-energy X-ray absorptiometry was used to measure BMD at L1-L2, L2-L4, and FN at baseline. Fracture risks were estimated using Cox proportional hazards models separately for each site. Predictive performances were compared using receiver operating characteristic curve analyses. There were 565 women and 179 men with a minimal trauma fracture during a mean of 11 ± 7 yr. L1-L2 BMD T-score was significantly lower than L2-L4 T-score in both genders (p < 0.0001). L1-L2 and L2-L4 BMD models had a similar fracture predictive ability. LS BMD was better than FN BMD in predicting vertebral fracture risk in women [area under the curve 0.73 (95% confidence interval, 0.68-0.79) vs 0.68 (95% confidence interval, 0.62-0.74), but FN was superior for hip fractures prediction in both women and men. The addition of L1-L2 or L2-L4 to FN BMD in women increased overall and vertebral predictive power compared with FN BMD alone by 1% and 4%, respectively (p < 0.05). In an elderly population, L1-L2 is as good as but not better than L2-L4 site in predicting fracture risk. The addition of LS BMD to FN BMD provided a modest additional benefit in overall fracture risk. Further studies in in iduals with spinal degenerative disease are needed.

Clinical Utility of Computer-Aided Diagnosis of Vertebral Fractures From Computed Tomography Images

Publisher: Wiley

Date: 03-11-2020

DOI: 10.1002/JBMR.4146

Femoral neck axis length, height loss and risk of hip fracture in males and females

Publisher: Springer Science and Business Media LLC

Date: 02-1998

DOI: 10.1007/S001980050051

Abstract: Hip axis length (HAL) has been proposed as an independent predictor of hip fracture risk in Caucasian females. Femoral neck axis length (FNAL) is a similar measure of femoral geometry but does not include acetabular structures. The aim of this study was to examine the association between hip geometry, using FNAL, and hip fractures in elderly males and females in relation to other anthropometric data. The study group comprised 123 females (23 hip fracture patients and 100 age-matched controls) and 137 males (13 hip fracture patients, 65 age-matched controls and 59 current-height-matched controls). All subjects had femoral neck bone mineral density measured by dual-energy X-ray absorptiometry. From these scans, FNAL was measured as the linear distance from the base of the greater trochanter to the apex of the femoral head. FNAL was correlated significantly with current height (r = 0.47 and r = 0.56 for females and males respectively p < 0.0001) and peak height (r = 0.45 and r = 0.57 for females and males respectively p < 0.0001) in both sexes. In females, FNAL in the fracture patients (91.5 +/- 5.4 mm, mean +/- SD) was not significantly different from FNAL in controls (89.7 +/- 5.4 mm p = 0.2). Fracture patients had the same current height as controls and a trend towards a greater peak height (163 +/- 6 cm vs 160 +/- cm p = 0.09). After adjusting FNAL for current or peak height there was no difference in FNAL between fracture patients and controls. In males, FNAL in the fracture patients (103.9 +/- 3.9 mm) was not significantly different from that of age-matched controls (103.4 +/- 6.3 mm p = 0.79). Fracture patients had a significantly lower current height (168 +/- 6 cm) than the age-matched controls (174 +/- 6 cm p = 0.0008) but had the same peak height. When adjusted for peak height there were no significant differences between height of hip fracture patients (102.0 +/- 4.9 cm), age-matched controls (102.1 +/- 5.1 cm) and current-height-matched controls (102.6 +/- 5.3 cm). Fracture patients had a significantly greater height loss (peak height minus current height) than either control group. In logistic regression analyses peak height in females and height loss in males but not FNAL were independent predictors of hip fracture. The greater height, FNAL and presumably HAL in males versus females is not associated with increased hip fracture risk. However, in this study of elderly males and females, peak height (females) and height loss (males) were independent risk factors for hip fracture. Moreover, FNAL appears to have limited utility in the prediction of hip fracture risk and any role of HAL in the prediction of hip fracture does not relate to its major component of femoral neck length.

A randomized study of two different information-based interventions on the management of osteoporosis in minimal and moderate trauma fractures

Publisher: Springer Science and Business Media LLC

Date: 21-06-2006

DOI: 10.1007/S00198-006-0078-1

Abstract: Despite the high risk for subsequent fracture following an initial osteoporotic fracture, the majority of subjects with minimal trauma fractures receive no treatment for osteoporosis. The primary aim of this investigation was to determine whether an information-based intervention could change post-fracture management of osteoporosis. A secondary aim was to define participant- and doctor-related barriers to osteoporosis management. Consecutive fracture patients (n=254) from the outpatient fracture clinic at St Vincent's Hospital, Sydney were interviewed over a 15-month period (February 2002-July 2003). Fracture risk factors, prior investigation and treatment for osteoporosis were collected at baseline. Participants were initially contacted after 3 months to ascertain follow-up management. All those not investigated or treated by their primary care physician were then randomized to either a personalized letter or the same letter plus an offer of a free bone mineral density (BMD) test. Participants were contacted after 9 months to record further investigations or treatment for osteoporosis. Less than 20% of the participants had a primary care physician follow-up 3 months after the fracture, leaving 159 who were randomized to a personalized letter (n=79) and a personalized letter plus the offer of a free BMD test (n=80). There was a significant increase in the number of people investigated for osteoporosis in the group receiving the letter plus BMD offer [38% (letter + BMD) vs. 7% (letter only) p=0.001). A high proportion of those tested had low BMD (49% osteopenia and 17% osteoporosis). However, the rates of treatment in both groups were very low (6%). Furthermore, even among the few in iduals (23%) who contacted their primary care physician, only 25% were recommended treatment. The belief that the fracture was osteoporotic was an independent predictor of having a BMD test, a primary care physician follow-up and treatment. Other independent predictors were age over 50 years for a primary care physician follow-up, female sex for having a BMD test and having had a BMD test for treatment. This study demonstrates that an information-based intervention led to a modest increase in the proportion of people investigated for osteoporosis however. there was no significant effect on treatment rates. The offer of a free BMD assessment was associated with a significantly higher rate of investigation than a personalized letter alone (odds ratio: 8.5 95% confidence interval: 3.1-24.5), but this investigation did not affect treatment rate. The low uptake of either a BMD or a visit to a primary care physician together with low rates of treatment recommendation even among people who contacted their primary care physician reflects significant participant and doctor-related barriers to osteoporosis management.

Vitamin D deficiency in critically ill patients

Publisher: Massachusetts Medical Society

Date: 30-04-2009

DOI: 10.1056/NEJMC0809996

Femoral Neck Bone Loss Predicts Fracture Risk Independent of Baseline BMD

Publisher: Wiley

Date: 07-2005

DOI: 10.1359/JBMR.050215

Bisphosphonate drugs have actions in the lung and inhibit the mevalonate pathway in alveolar macrophages

Publisher: eLife Sciences Publications, Ltd

Date: 30-12-2021

DOI: 10.7554/ELIFE.72430

Abstract: Bisphosphonates drugs target the skeleton and are used globally for the treatment of common bone disorders. Nitrogen-containing bisphosphonates act by inhibiting the mevalonate pathway in bone-resorbing osteoclasts but, surprisingly, also appear to reduce the risk of death from pneumonia. We overturn the long-held belief that these drugs act only in the skeleton and show that a fluorescently labelled bisphosphonate is internalised by alveolar macrophages and large peritoneal macrophages in vivo. Furthermore, a single dose of a nitrogen-containing bisphosphonate (zoledronic acid) in mice was sufficient to inhibit the mevalonate pathway in tissue-resident macrophages, causing the build-up of a mevalonate metabolite and preventing protein prenylation. Importantly, one dose of bisphosphonate enhanced the immune response to bacterial endotoxin in the lung and increased the level of cytokines and chemokines in bronchoalveolar fluid. These studies suggest that bisphosphonates, as well as preventing bone loss, may boost immune responses to infection in the lung and provide a mechanistic basis to fully examine the potential of bisphosphonates to help combat respiratory infections that cause pneumonia.

External Validation of the Garvan Nomograms for Predicting Absolute Fracture Risk: The Tromsø Study

Publisher: Public Library of Science (PLoS)

Date: 25-09-2014

DOI: 10.1371/JOURNAL.PONE.0107695

Mortality risk associated with low-trauma osteoporotic fracture and subsequent fracture in men and women

Publisher: American Medical Association (AMA)

Date: 04-02-2009

DOI: 10.1001/JAMA.2009.50

Abstract: There are few data on long-term mortality following osteoporotic fracture and fewer following subsequent fracture. To examine long-term mortality risk in women and men following all osteoporotic fractures and to assess the association of subsequent fracture with that risk. Prospective cohort from the Dubbo Osteoporosis Epidemiology Study of community-dwelling women and men aged 60 years and older from Dubbo, Australia, who sustained a fracture between April 1989 and May 2007. Age- and sex-specific standardized mortality ratios (SMRs) compared with the overall Dubbo population for hip, vertebral, major, and minor fractures. In women, there were 952 low-trauma fractures followed by 461 deaths, and in men, 343 fractures were followed by 197 deaths. Age-adjusted SMRs were increased following hip fractures (SMRs, 2.43 [95% confidence interval [CI], 2.02-2.93] and 3.51 [95% CI, 2.65-4.66]), vertebral fractures (SMRs, 1.82 [95% CI, 1.52-2.17] and 2.12 [95% CI, 1.66-2.72]), major fractures (SMRs, 1.65 [95% CI, 1.31-2.08] and 1.70 [95% CI, 1.23-2.36]), and minor fractures (SMRs, 1.42 [95% CI, 1.19-1.70] and 1.33 [95% CI, 0.99-1.80]) for both women and men, respectively. Mortality was increased for all ages for all fractures except minor fractures for which increased mortality was only apparent for those older than 75 years. Increased mortality risk persisted for 5 years for all fractures and up to 10 years for hip fractures. Increases in absolute mortality that were above expected, for 5 years after fracture, ranged from 1.3 to 13.2 per 100 person-years in women and from 2.7 to 22.3 per 100 person-years in men, depending on fracture type. Subsequent fracture was associated with an increased mortality hazard ratio of 1.91 (95% CI, 1.54-2.37) in women and 2.99 (95% CI, 2.11-4.24) in men. Mortality risk following a subsequent fracture then declined but beyond 5 years still remained higher than in the general population (SMR, 1.41 [95% CI, 1.01-1.97] and SMR, 1.78 [95% CI, 0.96-3.31] for women and men, respectively). Predictors of mortality after any fragility fracture for both men and women included age, quadriceps weakness, and subsequent fracture but not comorbidities. Low bone mineral density, having smoked, and sway were also predictors for women and less physical activity for men. In a s le of older women and men, all low-trauma fractures were associated with increased mortality risk for 5 to 10 years. Subsequent fracture was associated with increased mortality risk for an additional 5 years.

Bone Turnover Is Suppressed in Insulin Resistance, Independent of Adiposity.

Publisher: The Endocrine Society

Date: 23-01-2017

DOI: 10.1210/JC.2016-3282

Abstract: The contribution of insulin resistance vs adiposity to bone mineral density (BMD), bone turnover, and fractures in humans remains unclear. To evaluate BMD and bone turnover markers (BTMs) in lean (n = 18) and overweight/obese in iduals with (n = 17) and without (n = 34, insulin-sensitive [Obsensitive, n=15] or insulin-resistant [Obresistant, n=19] by homeostasis model assessment insulin resistance) diabetes mellitus. Observational study. Insulin sensitivity was assessed using the hyperinsulinemic-euglycemic cl whole body BMD and fat mass (FM) using dual energy X-ray absorptiometry and by measurement of BTMs [osteocalcin (OC), procollagen type 1 N-terminal propeptide (P1NP), and collagen type 1 cross-linked C-terminal telopeptide (CTx)], with the patient fasting and during cl hyperinsulinemia. Fasting BTMs correlated with glucose infusion rate/fat-free mass (GIR/FFM) and adiponectin and, inversely, with fasting insulin and visceral fat (P ≤ 0.04 for all). Obsensitive, Obresistant, and diabetic in iduals were matched by their FM percentage. Cl GIR/FFM was similar in the lean and Obsensitive subjects (P = 1) and approximately twofold greater (P < 0.001) than in the Obresistant and diabetic subjects. BMD was greater in Obresistant than in Obsensitive (P = 0.04) and lean (P = 0.001) subjects. At baseline, compared with Obsensitive and lean subjects, Obresistant and diabetic in iduals had lower OC, P1NP, and CTx levels. This reached statistical significance for Obresistant vs lean and Obresistant vs Obsensitive for both OC and CTx and for diabetic vs lean for CTx (P ≤ 0.04 for all). During hyperinsulinemia, lean in iduals suppressed CTx more than did diabetic in iduals (P = 0.03). On multiple regression analysis, visceral adiposity explained 16.7% and 19.3% of the baseline OC and CTx variability, respectively. Increased visceral adiposity and higher fasting insulin in insulin-resistant states are associated with lower fasting OC and CTx and failure to further suppress with more insulin.

Development of a simple prognostic nomogram for individualising 5-year and 10-year absolute risks of fracture: A population-based prospective study among postmenopausal women

Publisher: BMJ

Date: 27-09-2011

DOI: 10.1136/ARD.2010.131813

Abstract: Previous fracture prediction models have been based on the assumption of a stable risk of subsequent fractures over time. The aim of the present work was to develop a nomogram for prediction of 5-year and 10-year in idualised absolute fracture risks for postmenopausal women taking into account the time relation between fractures. A population-based prospective study was performed in 23 general practice centres located in the southern part of The Netherlands. At baseline (1992-1994), 4203 postmenopausal women between 50 and 80 years participated and 2372 of them also participated 10 years later. Baseline measurements included lumbar spine bone mineral density (BMD) and clinical risk factor evaluation. The incidence of fractures was ascertained. Bayesian model averaging and Cox's proportional hazards model were used. After enrolment, 382 (16.1%) women had a clinical fracture. Fracture risk was associated with advancing age (HR 1.09 per SD (5 years) 95% CI 1.01 to 1.17), lumbar spine BMD (HR 1.23 per -1 SD 95% CI 1.10 to 1.37) and a prior fracture, with HR 3.27 (95% CI 2.50 to 4.30) for a recent prior fracture (≤5 years previously) and HR 1.97 (95% CI 1.43 to 2.71) for a non-recent prior fracture after menopause (>5 years previously). Women with a recent prior fracture had 66% higher risk of an incident fracture than those with a non-recent prior fracture (HR 1.66 95% CI 1.15 to 2.40). The nomogram developed can help doctors to inform patients more effectively and thus better manage patient care by providing an in idualised fracture risk taking into account the time relationship for fractures.

Risk of subsequent fracture after low-trauma fracture in men and women

Publisher: American Medical Association (AMA)

Date: 24-01-2007

DOI: 10.1001/JAMA.297.4.387

Abstract: There are few published long-term data on absolute risk of subsequent fracture (refracture) following initial low-trauma fracture in women and fewer in men. To examine long-term risk of subsequent fracture following initial osteoporotic fracture in men and women. Prospective cohort study (Dubbo Osteoporosis Epidemiology Study) in Australia of 2245 community-dwelling women and 1760 men aged 60 years or older followed up for 16 years from July 1989 through April 2005. Incidence of first (initial) fracture and incidence of subsequent fracture according to sex, age group, and time since first fracture. Relative risk was determined by comparing risk of subsequent fracture with risk of initial fracture. There were 905 women and 337 men with an initial fracture, of whom 253 women and 71 men experienced a subsequent fracture. Relative risk (RR) of subsequent fracture in women was 1.95 (95% confidence interval [CI], 1.70-2.25) and in men was 3.47 (95% CI, 2.68-4.48). As a result, absolute risk of subsequent fracture was similar in women and men and at least as great as the initial fracture risk for a woman 10 years older. Thus, women and men aged 60 to 69 years had absolute refracture rates of 36/1000 person-years (95% CI, 26-48/1000) and 37/1000 person-years (95% CI, 23-59/1000), respectively. The increase in absolute fracture risk remained for up to 10 years, by which time 40% to 60% of surviving women and men experienced a subsequent fracture. All fracture locations apart from rib (men) and ankle (women) resulted in increased subsequent fracture risk, with highest RRs following hip (RR, 9.97 95% CI, 1.38-71.98) and clinical vertebral (RR, 15.12 95% CI, 6.06-37.69) fractures in younger men. In multivariate analyses, femoral neck bone mineral density, age, and smoking were predictors of subsequent fracture in women and femoral neck bone mineral density, physical activity, and calcium intake were predictors in men. After an initial low-trauma fracture, absolute risk of subsequent fracture was similar for men and women. This increased risk occurred for virtually all clinical fractures and persisted for up to 10 years.

Translational Genetics of Osteoporosis: From Population Association to Individualized Prognosis

Publisher: Wiley

Date: 19-07-2013

DOI: 10.1002/9781118453926.CH44

The risk of osteoporotic refracture

Publisher: Elsevier

Date: 2018

DOI: 10.1016/B978-0-12-813136-7.00002-8

The association between multimorbidity and osteoporosis investigation and treatment in high-risk fracture patients in Australia: A prospective cohort study

Publisher: Public Library of Science (PLoS)

Date: 17-01-2023

DOI: 10.1371/JOURNAL.PMED.1004142

Abstract: Multimorbidity is common among fracture patients. However, its association with osteoporosis investigation and treatment to prevent future fractures is unclear. This limited knowledge impedes optimal patient care. This study investigated the association between multimorbidity and osteoporosis investigation and treatment in persons at high risk following an osteoporotic fracture. The Sax Institute’s 45 and Up Study is a prospective population-based cohort of 267,153 people in New South Wales, Australia, recruited between 2005 and 2009. This analysis followed up participants until 2017 for a median of 6 years (IQR: 4 to 8). Questionnaire data were linked to hospital admissions (Admitted Patients Data Collection (APDC)), emergency presentations (Emergency Department Data Collection (EDDC)), Pharmaceutical Benefits Scheme (PBS), and Medicare Benefits Schedule (MBS). Data were linked by the Centre for Health Record Linkage and stored in a secured computing environment. Fractures were identified from APDC and EDDC, Charlson Comorbidity Index (CCI) from APDC, Dual-energy X-ray absorptiometry (DXA) investigation from MBS, and osteoporosis treatment from PBS. Out of 25,280 persons with index fracture, 10,540 were classified as high-risk based on 10-year Garvan Fracture Risk (age, sex, weight, prior fracture and falls) threshold ≥20%. The association of CCI with likelihood of investigation and treatment initiation was determined by logistic regression adjusted for education, socioeconomic and lifestyle factors). The high-risk females and males averaged 77 ± 10 and 86 ± 5 years, respectively % had a CCI ≥2. Only 17% of females and 7% of males received a DXA referral, and 22% of females and 14% males received osteoporosis medication following fracture. A higher CCI was associated with a lower probability of being investigated [adjusted OR, females: 0.73 (95% CI, 0.61 to 0.87) and 0.43 (95% CI, 0.30 to 0.62) males: 0.47 (95% CI, 0.33 to 0.68) and 0.52 (0.31 to 0.85) for CCI: 2 to 3, and ≥4 versus 0 to 1, respectively] and of receiving osteoporosis medication [adjusted OR, females: 0.85 (95% CI, 0.74 to 0.98) and 0.78 (95% CI, 0.61 to 0.99) males: 0.75 (95% CI, 0.59 to 0.94) and 0.37 (95% CI, 0.23 to 0.53) for CCI: 2 to 3, and ≥4 versus 0 to 1, respectively]. The cohort is relatively healthy therefore, the impact of multimorbidity on osteoporosis management may have been underestimated. Multimorbidity contributed significantly to osteoporosis treatment gap. This suggests that fracture risk is either underestimated or underprioritized in the context of multimorbidity and highlights the need for extra vigilance and improved fracture care in this setting.

Association between fat mass, lean mass, and bone loss: the Dubbo osteoporosis epidemiology study

Publisher: Springer Science and Business Media LLC

Date: 09-01-2015

DOI: 10.1007/S00198-014-3009-6

Abstract: Lower body fat mass is a risk factor for bone loss at lumbar spine in postmenopausal women, but not in men. Body lean mass and fat mass were not associated with femoral neck bone loss in either gender. Bone density and body mass are closely associated. Whole body lean mass (LM) and fat mass (FM) together account for approximately 95 % of body mass. Bone loss is associated with loss of body mass but which of the components of body mass (FM or LM) is related to bone loss is not well understood. Therefore, in this study, we sought to assess whether baseline FM or LM has predictive value for future relative rate of bone mineral density (BMD) changes (%/year). The present population-based cohort study was part of the ongoing Dubbo Osteoporosis Epidemiology Study (DOES). BMD, FM, and LM were measured with dual energy X-ray absorptiometry (GE-LUNAR Corp, Madison, WI). BMD measurements were taken in approximately every 2 years between 2000 and 2010. We only included the participants with at least two BMD measurements at the femoral neck and lumbar spine. In total, 717 in iduals (204 men and 513 women) aged 50 years or older were studied. Rate of bone loss at femoral neck and lumbar spine was faster in women than in men (all P < 0.01). In bivariable regression analysis, each 5 kg greater FM in women was associated with 0.4 %/year (P = 0.003) lower bone loss at lumbar spine. This magnitude of association remained virtually unchanged after adjusting for LM and/or other covariates (P = 0.03). After adjusting for covariates, variation of FM accounted for ∼1.5 % total variation in lumbar spine bone loss. However, there was no significant association between FM and change in femoral neck BMD in either men or women. Lower FM was an independent but modest risk factor for greater bone loss at the lumbar spine in women but not in men. If further studies confirm our findings, FM can help predict lumbar spine bone loss in women.

Oral Bisphosphonate Use and All‐Cause Mortality in Patients With Moderate–Severe (Grade 3B‐5D) Chronic Kidney Disease: A Population‐Based Cohort Study

Publisher: Wiley

Date: 18-02-2020

DOI: 10.1002/JBMR.3961

Abstract: Oral bisphosphonates (oBPs) have been associated with reduced fractures and mortality. However, their risks and benefits are unclear in patients with moderate-severe CKD. This study examined the association between oBPs and all-cause mortality in G3B-5D CKD. This is a population-based cohort study including all subjects with an estimated glomerular filtration rate (eGFR) <45/mL/min/1.73 m

Persistence of Excess Mortality Following Individual Nonhip Fractures: A Relative Survival Analysis

Publisher: The Endocrine Society

Date: 19-07-2018

DOI: 10.1210/JC.2017-02656

Abstract: Little is known about long-term excess mortality following fragility nonhip fractures. The study aimed to determine which fracture was associated with excess mortality and for how long the postfracture excess mortality persisted. This nationwide registry-based follow-up study included all in iduals in Denmark aged 50+ years who first experienced fragility fractures in 2001 and were followed up for up to 10 years for their mortality risk. The contribution of fracture to mortality at precise postfracture time intervals was examined using relative survival analysis, accounting for time-related mortality changes in the background population. There were 21,123 women (aged 72 ± 13 years) and 9481 men (aged 67 ± 12 years) with an incident fragility fracture in 2001, followed by 10,668 and 4745 deaths, respectively. Excess mortality was observed following all proximal and lower leg fractures. The majority of deaths occurred within the first year after fracture, and thereafter excess mortality gradually declined. Hip fractures were associated with the highest excess mortality (33% and 20% at 1 year after fracture in men and women, respectively). One-year excess mortality after fracture of a femur or pelvis was 20% to 25% vertebrae, 10% humerus, rib, or clavicle, 5% to 10% and lower leg, 3%. A significant although smaller excess mortality was still observed until 10 years for hip fractures and ~5 years after femur, other proximal, and lower leg fractures. This study highlights the important contribution of a wide variety of fragility fractures to long-term excess mortality and thus the potential for benefit from early intervention.

Natural language processing of radiology reports for the identification of patients with fracture

Publisher: Springer Science and Business Media LLC

Date: 06-01-2021

DOI: 10.1007/S11657-020-00859-5

Abstract: Text-search software can be used to identify people at risk of re-fracture. The software studied identified a threefold higher number of people with fractures compared with conventional case finding. Automated software could assist fracture liaison services to identify more people at risk than traditional case finding. Fracture liaison services address the post-fracture treatment gap in osteoporosis (OP). Natural language processing (NLP) is able to identify previously unrecognized patients by screening large volumes of radiology reports. The aim of this study was to compare an NLP software tool, XRAIT (X-Ray Artificial Intelligence Tool), with a traditional fracture liaison service at its development site (Prince of Wales Hospital [POWH], Sydney) and externally validate it in an adjudicated cohort from the Dubbo Osteoporosis Epidemiology Study (DOES). XRAIT searches radiology reports for fracture-related terms. At the development site (POWH), XRAIT and a blinded fracture liaison clinician (FLC) reviewed 5,089 reports and 224 presentations, respectively, of people 50 years or over during a simultaneous 3-month period. In the external cohort of DOES, XRAIT was used without modification to analyse digitally readable radiology reports (n = 327) to calculate its sensitivity and specificity. XRAIT flagged 433 fractures after searching 5,089 reports (421 true fractures, positive predictive value of 97%). It identified more than a threefold higher number of fractures (421 fractures/339 in iduals) compared with manual case finding (98 in iduals). Unadjusted for the local reporting style in an external cohort (DOES), XRAIT had a sensitivity of 70% and specificity of 92%. XRAIT identifies significantly more clinically significant fractures than manual case finding. High specificity in an untrained cohort suggests that it could be used at other sites. Automated methods of fracture identification may assist fracture liaison services so that limited resources can be spent on treatment rather than case finding.

New genetic loci link adipose and insulin biology to body fat distribution

Publisher: Springer Science and Business Media LLC

Date: 11-02-2015

DOI: 10.1038/NATURE14132

Prediction of Bone Mineral Density and Fragility Fracture by Genetic Profiling

Publisher: Wiley

Date: 26-10-2017

DOI: 10.1002/JBMR.2998

University Of Sydney

Location: Australia

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Mona Vale Private Practice

Location: Australia

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Royal Prince Alfred Medical Centre

Location: Australia

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St Vicent's Hospital

Location: Australia

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St Vincent’s Clinic And St Vincent’s Private Hospital

Location: Australia

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Brigham And Women's Hospital

Location: United States of America

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Garvan Institute Of Medical Research

Location: Australia

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Harvard School Of Public Health

Location: United States of America

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Harvard School Of Public Health

Location: No location found

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Garvan Institute Of Medical Research

Location: No location found

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St Vincent’s Hospital

Location: Australia

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University Of New South Wales

Location: Australia

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Bone Loss Prevention With Zoledronic Acid Or Denosumab In Postmenopausal Critically Ill Women Trial (Bone Zone Trial)

Start Date: 2021

End Date: 2025

Funder: National Health and Medical Research Council

JR Improving Outcomes In Osteoporosis And Bone Health

Start Date: 2018

End Date: 2022

Funder: National Health and Medical Research Council

Translation Of Best Practice Osteoporosis Prevention: Stopping Fragility Fractures To Keep Australians Out Of Hospital

Start Date: 2020

End Date: 2022

Funder: National Health and Medical Research Council

Premature Mortality Post Fracture: A NSW Linked Data Study

Start Date: 2016

End Date: 2018

Funder: National Health and Medical Research Council

AusGo-SHEMO….Let’s Go! Australian Gold Standard Health Economics Model Of Osteoporosis

Start Date: 2017

End Date: 2019

Funder: National Health and Medical Research Council

Osteoporotic Fracture Associated Mortality: A Multinational Study

Start Date: 2014

End Date: 2016

Funder: National Health and Medical Research Council

How Do Bone Active Drugs Increase Survival

Start Date: 2015

End Date: 2018

Funder: National Health and Medical Research Council

The Effect Of Antiresorptive Medication On Fracture Outcomes

Start Date: 2018

End Date: 2021

Funder: Amgen

Predicting Bone Loss In Patients With Inflammatory Bowel Disease

Start Date: 2020

End Date: 2020

Funder: St. Vincent's Clinic Foundation

Mortality Among Dialysis Patients On Non Calcium-based Phosphate Binders

Start Date: 2018

End Date: 2015

Funder: Kidney Health Australia

Validation Of XRAIT In Fracture Prediction In The Dubbo Study

Start Date: 2018

End Date: 2018

Funder: Osteoporosis Australia

Evaluation Of Fracture Risk Calculators For Clinical Practice

Start Date: 2018

End Date: 2014

Funder: HCF Research Foundation

Shine Translational Fellowship

Start Date: 2013

End Date: 2015

Funder: Garvan Institute of Medical Research

Dubbo Osteoporosis Epidemiology Study And International Collaboration On Mortality Prediction Following Fracture

Start Date: 2013

End Date: 2014

Funder: Bupa Health Foundation

Electronic Decision Support For Osteoporosis Care To Assist Clinicians And Patients In Primary Care And Hospitals

Start Date: 2012

End Date: 2014

Funder: National Health and Medical Research Council

Prediction Of Adverse Outcomes Following A Fragility Fracture

Start Date: 2012

End Date: 2014

Funder: National Health and Medical Research Council

Vitamin D, Bone Loss, Fracture And Mortality Outcome

Start Date: 2011

End Date: 2013

Funder: National Health and Medical Research Council

Prediction Of Fracture And Its Adverse Outcome

Start Date: 2011

End Date: 2015

Funder: National Health and Medical Research Council

Dubbo Osteoporosis Epidemiology Study

Start Date: 2004

End Date: 2006

Funder: National Health and Medical Research Council

Genetic Prediction Of Fractures In A Risk-stratified Population

Start Date: 2005

End Date: 2007

Funder: National Health and Medical Research Council

Garvan Institute Catalytic Funding For COVID-19 Research

Start Date: 2020

End Date: 2021

Funder: Garvan Institute of Medical Research

Fracture-associated Mortality: An International Study Combining Multiple Datasets

Start Date: 2013

End Date: 2012

Funder: Osteoporosis Australia