ORCID Profile
0000-0001-9682-2313
Current Organisation
Garvan Institute of Medical Research
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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.
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.
Publisher: The Endocrine Society
Date: 08-07-2020
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.
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).
Publisher: Wiley
Date: 30-07-2020
DOI: 10.1002/JBMR.4100
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.
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.
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.
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.
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.
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: 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.
Publisher: Wiley
Date: 21-06-2023
DOI: 10.1002/CAM4.6284
Abstract: Distant relapse of breast cancer complicates management of the disease and accounts for 90% of breast cancer‐related deaths. Monocyte chemoattractant protein‐1 (MCP‐1) has critical roles in breast cancer progression and is widely accepted as a pro‐metastatic chemokine. This study explored MCP‐1 expression in the primary tumour of 251 breast cancer patients. A simplified ‘histoscore’ was used to determine if each tumour had high or low expression of MCP‐1. Patient breast cancers were retrospectively staged based on available patient data. p 0.05 was used to determine significance and changes in hazard ratios between models were considered. Low MCP‐1 expression in the primary tumour was associated with breast cancer‐related death with distant relapse in ER− breast cancers ( p 0.01) however, this was likely a result of most low MCP‐1‐expressing ER− breast cancers being Stage III or Stage IV, with high MCP‐1 expression in the primary tumour significantly correlated with Stage I breast cancers ( p 0.05). Expression of MCP‐1 in the primary ER− tumours varied across Stage I, II, III and IV and we highlighted a switch in MCP‐1 expression from high in Stage I ER− cancers to low in Stage IV ER− cancers. This study has emphasised a critical need for further investigation into MCP‐1's role in breast cancer progression and improved characterisation of MCP‐1 in breast cancers, particularly in light of the development of anti‐MCP‐1, anti‐metastatic therapies.
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.
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.
Publisher: Wiley
Date: 08-06-2023
DOI: 10.1002/JBM4.10780
Abstract: Type 2 diabetes (T2D) may be associated with increased risk of fractures, despite preserved bone mineral density (BMD). Obesity and insulin resistance (IR) may have separate effects on bone turnover and bone strength, which contribute to skeletal fragility. We characterized and assessed the relative associations of obesity, body composition, IR, and T2D on bone turnover markers (BTMs), BMD, and advanced hip analysis (AHA). In this cross‐sectional analysis of Dubbo Osteoporosis Epidemiology Study, 525 (61.3% women) participants were grouped according to T2D, IR (homeostasis model assessment insulin resistance [HOMA‐IR] /≥2.5), and BMI ( /≥25 kg/m 2 ): insulin‐sensitive lean (IS‐L), insulin‐sensitive overweight/obese (IS‐O), insulin‐resistant (IR), and T2D. BMD, AHA, and body composition, including visceral adipose tissue (VAT) (on dual‐energy x‐ray absorptiometry scan) and fasting BTMs, were assessed. Analyses performed using Bayesian model averaging and principal component analysis. T2D was associated with low BTMs (by 26%–30% [95% confidence interval [CI] 11%–46%] in women, 35% [95% CI 18%–48%] in men compared to IS‐L), which persisted after adjustment for VAT. BTMs were similar among IR/IS‐O/IS‐L. BMD was similar among T2D/IR/IS‐O BMD was low only in IS‐L. All groups were similar after adjustment for BMI. Similarly, AHA components were lowest in IS‐L (attenuated following adjustment). On multivariate analysis, T2D was independently associated with BTMs. IR was also associated with C‐terminal telopeptide of type 1 collagen in men. Age and body size were the strongest independent contributors to BMD and AHA. VAT was inversely associated with section modulus, cross‐sectional area, cross‐sectional moment of inertia in women, and hip axis length in men. Low bone turnover is associated with T2D and IR (in men), while BMD and hip strength/geometry are predominantly associated with body size. VAT, indicative of dysglycemia, is also associated with impaired bone geometry. Establishing the role of BTMs and AHA fracture risk may improve skeletal assessment in T2D people. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
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.
Publisher: Elsevier BV
Date: 12-2020
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.
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.
Publisher: Wiley
Date: 20-07-2021
DOI: 10.1002/JBMR.4402
Abstract: Cognitive decline and osteoporosis often coexist and some evidence suggests a causal link. However, there are no data on the longitudinal relationship between cognitive decline, bone loss and fracture risk, independent of aging. This study aimed to determine the association between: (i) cognitive decline and bone loss and (ii) clinically significant cognitive decline (≥3 points) on Mini Mental State Examination (MMSE) over the first 5 years and subsequent fracture risk over the following 10 years. A total of 1741 women and 620 men aged ≥65 years from the population‐based Canadian Multicentre Osteoporosis Study were followed from 1997 to 2013. Association between cognitive decline and (i) bone loss was estimated using mixed‐effects models and (ii) fracture risk was estimated using adjusted Cox models. Over 95% of participants had normal cognition at baseline (MMSE ≥ 24). The annual % change in MMSE was similar for both genders (women −0.33, interquartile range [IQR] −0.70 to +0.00 and men −0.34, IQR: −0.99 to 0.01). After multivariable adjustment, cognitive decline was associated with bone loss in women (6.5% 95% confidence interval [CI], 3.2% to 9.9% for each percent decline in MMSE from baseline) but not men. Approximately 13% of participants experienced significant cognitive decline by year 5. In women, fracture risk was increased significantly (multivariable hazard ratio [HR], 1.61 95% CI, 1.11 to 2.34). There were too few men to analyze. There was a significant association between cognitive decline and both bone loss and fracture risk, independent of aging, in women. Further studies are needed to determine mechanisms that link these common conditions. © 2021 American Society for Bone and Mineral Research (ASBMR).
Publisher: Public Library of Science (PLoS)
Date: 25-09-2014
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.
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.
Publisher: The Endocrine Society
Date: 21-11-2022
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.
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.
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.
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.
Publisher: American Medical Association (AMA)
Date: 24-01-2007
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.
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.
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.
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.
Publisher: Public Library of Science (PLoS)
Date: 06-2018
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.
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
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).
Publisher: The Endocrine Society
Date: 19-07-2018
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.
Publisher: Wiley
Date: 14-03-2022
DOI: 10.1002/JBMR.4530
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1016/J.JSBMB.2018.10.002
Abstract: A proportion of circulating 25-hydroxy vitamin D
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.
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.
Start Date: 2014
End Date: 2017
Funder: National Health and Medical Research Council
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End Date: 2009
Funder: National Health and Medical Research Council
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End Date: 2014
Funder: National Health and Medical Research Council
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