ORCID Profile
0000-0002-8194-2512
Current Organisations
MRC Lifecourse Epidemiology Unit/University of Southampton
,
University of Southampton
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Publisher: Springer Science and Business Media LLC
Date: 22-04-2022
Publisher: Elsevier BV
Date: 12-2017
Publisher: Elsevier BV
Date: 05-2017
Publisher: Springer Science and Business Media LLC
Date: 04-09-2020
Publisher: Springer Science and Business Media LLC
Date: 27-02-2020
DOI: 10.1007/S11657-020-0710-2
Abstract: A retrospective population-based survey was undertaken in a region of Bulgaria to determine the incidence of hip fracture. The estimated number of hip fractures nationwide for 2015 was 9322 and is predicted to increase to 11,398 in 2050. The hip fracture rates were used to create a FRAX model. To describe the epidemiology of hip fractures in Bulgaria, which was then used to develop the country-specific fracture prediction FRAX® tool. We carried out a retrospective population-based survey in Stara Zagora, Bulgaria, representing approximately 4.6% of the country’s population. We identified hip fractures occurring in 2015, 2016 and 2017 from hospital registers and primary care sources held by the regional health insurance agency. Age- and sex-specific incidence of hip fracture and national mortality rates were incorporated into a FRAX model for Bulgaria. Fracture probabilities were compared with those from neighbouring countries having FRAX models. The incidence of hip fracture applied nationally suggested that the estimated number of hip fractures nationwide in persons over the age of 50 years for 2015 was 9322 and is predicted to increase to 11,398 in 2050. FRAX-based probabilities were higher in Bulgaria than those in Serbia or Romania, lower than those in Turkey and similar to those in Greece. The FRAX model should enhance accuracy of determining fracture probability among the Bulgarian population and help guide decisions about treatment.
Publisher: Springer Science and Business Media LLC
Date: 08-09-2022
Publisher: Springer Science and Business Media LLC
Date: 14-07-2022
Publisher: Springer Science and Business Media LLC
Date: 22-07-2020
DOI: 10.1007/S11657-020-00782-9
Abstract: Assessment and treatment pathways based on age-specific intervention thresholds in Singapore using FRAX paths can be used to identify patients at high risk of fracture and avoid unnecessary treatment in those at low risk. Intervention thresholds for the treatment of osteoporosis have been based historically on the measurement of bone mineral density. The development of FRAX® has permitted a more accurate assessment of fracture risk. The aim of the present study was to explore treatment paths and characteristics of women selected for treatment in Singapore based on FRAX. The approach to the setting of intervention and assessment thresholds used the methodology adopted by the National Osteoporosis Guideline Group for FRAX-based guidelines in the UK but based on the epidemiology of fracture and death in Singapore. The methodology was applied to women age 50 years or more drawn from the population-based Singapore Chinese Health Study (SCHS) cohort. Missing data for the calculation of FRAX was simulated using data from Chinese cohorts from Hong Kong. Intervention thresholds expressed as a 10-year probability of a major osteoporotic fracture ranged from 2.9% at the age of 50 years increasing to 32% at the age of 90 years. A total of 1927 of 29,323 women (7%) had a prior fragility fracture and would be eligible for treatment for this reason. An additional 3019 women (10.3%) would be eligible for treatment on the basis of age-dependent thresholds. The mean BMD T-score of women so selected was −2.94. Probability-based assessment of fracture risk using age-specific intervention thresholds was developed for Singapore to help guide decisions about treatment.
Publisher: Elsevier BV
Date: 07-2023
Publisher: Cold Spring Harbor Laboratory
Date: 11-06-2018
DOI: 10.1101/338863
Abstract: Osteoporosis is a common debilitating chronic disease diagnosed primarily using bone mineral density (BMD). We undertook a comprehensive assessment of human genetic determinants of bone density in 426,824 in iduals, identifying a total of 518 genome-wide significant loci, (301 novel), explaining 20% of the total variance in BMD—as estimated by heel quantitative ultrasound (eBMD). Next, meta-analysis identified 13 bone fracture loci in ~1.2M in iduals, which were also associated with BMD. We then identified target genes from cell-specific genomic landscape features, including chromatin conformation and accessible chromatin sites, that were strongly enriched for genes known to influence bone density and strength (maximum odds ratio = 58, P = 10 −75 ). We next performed rapid throughput skeletal phenotyping of 126 knockout mice lacking eBMD Target Genes and showed that these mice had an increased frequency of abnormal skeletal phenotypes compared to 526 unselected lines (P 0.0001). In-depth analysis of one such Target Gene, DAAM2 , showed a disproportionate decrease in bone strength relative to mineralization. This comprehensive human and murine genetic atlas provides empirical evidence testing how to link associated SNPs to causal genes, offers new insights into osteoporosis pathophysiology and highlights opportunities for drug development.
Publisher: Elsevier BV
Date: 03-2023
Publisher: Springer Science and Business Media LLC
Date: 28-01-2020
DOI: 10.1007/S11657-019-0669-Z
Abstract: Retrospective population-based survey in 2 regions of the Republic of Moldova determined the incidence of fractures at the hip, proximal humerus and distal forearm. The estimated number of such fractures nationwide for 2015 was 11,271 and is predicted to increase to 15,863 in 2050. The hip fracture rates were used to create a FRAX model to help guide decisions about treatment. This paper describes the epidemiology of osteoporotic fractures in Republic of Moldova that was used to develop the country-specific fracture prediction FRAX® tool. We carried out a retrospective population-based survey in 2 regions of the Republic of Moldova (Anenii Noi district and Orhei district) representing approximately 6% of the country’s population. We identified hip, forearm and humerus fractures in 2011 and 2012 from hospital registers and primary care sources. Age- and sex-specific incidence of hip fracture and national mortality rates were incorporated into a FRAX model for Moldova. Fracture probabilities were compared with those from neighbouring countries having FRAX models. The incidence of hip fracture applied nationally suggested that the estimated number of hip fractures nationwide in persons over the age of 50 years for 2015 was 3911 and is predicted to increase by 60% to 6492 in 2050. Hip fracture incidence was a good predictor of forearm and humeral fractures. FRAX-based probabilities were higher in Moldova than neighbouring countries (Ukraine and Romania). The FRAX model should enhance accuracy of determining fracture probability among the Moldavan population and help guide decisions about treatment.
Publisher: Springer Science and Business Media LLC
Date: 20-05-2022
Publisher: Springer Science and Business Media LLC
Date: 31-05-2022
DOI: 10.1007/S00198-022-06435-6
Abstract: We describe the collection of cohorts together with the analysis plan for an update of the fracture risk prediction tool FRAX with respect to current and novel risk factors. The resource comprises 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. The availability of the fracture risk assessment tool FRAX® has substantially enhanced the targeting of treatment to those at high risk of fracture with FRAX now incorporated into more than 100 clinical osteoporosis guidelines worldwide. The aim of this study is to determine whether the current algorithms can be further optimised with respect to current and novel risk factors. A computerised literature search was performed in PubMed from inception until May 17, 2019, to identify eligible cohorts for updating the FRAX coefficients. Additionally, we searched the abstracts of conference proceedings of the American Society for Bone and Mineral Research, European Calcified Tissue Society and World Congress of Osteoporosis. Prospective cohort studies with data on baseline clinical risk factors and incident fractures were eligible. Of the 836 records retrieved, 53 were selected for full-text assessment after screening on title and abstract. Twelve cohorts were deemed eligible and of these, 4 novel cohorts were identified. These cohorts, together with 60 previously identified cohorts, will provide the resource for constructing an updated version of FRAX comprising 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. For each known and candidate risk factor, multivariate hazard functions for hip fracture, major osteoporotic fracture and death will be tested using extended Poisson regression. Sex- and/or ethnicity-specific differences in the weights of the risk factors will be investigated. After meta-analyses of the cohort-specific beta coefficients for each risk factor, models comprising 10-year probability of hip and major osteoporotic fracture, with or without femoral neck bone mineral density, will be computed. These assembled cohorts and described models will provide the framework for an updated FRAX tool enabling enhanced assessment of fracture risk (PROSPERO (CRD42021227266)).
Publisher: Springer Science and Business Media LLC
Date: 20-08-2022
DOI: 10.1007/S00198-021-06087-Y
Abstract: We compared, for women in Pakistan, the utility of intervention thresholds either at a T-score ≤ - 2.5 or based on a FRAX probability equivalent to women of average body mass index (BMI) with a prior fragility fracture. Whereas the FRAX-based intervention threshold identified women at high fracture probability, the T-score threshold was less sensitive, and the associated fracture risk decreased markedly with age. The fracture risk assessment algorithm FRAX® has been recently calibrated for Pakistan, but guidance is needed on how to apply fracture probabilities to clinical practice. The age-specific 10-year probabilities of a major osteoporotic fracture were calculated in women with average BMI to determine fracture probabilities at two potential intervention thresholds. The first comprised the age-specific fracture probabilities associated with a femoral neck T-score of - 2.5. The second approach determined age-specific fracture probabilities that were equivalent to a woman with a prior fragility fracture, without bone mineral density (BMD). The parsimonious use of BMD was additionally explored by the computation of upper and lower assessment thresholds for BMD testing. When a BMD T-score ≤ - 2.5 was used as an intervention threshold, FRAX probabilities in women aged 50 years were approximately two-fold higher than in women of the same age but with no risk factors and average BMD. The relative increase in risk associated with the BMD threshold decreased progressively with age such that, at the age of 80 years or more, a T-score of - 2.5 was actually protective. The 10-year probability of a major osteoporotic fracture by age, equivalent to women with a previous fracture, rose with age from 2.1% at the age of 40 years to 17%, at the age of 90 years, and identified women at increased risk at all ages. Intervention thresholds based on BMD alone do not effectively target women at high fracture risk, particularly in the elderly. In contrast, intervention thresholds based on fracture probabilities equivalent to a 'fracture threshold' target women at high fracture risk.
Publisher: Springer Science and Business Media LLC
Date: 17-12-2015
Publisher: Springer Science and Business Media LLC
Date: 21-06-2019
Publisher: Informa UK Limited
Date: 28-07-2022
DOI: 10.1080/13697137.2021.1951206
Abstract: Osteoporosis is a disease characterized by impaired bone microarchitecture and reduced bone mineral density (BMD) resulting in bone fragility and increased risk of fracture. In western societies, one in three women and one in five men will sustain an osteoporotic fracture in their remaining lifetime from the age of 50 years. Fragility fractures, especially of the spine and hip, commonly give rise to increased morbidity and mortality. In the five largest European countries and Sweden, fragility fractures were the cause of 2.6 million disability-adjusted life years in 2016 and the fracture-related costs increased from €29.6 billion in 2010 to €37.5 billion in 2017. In the European Union and the USA, only a small proportion of women eligible for pharmacological treatment are being prescribed osteoporosis medication. Secondary fracture prevention, using Fracture Liaison Services, can be used to increase the rates of fracture risk assessment, BMD testing and use of osteoporosis medication in order to reduce fracture numbers. Additionally, established primary prevention strategies, based on case-finding methods utilizing fracture prediction tools, such as FRAX, to identify women without fracture but with elevated risk, are recommended in order to further reduce fracture numbers.
Publisher: American Medical Association (AMA)
Date: 03-06-2022
Publisher: Springer Science and Business Media LLC
Date: 14-10-2020
DOI: 10.1007/S00198-020-05542-6
Abstract: The COVID-19 pandemic, and its management, is markedly impacting the management of osteoporosis as judged by access to online FRAX fracture risk assessments. Globally, access was 58% lower in April than in February 2020. Strategies to improve osteoporosis care, with greater use of fracture risk assessments, offer a partial solution. The COVID-19 pandemic is having a significant detrimental impact on the management of chronic diseases including osteoporosis. We have quantified the global impact by examining changes in the usage of online FRAX fracture risk assessments before and after the declaration of the pandemic (11 March 2020). The study comprised a retrospective analysis using GoogleAnalytics data on daily sessions on the FRAX® website ( www.sheffield.ac.uk/FRAX ) from November 2019 to April 2020 (main analysis period February–April 2020), and the geographical source of that activity. Over February–April 2020, the FRAX website recorded 460,495 sessions from 184 countries, with 210,656 sessions in February alone. In March and April, the number of sessions fell by 23.1% and 58.3% respectively, a pattern not observed over the same period in 2019. There were smaller reductions in Asia than elsewhere, partly related to earlier and less-marked nadirs in some countries (China, Taiwan, Hong Kong, South Korea and Vietnam). In Europe, the majority of countries (24/31, 77.4%) reduced usage by at least 50% in April. Seven countries showed smaller reductions (range − 2.85 to − 44.1%) including Poland, Slovakia, Czech Republic, Germany, Norway, Sweden and Finland. There was no significant relationship between the reduction in FRAX usage and measures of disease burden such as COVID-attributed deaths per million of the population. This study documents a marked global impact of the COVID-19 pandemic on the management of osteoporosis as reflected by FRAX online fracture risk assessments. The analysis suggests that impact may relate to the societal and healthcare measures taken to ameliorate the pandemic.
Publisher: Springer Science and Business Media LLC
Date: 02-06-2021
DOI: 10.1007/S11657-020-00871-9
Abstract: This scorecard summarises key indicators of the burden of osteoporosis and its management in the 27 member states of the European Union, as well as the UK and Switzerland. The resulting scorecard elements, assembled on a single sheet, provide a unique overview of osteoporosis in Europe. The scorecard for osteoporosis in Europe (SCOPE) is a project of the International Osteoporosis Foundation (IOF) that seeks to raise awareness of osteoporosis care in Europe. The aim of this project was to develop a scorecard and background documents to draw attention to gaps and inequalities in the provision of primary and secondary prevention of fractures due to osteoporosis. The SCOPE panel reviewed the information available on osteoporosis and the resulting fractures for each of the 27 countries of the European Union plus the UK and Switzerland (termed EU27+2). The information obtained covered four domains: background information (e.g. the burden of osteoporosis and fractures), policy framework, service provision and service uptake, e.g. the proportion of men and women at high risk that do not receive treatment (the treatment gap). There was a marked difference in fracture risk among the EU27+2 countries. Of concern was the marked heterogeneity in the policy framework, service provision and service uptake for osteoporotic fracture that bore little relation to the fracture burden. For ex le, despite the wide availability of treatments to prevent fractures, in the majority of the EU27+2, only a minority of patients at high risk receive treatment even after their first fracture. The elements of each domain in each country were scored and coded using a traffic light system (red, orange, green) and used to synthesise a scorecard. The resulting scorecard elements, assembled on a single sheet, provide a unique overview of osteoporosis in Europe. The scorecard enables healthcare professionals and policy makers to assess their country’s general approach to the disease and provide indicators to inform the future provision of healthcare.
Publisher: Oxford University Press (OUP)
Date: 28-11-2019
Abstract: We investigated whether the incidence of death following myocardial infarction (MI) varied by season and latitude in the Swedish population. We studied deaths following MI from January 1987 to December 2009, using the Swedish National Cause of Death Register. County of residence was used to determine latitude and population density. An extension of Poisson regression was used to study the relationship between risk of death following MI with age, latitude, time (from 1987), population density and calendar days. Over the study period, there was a secular decrease in the incidence of MI-related death. In men, MI-related death incidence increased by 1.3% [95% confidence interval (CI) = 1.1–1.5] per degree of latitude (northwards). In women, MI-related death incidence increased by 0.6% (95% CI = 0.4–0.9) per degree of latitude. There was seasonal variation in the risk of MI-related death with peak values in the late winter and a nadir in the summer months in both the north and the south of Sweden. Findings were similar with incident MI as the outcome. The incidence of MI-related death varied markedly by season and latitude in Sweden, with summer months and more southerly latitude associated with lower rates than winter months and more northerly latitude.
Publisher: Publishing House Zaslavsky
Date: 30-06-2021
DOI: 10.22141/2224-1507.11.2.2021.236563
Abstract: Background. At present, FRAX is a well-known and widely-used risk assessment tool for major osteoporotic fractures. The Ukrainian version of the FRAX algorithm was presented in 2016 with the “intervention threshold” for additional DXA examination and antiosteoporotic treatment of the Ukrainian women published in 2019. However, the data on its possible uses in men are limited. The purpose of the study was to evaluate the possibilities of using the previously developed criteria of the Ukrainian FRAX algorithm in Ukrainian men. Materials and methods. We examined 653 outpatients aged 40–88 years (mean age (M±SD)— 60.5±11.8 years). We analyzed the results both in the general group and in the age subgroups in particular, with an account of low-trauma fractures, included in the FRAX calculation, and compared them with the corresponding indices of the Ukrainian women. Results. The most frequent (26.6 %) risk factor for osteoporotic fractures in the group of Ukrainian men was a history of low-trauma fracture (the corresponding index in women was 51.3 %), its presence being the reason for antiosteoporotic treatment initiating. Following upon the risk of major osteoporotic fractures calculated by FRAX, only 6.7 % of men without previous fractures were found to require additional DXA examination in order to re-evaluate the osteoporotic fracture risk, and none had a high fracture risk. 73 % of men without fractures did not have any risk factor included in the FRAX algorithm. Conclusions. This study showed a greater need for both antiosteoporotic treatment without DXA assessment and additional densitometric examination for the osteoporotic fracture risk assessment for the Ukrainian women rather than men, along with a special attention to the presence of previous fractures in men, and consideration of other risk factors for osteoporosis, even those not included in this FRAX algorithm.
Publisher: BMJ
Date: 24-10-2022
DOI: 10.1136/HEARTJNL-2022-321492
Abstract: To examine association of COVID-19 with incident cardiovascular events in 17 871 UK Biobank cases between March 2020 and 2021. COVID-19 cases were defined using health record linkage. Each case was propensity score-matched to two uninfected controls on age, sex, deprivation, body mass index, ethnicity, diabetes, prevalent ischaemic heart disease (IHD), smoking, hypertension and high cholesterol. We included the following incident outcomes: myocardial infarction, stroke, heart failure, atrial fibrillation, venous thromboembolism (VTE), pericarditis, all-cause death, cardiovascular death, IHD death. Cox proportional hazards regression was used to estimate associations of COVID-19 with each outcome over an average of 141 days (range 32–395) of prospective follow-up. Non-hospitalised cases (n=14 304) had increased risk of incident VTE (HR 2.74 (95% CI 1.38 to 5.45), p=0.004) and death (HR 10.23 (95% CI 7.63 to 13.70), p .0001). In iduals with primary COVID-19 hospitalisation (n=2701) had increased risk of all outcomes considered. The largest effect sizes were with VTE (HR 27.6 (95% CI 14.5 to 52.3) p .0001), heart failure (HR 21.6 (95% CI 10.9 to 42.9) p .0001) and stroke (HR 17.5 (95% CI 5.26 to 57.9) p .0001). Those hospitalised with COVID-19 as a secondary diagnosis (n=866) had similarly increased cardiovascular risk. The associated risks were greatest in the first 30 days after infection but remained higher than controls even after this period. In iduals hospitalised with COVID-19 have increased risk of incident cardiovascular events across a range of disease and mortality outcomes. The risk of most events is highest in the early postinfection period. In iduals not requiring hospitalisation have increased risk of VTE, but not of other cardiovascular-specific outcomes.
Publisher: Springer Science and Business Media LLC
Date: 17-12-2022
Publisher: Springer Science and Business Media LLC
Date: 15-04-2019
DOI: 10.1038/S41588-019-0415-X
Abstract: In the version of this article initially published, in Fig. 5a, the data in the right column of 'DAAM2 gRNA1' were incorrectly plotted as circles indicating 'untreated' rather than as squares indicating 'treated'. The error has been corrected in the HTML and PDF versions of the article.
Publisher: Springer Science and Business Media LLC
Date: 12-01-2018
Publisher: Springer Science and Business Media LLC
Date: 11-08-2023
Publisher: Public Library of Science (PLoS)
Date: 02-07-2020
Publisher: Springer Science and Business Media LLC
Date: 06-11-2020
Publisher: Springer Science and Business Media LLC
Date: 23-03-2021
DOI: 10.1007/S00198-021-05917-3
Abstract: In a simulated population of older women, we demonstrate that an upward shift in the population distribution of BMD by approximately 0.3SD may decrease the risk of incident fractures to the same extent as an intervention targeted to those with T-score less than -2.5. To investigate the impact of population level or targeted alterations to BMD on the incidence of fractures. We used a simulated cohort of 49,242 women with age and body mass index distribution from the UK, and prevalence of other clinical risk factors based on European FRAX® cohorts. Using FRAX probabilities of major osteoporotic fracture (MOF: hip, clinical vertebral, distal forearm, proximal humerus) and hip fracture, calculated with femoral neck BMD, we determined the expected number of fractures over 10 years, stratified by 10-year age band from 50 years. We then investigated the effect of (i) uplifting all in iduals with T-score below -2.5 to be exactly -2.5 (high-risk strategy) and (ii) shifting the entire BMD distribution upwards (population strategy). Overall, the high-risk strategy prevented 573 MOF including 465 hip fractures. Moving the BMD T-score distribution upward by 0.27SD gave an equivalent reduction in numbers of MOF for hip fractures prevented, this was 0.35SD. A global upward 0.25SD BMD shift prevented 524 MOF including 354 hip fractures, with corresponding figures for an increase of 0.5SD being 973 MOF prevented and 640 hip fractures prevented. The ratio of hip fracture to MOF prevented differed by the two approaches, such that for the high-risk strategy, the ratio was 0.81, and for the population strategy was 0.68 (0.25SD BMD uplift) and 0.66 (0.5SD BMD uplift). The numbers of fractures prevented by the high-risk strategy increased with age. In contrast, the age-related increase in numbers of fractures prevented with the population strategy rose with age, but peaked in the 70-79-year age band and declined thereafter. Both strategies reduced the numbers of expected incident fractures, with contrasting relative impacts by age and fracture site. Whilst the current analysis used UK/European anthropometric/risk factor distributions, further analyses calibrated to the distributions in other settings globally may be readily undertaken. Overall, these findings support the investigation of both population level interventions and those targeted at high fracture risk groups.
Publisher: Springer Science and Business Media LLC
Date: 26-01-2022
DOI: 10.1007/S11657-021-00969-8
Abstract: This report describes epidemiology, burden, and treatment of osteoporosis in each of the 27 countries of the European Union plus Switzerland and the UK (EU 27+2). The aim of this report was to characterize the burden of osteoporosis in each of the countries of the European Union plus Switzerland and the UK in 2019 and beyond. The data on fracture incidence and costs of fractures in the EU27+2 was taken from a concurrent publication in this journal (SCOPE 2021: a new scorecard for osteoporosis in Europe) and country-specific information extracted. The information extracted covered four domains: burden of osteoporosis and fractures policy framework service provision and service uptake. The clinical and economic burden of osteoporotic fractures in 2019 is given for each of the 27 countries of the EU plus Switzerland and the UK. Each domain was ranked and the country performance set against the scorecard for all nations studied. Data were also compared with the first SCOPE undertaken in 2010. Fifteen of the 16 score card metrics on healthcare provision were used in the two surveys. Scores had improved or markedly improved in 15 countries, remained constant in 8 countries and worsened in 3 countries. The average treatment gap increased from 55% in 2010 to 71% in 2019. Overall, 10.6 million women who were eligible for treatment were untreated in 2010. In 2019, this number had risen to 14.0 million. In spite of the high cost of osteoporosis, a substantial treatment gap and projected increase of the economic burden driven by aging populations, the use of pharmacological prevention of osteoporosis has decreased in recent years, suggesting that a change in healthcare policy concerning the disease is warranted.
Publisher: eLife Sciences Publications, Ltd
Date: 08-03-2022
DOI: 10.7554/ELIFE.71094
Abstract: Pregnancy 25-hydroxyvitamin D [25(OH)D] concentrations are associated with maternal and fetal health outcomes. Using physiological human placental perfusion and villous explants, we investigate the role of the placenta in regulating the relationships between maternal 25(OH)D and fetal physiology. We demonstrate active placental uptake of 25(OH)D 3 by endocytosis, placental metabolism of 25(OH)D 3 into 24,25-dihydroxyvitamin D 3 and active 1,25-dihydroxyvitamin D [1,25(OH) 2 D 3 ], with subsequent release of these metabolites into both the maternal and fetal circulations. Active placental transport of 25(OH)D 3 and synthesis of 1,25(OH) 2 D 3 demonstrate that fetal supply is dependent on placental function rather than simply the availability of maternal 25(OH)D 3 . We demonstrate that 25(OH)D 3 exposure induces rapid effects on the placental transcriptome and proteome. These map to multiple pathways central to placental function and thereby fetal development, independent of vitamin D transfer. Our data suggest that the underlying epigenetic landscape helps dictate the transcriptional response to vitamin D treatment. This is the first quantitative study demonstrating vitamin D transfer and metabolism by the human placenta, with widespread effects on the placenta itself. These data demonstrate a complex interplay between vitamin D and the placenta and will inform future interventions using vitamin D to support fetal development and maternal adaptations to pregnancy.
Publisher: Springer Science and Business Media LLC
Date: 27-02-2019
Publisher: Springer Science and Business Media LLC
Date: 05-11-2021
DOI: 10.1007/S11657-021-01024-2
Abstract: Assessment and treatment pathways based on age-specific intervention thresholds in Saudi Arabi can be used to identify patients at high risk of fracture and avoid unnecessary treatment in those at low fracture risk. Intervention thresholds for the treatment of osteoporosis have historically been based on the measurement of bone mineral density. The aim of the present study was to explore treatment paths and characteristics of women eligible for treatment in Saudi Arabia based on fracture probabilities derived from FRAX®. The approach to the setting of intervention and assessment thresholds used the methodology adopted by the National Osteoporosis Guideline Group for FRAX-based guidelines in the UK but based on the epidemiology of fracture and death in Saudi Arabia. The methodology was applied to women age 40 years or more drawn from a tertiary referral population for skeletal assessment. Missing data for the calculation of FRAX was simulated using data from the referral and FRAX derivation cohorts. Intervention thresholds expressed as a 10-year probability of a major osteoporotic fracture ranged from 2.0% at the age of 50 years increasing to 7.6% at the age of 70 years. A total of 163 of 1365 women (11.9%) had a prior fragility fracture and would be eligible for treatment for this reason. An additional 5 women were eligible for treatment in that MOF probabilities lay above the upper assessment threshold. A BMD test would be recommended for 593 women (43.4%) so that FRAX could be recalculated with the inclusion of femoral neck BMD. Of these, 220 in iduals would be eligible for treatment after a BMD test and 373 women categorised at low risk after a BMD test. Probability-based assessment of fracture risk using age-specific intervention thresholds was developed for Saudi Arabia to help guide decisions about treatment.
Publisher: Springer Science and Business Media LLC
Date: 16-12-2022
Publisher: Wiley
Date: 28-01-2021
DOI: 10.1002/JBMR.4239
Publisher: Springer Science and Business Media LLC
Date: 04-02-2021
DOI: 10.1007/S00198-020-05803-4
Abstract: The risk of a recurrent fragility fracture varies by age and sex, as by site and recency of sentinel fracture. The recency of prior fractures affects subsequent fracture risk. Variable recency may obscure other factors that affect subsequent fracture risk. The aim of this study was to quantify the effect of a sentinel fracture by site, age, and sex where the recency was held constant. The study used data from the Reykjavik Study fracture register that documented prospectively all fractures at all skeletal sites in a large s le of the population of Iceland. Fracture incidence was compared to that of the general population determined at fixed times after a sentinel fracture (humeral, clinical vertebral, forearm, hip, and minor fractures). Outcome fractures comprised a major osteoporotic fracture and hip fracture. Sentinel osteoporotic fractures were identified in 9504 men and women. Of these, 3616 in iduals sustained a major osteoporotic fracture as the first subsequent fracture, of whom 1799 sustained a hip fracture. Hazard ratios for prior fracture were consistently higher in men than in women and decreased progressively with age. Hazard ratios varied according to the site of sentinel fracture with higher ratios for hip and vertebral fracture than for humerus, forearm, or minor osteoporotic fracture. The risk of a recurrent fragility fracture varies by age, sex, and site of sentinel fracture when recency is held constant.
Publisher: Elsevier BV
Date: 07-2023
Publisher: Springer Science and Business Media LLC
Date: 17-02-2021
DOI: 10.1007/S11657-021-00894-W
Abstract: A surrogate FRAX® model for Pakistan has been constructed using age-specific hip fracture rates for Indians living in Singapore and age-specific mortality rates from Pakistan. FRAX models are frequently requested for countries with little or no data on the incidence of hip fracture. In such circumstances, the International Society for Clinical Densitometry and International Osteoporosis Foundation have recommended the development of a surrogate FRAX model, based on country-specific mortality data but using fracture data from a country, usually within the region, where fracture rates are considered to be representative of the index country. This paper describes the development and characteristics of a surrogate FRAX model for Pakistan. The FRAX model used the ethnic-specific incidence of hip fracture in Indian men and women living in Singapore, combined with the death risk for Pakistan. The surrogate model gave somewhat lower 10-year fracture probabilities for men and women at all ages compared to the model for Indians from Singapore, reflecting a higher mortality risk in Pakistan. There were very close correlations in fracture probabilities between the surrogate and authentic models ( r ≥ 0.998) so that the use of the Pakistan model had little impact on the rank order of risk. It was estimated that 36,524 hip fractures arose in 2015 in in iduals over the age of 50 years in Pakistan, with a predicted increase by 214% to 114,820 in 2050. The surrogate FRAX model for Pakistan provides an opportunity to determine fracture probability within the Pakistan population and help guide decisions about treatment.
Publisher: Springer Science and Business Media LLC
Date: 04-09-2017
DOI: 10.1038/NG.3949
Publisher: Springer Science and Business Media LLC
Date: 11-11-2022
DOI: 10.1007/S11657-022-01175-W
Abstract: The adoption of the management pathway proposed by the National Osteoporosis Guideline Group (NOGG), UK applied using the Austrian FRAX® tool in a referral population of Austrian women categorises 22–29% of women age 40 years or more eligible for treatment of whom 28–34% are classified at very high risk. The aim of this study is to provide a reference document for the further development of existing guidelines for the management of osteoporosis in Austria, considering FRAX-based intervention thresholds for high and very high fracture risk. The model development was based on two Austrian hospital referral cohorts. Baseline information was collected to compute the 10-year probability (using the Austrian FRAX model) of a major osteoporotic fracture (MOF) and hip fracture both with and without the inclusion of femoral neck bone mineral density (BMD). Assessment thresholds for BMD testing were defined, as well as intervention thresholds. In addition, thresholds that characterise men and women at high and very high fracture risk were established. The management pathway followed that currently recommended by the UK National Osteoporosis Guideline Group (NOGG). The two cohorts comprised a total of 1306 women and men with a mean age of 66.7 years. Slightly more than 50% were eligible for treatment by virtue of a prior fragility fracture. In those women without a prior fracture, 22% ( n = 120) were eligible for treatment based on MOF probabilities. Of these, 28% ( n = 33) were found to be at very high risk. When both MOF and hip fracture probabilities were used to characterise risk, 164 women without a prior fracture were eligible for treatment (29%). Of these, 34% ( n = 56) were found to be at very high risk. Fewer men without prior fracture were eligible for treatment compared with women. The management pathway as currently outlined is expected to reduce inequalities in patient management. The characterisation of very high risk may aid in the identification of patients suitable for treatment with osteoanabolic agents.
Publisher: Springer Science and Business Media LLC
Date: 07-2020
Publisher: Cold Spring Harbor Laboratory
Date: 03-2021
DOI: 10.1101/2021.03.01.431439
Abstract: Pregnancy 25-hydroxyvitamin D (25(OH)D) concentrations are associated with maternal and fetal health outcomes. Using physiological human placental perfusion and villous explants, we investigate the role of the placenta in regulating the relationships between maternal 25(OH)D and fetal physiology. We demonstrate active placental uptake of 25(OH)D3 by endocytosis, placental metabolism of 25(OH)D3 into 24,25-dihydroxyvitamin D3 and active 1,25-dihydroxyvitamin D [1,25(OH)2D3], with subsequent release of these metabolites into both the maternal and fetal circulations. Active placental transport of 25(OH)D3 and synthesis of 1,25(OH)2D3 demonstrate that fetal supply is dependent on placental function rather than simply the availability of maternal 25(OH)D3. We demonstrate that 25(OH)D3 exposure induces rapid effects on the placental transcriptome and proteome. These map to multiple pathways central to placental function and thereby fetal development, independent of vitamin D transfer. Our data suggest that the underlying epigenetic landscape helps dictate the transcriptional response to vitamin D treatment. This is the first quantitative study demonstrating vitamin D transfer and metabolism by the human placenta, with widespread effects on the placenta itself. These data demonstrate a complex interplay between vitamin D and the placenta and will inform future interventions using vitamin D to support fetal development and maternal adaptations to pregnancy.
Publisher: Springer Science and Business Media LLC
Date: 06-05-2020
DOI: 10.1007/S11657-020-00743-2
Abstract: The hip fracture rates from Kazakhstan were used to create a surrogate FRAX® model for the Kyrgyz Republic. The International Society for Clinical Densitometry and International Osteoporosis Foundation recommend utilizing a surrogate FRAX model, based on the country-specific risk of death, and fracture data based on a country where fracture rates are considered to be representative of the index country. This paper describes a surrogate FRAX model for the Kyrgyz Republic. The FRAX model used the incidence of hip fracture from the neighbouring country of Kazakhstan and the death risk for the Kyrgyz Republic. Compared with the model for Kazakhstan, the surrogate model gave somewhat higher 10-year fracture probabilities for men between 60 and 80 years of age and lower probabilities for men above the age of 80. For women the probabilities were similar up to the age of 75–80 years and then lower. There were very close correlations in fracture probabilities between the surrogate and authentic models (1.00) so that the use of the Kyrgyz model had little impact on the rank order of risk. It was estimated that 2752 hip fractures arose in 2015 in in iduals over the age of 50 years in the Kyrgyz Republic, with a predicted increase by 207% to 8435 in 2050. The surrogate FRAX model for the Kyrgyz Republic provides the opportunity to determine fracture probability among the Kyrgyz population and help guide decisions about treatment.
Publisher: Springer Science and Business Media LLC
Date: 13-11-2019
Publisher: eLife Sciences Publications, Ltd
Date: 06-12-2021
Publisher: Springer Science and Business Media LLC
Date: 02-2020
Publisher: Springer Science and Business Media LLC
Date: 02-04-2022
DOI: 10.1007/S11657-022-01085-X
Abstract: A prospective hospital-based survey in representative regions of Saudi Arabia determined the incidence of fractures at the hip. The hip fracture rates were used to create a FRAX® model to facilitate fracture risk assessment in Saudi Arabia. This paper describes the incidence of hip fracture in the Kingdom of Saudi Arabia that was used to characterize the current and future burden of hip fracture, to develop a country-specific FRAX® tool for fracture prediction and to compare fracture probabilities with neighbouring countries. During a 2-year (2017/2018) prospective survey in 15 hospitals with a defined catchment population, hip fractures in Saudi citizens were prospectively identified from hospital registers. The number of hip fractures and future burden was determined from national demography. Age- and sex-specific incidence of hip fracture and national mortality rates were incorporated into a FRAX model for Saudi Arabia. Fracture probabilities were compared with those from Kuwait and Abu Dhabi. The incidence of hip fracture applied nationally suggested that the estimated number of hip fractures nationwide in persons over the age of 50 years for 2015 was 2,949 and is predicted to increase nearly sevenfold to 20,328 in 2050. Hip fracture rates were comparable with estimates from Abu Dhabi and Kuwait. By contrast, probabilities of a major osteoporotic fracture or hip fracture from the age of 70 years were much lower than those seen in Abu Dhabi and Kuwait due to higher mortality estimates for Saudi Arabia. A country-specific FRAX tool for fracture prediction has been developed for Saudi Arabia which is expected to help guide decisions about treatment.
Publisher: Springer Science and Business Media LLC
Date: 18-03-2022
DOI: 10.1007/S11657-022-01083-Z
Abstract: Hip fracture data were retrieved from electronical medical records for the years 2017–2019 in the State of Qatar and used to create a FRAX® model to facilitate fracture risk assessment. Hip fracture rates were comparable with estimates from Saudi Arabia, Abu Dhabi, and Kuwait but fracture probabilities varied due to differences in mortality. This paper describes the epidemiology of osteoporotic fractures in the State of Qatar that was used to develop the country-specific fracture prediction FRAX® tool. Hip fracture data were retrieved from electronic medical records for the years 2017–2019 in the State of Qatar. The age and sex specific incidence of hip fracture in Qatari residents and national mortality rates were used to create a FRAX® model. Fracture probabilities were compared with those from neighboring countries having FRAX models. Hip fracture rates were comparable with estimates from Saudi Arabia, Abu Dhabi and Kuwait. In contrast, probabilities of a major osteoporotic fracture or hip fracture were lower in Qatar than in Kuwait but higher than those in Abu Dhabi and Saudi Arabia due to differences in mortality. The FRAX model should enhance accuracy of determining fracture probability among the Qatari population and help guide decisions about treatment.
Publisher: Springer Science and Business Media LLC
Date: 31-12-2018
Publisher: Springer Science and Business Media LLC
Date: 31-10-2018
Publisher: Wiley
Date: 08-02-2018
DOI: 10.1002/JBMR.3375
Publisher: Springer Science and Business Media LLC
Date: 12-06-2018
Publisher: Springer Science and Business Media LLC
Date: 08-01-2019
Publisher: Springer Science and Business Media LLC
Date: 20-10-2020
DOI: 10.1007/S00198-020-05700-W
Abstract: The increase in fracture risk associated with a recent fragility fracture is more appropriately captured using a 10-year fracture probability than 2- or 5-year probabilities. The recency of prior fractures affects subsequent fracture risk. The aim of this study was to quantify the effect of a recent sentinel fracture, by site, on the 2-, 5-, and 10-year probability of fracture. The study used data from the Reykjavik Study fracture register that documented prospectively all fractures at all skeletal sites in a large s le of the population of Iceland. Fracture probabilities were determined after a sentinel fracture (humeral, clinical vertebral, forearm and hip fracture) occurring within the previous 2 years and probabilities for a prior osteoporotic fracture irrespective of recency. The probability ratios were used to adjust fracture probabilities over a 2-, 5-, and 10-year time horizon. As expected, probabilities decreased with decreasing time horizon. Probability ratios varied according to age and the site of sentinel fracture. Probability ratios to adjust for a prior fracture within the previous 2 years were higher the shorter the time horizon, but the absolute increases in fracture probabilities were much reduced. Thus, fracture probabilities were substantially lower with time horizons less than 10 years. The 10-year probability of fractures is the appropriate metric to capture the impact of the recency of sentinel fractures. The probability ratios provide adjustments to conventional FRAX estimates of fracture probability for recent sentinel fractures, adjustments which can readily inform clinical decision-making.
Publisher: Springer Science and Business Media LLC
Date: 04-04-2021
DOI: 10.1007/S00198-021-05942-2
Abstract: The National Osteoporosis Guideline Group (NOGG) has developed intervention thresholds based on FRAX® to characterise patients at high and very high risk of fracture. Guidelines for the assessment of fracture risk have begun to categorise patients eligible for treatment into high and very high risk of fracture to inform choice of therapeutic approach. The aim of the present study was to develop intervention thresholds based on the hybrid assessment model of NOGG. We examined the impact of intervention thresholds in a simulated cross-sectional cohort of women age 50 years or more from the UK with the distribution of baseline characteristics based on that in the FRAX cohorts. The prevalence of very high risk using the hybrid model was compared with age-dependent thresholds used by the International Osteoporosis Foundation and the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (IOF/ESCEO). The appropriateness of thresholds was tested based on the populations treated with anabolic agents. With an upper intervention threshold using the IOF/ESCEO criteria, 56% of women age 50 years or more would be characterised at very high risk. This compares with 36% using the IOF/ESCEO criteria and an age-specific intervention threshold over all ages. With an upper intervention threshold of 1.6 times the pre-existing intervention threshold, 10% of women age 50 years or more would be characterised at very high risk. The data from phase 3 studies indicate that most trial participants exposed to romosozumab or teriparatide would fall into the very high-risk category. Proposals for FRAX-based criteria for very high risk for the NOGG hybrid model categorise a small proportion of women age 50 years or more (10%) in this highest risk stratum. The level of risk identified was comparable to that of women enrolled in trials of anabolic agents.
Publisher: Springer Science and Business Media LLC
Date: 26-09-2022
DOI: 10.1007/S00198-022-06550-4
Abstract: The risk of a recurrent fragility fracture is high following a first fracture and higher still with more than one prior fracture. This study provides adjustments to FRAX-based fracture probabilities accounting for the number of prior fractures. Prior fractures increase subsequent fracture risk. The aim of this study was to quantify the effect of the number of prior fractures on the 10-year probability of fracture determined with FRAX®. The study used data from the Reykjavik Study fracture register that documented prospectively all fractures at all skeletal sites in a large s le of the population of Iceland. Ten-year probabilities of hip fracture and major osteoporotic fracture (MOF) were determined according to the number of prior osteoporotic fractures over a 20-year interval from the hazards of death and fracture. Fracture probabilities were also computed for a prior osteoporotic fracture irrespective of the number of previous fractures. The probability ratios provided adjustments to conventional FRAX estimates of fracture probability according to the number of prior fractures. Probability ratios to adjust 10-year FRAX probabilities of a hip fracture and MOF increased with the number of prior fractures but decreased with age in both men and women. Probability ratios were similar in men and women and for hip fracture and MOF. Mean probability ratios according to the number of prior fractures for all scenarios were 0.95, 1.08, 1.21 and 1.35, for 1,2, 3 and 4 or more prior fractures, respectively. Thus, a simple rule of thumb is to downward adjust FRAX-based fracture probabilities by 5% in the presence of a single prior fracture and to uplift probabilities by 10, 20 and 30% with a history of 2, 3 and 4 or more prior fractures, respectively. The probability ratios provide adjustments to conventional FRAX estimates of fracture probability according to the number of prior fractures.
Publisher: Wiley
Date: 20-04-2022
DOI: 10.1002/JBMR.4548
Abstract: Nonsteroidal anti‐inflammatory drugs (NSAIDs) have been reported to have weak but beneficial effects on bone health, including fracture risk, but many epidemiological studies are likely confounded. We explored the relationship between NSAIDs and fracture risk in a post hoc analysis of a well‐documented, randomized, placebo‐controlled study of the bisphosphonate, clodronate, in which treatment reduced osteoporotic fracture risk by 23%. Concurrent medication use at baseline was used to identify those prescribed oral NSAIDs. Only verified, incident fractures were included in the analysis. A total of 1082 (20.8%) women reported use of NSAIDs at baseline. They were slightly, but significantly, younger (mean 79 versus 80 years, p = 0.004), heavier (mean 66.7 versus 64.7 kg, p 0.001) than nonusers, with slightly higher femoral neck bone mineral density (FN‐BMD, 0.66 versus 0.64 g/cm 2 , p 0.001). In an adjusted model, NSAID use was associated with a significant increase in osteoporotic fracture risk over the 3‐year study period (hazard ratio [HR] 1.27 95% confidence interval [CI], 1.01–1.62 p = 0.039). However, this increase in risk was not statistically significant in the placebo group (HR 1.11 95% CI, 0.81–1.52). In women receiving clodronate, the effect of the bisphosphonate to reduce osteoporotic fracture risk was not observed in those receiving NSAIDs (HR 0.95 95% CI, 0.65–1.41 p = 0.81) in contrast to those not using NSAIDs (HR 0.71 95% CI, 0.58–0.89 p = 0.002). In a subset with hip BMD repeated at 3 years, BMD loss during clodronate therapy was greater in those women receiving NSAIDs than in nonusers (eg, total hip −2.75% versus −1.27%, p = 0.078 femoral neck −3.06% versus −1.12%, p = 0.028), and was not significantly different from that observed in women receiving placebo. The efficacy of the bisphosphonate, clodronate, to reduce fracture risk was largely negated in those receiving NSAIDs. Although the mechanism is unclear, this clinically significant observation requires exploration in studies of commonly used bisphosphonates. © 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: Wiley
Date: 08-04-2021
DOI: 10.1002/JBMR.4293
Abstract: Dual‐energy X‐ray absorptiometry (DXA)‐derived appendicular lean mass/height 2 (ALM/ht 2 ) is the most commonly used estimate of muscle mass in the assessment of sarcopenia, but its predictive value for fracture is substantially attenuated by femoral neck (fn) bone mineral density (BMD). We investigated predictive value of 11 sarcopenia definitions for incident fracture, independent of fnBMD, fracture risk assessment tool (FRAX ® ) probability, and prior falls, using an extension of Poisson regression in US, Sweden, and Hong Kong Osteoporois Fractures in Men Study (MrOS) cohorts. Definitions tested were those of Baumgartner and Delmonico (ALM/ht 2 only), Morley, the International Working Group on Sarcopenia, European Working Group on Sarcopenia in Older People (EWGSOP1 and 2), Asian Working Group on Sarcopenia, Foundation for the National Institutes of Health (FNIH) 1 and 2 (using ALM/body mass index [BMI], incorporating muscle strength and/or physical performance measures plus ALM/ht 2 ), and Sarcopenia Definitions and Outcomes Consortium (gait speed and grip strength). Associations were adjusted for age and time since baseline and reported as hazard ratio (HR) for first incident fracture, here major osteoporotic fracture (MOF clinical vertebral, hip, distal forearm, proximal humerus). Further analyses adjusted additionally for FRAX‐MOF probability ( n = 7531 calculated ± fnBMD), prior falls (y/n), or fnBMD T ‐score. Results were synthesized by meta‐analysis. In 5660 men in USA, 2764 Sweden and 1987 Hong Kong (mean ages 73.5, 75.4, and 72.4 years, respectively), sarcopenia prevalence ranged from 0.5% to 35%. Sarcopenia status, by all definitions except those of FNIH, was associated with incident MOF (HR = 1.39 to 2.07). Associations were robust to adjustment for prior falls or FRAX probability (without fnBMD) adjustment for fnBMD T ‐score attenuated associations. EWGSOP2 severe sarcopenia (incorporating chair stand time, gait speed, and grip strength plus ALM) was most predictive, albeit at low prevalence, and appeared only modestly influenced by inclusion of fnBMD. In conclusion, the predictive value for fracture of sarcopenia definitions based on ALM is reduced by adjustment for fnBMD but strengthened by additional inclusion of physical performance measures. © 2021 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: Springer Science and Business Media LLC
Date: 03-2021
DOI: 10.1007/S11657-021-00905-W
Abstract: The hip fracture rates in South Africa were used to create ethnic-specific FRAX® models to facilitate fracture risk assessment. The aim of this study was to develop FRAX models to compute the 10-year probability of hip fracture and major osteoporotic fracture and assess their potential clinical application. Age- and sex-specific incidence of hip fracture and national mortality rates were incorporated into a FRAX model for the White, Black African, Coloured and Indian population of South Africa. Age-specific 10-year probabilities of a major osteoporotic fracture were calculated in women to determine fracture probabilities at a femoral neck T score of -2.5 SD, or those equivalent to a woman with a prior fragility fracture. Fracture probabilities were compared with those from selected countries. Probabilities were consistently higher in Indian than in Coloured men and women, in turn, higher than in Black South Africans. For White South Africans, probabilities were lower than in Indians at young ages up to the age of about 80 years. When a BMD T score of −2.5 SD was used as an intervention threshold, FRAX probabilities in women age 50 years were approximately 2-fold higher than in women of the same age but with an average BMD and no risk factors. The increment in risk associated with the BMD threshold decreased progressively with age such that, at the age of 80 years or more, a T score of −2.5 SD was no longer a risk factor. Probabilities equivalent to women with a previous fracture rose with age and identified women at increased risk at all ages. These FRAX models should enhance accuracy of determining fracture probability amongst the South African population and help guide decisions about treatment.
Publisher: Elsevier BV
Date: 09-2023
Publisher: Springer Science and Business Media LLC
Date: 26-02-2018
Publisher: Springer Science and Business Media LLC
Date: 03-2017
Publisher: Springer Science and Business Media LLC
Date: 23-06-2023
Publisher: The Endocrine Society
Date: 05-07-2023
Abstract: Anemia and decreasing levels of hemoglobin (Hb) have previously been linked to increased fracture risk, but the added value to FRAX, the most utilized fracture prediction tool worldwide, is unknown. To investigate the association between anemia, Hb levels, bone microstructure, and risk of incident fracture and to evaluate whether Hb levels improve fracture risk prediction in addition to FRAX clinical risk factors (CRFs). A total of 2778 community-dwelling women, aged 75-80 years, and part of a prospective population-based cohort study in Sweden were included. At baseline, information on anthropometrics, CRFs, and falls was gathered, blood s les were collected, and skeletal characteristics were investigated using dual-energy x-ray absorptiometry and high-resolution peripheral quantitative computed tomography. At the end of follow-up, incident fractures were retrieved from a regional x-ray archive. The median follow-up time was 6.4 years. Low Hb was associated with worse total hip and femoral neck bone mineral density (BMD), and lower tibia cortical and total volumetric BMD, and anemia was associated with increased risk of major osteoporotic fracture (MOF hazard ratio 2.04 95% CI 1.58-2.64). Similar results were obtained for hip fracture and any fracture, also when adjusting for CRFs. The ratio between 10-year fracture probabilities of MOF assessed in models with Hb levels included and not included ranged from 1.2 to 0.7 at the 10th and 90th percentile of Hb, respectively. Anemia and decreasing levels of Hb are associated with lower cortical BMD and incident fracture in older women. Considering Hb levels may improve the clinical evaluation of patients with osteoporosis and the assessment of fracture risk.
Publisher: Springer Science and Business Media LLC
Date: 21-10-2020
Publisher: Springer Science and Business Media LLC
Date: 03-02-2021
Publisher: Springer Science and Business Media LLC
Date: 23-12-2022
Publisher: Springer Science and Business Media LLC
Date: 27-02-2020
DOI: 10.1007/S11657-020-0701-3
Abstract: Retrospective and prospective population-based survey in a region of the Republic of Kazakhstan determined the incidence of fractures at the hip, proximal humerus and distal forearm. The hip fracture rates were used to create a FRAX® model to enhance fracture risk assessment in Kazakhstan. This paper describes the epidemiology of osteoporotic fractures in the Republic of Kazakhstan that was used to develop a country specific FRAX® tool for fracture prediction. We carried out a retrospective population-based survey in Taldykorgan in the Republic of Kazakhstan representing approximately 1% of the country’s population. Hip, forearm and humerus fractures were identified retrospectively in 2015 and 2016 from hospital registers and the trauma centre. Hip fractures were prospectively identified in 2017 from the same sources and additionally from primary care data. Age- and sex-specific incidence of hip fracture and national mortality rates were incorporated into a FRAX model for Kazakhstan. Fracture probabilities were compared with those from neighbouring countries having FRAX models. The difference in hip fracture incidence between the retrospective and prospective survey indicated that approximately 25% of hip fracture cases did not come to hospital attention. The incidence of hip fracture applied nationally suggested that the estimated number of hip fractures nationwide in persons over the age of 50 years for 2015 was 11,690 and is predicted to increase by 140% to 28,000 in 2050. Hip fracture incidence was a good predictor of forearm and humeral fractures in men but not in women. The FRAX model should enhance accuracy of determining fracture probability among the Kazakh population and help guide decisions about treatment.
Publisher: Springer Science and Business Media LLC
Date: 19-04-2020
DOI: 10.1007/S11657-020-0706-Y
Abstract: This report provides an overview and a comparison of the burden and management of fragility fractures in the largest five countries of the European Union plus Sweden (EU6). In 2017, new fragility fractures in the EU6 are estimated at 2.7 million with an associated annual cost of €37.5 billion and a loss of 1.0 million quality-adjusted life years. Osteoporosis is characterized by reduced bone mass and strength, which increases the risk of fragility fractures, which in turn, represent the main consequence of the disease. This report provides an overview and a comparison of the burden and management of fragility fractures in the largest five EU countries and Sweden (designated the EU6). A series of metrics describing the burden and management of fragility fractures were defined by a scientific steering committee. A working group performed the data collection and analysis. Data were collected from current literature, available retrospective data and public sources. Different methods were applied (e.g. standard statistics and health economic modelling), where appropriate, to perform the analysis for each metric. Total fragility fractures in the EU6 are estimated to increase from 2.7 million in 2017 to 3.3 million in 2030 a 23% increase. The resulting annual fracture-related costs (€37.5 billion in 2017) are expected to increase by 27%. An estimated 1.0 million quality-adjusted life years (QALYs) were lost in 2017 due to fragility fractures. The current disability-adjusted life years (DALYs) per 1000 in iduals age 50 years or more were estimated at 21 years, which is higher than the estimates for stroke or chronic obstructive pulmonary disease. The treatment gap (percentage of eligible in iduals not receiving treatment with osteoporosis drugs) in the EU6 is estimated to be 73% for women and 63% for men an increase of 17% since 2010. If all patients who fracture in the EU6 were enrolled into fracture liaison services, at least 19,000 fractures every year might be avoided. Fracture-related burden is expected to increase over the coming decades. Given the substantial treatment gap and proven cost-effectiveness of fracture prevention schemes such as fracture liaison services, urgent action is needed to ensure that all in iduals at high risk of fragility fracture are appropriately assessed and treated.
Publisher: Wiley
Date: 05-01-2023
DOI: 10.1002/JCSM.13160
Abstract: The 2019 European Working Group on Sarcopenia in Older People (EWGSOP2) and the Sarcopenia Definitions and Outcomes Consortium (SDOC) have recently proposed sarcopenia definitions. However, comparisons of the performance of these approaches in terms of thresholds employed, concordance in in iduals and prediction of important health‐related outcomes such as death are limited. We addressed this in a large multinational assembly of cohort studies that included information on lean mass, muscle strength, physical performance and health outcomes. White men from the Health Aging and Body Composition (Health ABC) Study, Osteoporotic Fractures in Men (MrOS) Study cohorts (Sweden, USA), the Hertfordshire Cohort Study (HCS) and the Sarcopenia and Physical impairment with advancing Age (SarcoPhAge) Study were analysed. Appendicular lean mass (ALM) was ascertained using DXA muscle strength by grip dynamometry and usual gait speed over courses of 2.4–6 m. Deaths were recorded and verified. Definitions of sarcopenia were as follows: EWGSOP2 (grip strength kg and ALM index .0 kg/m 2 ), SDOC (grip strength .5 kg and gait speed .8 m/s) and Modified SDOC (grip strength .5 kg and gait speed .0 m/s). Cohen's kappa statistic was used to assess agreement between original definitions (EWGSOP2 and SDOC). Presence versus absence of sarcopenia according to each definition in relation to mortality risk was examined using Cox regression with adjustment for age and weight estimates were combined across cohorts using random‐effects meta‐analysis. Mean (SD) age of participants ( n = 9170) was 74.3 (4.9) years 5929 participants died during a mean (SD) follow‐up of 12.1 (5.5) years. The proportion with sarcopenia according to each definition was EWGSOP2 (1.1%), SDOC (1.7%) and Modified SDOC (5.3%). Agreement was weak between EWGSOP2 and SDOC (κ = 0.17). Pooled hazard ratios (95% CI) for mortality for presence versus absence of each definition were EWGSOP2 [1.76 (1.42, 2.18), I 2 : 0.0%] SDOC [2.75 (2.28, 3.31), I 2 : 0.0%] and Modified SDOC [1.93 (1.54, 2.41), I 2 : 58.3%]. There was low prevalence and poor agreement among recent sarcopenia definitions in community‐dwelling cohorts of older white men. All indices of sarcopenia were associated with mortality. The strong relationship between sarcopenia and mortality, regardless of the definition, illustrates that identification of appropriate management and lifecourse intervention strategies for this condition is of paramount importance.
Publisher: Springer Science and Business Media LLC
Date: 28-05-2015
DOI: 10.1007/S00198-015-3180-4
Abstract: The incidence of hip fracture in Sweden is substantially lower in immigrants than in the population born in Sweden. Thus, the use of a FRAX® model in immigrants overestimates the risk of fracture, and the use of country of origin-specific models may be more appropriate. Age-specific fracture and mortality rates vary between countries so that FRAX tools are country-specific. In the case of immigrants, it is not known whether the model for the original or the new country is most appropriate. The aim of this study was to compare the incidence of hip fractures in foreign-born and Swedish-born in iduals residing in Sweden. We studied the incidence of hip fracture in all men and women aged 50 years or more in Sweden between 1987 and 2002. The population comprised 2.8 million Swedish-born and 270,000 foreign-born in iduals. Incident hip fractures occurred in 239,842 Swedish-born and 12,563 foreign-born in iduals. The hip fracture incidence rose with age for both groups and was higher for women than men amongst both Swedish-born and foreign-born in iduals. The hip fracture incidence for the Swedish-born cohort was approximately twice that of immigrants. For ex le, at the age of 70 years, the annual hip fracture incidence (per 100,000) was 450 (95 % CI 446-454) for a Swedish-born woman and 239 (95 % CI 223-257) for a foreign-born woman at the time of immigration. The hip fracture incidence rose slowly with time from immigration (0.6 % per annum, 95 % CI 0.5-0.8 %) but remained significantly lower than for Swedish-born in iduals even after 40 years of residence. The incidence of hip fracture in Sweden is substantially lower in immigrants than in the population native to Sweden. Although there was a small rise in age- and sex-specific incidence after immigration, the incidence remained markedly lower than that observed in Swedish-born in iduals. Thus, the use of a FRAX model for Sweden will overestimate the risk of fracture for foreign-born in iduals living in Sweden.
Publisher: Springer Science and Business Media LLC
Date: 08-2019
DOI: 10.1007/S00198-019-05078-4
Abstract: We compared the utility of the current Iranian guidelines that recommend treatment in women with a T-score ≤ - 2.5 SD with a FRAX-based intervention threshold equivalent to women of average BMI with a prior fragility fracture. Whereas the FRAX-based intervention threshold identified women at high fracture probability, the T-score threshold was less sensitive, and the associated fracture risk decreased markedly with age. The fracture risk assessment algorithm FRAX® has been recently calibrated for Iran, but guidance is needed on how to apply fracture probabilities to clinical practice. The age-specific ten-year probabilities of a major osteoporotic fracture were calculated in women with average BMI to determine fracture probabilities at two potential intervention thresholds. The first comprised the age-specific fracture probabilities associated with a femoral neck T-score of - 2.5 SD, in line with current guidelines in Iran. The second approach determined age-specific fracture probabilities that were equivalent to a woman with a prior fragility fracture, without BMD. The parsimonious use of BMD was additionally explored by the computation of upper and lower assessment thresholds for BMD testing. When a BMD T-score ≤ - 2.5 SD was used as an intervention threshold, FRAX probabilities in women aged 50 years was approximately two-fold higher than in women of the same age but with an average BMD and no risk factors. The relative increase in risk associated with the BMD threshold decreased progressively with age such that, at the age of 80 years or more, a T-score of - 2.5 SD was actually protective. The 10-year probability of a major osteoporotic fracture by age, equivalent to women with a previous fracture rose with age from 4.9% at the age of 50 years to 17%, at the age of 80 years, and identified women at increased risk at all ages. Intervention thresholds based on BMD alone do not effectively target women at high fracture risk, particularly in the elderly. In contrast, intervention thresholds based on fracture probabilities equivalent to a "fracture threshold" target women at high fracture risk.
Publisher: Informa UK Limited
Date: 28-07-2022
DOI: 10.1080/13697137.2021.1945027
Abstract: The introduction of the FRAX algorithms has facilitated the assessment of fracture risk on the basis of fracture probability. FRAX integrates the influence of several well-validated risk factors for fracture with or without the use of bone mineral density. Since age-specific rates of fracture and death differ across the world, FRAX models are calibrated with regard to the epidemiology of hip fracture (preferably from national sources) and mortality (usually United Nations sources). Models are currently available for 73 nations or territories covering more than 80% of the world population. FRAX has been incorporated into more than 80 guidelines worldwide, although the nature of this application has been heterogeneous. The limitations of FRAX have been extensively reviewed. Arithmetic procedures have been proposed in order to address some of these limitations, which can be applied to conventional FRAX estimates to accommodate knowledge of dose exposure to glucocorticoids, concurrent data on lumbar spine bone mineral density, information on trabecular bone score, hip axis length, falls history, type 2 diabetes, immigration status and recency of prior fracture.
Publisher: Wiley
Date: 22-11-2022
DOI: 10.1002/JBM4.10696
Abstract: We investigated the predictive performance of peripheral quantitative computed tomography (pQCT) measures of both calf muscle density (an established surrogate for muscle adiposity, with higher values indicating lower muscle adiposity and higher muscle quality) and size (cross‐sectional area [CSA]) for incident fracture. pQCT (Stratec XCT2000/3000) measurements at the tibia were undertaken in Osteoporotic Fractures in Men (MrOS) United States (US), Hong Kong (HK), and Swedish (SW) cohorts. Analyses were by cohort and synthesized by meta‐analysis. The predictive value for incident fracture outcomes, illustrated here for hip fracture (HF), using an extension of Poisson regression adjusted for age and follow‐up time, was expressed as hazard ratio (HR) per standard deviation (SD) increase in exposure (HR/SD). Further analyses adjusted for femoral neck (fn) bone mineral density (BMD) T ‐score, Fracture Risk Assessment Tool (FRAX) 10‐year fracture probability (major osteoporotic fracture) and prior falls. We studied 991 (US), 1662 (HK), and 1521 (SW) men, mean ± SD age 77.0 ± 5.1, 73.9 ± 4.9, 80 ± 3.4 years, followed for a mean ± SD 7.8 ± 2.2, 8.1 ± 2.3, 5.3 ± 2.0 years, with 31, 47, and 78 incident HFs, respectively. Both greater muscle CSA and greater muscle density were associated with a lower risk of incident HF [HR/SD: 0.84 95% confidence interval [CI], 0.72–1.0 and 0.78 95% CI, 0.66–0.91, respectively]. The pattern of associations was not materially changed by adjustment for prior falls or FRAX probability. In contrast, after inclusion of fn BMD T ‐score, the association for muscle CSA was no longer apparent (1.04 95% CI, 0.88–1.24), whereas that for muscle density was not materially changed (0.69 95% CI, 0.59–0.82). Findings were similar for osteoporotic fractures. pQCT measures of greater calf muscle density and CSA were both associated with lower incidence of fractures in older men, but only muscle density remained an independent risk factor for fracture after accounting for fn BMD. These findings demonstrate a complex interplay between measures of bone, muscle size, and quality, in determining fracture risk. © 2022 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: 07-01-2019
Publisher: Springer Science and Business Media LLC
Date: 29-04-2021
Publisher: Springer Science and Business Media LLC
Date: 08-03-2021
DOI: 10.1007/S40520-021-01808-Z
Abstract: Coronavirus disease 2019 (COVID-19) disproportionately affects older people. Observational studies suggest indolent cardiovascular involvement after recovery from acute COVID-19. However, these findings may reflect pre-existing cardiac phenotypes. We tested the association of baseline cardiovascular magnetic resonance (CMR) phenotypes with incident COVID-19. We studied UK Biobank participants with CMR imaging and COVID-19 testing. We considered left and right ventricular (LV, RV) volumes, ejection fractions, and stroke volumes, LV mass, LV strain, native T1, aortic distensibility, and arterial stiffness index. COVID-19 test results were obtained from Public Health England. Co-morbidities were ascertained from self-report and hospital episode statistics (HES). Critical care admission and death were from HES and death register records. We investigated the association of each cardiovascular measure with COVID-19 test result in multivariable logistic regression models adjusting for age, sex, ethnicity, deprivation, body mass index, smoking, diabetes, hypertension, high cholesterol, and prior myocardial infarction. We studied 310 participants ( n = 70 positive). Median age was 63.8 [57.5, 72.1] years 51.0% ( n = 158) were male. 78.7% ( n = 244) were tested in hospital, 3.5% ( n = 11) required critical care admission, and 6.1% ( n = 19) died. In fully adjusted models, smaller LV/RV end-diastolic volumes, smaller LV stroke volume, and poorer global longitudinal strain were associated with significantly higher odds of COVID-19 positivity. We demonstrate association of pre-existing adverse CMR phenotypes with greater odds of COVID-19 positivity independent of classical cardiovascular risk factors. Observational reports of cardiovascular involvement after COVID-19 may, at least partly, reflect pre-existing cardiac status rather than COVID-19 induced alterations.
Publisher: Elsevier BV
Date: 08-2023
Publisher: Elsevier BV
Date: 06-2021
Publisher: Springer Science and Business Media LLC
Date: 28-06-2022
DOI: 10.1007/S11657-022-01117-6
Abstract: The IOF Epidemiology and Quality of Life Working Group has reviewed the potential role of population screening for high hip fracture risk against well-established criteria. The report concludes that such an approach should strongly be considered in many health care systems to reduce the burden of hip fractures. The burden of long-term osteoporosis management falls on primary care in most healthcare systems. However, a wide and stable treatment gap exists in many such settings most of which appears to be secondary to a lack of awareness of fracture risk. Screening is a public health measure for the purpose of identifying in iduals who are likely to benefit from further investigations and/or treatment to reduce the risk of a disease or its complications. The purpose of this report was to review the evidence for a potential screening programme to identify postmenopausal women at increased risk of hip fracture. The approach took well-established criteria for the development of a screening program, adapted by the UK National Screening Committee, and sought the opinion of 20 members of the International Osteoporosis Foundation’s Working Group on Epidemiology and Quality of Life as to whether each criterion was met (yes, partial or no). For each criterion, the evidence base was then reviewed and summarized. The report concludes that evidence supports the proposal that screening for high fracture risk in primary care should strongly be considered for incorporation into many health care systems to reduce the burden of fractures, particularly hip fractures. The key remaining hurdles to overcome are engagement with primary care healthcare professionals, and the implementation of systems that facilitate and maintain the screening program.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Nicholas Harvey.