Publications by authors named "Eugene McCloskey"

199 Publications

Menopausal hormone therapy reduces the risk of fracture regardless of falls risk or baseline FRAX probability-results from the Women's Health Initiative hormone therapy trials.

Osteoporos Int 2022 Jul 14. Epub 2022 Jul 14.

Mary McKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia.

In a combined analysis of 25,389 postmenopausal women aged 50-79 years, enrolled in the two Women's Health Initiative hormone therapy trials, menopausal hormone therapy vs. placebo reduced the risk of fracture regardless of baseline FRAX fracture probability and falls history.

Introduction: The aim of this study was to determine if the anti-fracture efficacy of menopausal hormone therapy (MHT) differed by baseline falls history or fracture risk probability as estimated by FRAX, in a combined analysis of the two Women's Health Initiative (WHI) hormone therapy trials.

Methods: A total of 25,389 postmenopausal women aged 50-79 years were randomized to receive MHT (n = 12,739) or matching placebo (n = 12,650). At baseline, questionnaires were used to collect information on falls history, within the last 12 months, and clinical risk factors. FRAX 10-year probability of major osteoporotic fracture (MOF) was calculated without BMD. Incident clinical fractures were verified using medical records. An extension of Poisson regression was used to investigate the relationship between treatment and fractures in (1) the whole cohort; (2) those with prior falls; and (3) those without prior falls. The effect of baseline FRAX probability on efficacy was investigated in the whole cohort.

Results: Over 4.3 ± 2.1 years (mean ± SD), MHT (vs. placebo) significantly reduced the risk of any clinical fracture (hazard ratio [HR] 0.72 [95% CI, 0.65-0.78]), MOF (HR 0.60 [95% CI, 0.53-0.69]), and hip fracture (0.66 [95% CI, 0.45-0.96]). Treatment was effective in reducing the risk of any clinical fracture, MOF, and hip fracture in women regardless of baseline FRAX MOF probability, with no evidence of an interaction between MHT and FRAX (p > 0.30). Similarly, there was no interaction (p > 0.30) between MHT and prior falls.

Conclusion: In the combined WHI trials, compared to placebo, MHT reduces fracture risk regardless of FRAX probability and falls history in postmenopausal women.
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http://dx.doi.org/10.1007/s00198-022-06483-yDOI Listing
July 2022

An updated hip fracture incidence rate for Brazil: the Brazilian Validation Osteoporosis Study (BRAVOS).

Arch Osteoporos 2022 07 2;17(1):90. Epub 2022 Jul 2.

Federal University of São Paulo, Sao Paulo, Brazil.

Hip fracture incidence rates in three representative geographic areas in Brazil over a period of 2 years (2010-2012) were assessed for the first time. Estimated incidence rates varied regionally, and markedly differed from those previously reported. Thus, national guidelines as well as FRAX Brazil should be revised in light of this new data.

Purpose: To determine the annual incidence of hip fractures in individuals aged 50 years and over, living in 3 cities located in different regions of the country. To investigate the age, gender, and regional differences in fracture rates. Based on the obtained data, to estimate the national incidence of hip fractures resulting from osteoporosis, in order to improve prevention strategies.

Methods: Retrospective, observational study including all patients aged ≥ 50 years admitted in hospitals because of a hip fracture in three cities (Belem, Joinville, and Vitoria) from representative geographic areas in Brazil from 2010 to 2012. Data were obtained from medical records in those cities. We analyzed incidence rates (crude and age- and gender-standardized rates) for hip fractures.

Results: There were 1025 (310 in men and 715 in women) hip fractures in the over 50-year-old merged population from the three cities. The crude incidence rate for hip fracture was 103.3/100,000 (95% confidence interval [CI = 97.0; 109.7), in men 77.4/100,000 (95% CI = 68.8; 86.0), and in women 125.2/100,000 (95% CI = 116.0; 134.4). Incidence standardized for age and gender was 105.9 cases per 100,000 persons per year (95% CI = 99.4; 112.4); 78.5 cases per 100,000 (95% CI = 69.8; 87.3) in men and 130.6 cases 100,000 in women (95% CI = 121.0, 140.2) per year. Belem, located in the equatorial region (latitude 1° 27' S), had significantly lower crude and age-adjusted incidence than Joinville (latitude 26° 18' S) and Vitoria (latitude 20° 19' S), which were no different from each other. The incidence of fractures increased exponentially with age, and women had about twice the risk of fractures than men.

Conclusions: Hip fracture mainly affects elderly women and presents great variability in incidence between the different regions in Brazil. The incidence of hip fractures in Brazil differed markedly from that reported previously, so that national guidelines and the FRAX model for Brazil should be revised.
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http://dx.doi.org/10.1007/s11657-022-01127-4DOI Listing
July 2022

Quantitating Age-Related BMD Textural Variation from DXA Region-Free-Analysis: A Study of Hip Fracture Prediction in Three Cohorts.

J Bone Miner Res 2022 Jun 24. Epub 2022 Jun 24.

Department of Oncology and Metabolism, The University of Sheffield, Sheffield, UK.

The risk of osteoporotic fracture is inversely related to bone mineral density (BMD), but how spatial BMD pattern influences fracture risk remains incompletely understood. This study used a pixel-level spatiotemporal atlas of proximal femoral BMD in 13,338 white European women (age 20-97 years) to quantitate age-related texture variation in BMD maps and generate a "reference" map of bone aging. We introduce a new index, called Densitometric Bone Age (DBA), as the age at which an individual site-specific BMD map (the proximal femur is studied here) best matches the median aging trajectory at that site in terms of the root mean squared error (RMSE). The ability of DBA to predict incident hip fracture and hip fracture pattern over 5 years following baseline BMD was compared against conventional region-based BMD analysis in a subset of 11,899 women (age 45-97 years), for which follow-up fracture records exist. There were 208 subsequent incident hip fractures in the study populations (138 femoral necks [FNs], 52 trochanteric [TR], 18 sites unspecified). DBA had modestly better performance compared to the conventional FN-BMD, TR-BMD, and total hip (TOT)-BMD in identifying hip fractures measured as the area under the curve (AUC) using receiver operating characteristics (ROC) curve analysis by 2% (95% confidence interval [CI], -0.5% to 3.5%), 3% (95% CI, 1.0% to 4.0%), and 1% (95% CI, 0.4% to 1.6%), respectively. Compared to FN-BMD T-score, DBA improved the ROC-AUC for predicting TR fractures by ~5% (95% CI, 1.1% to 9.8%) with similar performance in identifying FN fractures. Compared to TR-BMD T-score, DBA improved the ROC-AUC for the prediction of FN fractures by ~3% (95% CI, 1.1% to 4.9%), with similar performance in identifying TR fractures. Our findings suggest that DBA may provide a spatially sensitive measure of proximal femoral fragility that is not captured by FN-BMD or TR-BMD alone. © 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).
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http://dx.doi.org/10.1002/jbmr.4638DOI Listing
June 2022

Analysis of Comorbidities, Clinical Outcomes, and Parathyroidectomy in Adults With Primary Hyperparathyroidism.

JAMA Netw Open 2022 06 1;5(6):e2215396. Epub 2022 Jun 1.

Sahlgrenska Osteoporosis Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.

Importance: Patients with primary hyperparathyroidism (pHPT) appear to have an increased risk of fractures and other comorbidities, such as cardiovascular disease, although results from previous studies have been inconsistent. Evidence of the association of parathyroidectomy (PTX) with these outcomes is also limited because of the lack of large well-controlled trials.

Objective: To investigate whether untreated pHPT was associated with an increased risk of incident fractures and cardiovascular events (CVEs) and whether PTX was associated with a reduced risk of these outcomes.

Design, Setting, And Participants: This cohort study included all patients who were diagnosed with pHPT at hospitals in Sweden between July 1, 2006, and December 31, 2017. Each patient was matched with 10 control individuals from the general population by sex, birth year, and county of residence. The patients were followed up until December 31, 2017. Data analyses were performed from October 2021 to April 2022.

Main Outcomes And Measures: The primary outcomes were fractures, CVEs, and death. Cumulative incidence of events was estimated using the 1-minus Kaplan-Meier estimator of corresponding survival function. Cox proportional hazards regression models were used to calculate hazard ratios (HRs).

Results: A total of 16 374 patients with pHPT were identified (mean [SD] age, 67.5 [12.9] years; 12 806 women [78.2%]), with 163 740 control individuals. The follow-up time was 42 310 person-years for the pHPT group and 803 522 person-years for the control group. Compared with the control group, the pHPT group had a higher risk of any fracture (unadjusted HR, 1.39; 95% CI, 1.31-1.48), hip fracture (unadjusted HR, 1.51; 95% CI, 1.35-1.70), CVEs (unadjusted HR, 1.45; 95% CI, 1.34-1.57), and death (unadjusted HR, 1.72; 95% CI, 1.65-1.80). In a time-dependent Poisson regression model, PTX was associated with a reduced risk of any fracture (HR, 0.83; 95% CI, 0.75-0.93), hip fracture (HR, 0.78; 95% CI, 0.61-0.98), CVEs (HR, 0.84; 95% CI, 0.73-0.97), and death (HR, 0.59; 95% CI, 0.53-0.65).

Conclusions And Relevance: Results of this study suggest that pHPT is associated with increased risk of fractures, CVEs, and death, highlighting the importance of identifying patients with this condition to prevent serious unfavorable outcomes. The reduced risk of these outcomes associated with PTX suggests a clinical benefit of surgery.
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http://dx.doi.org/10.1001/jamanetworkopen.2022.15396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9166253PMC
June 2022

Trabecular Bone Score Adjustment for the Fracture Risk Assessment Tool (FRAX®).

Calcif Tissue Int 2022 08 20;111(2):226-227. Epub 2022 May 20.

Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield, UK.

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http://dx.doi.org/10.1007/s00223-022-00994-wDOI Listing
August 2022

Potential Adverse Effect of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) on Bisphosphonate Efficacy: An Exploratory Post Hoc Analysis From a Randomized Controlled Trial of Clodronate.

J Bone Miner Res 2022 06 20;37(6):1117-1124. Epub 2022 Apr 20.

Mellanby Centre for Musculoskeletal Research, Medical Research Council (MRC) Versus Arthritis Centre for Integrated Research in Musculoskeletal Ageing, Department of Oncology & Metabolism, University of Sheffield, Sheffield, UK.

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 , 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).
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http://dx.doi.org/10.1002/jbmr.4548DOI Listing
June 2022

UK clinical guideline for the prevention and treatment of osteoporosis.

Arch Osteoporos 2022 04 5;17(1):58. Epub 2022 Apr 5.

University of Cambridge, School of Clinical Medicine, Cambridge, UK.

The National Osteoporosis Guideline Group (NOGG) has revised the UK guideline for the assessment and management of osteoporosis and the prevention of fragility fractures in postmenopausal women, and men age 50 years and older. Accredited by NICE, this guideline is relevant for all healthcare professionals involved in osteoporosis management.

Introduction: The UK National Osteoporosis Guideline Group (NOGG) first produced a guideline on the prevention and treatment of osteoporosis in 2008, with updates in 2013 and 2017. This paper presents a major update of the guideline, the scope of which is to review the assessment and management of osteoporosis and the prevention of fragility fractures in postmenopausal women, and men age 50 years and older.

Methods: Where available, systematic reviews, meta-analyses and randomised controlled trials were used to provide the evidence base. Conclusions and recommendations were systematically graded according to the strength of the available evidence.

Results: Review of the evidence and recommendations are provided for the diagnosis of osteoporosis, fracture-risk assessment and intervention thresholds, management of vertebral fractures, non-pharmacological and pharmacological treatments, including duration and monitoring of anti-resorptive therapy, glucocorticoid-induced osteoporosis, and models of care for fracture prevention. Recommendations are made for training; service leads and commissioners of healthcare; and for review criteria for audit and quality improvement.

Conclusion: The guideline, which has received accreditation from the National Institute of Health and Care Excellence (NICE), provides a comprehensive overview of the assessment and management of osteoporosis for all healthcare professionals involved in its management. This position paper has been endorsed by the International Osteoporosis Foundation and by the European Society for the Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases.
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http://dx.doi.org/10.1007/s11657-022-01061-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8979902PMC
April 2022

Digital health interventions for osteoporosis and post-fragility fracture care.

Ther Adv Musculoskelet Dis 2022 28;14:1759720X221083523. Epub 2022 Mar 28.

University of Cambridge School of Clinical Medicine, CB2 0QQ Cambridge, UK.

The growing burden from osteoporosis and fragility fractures highlights a need to improve osteoporosis management across healthcare systems. Sub-optimal management of osteoporosis is an area suitable for digital health interventions. While fracture liaison services (FLSs) are proven to greatly improve care for people with osteoporosis, such services might benefit from technologies that enhance automation. The term 'Digital Health' covers a variety of different tools including clinical decision support systems, electronic medical record tools, patient decision aids, patient apps, education tools, and novel artificial intelligence (AI) algorithms. Within the scope of this review are AI solutions that use algorithms within health system registries to target interventions. Clinician-targeted, patient-targeted, or system-targeted digital health interventions could be used to improve management and prevent fragility fractures. This review was commissioned by The Royal Osteoporosis Society and Bone Research Academy during the production of the 2020 Research Roadmap (https://theros.org.uk), with the intention of identifying gaps where targeted research funding could lead to improved patient health. We explore potential uses of digital technology in the general management of osteoporosis. Evidence suggests that digital technologies can support multidisciplinary teams to provide the best possible patient care based on current evidence and to support patients in self-management. However, robust randomised controlled studies are still needed to assess the effectiveness and cost-effectiveness of these technologies.
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http://dx.doi.org/10.1177/1759720X221083523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8966117PMC
March 2022

Incidence of hip fracture in Saudi Arabia and the development of a FRAX model.

Arch Osteoporos 2022 04 2;17(1):56. Epub 2022 Apr 2.

Mary McKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia.

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.

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: A country-specific FRAX tool for fracture prediction has been developed for Saudi Arabia which is expected to help guide decisions about treatment.
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http://dx.doi.org/10.1007/s11657-022-01085-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8976798PMC
April 2022

Epidemiology of hip fracture in Qatar and development of a country specific FRAX model.

Arch Osteoporos 2022 03 18;17(1):49. Epub 2022 Mar 18.

Mary McKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia.

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.

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: The FRAX model should enhance accuracy of determining fracture probability among the Qatari population and help guide decisions about treatment.
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http://dx.doi.org/10.1007/s11657-022-01083-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8933304PMC
March 2022

FREM predicts 10-year incident fracture risk independent of FRAX® probability: a registry-based cohort study.

Osteoporos Int 2022 Jul 17;33(7):1457-1463. Epub 2022 Feb 17.

Research Unit OPEN, Department of Clinical Research, University of Southern Denmark, Odense, Denmark.

The Danish Fracture Risk Evaluation Model (FREM) was found to predict fracture risk independent of 10-year fracture probability derived with the FRAX® tool including bone mineral density from DXA.

Introduction: FREM was developed from Danish public health registers without DXA information to identify high imminent risk of major osteoporotic fracture (MOF) and hip fracture (HF), while FRAX® estimates 10-year fracture probability from clinical risk factors and femoral neck bone mineral density (BMD) from DXA. The FREM algorithm showed significant 1- and 2-year fracture risk stratification when applied to a clinical population from Manitoba, Canada. We examined whether FREM predicts 10-year fracture risk independent of 10-year FRAX probability computed with BMD.

Methods: Using the Manitoba BMD Program registry, we identified women and men aged ≥ 45 years undergoing baseline BMD assessment. We calculated FREM and FRAX scores, and identified incident fractures over 10 years. Hazard ratios (HRs) for incident fracture were estimated according to FREM quintile, adjusted for FRAX probability. We compared predicted with observed 10-year cumulative fracture probability estimated with competing mortality.

Results: The study population comprised 74,446 women, mean age 65.2 years; 7945 men, mean age 67.5 years. There were 7957 and 646 incident MOF and 2554 and 294 incident HF in women and men, respectively. Higher FREM scores were associated with increased risk for MOF (highest vs middle quintile HRs 1.49 women, 2.06 men) and HF (highest vs middle quintile HRs 2.15 women, 2.20 men) even when adjusted for FRAX. Greater mortality with higher FREM scores attenuated its effect on 10-year fracture probability. In the highest FREM quintile, observed slightly exceeded predicted 10-year probability for MOF (ratios 1.05 in women, 1.49 in men) and HF (ratios 1.29 in women, 1.34 in men).

Conclusions: Higher FREM scores identified women and men at increased fracture risk even when adjusted for FRAX probability that included BMD; hence, FREM provides additional predictive information to FRAX. FRAX slightly underestimated 10-year fracture probability in those falling within the highest FREM quintile.
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http://dx.doi.org/10.1007/s00198-022-06349-3DOI Listing
July 2022

The Effect of Fracture Recency on Observed 10-Year Fracture Probability: A Registry-Based Cohort Study.

J Bone Miner Res 2022 05 22;37(5):848-855. Epub 2022 Feb 22.

Centre for Metabolic Bone Diseases, University of Sheffield Medical School, Sheffield, UK.

FRAX estimates 10-year fracture major osteoporotic fracture (MOF) and hip fracture probability from multiple risk factors. FRAX does not consider prior fracture site or time since fracture. Fracture risk is greater in the initial 2-year post-fracture period (imminent risk), implying that FRAX may underestimate risk in this setting. We used the population-based Manitoba Bone Mineral Density (BMD) Program registry to examine the effect of fracture recency and site on incident fracture risk predictions using FRAX. We identified women aged 40 years or older with baseline BMD and FRAX scores. Observed fracture outcomes to 10 years were compared with predicted 10-year fracture probability stratified by prior fracture status: none, recent (<2 years [median 0.3 years]), and remote (≥2 years [median 10.6 years]). For women with recent fractures, we also examined proposed multipliers to adjust FRAX for the effect of fracture recency and site. The cohort comprised 33,465 women aged 40 to 64 years (1897 recent fracture, 2120 remote fracture) and 33,806 women aged ≥65 years (2365 fracture, 4135 remote fracture). Observed fracture probability was consistent with predicted probability in most analyses. In women aged 40 to 64 years, there was a significant effect of recent vertebral and humerus fracture on MOF (observed to predicted 1.61 and 1.48, respectively), but these effects were still lower than the proposed multipliers (2.32 and 1.67, respectively). No significant effect of fracture recency was found after hip or forearm fracture in either age group. Our findings contribute to accumulating evidence of the importance of recent fracture. The effect of fracture recency was not consistent across fracture sites and with a lower magnitude than previously reported. Further quantification of effect size and specificity in additional independent cohorts is warranted to validate and refine recent-fracture multipliers in fracture risk assessment. © 2022 American Society for Bone and Mineral Research (ASBMR).
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http://dx.doi.org/10.1002/jbmr.4526DOI Listing
May 2022

Osteoporosis in Europe: a compendium of country-specific reports.

Arch Osteoporos 2022 01 26;17(1):23. Epub 2022 Jan 26.

Mary McKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia.

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).

Introduction: 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.

Methods: 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.

Results: 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.

Conclusions: 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.
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http://dx.doi.org/10.1007/s11657-021-00969-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8789736PMC
January 2022

Prevalence of FRAX risk factors and the osteoporosis treatment gap among women ≥ 70 years of age in routine primary care across 8 countries in Europe.

Arch Osteoporos 2022 01 22;17(1):20. Epub 2022 Jan 22.

Leiden University Medical Center, Leiden, Netherlands.

We studied whether elderly women at risk for fractures receive primary care treatment to prevent fracture. We found that across Europe, women at risk are often not identified, and less than half of such women receive appropriate treatment. Finally, women diagnosed with osteoporosis are much more likely to receive treatment.

Purpose: To examine the relationship between risk factors for fragility fracture (FF) and osteoporosis (OP) treatment gap in elderly women across Europe, and compare the prevalence of risk factors between countries.

Methods: Demographic and clinical information was collected from women ≥ 70 years visiting primary care physicians in Belgium, France, Germany, Ireland, Poland, Slovakia, Switzerland, and the UK. Increased risk of FF was defined by the presence of 1 or more criteria (history of fracture, 10-year fracture probability, or T-score ≤  - 2.5).

Results: There were 3798 women in total. Treatment gap (proportion at increased risk of FF not receiving treatment for OP) varied from 53.1 to 90.8% across countries, and the proportion of patients at increased risk of FF varied from 41.2 to 76.1%. Across countries, less than 50% of patients with increased risk of FF had a diagnosis of OP. Previous fracture was the most common risk factor, with similar prevalence across most countries; other risk factors varied widely. The treatment gap was reduced in patients with an OP diagnosis in all countries, but this reduction varied from 36.5 to 79.4%. The countries with the lowest rates of bone densitometry scans (Poland, France, and Germany; 8.3-12.3%) also had the highest treatment gap (82.2 to 90.8%).

Conclusions: This study highlights differences across Europe in clinical risk factors for fracture, rates of densitometry scanning, and the rates of OP diagnosis. More emphasis is needed on risk assessment to improve the identification and treatment of elderly women at risk for fracture.
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http://dx.doi.org/10.1007/s11657-021-01048-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8783912PMC
January 2022

Towards a cure for osteoporosis: the UK Royal Osteoporosis Society (ROS) Osteoporosis Research Roadmap.

Arch Osteoporos 2022 01 6;17(1):12. Epub 2022 Jan 6.

Department of Medicine, Cambridge Biomedical Campus, University of Cambridge, Cambridge, UK.

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http://dx.doi.org/10.1007/s11657-021-01049-7DOI Listing
January 2022

The application of FRAX in Saudi Arabia.

Arch Osteoporos 2021 11 5;16(1):166. Epub 2021 Nov 5.

Mary McKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia.

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.

Purpose: 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®.

Methods: 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.

Results: 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 individuals would be eligible for treatment after a BMD test and 373 women categorised at low risk after a BMD test.

Conclusion: Probability-based assessment of fracture risk using age-specific intervention thresholds was developed for Saudi Arabia to help guide decisions about treatment.
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http://dx.doi.org/10.1007/s11657-021-01024-2DOI Listing
November 2021

Prediction of imminent fracture risk in Canadian women and men aged 45 years or older: external validation of the Fracture Risk Evaluation Model (FREM).

Osteoporos Int 2022 Jan 1;33(1):57-66. Epub 2021 Oct 1.

University of Manitoba, Winnipeg, Canada.

The Fracture Risk Evaluation Model (FREM) identifies individuals at high imminent risk of major osteoporotic fractures. We validated FREM on 74,828 individuals from Manitoba, Canada, and found significant fracture risk stratification for all FREM scores. FREM performed better than age alone but not as well as FRAX® with BMD.

Introduction: The FREM is a tool developed from Danish public health registers (hospital diagnoses) to identify individuals over age 45 years at high imminent risk of major osteoporotic fractures (MOF) and hip fracture (HF). In this study, our aim was to examine the ability of FREM to identify individuals at high imminent fracture risk in women and men from Manitoba, Canada.

Methods: We used the population-based Manitoba Bone Mineral Density (BMD) Program registry, and identified women and men aged 45 years or older undergoing baseline BMD assessment with 2 years of follow-up data. From linked population-based data sources, we constructed FREM scores using up to 10 years of prior healthcare information.

Results: The study population comprised 74,828 subjects, and during the 2 years of observation, 1612 incident MOF and 299 incident HF occurred. We found significant fracture risk stratification for all FREM scores, with AUC estimates of 0.63-0.66 for MOF for both sexes and 0.84 for women and 0.65-0.67 for men for HF. FREM performed better than age alone but not as well as FRAX® with BMD. The inclusion of physician claims data gave slightly better performance than hospitalization data alone. Overall calibration for 1-year MOF prediction was reasonable, but HF prediction was overestimated.

Conclusion: In conclusion, the FREM algorithm shows significant fracture risk stratification when applied to an independent clinical population from Manitoba, Canada. Overall calibration for MOF prediction was good, but hip fracture risk was systematically overestimated indicating the need for recalibration.
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http://dx.doi.org/10.1007/s00198-021-06165-1DOI Listing
January 2022

miR-24 and its target gene Prdx6 regulate viability and senescence of myogenic progenitors during aging.

Aging Cell 2021 10 24;20(10):e13475. Epub 2021 Sep 24.

Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK.

Satellite cell-dependent skeletal muscle regeneration declines during aging. Disruptions within the satellite cells and their niche, together with alterations in the myofibrillar environment, contribute to age-related dysfunction and defective muscle regeneration. In this study, we demonstrated an age-related decline in satellite cell viability and myogenic potential and an increase in ROS and cellular senescence. We detected a transient upregulation of miR-24 in regenerating muscle from adult mice and downregulation of miR-24 during muscle regeneration in old mice. FACS-sorted satellite cells were characterized by decreased levels of miR-24 and a concomitant increase in expression of its target: Prdx6. Using GFP reporter constructs, we demonstrated that miR-24 directly binds to its predicted site within Prdx6 mRNA. Subtle changes in Prdx6 levels following changes in miR-24 expression indicate miR-24 plays a role in fine-tuning Prdx6 expression. Changes in miR-24 and Prdx6 levels were associated with altered mitochondrial ROS generation, increase in the DNA damage marker: phosphorylated-H2Ax and changes in viability, senescence, and myogenic potential of myogenic progenitors from mice and humans. The effects of miR-24 were more pronounced in myogenic progenitors from old mice, suggesting a context-dependent role of miR-24 in these cells, with miR-24 downregulation likely a part of a compensatory response to declining satellite cell function during aging. We propose that downregulation of miR-24 and subsequent upregulation of Prdx6 in muscle of old mice following injury are an adaptive response to aging, to maintain satellite cell viability and myogenic potential through regulation of mitochondrial ROS and DNA damage pathways.
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http://dx.doi.org/10.1111/acel.13475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8520721PMC
October 2021

FRAX-Based Intervention Thresholds for Osteoporosis Treatment in Ukraine.

J Osteoporos 2021 10;2021:2043479. Epub 2021 Jun 10.

State Institution, D.F. Chebotarev Institute of Gerontology NAMS of Ukraine, Kyiv, Ukraine.

Objectives: Osteoporosis, in addition to its consequent fracture burden, is a common and costly condition. FRAX is a well-established, validated, web-based tool which calculates the 10-year probability of fragility fractures. A FRAX model for Ukraine has been available since 2016 but its output has not yet been translated into intervention thresholds for the treatment of osteoporosis in Ukraine; we aimed to address this unmet need in this analysis.

Methods: In a referral population sample of 3790 Ukrainian women, 10-year probabilities of major osteoporotic fracture (MOF) and hip fracture separately were calculated using the Ukrainian FRAX model, with and without femoral neck bone mineral density (BMD). We used a similar approach to that first proposed by the UK National Osteoporosis Guideline Group, whereby treatment is indicated if the probability equals or exceeds that of a woman of the same age with a prior fracture.

Results: The MOF intervention threshold in females (the age-specific 10-year fracture probability) increased with age from 5.5% at the age of 40 years to 11% at the age of 75 years where it plateaued and then decreased slightly at age 90 (10%). Lower and upper thresholds were also defined to determine the need for BMD, if not already measured; the approach targets BMD measurements to those at or near the intervention threshold. The proportion of the referral populations eligible for treatment, based on prior fracture or similar or greater probability, ranged from 44% to 69% depending on age. The prevalence of the previous fracture rose with age, as did the proportion eligible for treatment. In contrast, the requirement for BMD testing decreased with age.

Conclusions: The present study describes the development and application of FRAX-based assessment guidelines in Ukraine. The thresholds can be used in the presence or absence of access to BMD and optimize the use of BMD where access is restricted.
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http://dx.doi.org/10.1155/2021/2043479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214495PMC
June 2021

FRAX-based intervention thresholds in eight Eurasian countries: Armenia, Belarus, Georgia, Kazakhstan, the Kyrgyz Republic, Moldova, the Russian Federation, and Uzbekistan.

Arch Osteoporos 2021 06 5;16(1):87. Epub 2021 Jun 5.

Mary McKillop Institute for Health Research, Catholic University of Australia, Melbourne, Australia.

Age-specific intervention and assessment thresholds based on FRAX® were developed for eight Eurasian countries participating in the EVA study (Armenia, Belarus, Georgia, Moldova, Kazakhstan, the Kyrgyz Republic, the Russian Federation, and Uzbekistan). The intervention thresholds (major osteoporotic fracture) ranged from 3.6 (Armenia and Georgia) to 12.3% (Uzbekistan) for people at age 50 years, and from 16 (Armenia) to 27% (Belarus) at the age of 90 years. These thresholds enable a substantial advance in the ease of detection of individuals at high fracture risk.

Introduction: The purpose of this study was to derive and compare FRAX-based intervention and BMD assessment thresholds for 8 Eurasian countries in the EVA study.

Methods: The intervention threshold (IT) was set at a 10-year probability of a major osteoporotic fracture (MOF), calculated without BMD, equivalent to a woman with a prior fragility fracture but no other clinical risk factors, and a body mass index (BMI) of 25.0 kg/m. The lower assessment threshold was set at a 10-year probability of a MOF in women with BMI of 25.0 kg/m, without previous fracture or other clinical risk factors. The upper assessment threshold was set at 1.2 times the IT.

Results: The age-specific intervention thresholds ranged from 3.6 (Armenia and Georgia) to 12.3% (Uzbekistan) for men and women at the age of 50 years and from 16 (Armenia) to 27% (Belarus) at the age of 90 years. The difference between countries was most evident at younger ages and become progressively less with advancing age.

Conclusions: For the 8 Eurasian countries, the newly established FRAX-based intervention thresholds provide an opportunity to improve the clinical detection of both men and women with a high risk of fracture and improve treatment rates.
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http://dx.doi.org/10.1007/s11657-021-00962-1DOI Listing
June 2021

SCOPE 2021: a new scorecard for osteoporosis in Europe.

Arch Osteoporos 2021 06 2;16(1):82. Epub 2021 Jun 2.

Quantify Research, Stockholm, Sweden.

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.

Introduction: 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.

Methods: 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).

Results: 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 example, 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.

Conclusions: 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.
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http://dx.doi.org/10.1007/s11657-020-00871-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172408PMC
June 2021

Sarcopenia Definitions as Predictors of Fracture Risk Independent of FRAX , Falls, and BMD in the Osteoporotic Fractures in Men (MrOS) Study: A Meta-Analysis.

J Bone Miner Res 2021 07 8;36(7):1235-1244. Epub 2021 Apr 8.

Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield, UK.

Dual-energy X-ray absorptiometry (DXA)-derived appendicular lean mass/height (ALM/ht ) 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 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 ), 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).
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http://dx.doi.org/10.1002/jbmr.4293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611727PMC
July 2021

FRAX-based fracture probabilities in South Africa.

Arch Osteoporos 2021 03 1;16(1):51. Epub 2021 Mar 1.

Mary McKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia.

The hip fracture rates in South Africa were used to create ethnic-specific FRAX® models to facilitate fracture risk assessment.

Introduction: 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.

Methods: 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.

Results: 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.

Conclusions: These FRAX models should enhance accuracy of determining fracture probability amongst the South African population and help guide decisions about treatment.
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http://dx.doi.org/10.1007/s11657-021-00905-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921059PMC
March 2021

Improved prediction of fracture risk leveraging a genome-wide polygenic risk score.

Genome Med 2021 02 3;13(1):16. Epub 2021 Feb 3.

Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, Room H-413, 3755 Chemin de la Côte-Sainte-Catherine, Montreal, Quebec, H3T 1E2, Canada.

Background: Accurately quantifying the risk of osteoporotic fracture is important for directing appropriate clinical interventions. While skeletal measures such as heel quantitative speed of sound (SOS) and dual-energy X-ray absorptiometry bone mineral density are able to predict the risk of osteoporotic fracture, the utility of such measurements is subject to the availability of equipment and human resources. Using data from 341,449 individuals of white British ancestry, we previously developed a genome-wide polygenic risk score (PRS), called gSOS, that captured 25.0% of the total variance in SOS. Here, we test whether gSOS can improve fracture risk prediction.

Methods: We examined the predictive power of gSOS in five genome-wide genotyped cohorts, including 90,172 individuals of European ancestry and 25,034 individuals of Asian ancestry. We calculated gSOS for each individual and tested for the association between gSOS and incident major osteoporotic fracture and hip fracture. We tested whether adding gSOS to the risk prediction models had added value over models using other commonly used clinical risk factors.

Results: A standard deviation decrease in gSOS was associated with an increased odds of incident major osteoporotic fracture in populations of European ancestry, with odds ratios ranging from 1.35 to 1.46 in four cohorts. It was also associated with a 1.26-fold (95% confidence interval (CI) 1.13-1.41) increased odds of incident major osteoporotic fracture in the Asian population. We demonstrated that gSOS was more predictive of incident major osteoporotic fracture (area under the receiver operating characteristic curve (AUROC) = 0.734; 95% CI 0.727-0.740) and incident hip fracture (AUROC = 0.798; 95% CI 0.791-0.805) than most traditional clinical risk factors, including prior fracture, use of corticosteroids, rheumatoid arthritis, and smoking. We also showed that adding gSOS to the Fracture Risk Assessment Tool (FRAX) could refine the risk prediction with a positive net reclassification index ranging from 0.024 to 0.072.

Conclusions: We generated and validated a PRS for SOS which was associated with the risk of fracture. This score was more strongly associated with the risk of fracture than many clinical risk factors and provided an improvement in risk prediction. gSOS should be explored as a tool to improve risk stratification to identify individuals at high risk of fracture.
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http://dx.doi.org/10.1186/s13073-021-00838-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7860212PMC
February 2021

Femoral neck strain prediction during level walking using a combined musculoskeletal and finite element model approach.

PLoS One 2021 1;16(2):e0245121. Epub 2021 Feb 1.

Department of Mechanical Engineering, University of Sheffield, Sheffield, United Kingdom.

Recently, coupled musculoskeletal-finite element modelling approaches have emerged as a way to investigate femoral neck loading during various daily activities. Combining personalised gait data with finite element models will not only allow us to study changes in motion/movement, but also their effects on critical internal structures, such as the femur. However, previous studies have been hampered by the small sample size and the lack of fully personalised data in order to construct the coupled model. Therefore, the aim of this study was to build a pipeline for a fully personalised multiscale (body-organ level) model to investigate the strain levels at the femoral neck during a normal gait cycle. Five postmenopausal women were included in this study. The CT and MRI scans of the lower limb, and gait data were collected for all participants. Muscle forces derived from the body level musculoskeletal models were used as boundary constraints on the finite element femur models. Principal strains were estimated at the femoral neck region during a full gait cycle. Considerable variation was found in the predicted peak strain among individuals with mean peak first principal strain of 0.24% ± 0.11% and mean third principal strain of -0.29% ± 0.24%. For four individuals, two overall peaks of the maximum strains were found to occur when both feet were in contact with the floor, while one individual had one peak at the toe-off phase. Both the joint contact forces and the muscular forces were found to substantially influence the loading at the femoral neck. A higher correlation was found between the predicted peak strains and the gluteus medius (R2 ranged between 0.95 and 0.99) than the hip joint contact forces (R2 ranged between 0.63 and 0.96). Therefore, the current findings suggest that personal variations are substantial, and hence it is important to consider multiple subjects before deriving general conclusions for a target population.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245121PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850486PMC
July 2021

Predictive Value of DXA Appendicular Lean Mass for Incident Fractures, Falls, and Mortality, Independent of Prior Falls, FRAX, and BMD: Findings from the Women's Health Initiative (WHI).

J Bone Miner Res 2021 04 28;36(4):654-661. Epub 2021 Jan 28.

Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield, UK.

In the Women's Health Initiative (WHI), we investigated associations between baseline dual-energy X-ray absorptiometry (DXA) appendicular lean mass (ALM) and risk of incident fractures, falls, and mortality (separately for each outcome) among older postmenopausal women, accounting for bone mineral density (BMD), prior falls, and Fracture Risk Assessment Tool (FRAX ) probability. The WHI is a prospective study of postmenopausal women undertaken at 40 US sites. We used an extension of Poisson regression to investigate the relationship between baseline ALM (corrected for height ) and incident fracture outcomes, presented here for major osteoporotic fracture (MOF: hip, clinical vertebral, forearm, or proximal humerus), falls, and death. Associations were adjusted for age, time since baseline and randomization group, or additionally for femoral neck (FN) BMD, prior falls, or FRAX probability (MOF without BMD) and are reported as gradient of risk (GR: hazard ratio for first incident fracture per SD increment) in ALM/height (GR). Data were available for 11,187 women (mean [SD] age 63.3 [7.4] years). In the base models (adjusted for age, follow-up time, and randomization group), greater ALM/height was associated with lower risk of incident MOF (GR = 0.88; 95% confidence interval [CI] 0.83-0.94). The association was independent of prior falls but was attenuated by FRAX probability. Adjustment for FN BMD T-score led to attenuation and inversion of the risk relationship (GR = 1.06; 95% CI 0.98-1.14). There were no associations between ALM/height and incident falls. However, there was a 7% to 15% increase in risk of death during follow-up for each SD greater ALM/height , depending on specific adjustment. In WHI, and consistent with our findings in older men (Osteoporotic Fractures in Men [MrOS] study cohorts), the predictive value of DXA-ALM for future clinical fracture is attenuated (and potentially inverted) after adjustment for femoral neck BMD T-score. However, intriguing positive, but modest, associations between ALM/height and mortality remain robust. © 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).
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http://dx.doi.org/10.1002/jbmr.4239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610603PMC
April 2021

Increased development of radiographic hip osteoarthritis in individuals with high bone mass: a prospective cohort study.

Arthritis Res Ther 2021 01 6;23(1). Epub 2021 Jan 6.

Musculoskeletal Research Unit, Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.

Background: Individuals with high bone mass (HBM) have a greater odds of prevalent radiographic hip osteoarthritis (OA), reflecting an association with bone-forming OA sub-phenotypes (e.g. osteophytosis, subchondral sclerosis). As the role of bone mineral density (BMD) in hip OA progression is unclear, we aimed to determine if individuals with HBM have increased incidence and/or progression of bone-forming OA sub-phenotypes.

Methods: We analysed an adult cohort with and without HBM (L1 and/or total hip BMD Z-score > + 3.2) with pelvic radiographs collected at baseline and 8-year follow-up. Sub-phenotypes were graded using the OARSI atlas. Superior/inferior acetabular/femoral osteophyte and medial/superior joint space narrowing (JSN) grades were summed and Δosteophyte and ΔJSN derived. Pain and functional limitations were quantified using the WOMAC questionnaire. Associations between HBM status and change in OA sub-phenotypes were determined using multivariable linear/logistic regression, adjusting for age, sex, height, total body fat mass, follow-up time and baseline sub-phenotype grade. Generalised estimating equations accounted for individual-level clustering.

Results: Of 136 individuals, 62% had HBM at baseline, 72% were female and mean (SD) age was 59 (10) years. HBM was positively associated with both Δosteophytes and ΔJSN (adjusted mean grade differences between individuals with and without HBM β = 0.30 [0.01, 0.58], p = 0.019 and β = 0.10 [0.01, 0.18], p = 0.019). Incident subchondral sclerosis was rare. HBM individuals had higher WOMAC hip functional limitation scores (β = 8.3 [0.7, 15.98], p = 0.032).

Conclusions: HBM is associated with the worsening of hip osteophytes and JSN over an average of 8 years, as well as increased hip pain and functional limitation.
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http://dx.doi.org/10.1186/s13075-020-02371-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788917PMC
January 2021

Transmission of whole body vibration - Comparison of three vibration platforms in healthy subjects.

Bone 2021 03 10;144:115802. Epub 2020 Dec 10.

Academic Unit of Bone Metabolism, Metabolic Bone Centre, Sorby Wing, EU14, E Floor, The Medical School, Beech Hill Road, Sheffield S10 2RX, UK; NIHR Bone Biomedical Research Unit, Northern General Hospital, Herries Road, Sheffield S5 7AU, UK. Electronic address:

The potential of whole body vibration (WBV) to maintain or enhance musculoskeletal strength during ageing is of increasing interest, with both low and high magnitude WBV having been shown to maintain or increase bone mineral density (BMD) at the lumbar spine and femoral neck. The aim of this study was to determine how a range of side alternating and vertical WBV platforms deliver vibration stimuli up through the human body. Motion capture data were collected for 6 healthy adult participants whilst standing on the Galileo 900, Powerplate Pro 5 and Juvent 100 WBV platforms. The side alternating Galileo 900 WBV platform delivered WBV at 5-30 Hz and amplitudes of 0-5 mm. The Powerplate Pro 5 vertical WBV platform delivered WBV at 25 and 30 Hz and amplitude settings of 'Low' and 'High'. The Juvent 1000 vertical WBV platform delivered a stimulus at a frequency between 32 and 37 Hz and amplitude 10 fold lower than either the Galileo or Powerplate, resulting in accelerations of 0.3 g. Motion capture data were recorded using an 8 camera Vicon Nexus system with 21 reflective markers placed at anatomical landmarks between the toe and the forehead. Vibration was expressed as vertical RMS accelerations along the z-axis which were calculated as the square root of the mean of the squared acceleration values in g. The Juvent 1000 did not deliver detectable vertical RMS accelerations above the knees. In contrast, the Powerplate Pro 5 and Galileo 900 delivered vertical RMS accelerations sufficiently to reach the femoral neck and lumbar spine. The maximum vertical RMS accelerations at the anterior superior iliac spine (ASIS) were 1.00 g ±0.30 and 0.85 g ±0.49 for the Powerplate and Galileo respectively. For similar accelerations at the ASIS, the Galileo achieved greater accelerations within the lower limbs, whilst the Powerplate recorded higher accelerations in the thoracic spine at T10. The Powerplate Pro 5 and Galileo 900 deliver vertical RMS accelerations sufficiently to reach the femoral neck and lumbar spine, whereas the Juvent 1000 did not deliver detectable vertical RMS accelerations above the knee. The side alternating Galileo 900 showed greater attenuation of the input accelerations than the vertical vibrations of the Powerplate Pro 5. The platforms differ markedly in the transmission of vibration with strong influences of frequency and amplitude. Researchers need to take account of the differences in transmission between platforms when designing and comparing trials of whole body vibration.
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http://dx.doi.org/10.1016/j.bone.2020.115802DOI Listing
March 2021

MRI-based anatomical characterisation of lower-limb muscles in older women.

PLoS One 2020 1;15(12):e0242973. Epub 2020 Dec 1.

Department of Mechanical Engineering, University of Sheffield, Sheffield, United Kingdom.

The ability of muscles to produce force depends, among others, on their anatomical features and it is altered by ageing-associated weakening. However, a clear characterisation of these features, highly relevant for older individuals, is still lacking. This study hence aimed at characterising muscle volume, length, and physiological cross-sectional area (PCSA) and their variability, between body sides and between individuals, in a group of post-menopausal women. Lower-limb magnetic resonance images were acquired from eleven participants (69 (7) y. o., 66.9 (7.7) kg, 159 (3) cm). Twenty-three muscles were manually segmented from the images and muscle volume, length and PCSA were calculated from this dataset. Personalised maximal isometric force was then calculated using the latter information. The percentage difference between the muscles of the two lower limbs was up to 89% and 22% for volume and length, respectively, and up to 84% for PCSA, with no recognisable pattern associated with limb dominance. Between-subject coefficients of variation reached 36% and 13% for muscle volume and length, respectively. Generally, muscle parameters were similar to previous literature, but volumes were smaller than those from in-vivo young adults and slightly higher than ex-vivo ones. Maximal isometric force was found to be on average smaller than those obtained from estimates based on linear scaling of ex-vivo-based literature values. In conclusion, this study quantified for the first time anatomical asymmetry of lower-limb muscles in older women, suggesting that symmetry should not be assumed in this population. Furthermore, we showed that a scaling approach, widely used in musculoskeletal modelling, leads to an overestimation of the maximal isometric force for most muscles. This heavily questions the validity of this approach for older populations. As a solution, the unique dataset of muscle segmentation made available with this paper could support the development of alternative population-based scaling approaches, together with that of automatic tools for muscle segmentation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242973PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7707470PMC
January 2021
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