Search

Summary: A surrogate FRAX® model for Nepal has been constructed using age- and sex-specific hip fracture rates for Indians living in Singapore and age- and sex-specific mortality rates from Nepal. Introduction: FRAX models are frequently requested for countries with little or no data on the incidence of hip fractures. In such circumstances, the development of a surrogate FRAX model is recommended 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. Objective: This report describes the development and characteristics of a surrogate FRAX model for Nepal. Methods: The FRAX model used the ethnic-specific incidence of hip fracture in the Indian community of Singapore, combined with the death risk for Nepal in 2015–2019. The number of hip fractures in 2015 and 2050 was estimated based on the United Nations' predicted changes in population demography. Results: The surrogate model gave similar hip fracture probabilities to estimates from Sri Lanka, India and Pakistan but lower 10-year fracture probabilities for men and women at older ages compared to the model for Singapore, reflecting a higher mortality risk in Nepal compared with Singapore. There were very close correlations in fracture probabilities between the Nepalese and the Singapore models (r> 0.995) so that the use of the Nepalese model had little impact on the rank order of risk, i.e. a person at the xth percentile of risk with one model will be at the xth percentile of risk with the other. It was estimated that 6897 hip fractures arose in 2015 in individuals aged 50 years and older in Nepal, with a predicted 3-fold increase expected by 2050, when 23,409 hip fractures are expected nationally. Conclusion: The surrogate FRAX model for Nepal provides an opportunity to determine fracture probability within the Nepalese population and help guide decisions about treatment. [ABSTRACT FROM AUTHOR]

Summary: Fracture probabilities derived from the original FRAX model for Brazil were compared to those from an updated model based on more recent regional estimates of the incidence of hip fracture. Fracture probabilities were consistently lower in the updated FRAX model. Despite large differences between models, differences in the rank order of fracture probabilities were minimal. Objective: Recent epidemiological data indicate that the risk of hip fracture in Brazil is lower than that used to create the original FRAX model. This paper describes the epidemiology of hip fracture in Brazil and the synthesis of an updated FRAX model with the aim of comparing this new model with the original model. Methods: Hip fracture rates from three cities in three regions were combined, weighted by the population of each region. For other major fractures, incidence rates for Brazil were estimated using Swedish ratios for hip to other major osteoporotic fracture (humerus, forearm or clinical vertebral fractures). Mortality estimates were taken from the UN. Results: Compared to the original FRAX model, the updated model gave lower 10-year fracture probabilities in men and women at all ages. Notwithstanding, there was a very close correlation in fracture probabilities between the original and updated models (r > 0.99) so that the revisions had little impact on the rank order of risk. Conclusion: The disparities between the original and updated FRAX models indicate the importance of updating country-specific FRAX models with the advent of significant changes in fracture epidemiology. [ABSTRACT FROM AUTHOR]

An editorial is presented on the approaches to improving the management and treatment of patients with osteoporotic fractures are increasingly advocated in many countries. It outlines the management of those presenting with nonhip fractures is also addressed through the establishment of Fracture Liaison Services. An overview of the systematic approaches for the identification of high fracture risk is presented.

Summary: Vertebral fracture (VF) is a strong predictor of subsequent fracture. In this study of older women, VF, identified by dual-energy X-ray absorptiometry (DXA) vertebral fracture assessment (VFA), were associated with an increased risk of incident fractures and had a substantial impact on fracture probability, supporting the utility of VFA in clinical practice. Purpose: Clinical and occult VF can be identified using VFA with dual-energy X-ray absorptiometry (DXA). The aim of this study was to investigate to what extent VFA-identified VF improve fracture risk prediction, independently of bone mineral density (BMD) and clinical risk factors used in FRAX. Methods: A total of 2852 women, 75–80 years old, from the prospective population-based study SUPERB cohort, were included in this study. At baseline, BMD was measured by DXA, VF diagnosed by VFA, and questionnaires used to collect data on risk factors for fractures. Incident fractures were captured by X-ray records or by diagnosis codes. An extension of Poisson regression was used to estimate the association between VFA-identified VF and the risk of fracture and the 5- and 10-year probability of major osteoporotic fracture (MOF) was calculated from the hazard functions for fracture and death. Results: During a median follow-up of 5.15 years (IQR 4.3–5.9 years), the number of women who died or suffered a MOF, clinical VF, or hip fracture was 229, 422, 160, and 124, respectively. A VFA-identified VF was associated with an increased risk of incident MOF (hazard ratio [HR] = 1.78; 95% confidence interval [CI] 1.46–2.18), clinical VF (HR = 2.88; 95% [CI] 2.11–3.93), and hip fracture (HR = 1.67; 95% [CI] 1.15–2.42), adjusted for age, height, and weight. For women at age 75 years, a VFA-identified VF was associated with 1.2–1.4-fold greater 10-year MOF probability compared with not taking VFA into account, depending on BMD. Conclusion: Identifying an occult VF using VFA has a substantial impact on fracture probability, indicating that VFA is an efficient method to improve fracture prediction in older women. [ABSTRACT FROM AUTHOR]

Summary: 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. Introduction: 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 individuals 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. Methods: 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. Results and Conclusion: 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. [ABSTRACT FROM AUTHOR]

Summary : In this retrospective cohort study, men and women with eating disorders (n = 8867) had higher risk of injurious falls and hip fractures than age, sex, and county-matched controls (n = 88670). Introduction: Eating disorders have been associated with decreased bone mineral density and increased fracture risk, but the association with fall injuries without fracture has not previously been investigated. Furthermore, fracture risk in men with eating disorders has been insufficiently studied. Methods: In the present study, 8867 patients (9.4% men) with a diagnosed eating disorders and 88670 age-, sex-, and county-matched controls were investigated. Results: The mean (standard deviation) age of the patients and controls was 41.6 (13.7) years and the follow-up time 9.6 (5.2, 14.4) years (median, interquartile range) for patients and 10.1 (5.5, 14.2) years for controls. The proportions of injurious falls without fracture (17.3% vs. 9.0%) and of hip fracture (1.6% vs. 0.7%) were substantially greater in patients with an eating disorder than in their corresponding population controls. In an unadjusted Cox proportional hazards model, individuals with an eating disorder had a higher risk of injurious falls without fracture (Hazard ratio (HR) 95% confidence interval (CI): 2.07 (1.96–2.18), and hip fracture (HR 2.30 (1.92–2.75)) than the risk observed in the controls. The HR for any investigated outcome associated with an eating disorder did not differ by sex or age (interaction term p > 0.10). The risk of injurious falls without fracture and hip fracture was increased in both women (HR 2.07 (1.95–2.19) and HR 2.41 (1.98–2.93), respectively) and men (HR 2.09 (1.76–2.49) and HR 1.84(1.12–3.02), respectively), with an eating disorder. Conclusion: The risk of injurious falls without fracture and of hip fracture is increased in both women and men with eating disorders, indicating measures to prevent both falls and fractures are important in these patients, regardless of age and sex. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Summary: In women of ages 75–80 years, a low one leg standing time (OLST) was associated with an increased risk of incident fractures, independently of bone mineral density and clinical risk factors. OLST contributed substantially to fracture probability, indicating that the test should be considered when evaluating fracture risk in older women. Introduction: Physical function and risk of falls are important risk factors for fracture. A few previous studies have suggested that a one leg standing time (OLST) less than 10 s predicts fracture risk, but the impact of OLST, in addition to known clinical risk factors, for fracture probability is unknown. The aim of this study was to determine the independent contribution of OLST to fracture probability in older women. Methods: The Sahlgrenska University Hospital Prospective Evaluation of Risk of Bone Fractures (SUPERB) is a prospective population-based study of 3028 women 75–80 years old, recruited from the greater Gothenburg area in Sweden. At baseline, information on risk factors was collected using questionnaires, bone mineral density was measured with dual-energy X-ray absorptiometry (DXA), and OLST was performed. Results: During a median follow-up of 3.6 years (IQR 1.5 years), X-ray-verified incident fractures were identified using health records. OLST was available in 2405 women. OLST less than 10 s was associated with an increased risk for incident hip fracture (Hazard Ratio (HR) 3.02, 95% Confidence Interval (CI) [1.49–6.10]), major osteoporotic fracture (HR 95% CI 1.76 [1.34–1.46]), and nonvertebral fracture (HR 95% CI 1.61 [1.26–2.05]) in Cox regression analyses adjusted for age, height, and weight. Depending on BMD, the 4-year fracture probability increased by a factor of 1.3 to 1.5 in a 75-year-old woman with a low OLST (<10 s). Conclusion: A low OLST has a substantial impact on fracture probability and should be considered when evaluating fracture risk in older women. [ABSTRACT FROM AUTHOR]

Summary: 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. Purpose: 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. Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Summary: Patients with ankylosing spondylitis (AS) have impaired volumetric bone mineral density (vBMD) assessed with high-resolution peripheral computed tomography (HRpQCT). This first longitudinal HRpQCT study in AS shows that cortical and trabecular vBMD decreased at tibia and that signs of inflammation were associated with cortical bone loss at tibia and radius. Introduction: Patients with ankylosing spondylitis (AS) have reduced volumetric bone mineral density (vBMD) in the peripheral skeleton assessed with high-resolution peripheral quantitative computed tomography (HRpQCT). The aims were to investigate longitudinal changes in vBMD, cortical area, and microarchitecture and to assess factors associated with changes in vBMD and cortical area in men with AS. Methods: HRpQCT of radius and tibia was performed in 54 men with AS at baseline and after 5 years. Univariate and multivariable linear regression analyses were used. Results: At tibia, there were significant decreases exceeding least significant changes (LSC) in cortical and trabecular vBMD, mean (SD) percent change −1.0 (1.9) and −2.7 (5.0) respectively (p<0.001). In multivariable regression analyses, increase in disease activity measured by ASDAS_CRP from baseline to follow-up was associated with decreases in cortical vBMD (β −0.86, 95% CI −1.31 to −0.41) and cortical area (β −1.66, 95% CI −3.21 to −0.10) at tibia. At radius, no changes exceeded LSC. Nonetheless, increase in ASDAS_CRP was associated with decreases in cortical vBMD, and high time-averaged ESR was associated with decreases in cortical area. Treatment with TNF inhibitor ≥ 4 years during follow-up was associated with increases in cortical vBMD and cortical area at tibia, whereas exposure to bisphosphonates was associated with increases in cortical measurements at radius. No disease-related variables or treatments were associated with changes in trabecular vBMD. Conclusion: The findings in this first longitudinal HRpQCT study in patients with AS strengthen the importance of controlling disease activity to maintain bone density in the peripheral skeleton. [ABSTRACT FROM AUTHOR]

Summary: In this retrospective cohort study of 6604 adults, 65 years or older, admitted with seasonal influenza at Swedish hospitals, and 330,200 age- and sex-matched controls from the general population admitted for other reasons, were included. Patients with influenza had increased risk of fall injuries and fractures compared to controls. Introduction: Fractures and fall injuries often lead to disability, increased morbidity, and mortality. Older adults are at higher risk of influenza-related complications such as pneumonia, cardiovascular events, and deaths, but the risk of fractures and fall injuries is unclear. The primary objective of this study was to investigate the risk of fractures and fall injuries in older patients after admission with seasonal influenza. Methods: In this retrospective cohort study of 6604 adults, 65 years or older, admitted with seasonal influenza at Swedish hospitals (from December 1, 2015, to December 31, 2017) and 330,200 age- and sex-matched controls from the general population and admitted for other reasons, the risk of fracture or fall injury was investigated. Results: The mean (SD) age of the 6604 influenza patients was 80.9 (8.1) years and 50.1% were women. During the first year after hospital discharge, there were 680 (10.3%) patients suffering from a fracture or fall injury among the patients with influenza, and 25,807 (7.8%) among the controls, corresponding to incident rates of 141 (95% CI, 131–152) and 111 (95% CI, 110–112) fractures or fall injuries per 1000 person-years respectively, translating to a significantly increased risk of fracture or fall injury in a Cox regression model (hazard ratio (HR) 1.28 (95% CI, 1.19–1.38)), a risk that was maintained after multivariable adjustment (HR 1.22 (95% CI 1.13–1.31)). Conclusions: Older adults admitted with influenza diagnosis have an increased risk of fracture or fall injury during the first year after discharge. [ABSTRACT FROM AUTHOR]

Summary: In elderly men included in MrOS-Sweden, subclinical hyperthyroidism (SHyper) was markedly associated with increased risk of vertebral fractures. Introduction: Overt hyperthyroidism is associated with increased risk of fractures. However, only a few studies have investigated whether SHyper is associated with fracture risk in elderly men. We therefore investigated if SHyper was a risk factor for fractures in Swedish men. Methods: We followed (median 9.8 years) elderly men (n = 1856; mean age 75, range 69–81 years) participating in the Gothenburg and Malmö subcohorts of the prospective, population-based MrOS-Sweden study. The statistical analyses included Cox proportional hazards regression. SHyper was defined as serum thyroid-stimulating hormone (TSH) < 0.45 mIU/L (n = 38). Results: SHyper was associated with increased risk of all fractures [n = 456; hazard ratio (HR) adjusted for age, study center, and levothyroxine treatment = 1.99, 95% confidence interval (CI): 1.20–3.32], major osteoporotic fractures (MOF, n = 338; HR 2.44, 95% CI: 1.42–4.21), and vertebral fractures (n = 176; HR 3.79, 95% CI: 2.02–7.11). These associations remained after full adjustment for covariates including total hip bone mineral density and in subanalyses including only men with serum free thyroxine ≤ the upper normal limit. However, after exclusion of men receiving levothyroxine treatment, the associations with all fractures and MOF lost significance. Conclusions: In elderly Swedish men, there was a strong association between SHyper and increased risk of vertebral fractures, whereas the associations with all incident fractures and MOF need to be confirmed in further studies. [ABSTRACT FROM AUTHOR]

Summary: The National Osteoporosis Guideline Group (NOGG) has developed intervention thresholds based on FRAX® to characterise patients at high and very high risk of fracture. Introduction: 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. Methods: 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. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Summary: 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. Introduction: To investigate the impact of population level or targeted alterations to BMD on the incidence of fractures. Methods: 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 individuals with T-score below −2.5 to be exactly −2.5 (high-risk strategy) and (ii) shifting the entire BMD distribution upwards (population strategy). Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Summary: This study aimed to determine the interaction between baseline FRAX® fracture probability and romosozumab efficacy. Using an ITT approach, it was determined that the efficacy of romosozumab on clinical fracture, osteoporotic fracture, and major osteoporotic fracture is significantly greater in patients at high baseline fracture risk, when compared with placebo. Introduction: Post hoc analyses of placebo-controlled osteoporosis treatment studies have shown significantly greater reductions of fracture incidence for higher fracture risk patients. This study determined the interaction between baseline FRAX® fracture probability and romosozumab efficacy in the placebo-controlled first year of the phase 3 FRAME study (NCT01575834). Methods: Using an ITT approach, an extension of Poisson regression analysis studied the relationship between treatment, FRAX® 10-year probability of major osteoporotic fracture (MOF, calculated without BMD) and risk of first incident fracture (adjusting for age and follow-up time). Treatment interactions considered outcomes of all clinical fractures, osteoporotic fractures, MOF, clinical vertebral fractures, and morphometric vertebral fractures. Two-sided p value of < 0.1 for the interaction between treatment and FRAX® was considered significant. Results: Compared with placebo, romosozumab reduced the incidence of all fracture outcomes in the first year (range: 32% reduction in MOF [p = 0.07] to 80% reduction in clinical vertebral fractures [p = 0.038]). Significant interactions were observed between efficacy and baseline FRAX® probability for composite outcomes of clinical fractures, osteoporotic fractures, and MOF (p = 0.064–0.084), but not vertebral fractures (p > 0.3). For example, romosozumab decreased all clinical fractures by 22% at the 25th centile of FRAX® probability but the reduction was 41% at the 75th centile. Exclusion of vertebral fractures from each composite fracture outcome (i.e. only nonvertebral fractures included) showed even stronger interactions with baseline FRAX® probability (p = 0.036–0.046). Conclusions: Efficacy of romosozumab on clinical fracture, osteoporotic fracture, and MOF is significantly greater in patients at high baseline fracture risk compared with placebo. [ABSTRACT FROM AUTHOR]

Summary: The risk of a recurrent fragility fracture varies by age and sex, as by site and recency of sentinel fracture. Introduction: 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. Methods: The study used data from the Reykjavik Study fracture register that documented prospectively all fractures at all skeletal sites in a large sample 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. Results: Sentinel osteoporotic fractures were identified in 9504 men and women. Of these, 3616 individuals 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. Conclusion: The risk of a recurrent fragility fracture varies by age, sex, and site of sentinel fracture when recency is held constant. [ABSTRACT FROM AUTHOR]

The authors reflect on the risk factors for future fracture, particularly prior fragility fracture, and the short time horizons for fracture prediction tools. Topics include the risks of osteoporotic fractures, the heterogeneity of fracture risk between countries, the studies using machine learning methods, as well as the use of the FRAX tool to estimate the probability of a major osteoporotic fracture.

Summary: In elderly ambulatory men, high platelet and high neutrophil counts are related to low bone mineral density (BMD), after adjustment for relevant covariates. Low hemoglobin (hgb) is even associated with low BMD, but this relationship seems to be dependent on estradiol and osteocalcin. Purpose: Blood and bone cells exist in close proximity to each other in the bone marrow. Accumulating evidence, from both preclinical and clinical studies, indicates that these cell types are interconnected. Our hypothesis was that BMD measurements are associated with blood count variables and bone remodeling markers. Methods: We analyzed blood count variables, bone remodeling markers, and BMD, in subjects from the MrOS cohort from Gothenburg, Sweden. Men with at least one blood count variable (hgb, white blood cell count, or platelet count) analyzed were included in the current analysis (n = 1005), median age 75.3 years (range 69–81 years). Results: Our results show that high platelet counts were related to low BMD at all sites (total hip BMD; r = − 0.11, P = 0.003). No statistically significant association was seen between platelet counts and bone remodeling markers. Neutrophil counts were negatively associated with total body BMD (r = − 0.09, P = 0.006) and total hip BMD (r = − 0.08, P = 0.010), and positively related to serum ALP (r = 0.15, P < 0.001). Hgb was positively related to total hip BMD (r = 0.16, P < 0.001), and negatively to serum osteocalcin (r = − 0.13, P < 0.001). The association between platelet and neutrophil counts and total hip BMD was statistically significant after adjustments for other covariates, but the association between hgb and total hip BMD was dependent on estradiol and osteocalcin. Conclusions: Our observations support the hypothesis of an interplay between blood and bone components. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Summary: Romosozumab is a novel bone-building drug that reduces fracture risk. This health economic analysis indicates that sequential romosozumab-to-alendronate can be a cost-effective treatment option for postmenopausal women with severe osteoporosis at high risk of fracture. Purpose: To estimate the cost-effectiveness of sequential treatment with romosozumab followed by alendronate ("romosozumab-to-alendronate") compared with alendronate alone in patients with severe osteoporosis at high risk of fracture in Sweden. Methods: A microsimulation model with a Markov structure was used to simulate fractures, costs, and quality-adjusted life years (QALYs), for women treated with romosozumab-to-alendronate or alendronate alone. Patients aged 74 years with a recent major osteoporotic fracture (MOF) were followed from the start of treatment until the age of 100 years or death. Treatment with romosozumab for 12 months was followed by alendronate for up to 48 months or alendronate alone with a maximum treatment duration of 60 months. The analysis had a societal perspective. Efficacy of romosozumab and alendronate were derived from phase III randomized controlled trials. Resource use and unit costs were collected from the literature. Cost-effectiveness was estimated using incremental cost-effectiveness ratio (ICER) with QALYs as effectiveness measures. Results: The base case analysis showed that sequential romosozumab-to-alendronate treatment was associated with 0.089 additional QALYs at an additional cost of €3002 compared to alendronate alone, resulting in an ICER of €33,732. At a Swedish reference willingness-to-pay per QALY of €60,000, romosozumab-to-alendronate had a 97.9% probability of being cost-effective against alendronate alone. The results were most sensitive to time horizon, persistence assumptions, patient age, and treatment efficacy. Conclusion: The results of this study indicate that sequential romosozumab-to-alendronate can be a cost-effective treatment option for postmenopausal women with severe osteoporosis at high risk of fracture. [ABSTRACT FROM AUTHOR]

Summary: 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. Introduction: 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. Objective: This paper describes the development and characteristics of a surrogate FRAX model for Pakistan. Methods: 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. Results: 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 individuals over the age of 50 years in Pakistan, with a predicted increase by 214% to 114,820 in 2050. Conclusion: The surrogate FRAX model for Pakistan provides an opportunity to determine fracture probability within the Pakistan population and help guide decisions about treatment. [ABSTRACT FROM AUTHOR]

Summary: This paper explores use of metrics that combine fracture outcomes that add power to phase 3 studies and provide a surrogate outcome for regulatory agencies. Introduction: The aim of this study was to develop an analytic framework that would combine information from all fracture outcomes (including radiographic vertebral fractures) in phase 3 studies to provide a metric for the assessment of treatment efficacy. Methods: Data from the phase 3 study of denosumab were used as an exemplar comparing the effects of active intervention with placebo on the risk of all fractures associated with osteoporosis. Fracture outcomes were assigned utility weights drawn from the published literature and applied to age-specific health state values of the general population. For each fracture outcome in each arm of the study, cumulative disutility was computed to serve as the principal end point. The hypothesis tested was that treatment with denosumab results in a significant reduction in mean fracture-related disutility. Results: Treatment with denosumab was associated with significantly lower utility loss compared with placebo. For patients treated with denosumab, mean utility loss was 42% less than with placebo (4.5 vs. 7.5 QALYs/1000 patient years, respectively, p < 0.001). Conclusions: Denosumab significantly decreased utility loss. The use of metrics that combine fracture outcomes may provide added power to phase 3 studies and provide a surrogate outcome for regulatory agencies. [ABSTRACT FROM AUTHOR]

Summary: 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. Introduction: 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. Methods: The study used data from the Reykjavik Study fracture register that documented prospectively all fractures at all skeletal sites in a large sample 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Summary: The timed up and go (TUG) test measures physical performance and predicts falls in the elderly. In older women, TUG time predicts the risk of major osteoporotic fracture and hip fracture independently of clinical risk factors and bone mineral density, and has a substantial impact on fracture probabilities. Introduction: The timed up and go (TUG) test measures physical performance and predicts falls in the elderly. A slow TUG has been associated with an increased fracture risk, but it is unclear whether the association is independent of clinical risk factors and bone mineral density (BMD). The aim of this study was to investigate if TUG time was associated with fracture risk independently of clinical risk factors and BMD and to determine its impact on fracture probabilities in older women. Methods: A standardized questionnaire was used to assess information regarding clinical risk factors in the large population-based SUPERB study of 3028 older women (75–80 years). At baseline, the TUG test was performed and BMD measured with DXA. The association between TUG time and the risk of hip fracture and major osteoporotic fracture (MOF) was examined using an extension of Poisson regression. Results: Fracture incidence increased steeply with increasing TUG time up to 12 s and subsequently started to level off. A slow TUG time was therefore defined as TUG > 12 s, a cutoff level then used in Cox models to study the association between slow TUG and fracture risk. A slow TUG time was associated with an increased risk of fracture (MOF 2.39 [1.80–3.18] and hip fracture 2.96 [1.62–5.40]). These associations were slightly attenuated but remained significant after adjustment for clinical risk factors and femoral neck BMD. Depending on BMD, the 4-year fracture probability of MOF increased by a factor of 1.5–1.9 in a 75-year-old woman with slow TUG (> 12 s). Conclusion: The TUG time predicts the risk of MOF and hip fracture independently of clinical risk factors and BMD and has a substantial impact on fracture probabilities, indicating that inclusion of the TUG test in patient evaluation should be considered in order to improve fracture prediction in older women. [ABSTRACT FROM AUTHOR]

Summary: 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. Introduction: 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). Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

An editorial is presented regarding FRAX and ethnicity. It mentions the key messages from the epidemiology of fracture globally, key considerations in building risk assessment tools, the specific contribution of race/ethnicity and practical considerations related to any move to alter race/ethnicity categorization or remove them entirely.

Summary: The risk of a recurrent fragility fracture is particularly high immediately following the fracture. This study provides adjustments to FRAX-based fracture probabilities accounting for the site of a recent fracture. Introduction: 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 10-year probability of fracture determined with FRAX. Methods: The study used data from the Reykjavik Study fracture register that documented prospectively all fractures at all skeletal sites in a large sample of the population of Iceland. Fracture probabilities were determined after a sentinel fracture (humeral, clinical vertebral, forearm and hip fracture) from the hazards of death and fracture. Fracture probabilities were computed on the one hand for sentinel fractures occurring within the previous 2 years and on the other hand, probabilities for a prior osteoporotic fracture irrespective of recency. The probability ratios provided adjustments to conventional FRAX estimates of fracture probability for recent sentinel fractures. Results: Probability ratios to adjust 10-year FRAX probabilities of a major osteoporotic fracture for recent sentinel fractures were age dependent, decreasing with age in both men and women. Probability ratios varied according to the site of sentinel fracture with higher ratios for hip and vertebral fracture than for humerus or forearm fracture. Probability ratios to adjust 10-year FRAX probabilities of a hip fracture for recent sentinel fractures were also age dependent, decreasing with age in both men and women with the exception of forearm fractures. Conclusion: The probability ratios provide adjustments to conventional FRAX estimates of fracture probability for recent sentinel fractures. [ABSTRACT FROM AUTHOR]

Summary: The hip fracture rates from Kazakhstan were used to create a surrogate FRAX® model for the Kyrgyz Republic. Introduction: 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. Objective: This paper describes a surrogate FRAX model for the Kyrgyz Republic. Methods: The FRAX model used the incidence of hip fracture from the neighbouring country of Kazakhstan and the death risk for the Kyrgyz Republic. Results: 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 individuals over the age of 50 years in the Kyrgyz Republic, with a predicted increase by 207% to 8435 in 2050. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Summary: We studied the risk for hip fracture before and after total knee replacement (TKR) in the entire population in Sweden. Women and men had a low risk for hip fracture before TKR but an increased risk the first year after TKR. Purpose: It is known that osteoarthritis is associated with high bone mass. We therefore studied the risk of hip fracture before and after total knee replacement (TKR), risk of different hip fracture types, and risk subdivided in genders and age groups. Methods: We followed the total Swedish population born between 1902 and 1952 (n = 4,258,934) during the period 1987–2002 and identified all patients with TKR due to primary OA (n = 39,291), and all patients with hip fracture (n = 195,860) in the Swedish National Inpatient Register. The risk time analyses were based on Poisson regression models. Results: The hazard ratio (HR) for hip fracture the last year before TKR was 0.86 (95% CI 0.74 to 1.00) and the first year after 1.26 (95% CI 1.11 to 1.42) compared to individuals without TKR. The HR for femoral neck fracture 0–10 years after TKR was 0.95 (95% CI 0.89 to 1.01) and for trochanteric fracture was 1.13 (95% CI 1.06 to 1.21). The HR for hip fracture in the age group 50–74 was 1.28 (95% CI 1.14 to 1.43) and in the age group 75–90 years was 0.99 (95% CI 0.94 to 1.04) 0–10 years after TKR, compared to individuals without TKR. Conclusion: Individuals had a low risk for hip fracture before TKR but an increased risk the first year after TKR. The risk in individuals below age 75 years and for trochanteric fractures was increased after TKR. Possible explanations include changed knee kinematics after a TKR, physical activity level, fall risk, and other unknown factors. [ABSTRACT FROM AUTHOR]

Summary: Death of a spouse is associated with poorer physical and mental health. We followed all married individuals, born from 1902 to 1942, during the period from 1987 to 2002, and found that widows and widowers had higher risk for hip fracture, compared with still married women and men. Introduction: Spousal bereavement can lead to poorer physical and mental health. We aimed to determine whether married women and men had an elevated risk of hip fracture after death of a spouse. Methods: In a retrospective cohort study, we followed all Swedish married individuals aged 60 to 100 years (n = 1,783,035), from 1987 to 2002. Data are presented as mean with 95% confidence interval (CI). Results: During the follow-up period, 21,305 hip fractures among widows and 6538 hip fractures among widowers were noted. The hazard ratio (HR) for hip fracture in widows compared with married women was 1.34 (95% CI 1.31 to 1.37) and for widowers compared with married men 1.32 (95% CI 1.29 to 1.35). The HR for hip fracture in the first 6 months after death of a spouse was in widows compared with married women 1.62 (95% CI 1.53 to 1.71) and in widowers compared with married men 1.84 (95% CI 1.68 to 2.03). The elevated risk was especially prominent in young widowers in the age range 60–69 years. During the first 6 months they showed a HR of 2.76 (95% CI 1.66 to 4.58) for a hip fractvure compared with age matched married men. Widows aged 60–69 years showed a HR of 1.59 (95% CI 1.26 to 1.99) compared with age matched married women. Conclusion: Our observation of a higher hip fracture risk in both genders in connection with the death of a spouse indicates a possible effect of bereavement on frailty. [ABSTRACT FROM AUTHOR]

Summary: 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. Objective: 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. Methods: 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. Results: 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. Conclusion: The FRAX model should enhance accuracy of determining fracture probability among the Kazakh population and help guide decisions about treatment. [ABSTRACT FROM AUTHOR]

Summary: 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. Objective: To describe the epidemiology of hip fractures in Bulgaria, which was then used to develop the country-specific fracture prediction FRAX® tool. Methods: 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. 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 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. Conclusion: The FRAX model should enhance accuracy of determining fracture probability among the Bulgarian population and help guide decisions about treatment. [ABSTRACT FROM AUTHOR]

Summary: Guidance is provided in an international setting on the assessment and specific treatment of postmenopausal women at low, high and very high risk of fragility fractures. Introduction: The International Osteoporosis Foundation and European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis published guidance for the diagnosis and management of osteoporosis in 2019. This manuscript seeks to apply this in an international setting, taking additional account of further categorisation of increased risk of fracture, which may inform choice of therapeutic approach. Methods: Clinical perspective and updated literature search. Results: The following areas are reviewed: categorisation of fracture risk and general pharmacological management of osteoporosis. Conclusions: A platform is provided on which specific guidelines can be developed for national use to characterise fracture risk and direct interventions. [ABSTRACT FROM AUTHOR]

Summary: 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. Introduction: 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. Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Summary: In a population-based study of older Swedish women, we investigated if clinical vertebral fracture was associated with lower health-related quality of life (HRQoL) and determined whether the association remained over time. Clinical vertebral fracture was associated with lower HRQoL and the effect persisted for up to 18.9 years. Introduction: Vertebral fractures are often associated with back pain and reduced physical function, which might result in isolation and depression. As a result, women with vertebral fractures often have lower health-related quality of life (HRQoL), but during what time frame the decrease lingers is unclear. Therefore, the aim of this study was to investigate if clinical vertebral fracture and hip fracture were associated with lower HRQoL and to determine whether the associations remained over time. Methods: Vertebral fracture assessments (VFA) were performed using dual-energy X-ray absorptiometry. Data regarding prior fractures, medications, medical history, and physical activity was collected using a questionnaire. Self-rated physical HRQoL was assessed using the 12-Item Short-Form Health Survey (SF-12). Women with clinical vertebral fractures were divided into tertiles according to time since fracture onset and their HRQoL was compared with non-fractured women. Results: In a population-based cross-sectional study of 3028 women aged 77.8 ± 1.63 (mean ± SD), a total of 130 (4.3%) women reported at least one clinical vertebral fracture. Women with a clinical vertebral fracture, divided into tertiles (T1–T3) depending on time since the fracture occurred, had lower HRQoL (T1: 36.3 ± 10.8; T2: 41.0 ± 9.94; and T3:41.6 ± 11.4) than women without fracture (46.2 ± 10.6; p < 0.001). Using linear regression analysis, clinical vertebral fracture was associated with reduced physical HRQoL for up to 18.9 years, independently of covariates (age, height, weight, smoking, prior stroke, mental HRQoL, grip strength, and lumbar spine BMD). Conclusions: Clinical vertebral fracture was associated with lower self-rated physical HRQoL, for up to 18.9 years after time of fracture. [ABSTRACT FROM AUTHOR]

Summary: In a population-based study of older Swedish women, we investigated the proportion of women treated with osteoporosis medication in relation to the proportion of women eligible for treatment according to national guidelines. We found that only a minority (22%) of those eligible for treatment were prescribed osteoporosis medication. Introduction: Fracture rates increase markedly in old age and the incidence of hip fracture in Swedish women is among the highest in the world. Although effective pharmacological treatment is available, treatment rates remain low. Limited data are available regarding treatment rates in relation to fracture risk in a population-based setting in older women. Therefore, we aimed to investigate the proportion of older women eligible for treatment according to Swedish Osteoporosis Society (SvOS) guidelines. Methods: A population-based study was performed in Gothenburg in 3028 older women (77.8 ± 1.6 years [mean ± SD]). Bone mineral density of the spine and hip was measured with dual-energy X-ray absorptiometry. Clinical risk factors for fracture and data regarding osteoporosis medication was collected with self-administered questionnaires. Logistic regression was used to evaluate whether the 10-year probability of sustaining a major osteoporotic fracture (FRAX-score) or its components predicted treatment with osteoporosis medication. Results: For the 2983 women with complete data, 1107 (37%) women were eligible for treatment using SvOS criteria. The proportion of these women receiving treatment was 21.8%. For women eligible for treatment according to SvOS guidelines, strong predictors for receiving osteoporosis medication were glucocorticoid treatment (odds ratio (95% CI) 2.88 (1.80–4.59)) and prior fracture (2.58 (1.84–3.61)). Conclusion: This study demonstrates that a substantial proportion of older Swedish women should be considered for osteoporosis medication given their high fracture risk, but that only a minority receives treatment. [ABSTRACT FROM AUTHOR]

Summary: Osteoporosis is a common complication of androgen deprivation therapy (ADT). In this large Swedish cohort study consisting of a total of nearly 180,000 older men, we found that those with prostate cancer and ADT have a significantly increased risk of future osteoporotic fractures.Introduction: Androgen deprivation therapy (ADT) in patients with prostate cancer is associated to increased risk of fractures. In this study, we investigated the relationship between ADT in patients with prostate cancer and the risk of incident fractures and non-skeletal fall injuries both compared to those without ADT and compared to patients without prostate cancer.Methods: We included 179,744 men (79.1 ± 7.9 years (mean ± SD)) from the Swedish registry to which national directories were linked in order to study associations regarding fractures, fall injuries, morbidity, mortality and medications. We identified 159,662 men without prostate cancer, 6954 with prostate cancer and current ADT and 13,128 men with prostate cancer without ADT. During a follow-up of approximately 270,300 patient-years, we identified 10,916 incident fractures including 4860 hip fractures.Results: In multivariable Cox regression analyses and compared to men without prostate cancer, those with prostate cancer and ADT had increased risk of any fracture (HR 95% CI 1.40 (1.28-1.53)), hip fracture (1.38 (1.20-1.58)) and MOF (1.44 (1.28-1.61)) but not of non-skeletal fall injury (1.01 (0.90-1.13)). Patients with prostate cancer without ADT did not have increased risk of any fracture (0.97 (0.90-1.05)), hip fracture (0.95 (0.84-1.07)), MOF (1.01 (0.92-1.12)) and had decreased risk of non-skeletal fall injury (0.84 (0.77-0.92)).Conclusions: Patients with prostate cancer and ADT is a fragile patient group with substantially increased risk of osteoporotic fractures both compared to patients without prostate cancer and compared to those with prostate cancer without ADT. We believe that this must be taken in consideration in all patients with prostate cancer already at the initiation of ADT. [ABSTRACT FROM AUTHOR]

Background: The importance of the gut microbiome for bone metabolism in mice has recently been demonstrated, but no studies are available in humans. Lactobacillus reuteri ATCCPTA 6475 (L. reuteri 6475) has been reported to increase bone mineral density (BMD) in mice but its effect on the human skeleton is unknown. The objective of this trial was to investigate if L. reuteri 6475 affects bone loss in older women with low BMD.Methods: In this double-blind, placebo-controlled study, women from the population who were 75 to 80 years old and had low BMD were randomized to orally receive 1010 colony-forming units of L. reuteri 6475 daily or placebo. The predefined primary end-point was relative change after 12 months in tibia total volumetric BMD (vBMD).Results: Ninety women were included and 70 completed the study. L. reuteri 6475 reduced loss of total vBMD compared to placebo both in the intention-to-treat (ITT) analysis [-0.83% (95% confidence interval [CI], -1.47 to -0.19%) vs. -1.85% (95% CI, -2.64 to -1.07%); mean difference 1.02% (95% CI, 0.02-2.03)] and per protocol analysis [-0.93% (95% CI, -1.45 to -0.40) vs. -1.86% (95% CI, -2.35 to -1.36); mean difference 0.93% (95% CI, 0.21-1.65)]. In general, similar but smaller effects were observed in the secondary bone variable outcomes, but these differences did not reach statistical significance in the ITT population. Adverse events did not differ between groups.Conclusions: Supplementation with L. reuteri 6475 should be further explored as a novel approach to prevent age-associated bone loss and osteoporosis. [ABSTRACT FROM AUTHOR]

Summary: We aimed to study the risk of hip fracture and risk of hip arthroplasty among farmers in Sweden. Our results indicate that farming, representing an occupation with high physical activity, in men is associated with a lower risk of hip fracture but an increased risk of hip arthroplasty.Introduction: The risks of hip fracture and hip arthroplasty are influenced by factors including socioeconomic status, education, urbanization, latitude of residence, and physical activity. Farming is an occupation encompassing rural living and high level of physical activity. Therefore, we aimed to study the risk of hip fracture and risk of hip arthroplasty among farmers in Sweden.Methods: We studied the risk of hip fracture, and hip arthroplasty due to primary osteoarthritis, in all men and women aged 35 years or more in Sweden between 1987 and 2002. Documented occupations were available in 3.5 million individuals, of whom 97,136 were farmers. The effects of age, sex, income, education, location of residence, and occupation on risk of hip fracture or hip arthroplasty were examined using a modification of Poisson regression.Results: A total of 4027 farmers and 93,109 individuals with other occupations sustained a hip fracture, while 5349 farmers and 63,473 others underwent a hip arthroplasty. Risk of hip fracture was higher with greater age, lower income, lower education, higher latitude, and urban area for all men and women. Compared to all other occupations, male farmers had a 20% lower age-adjusted risk of hip fracture (hazard ratio (HR) 0.80, 95%CI 0.77-0.84), an effect that was not seen in female farmers (HR 0.96, 95% CI 0.91-1.01). Both male and female farmers had a higher age-adjusted risk for hip arthroplasty.Conclusions: Our results indicate that farming, representing an occupation with high physical activity, in men is associated with a lower risk of hip fracture but an increased risk of hip arthroplasty. [ABSTRACT FROM AUTHOR]

Background: There is high evidence for secondary prevention of fractures, including hip fracture, with alendronate treatment, but alendronate's efficacy to prevent hip fractures in the oldest-old (≥80 years old), the population with the highest fracture risk, has not been studied.Objective: To investigate whether alendronate treatment amongst the oldest-old with prior fracture was related to decreased hip fracture rate and sustained safety.Methods: Using a national database of men and women undergoing a fall risk assessment at a Swedish healthcare facility, we identified 90 795 patients who were 80 years or older and had a prior fracture. Propensity score matching (four to one) was then used to identify 7844 controls to 1961 alendronate-treated patients. The risk of incident hip fracture was investigated with Cox models and the interaction between age and treatment was investigated using an interaction term.Results: The case and control groups were well balanced in regard to age, sex, anthropometrics and comorbidity. Alendronate treatment was associated with a decreased risk of hip fracture in crude (hazard ratio (HR) 0.62 (0.49-0.79), P < 0.001) and multivariable models (HR 0.66 (0.51-0.86), P < 0.01). Alendronate was related to reduced mortality risk (HR 0.88 (0.82-0.95) but increased risk of mild upper gastrointestinal symptoms (UGI) (HR 1.58 (1.12-2.24). The alendronate association did not change with age for hip fractures or mild UGI.Conclusion: In old patients with prior fracture, alendronate treatment reduces the risk of hip fracture with sustained safety, indicating that this treatment should be considered in these high-risk patients. [ABSTRACT FROM AUTHOR]

Background: Hip fractures cause increased mortality and disability and consume enormous healthcare resources. Only 46% of hip fracture patients have osteoporosis at the total hip according to dual-energy X-ray absorptiometry (DXA) measurement. Cortical porosity increases with ageing and is believed to be important for bone strength.Objective: To investigate whether older women with hip fracture have higher cortical porosity than controls, and if so whether this difference is independent of clinical risk factors and areal bone mineral density (aBMD).Methods: From an ongoing population-based study, we identified 46 women with a prevalent X-ray-verified hip fracture and 361 control subjects without any fractures. aBMD was measured with DXA. High-resolution peripheral quantitative computed tomography was used to measure bone microstructure at the standard (ultradistal) site and at 14% (distal) of the tibial length.Results: Women with a previous hip fracture had lower aBMD at the femoral neck (-11.8%) and total hip (-14.6%) as well as higher cortical porosity at the ultradistal (32.1%) and distal (29.3%) tibia compared with controls. In multivariable logistic regression analysis, with adjustment for covariates (age, height, weight, smoking, calcium intake, physical activity, walk time, oral glucocorticoids, parental hip fracture, rheumatoid arthritis, previous fall, current bisphosphonate treatment and femoral neck aBMD), cortical porosity at the ultradistal [odds ratio per standard deviation increase (95% confidence interval) 2.61 (1.77-3.85)] and distal [1.57 (1.12-2.20)] sites was associated with prevalent hip fracture.Conclusion: Cortical porosity was associated with prevalent hip fracture in older women independently of femoral neck aBMD and clinical risk factors. [ABSTRACT FROM AUTHOR]

Summary: Spouses tend to share habits and therefore have an increased risk of same diseases. We followed all married couples in Sweden, born 1902 to 1942, in hospital records from 1987 to 2002, and found that individuals whose spouse had a hip fracture had an increased risk of hip fracture. Introduction: The purpose of this study was to determine whether spouses of hip fracture patients have an elevated risk of hip fracture. Methods: We performed a retrospective cohort study of all couples married for at least 5 years in Sweden and born between 1902 and 1942 ( n = 904,451) and all patients registered with a hip fracture ( n = 218,285) in the National Inpatients Register in Sweden from 1987 to 2002. Results: During the period 1987 to 2002 hip fractures occurred among spouses in 4212 married couples. The hazard ratio (HR) for hip fracture in a married woman following hip fracture in the husband was 1.11 (95 % confidence interval 1.07 to 1.16) compared to a woman whose husband did not have hip fracture. The corresponding HR for a married man was 1.20 (1.15 to 1.26) compared to a man whose wife did not have hip fracture. The risk was significantly elevated over the age range 60 to 90 years. The increased risk for hip fracture among spouses remained after adjustments for income, education, geographical latitude and urbanisation. In a common model with spouses and their siblings, the HR for spousal effect were 1.63 (1.01 to 2.64) and for sibling effect 2.18 (1.55 to 3.06) compared to married with spouse and sibling respectively without hip fracture. Conclusion: The novel finding of an increased risk for hip fracture among spouses provides evidence indicating that there is a homogamy effect due to common social and lifestyle factors but could also be due to assortative mating. [ABSTRACT FROM AUTHOR]

The article offers information on studies related to sarcopenia and its association with appendicular lean mass (ALM). Topics discussed include age-related sarcopenia that contribute to functional decline, fractures, and mortality of elderly people; estimation of ALM by body dual-energy X-ray absorptiometry (DXA) scanning; and the evidences showing that the use of DXA-derived ALM in prediction of fractures do not yield additional risk information when bone mineral density is also considered.

Objective: To identify and describe characteristics of the bias of reported energy intake of participants in the Gothenburg Osteoporosis and Obesity Determinants (GOOD) study.Design: A validated diet history with a detailed questionnaire and an interview was used. Body fat was analysed by dual-energy X-ray absorptiometry. The ratio of energy intake (EI) to BMR was used to define under-reporters (EI:BMR<1.30), acceptable reporters (EI:BMR >or= 1.30 to <2.64) and over-reporters (EI:BMR >or= 2.64).Setting: Sahlgrenska University Hospital, Gothenburg, Sweden.Subjects: A total of 695 males (18-20 years).Results: Sixty-eight per cent were classed as acceptable reporters, 22% as over-reporters and 10% as under-reporters. The under-reporters had higher BMI and body fat percentage than acceptable reporters (P<0.001), while over-reporters had lower BMI and body fat percentage (P<0.001). Over-reporters had more frequent use of protein supplements than acceptable reporters and higher physical activity. Over-reporters had a more regular and under-reporters a less regular meal pattern compared with acceptable reporters.Conclusions: Important knowledge of dietary reporting bias in a previously sparsely studied population has been provided. Over-reporting of energy intake was more common than under-reporting in the present population of young men and characteristics of under- and over-reporters were identified. The GOOD study was initiated with the central aim to determine environmental and genetic factors involved in the regulation of bone and fat mass, and the nutrient data of the acceptable reporters can be used for further investigation of the health effects of energy and nutrient intake. [ABSTRACT FROM AUTHOR]

Background: Bone loss at peripheral sites in the elderly is mainly cortical and involves increased cortical porosity. However, an association between bone loss at these sites and 25-hydroxyvitamin D has not been reported.Objective: To investigate the association between serum levels of 25-hydroxyvitamin D, bone microstructure and areal bone mineral density (BMD) in elderly men.Methods: A population-based cohort of 444 elderly men (mean ± SD age 80.2 ± 3.5 years) was investigated. Bone microstructure was measured by high-resolution peripheral quantitative computed tomography, areal BMD by dual-energy X-ray absorptiometry and serum 25-hydroxyvitamin D and parathyroid hormone levels by immunoassay.Results: Mean cortical porosity at the distal tibia was 14.7% higher (12.5 ± 4.3% vs. 10.9 ± 4.1%, P < 0.05) whilst cortical volumetric BMD, area, trabecular bone volume fraction and femoral neck areal BMD were lower in men in the lowest quartile of vitamin D levels compared to the highest. In men with vitamin D deficiency (<25 nmol L-1 ) or insufficiency [25-49 nmol L-1 , in combination with an elevated serum level of parathyroid hormone (>6.8 pmol L-1 )], cortical porosity was 17.2% higher than in vitamin D-sufficient men (P < 0.01). A linear regression model including age, weight, height, daily calcium intake, physical activity, smoking vitamin D supplementation and parathyroid hormone showed that 25-hydroxyvitamin D independently predicted cortical porosity (standardized β = -0.110, R2 = 1.1%, P = 0.024), area (β = 0.123, R2 = 1.4%, P = 0.007) and cortical volumetric BMD (β = 0.125, R2 = 1.4%, P = 0.007) of the tibia as well as areal BMD of the femoral neck (β = 0.102, R2 = 0.9%, P = 0.04).Conclusion: Serum vitamin D is associated with cortical porosity, area and density, indicating that bone fragility as a result of low vitamin D could be due to changes in cortical bone microstructure and geometry. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to investigate if a 2-year intervention with a minimal resource fracture liaison service (FLS) was associated with increased investigation and medical treatment and if treatment was related to reduced re-fracture risk. Methods: The FLS started in 2013 using existing secretaries (without an FLS coordinator) at the emergency department and orthopaedic wards to identify risk patients. All patients older than 50 years of age with a fractured hip, vertebra, shoulder, wrist or pelvis were followed during 2013-2014 ( n = 2713) and compared with their historic counterparts in 2011-2012 ( n = 2616) at the same hospital. Re-fractures were X-ray verified. A time-dependent adjusted (for age, sex, previous fracture, index fracture type, prevalent treatment, comorbidity and secondary osteoporosis) Cox model was used. Results: The minimal resource FLS increased the proportion of DXA-investigated patients after fracture from 7.6 to 39.6 % ( p < 0.001) and the treatment rate after fracture from 12.6 to 31.8 %, which is well in line with FLS types using the conventional coordinator model. Treated patients had a 51 % lower risk of any re-fracture than untreated patients (HR 0.49, 95 % CI 0.37-0.65 p < 0.001). Conclusions: We found that our minimal resource FLS was effective in increasing investigation and treatment, in line with conventional coordinator-based services, and that treated patients had a 51 % reduced risk of new fractures, indicating that also non-coordinator based fracture liaison services can improve secondary prevention of fractures. [ABSTRACT FROM AUTHOR]

Background: It has been suggested that osteoblasts are involved in the regulation of haematopoietic stem cells. Whether osteocalcin, which is derived from osteoblasts and is metabolically active, influences blood haemoglobin (Hb) levels is not known.Objective: To determine whether plasma osteocalcin is a determinant of Hb in elderly men.Methods: A total of 993 men (mean age 75.3 ± 3.2 years) participated in the population-based MrOS (osteoporotic fractures in men) study. Plasma osteocalcin concentration was evaluated in relation to Hb and adjustments were made for potential confounders (i.e. age, body mass index, erythropoietin, total oestradiol, fasting insulin, adiponectin, ferritin and cystatin C).Results: Hb correlated (age adjusted) negatively with osteocalcin in the total study group (r = -0.12, P < 0.001) as well as in the subgroup of nondiabetic men (r = -0.16, P < 0.001). In nondiabetic men with higher osteocalcin levels, it was more likely that Hb would be in the lowest quartile (odds ratio per SD decrease in osteocalcin 1.32, 95% confidence interval 1.13-1.53). Quartiles of Hb were negatively associated (age adjusted) with osteocalcin (P < 0.001). Anaemic men (47/812) (Hb <130 g L(-1) ) had significantly higher mean osteocalcin levels than nonanaemic men (33.9 vs. 27.1 μg L(-1) , P < 0.001). In multiple stepwise linear regression analyses (adjusted for age, body mass index, total oestradiol, adiponectin, erythropoietin, fasting insulin, cystatin C, leptin, ferritin and holotranscobalamin), osteocalcin was an independent predictor of Hb concentration in nondiabetic men (P < 0.05).Conclusions: These data add further support to the evidence indicating that the bone-specific protein osteocalcin has several endocrine functions targeting the pancreas, testes, adipocytes, brain. An additional novel finding is that osteocalcin may also have a paracrine function as a regulator of haematopoiesis. [ABSTRACT FROM AUTHOR]

Objectives: Aortic valvular sclerosis (AS) is an inflammatory process and not a result of normal ageing. The sclerotic process is accelerated by risk factors such as smoking and high cholesterol levels. The genetic factors for the development of AS are however unknown. Therefore the purpose of the present study was to investigate whether polymorphisms in the oestrogen receptor alpha (ORalpha) gene and in the transforming growth factor beta (TGF-beta1) gene were related to the presence of AS in postmenopausal women.Design: Case-control study.Subjects and Methods: Relationships were tested between polymorphisms in the ORalpha gene defined by the restriction enzymes PvuII and XbaI, and in the TGF-beta1 gene defined by AocI, and AS, lipid levels, and lipoprotein(a) [Lp(a)] in 41 postmenopausal female patients and 41 age- and sex-matched controls. These polymorphisms were also tested in relation to lipid levels and Lp(a), in 99 healthy Caucasian girls, aged 16.9 +/- 1.2 years.Results: In the postmenopausal patients and age-matched controls, the PvuII polymorphism was independently associated with an increased risk of AS [odds ratio (OR) = 3.38; 95% confidence interval (CI) 1.13-10.09). A genotype defined by at least one restriction site in the PvuII polymorphism and two restriction sites in the TGF-beta1 polymorphism was related to a highly significantly increased risk of AS (OR = 4.58; 95% CI 1.68-12.51). In the adolescent female cohort, presence of two restriction sites in the PvuII polymorphism was associated with higher levels of total cholesterol (TC) (P = 0.02), and low-density lipoprotein cholesterol (LDL) (P = 0.04).Conclusions: We have demonstrated that the PvuII polymorphism in the ORalpha gene is related to both the presence of AS in postmenopausal women and to lipid levels in adolescent females, suggesting that this polymorphism may influence the risk of AS partly by affecting lipid levels. [ABSTRACT FROM AUTHOR]