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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.

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., (© 2021. The Author(s).)

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.

This report provides an overview and a comparison of the burden and management of fragility fractures in the largest five countries of the European Union plus Sweden (EU6). In 2017, new fragility fractures in the EU6 are estimated at 2.7 million with an associated annual cost of €37.5 billion and a loss of 1.0 million quality-adjusted life years., Introduction: Osteoporosis is characterized by reduced bone mass and strength, which increases the risk of fragility fractures, which in turn, represent the main consequence of the disease. This report provides an overview and a comparison of the burden and management of fragility fractures in the largest five EU countries and Sweden (designated the EU6)., Methods: A series of metrics describing the burden and management of fragility fractures were defined by a scientific steering committee. A working group performed the data collection and analysis. Data were collected from current literature, available retrospective data and public sources. Different methods were applied (e.g. standard statistics and health economic modelling), where appropriate, to perform the analysis for each metric., Results: Total fragility fractures in the EU6 are estimated to increase from 2.7 million in 2017 to 3.3 million in 2030; a 23% increase. The resulting annual fracture-related costs (€37.5 billion in 2017) are expected to increase by 27%. An estimated 1.0 million quality-adjusted life years (QALYs) were lost in 2017 due to fragility fractures. The current disability-adjusted life years (DALYs) per 1000 individuals age 50 years or more were estimated at 21 years, which is higher than the estimates for stroke or chronic obstructive pulmonary disease. The treatment gap (percentage of eligible individuals not receiving treatment with osteoporosis drugs) in the EU6 is estimated to be 73% for women and 63% for men; an increase of 17% since 2010. If all patients who fracture in the EU6 were enrolled into fracture liaison services, at least 19,000 fractures every year might be avoided., Conclusions: Fracture-related burden is expected to increase over the coming decades. Given the substantial treatment gap and proven cost-effectiveness of fracture prevention schemes such as fracture liaison services, urgent action is needed to ensure that all individuals at high risk of fragility fracture are appropriately assessed and treated.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

Background: Obesity is associated with vitamin D deficiency, and both are areas of active public health concern. We explored the causality and direction of the relationship between body mass index (BMI) and 25-hydroxyvitamin D [25(OH)D] using genetic markers as instrumental variables (IVs) in bi-directional Mendelian randomization (MR) analysis., Methods and Findings: We used information from 21 adult cohorts (up to 42,024 participants) with 12 BMI-related SNPs (combined in an allelic score) to produce an instrument for BMI and four SNPs associated with 25(OH)D (combined in two allelic scores, separately for genes encoding its synthesis or metabolism) as an instrument for vitamin D. Regression estimates for the IVs (allele scores) were generated within-study and pooled by meta-analysis to generate summary effects. Associations between vitamin D scores and BMI were confirmed in the Genetic Investigation of Anthropometric Traits (GIANT) consortium (n = 123,864). Each 1 kg/m(2) higher BMI was associated with 1.15% lower 25(OH)D (p = 6.52×10⁻²⁷). The BMI allele score was associated both with BMI (p = 6.30×10⁻⁶²) and 25(OH)D (-0.06% [95% CI -0.10 to -0.02], p = 0.004) in the cohorts that underwent meta-analysis. The two vitamin D allele scores were strongly associated with 25(OH)D (p≤8.07×10⁻⁵⁷ for both scores) but not with BMI (synthesis score, p = 0.88; metabolism score, p = 0.08) in the meta-analysis. A 10% higher genetically instrumented BMI was associated with 4.2% lower 25(OH)D concentrations (IV ratio: -4.2 [95% CI -7.1 to -1.3], p = 0.005). No association was seen for genetically instrumented 25(OH)D with BMI, a finding that was confirmed using data from the GIANT consortium (p≥0.57 for both vitamin D scores)., Conclusions: On the basis of a bi-directional genetic approach that limits confounding, our study suggests that a higher BMI leads to lower 25(OH)D, while any effects of lower 25(OH)D increasing BMI are likely to be small. Population level interventions to reduce BMI are expected to decrease the prevalence of vitamin D deficiency.

Background: Vitamin D is crucial for maintenance of musculoskeletal health, and might also have a role in extraskeletal tissues. Determinants of circulating 25-hydroxyvitamin D concentrations include sun exposure and diet, but high heritability suggests that genetic factors could also play a part. We aimed to identify common genetic variants affecting vitamin D concentrations and risk of insufficiency., Methods: We undertook a genome-wide association study of 25-hydroxyvitamin D concentrations in 33 996 individuals of European descent from 15 cohorts. Five epidemiological cohorts were designated as discovery cohorts (n=16 125), five as in-silico replication cohorts (n=9367), and five as de-novo replication cohorts (n=8504). 25-hydroxyvitamin D concentrations were measured by radioimmunoassay, chemiluminescent assay, ELISA, or mass spectrometry. Vitamin D insufficiency was defined as concentrations lower than 75 nmol/L or 50 nmol/L. We combined results of genome-wide analyses across cohorts using Z-score-weighted meta-analysis. Genotype scores were constructed for confirmed variants., Findings: Variants at three loci reached genome-wide significance in discovery cohorts for association with 25-hydroxyvitamin D concentrations, and were confirmed in replication cohorts: 4p12 (overall p=1.9x10(-109) for rs2282679, in GC); 11q12 (p=2.1x10(-27) for rs12785878, near DHCR7); and 11p15 (p=3.3x10(-20) for rs10741657, near CYP2R1). Variants at an additional locus (20q13, CYP24A1) were genome-wide significant in the pooled sample (p=6.0x10(-10) for rs6013897). Participants with a genotype score (combining the three confirmed variants) in the highest quartile were at increased risk of having 25-hydroxyvitamin D concentrations lower than 75 nmol/L (OR 2.47, 95% CI 2.20-2.78, p=2.3x10(-48)) or lower than 50 nmol/L (1.92, 1.70-2.16, p=1.0x10(-26)) compared with those in the lowest quartile., Interpretation: Variants near genes involved in cholesterol synthesis, hydroxylation, and vitamin D transport affect vitamin D status. Genetic variation at these loci identifies individuals who have substantially raised risk of vitamin D insufficiency., Funding: Full funding sources listed at end of paper (see Acknowledgments)., (Copyright 2010 Elsevier Ltd. All rights reserved.)