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Summary In this study of 695 Australian older adults (aged ≥50 years), we found that men and women had a similar trajectory of health-related quality of life (HRQoL) recovery following fragility fracture at any skeletal site. These results provide us with critical knowledge that improves our understanding of health outcomes post-fracture. Introduction Mortality is higher in men than that in women following a fragility fracture, but it is unclear whether recovery of patient-reported outcomes such as health-related quality of life (HRQoL) differs between sexes. This study aimed to identify sex differences in HRQoL recovery 12 months post-fracture. Methods Data were from the Australian arm of the International Costs and Utilities Related to Osteoporotic Fractures Study (AusICUROS). Participants recruited to AusICUROS were adults aged ≥50 years who sustained a fragility fracture. HRQoL was measured using the EQ-5D-3L at three time-points post-fracture: within 2 weeks (including pre-fracture recall) and at 4 and 12 months. Multivariate logistic regression analyses were undertaken, adjusting for confounders including age, education, income, and healthcare utilization post-fracture. Results Overall, 695 AusICUROS participants (536 women, 77.1%) were eligible for analysis with fractures at the hip (n = 150), distal forearm (n = 261), vertebrae (n = 61), humerus (n = 52), and other skeletal sites (n = 171). At the time of fracture, men were younger, reported a higher income, and were more likely to be employed, compared with women. For all fracture sites combined, there were no differences between men and women in recovery to pre-fracture HRQoL at 12-month follow-up (adjusted OR = 1.09; 95% CI: 0.75–1.61). When stratified by fracture site, no significant sex differences were seen for hip (OR = 1.02; 95% CI: 0.42–2.52), distal forearm (OR = 1.60; 95% CI: 0.68–3.78), vertebral (OR = 2.28; 95% CI: 0.61–8.48), humeral (OR = 1.62; 95% CI: 0.16–9.99), and other fractures (OR = 1.00; 95% CI: 0.44–2.26). Conclusion Community-dwelling men and women who survived the 12 months following fragility fracture had a similar trajectory of HRQoL recovery at any skeletal site.

[Extract] Prior fragility fracture is a well-established risk factor for a future fracture [1,2,3,4]. The population relative risk of having a subsequent hip fracture or other osteoporotic fracture is approximately 2-fold higher for most types of prior fracture. However, many studies suggest that the increase in risk is not constant with time or age. Indeed, the risk of a subsequent osteoporotic fracture is particularly acute immediately after an index fracture and wanes progressively over the next 2 years [4,5,6,7,8,9] but thereafter remains higher than that of the general population (Fig. 1). The early phase of particularly high risk has been termed imminent risk [9]. This transiency, which is not currently accommodated in any of the available fracture risk assessment tools, suggests that treatment given to patients immediately after a fracture might avoid a higher number of new fractures compared with treatment given at a later date.

Summary A novel cost-effectiveness model framework was developed to incorporate the elevated fracture risk associated with a recent fracture and to allow sequential osteoporosis therapies to be evaluated. Treating patients with severe osteoporosis after a recent fracture with a bone-forming agent followed by antiresorptive therapy can be cost-effective compared with antiresorptive therapy alone. Incorporating these novel technical attributes in economic evaluations can support appropriate policy and reimbursement decision-making. Purpose To develop a cost-effectiveness model accommodating increased fracture risk after a recent fracture and treatment sequencing. Methods A micro-simulation cost-utility model was developed to accommodate both treatment sequencing and increased risk with recent fracture. The risk of fracture was estimated and simulated using the FRAX® algorithms combined with Swedish registry data on imminent fracture relative risk. In the base-case cost-effectiveness analysis, a sequential treatment starting with a bone-forming agent for 12 months followed by an antiresorptive agent for 48 months initiated immediately after a major osteoporotic fracture (MOF) in a 70-year-old woman with a T-score of 2.5 or less was compared to an antiresorptive treatment alone for 60 months. The model was populated with data relevant for a UK population reflecting a personal social service perspective. Results The cost per additional quality-adjusted life year (QALY) gained in the base-case setting was estimated at £34,584. Sensitivity analyses revealed the sequential treatment to be cost-saving compared with administering a bone-forming treatment alone. Without simulating an elevated fracture risk immediately after a recent fracture, the cost per QALY changed from £34,584 to £62,184. Conclusion Incorporating imminent fracture risk in economic evaluations has a significant impact on the cost-effectiveness when evaluating fracture prevention treatments in patients with osteoporosis who sustained a recent fracture. Bone-forming treatment followed by antiresorptive therapy can be cost-effective compared to antiresorptive therapy alone depending on treatment acquisition costs. Supplementary Information The online version contains supplementary material available at 10.1007/s00198-020-05765-7.

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. Supplementary Information The online version contains supplementary material available at 10.1007/s00198-020-05780-8.

The purpose of this study was to review and summarise the literature on appropriateness criteria for treatment of osteoporotic vertebral compression fractures (OVCF), with appropriateness defined as a treatment where the expected benefits outweigh the expected harms, confirmed by available evidence and expert opinion. A comprehensive search of peer-reviewed publications (PubMed, EMBASE) and grey literature was performed. To be included for analysis, documents had to be a review article (e.g. clinical guideline or meta-analysis), focus on OVCF and make a statement on treatment appropriateness. Eleven publications fulfilled the eligibility criteria. Among the five publications that made recommendations about non-surgical management (NSM), there is agreement that conservative methods are appropriate in OVCF patients who have low level of pain, and that the majority of patients should be treated with conservative methods before other treatments are initiated. All publications made recommendations about vertebral augmentation procedures (VAP), i.e. vertebroplasty (VP) and/or balloon kyphoplasty (BKP). VAP are mostly considered appropriate in patients with high level of pain who do not respond to NSM. However, results cannot be generalised due to heterogeneity of treatment recommendations and patient selection. Although there is a consensus that NSM should be considered as the first-line treatment, there is more heterogeneity in treatment recommendations for VAP. This could most likely be explained by an insufficient clinical evidence base for VAP and heterogeneity of OVCF patients, leading to greater reliance on expert opinion affecting the quality of evidence in the primary sources.

Summary: FRAX-based cost-effective intervention thresholds in the Swiss setting were determined. Assuming a willingness to pay at 2× Gross Domestic Product per capita, an intervention aimed at reducing fracture risk in women and men with a 10-year probability for a major osteoporotic fracture at or above 15% is cost-effective. Introduction: The fracture risk assessment algorithm FRAX® has been recently calibrated for Switzerland. The aim of the present analysis was to determine FRAX-based fracture probabilities at which intervention becomes cost-effective. Methods: A previously developed and validated state transition Markov cohort model was populated with Swiss epidemiological and cost input parameters. Cost-effective FRAX-based intervention thresholds ( cost-effectiveness approach ) and the cost-effectiveness of intervention with alendronate ( original molecule ) in subjects with a FRAX-based fracture risk equivalent to that of a woman with a prior fragility fracture and no other risk factor ( translational approach ) were calculated based on the Swiss FRAX model and assuming a willingness to pay of 2 times Gross Domestic Product per capita for one Quality-adjusted Life-Year. Results: In Swiss women and men aged 50 years and older, drug intervention aimed at decreasing fracture risk was cost-effective with a 10-year probability for a major osteoporotic fracture at or above 13.8% ( range 10.8% to 15.0% ) and 15.1% ( range 9.9% to 19.9% ), respectively. Age-dependent variations around these mean values were modest. Using the translational approach, treatment was cost-effective or cost-saving after the age 60 years in women and 55 in men who had previously sustained a fragility fracture. Using the latter approach leads to considerable underuse of the current potential for cost-effective interventions against fractures. Conclusions: Using a FRAX-based intervention threshold of 15% for both women and men should permit cost-effective access to therapy to patients at high fracture probability based on clinical risk factors and thereby contribute to further reduce the growing burden of osteoporotic fractures in Switzerland.

Summary: the present study, drawn from a sample of the Icelandic population, quantified high immediate risk and utility loss of subsequent fracture after a sentinel fracture (at the hip, spine, distal forearm and humerus) that attenuated with time. Introduction: The risk of a subsequent osteoporotic fracture is particularly acute immediately after an index fracture and wanes progressively with time. The aim of this study was to quantify the risk and utility consequences of subsequent fracture after a sentinel fracture (at the hip, spine, distal forearm and humerus) with an emphasis on the time course of recurrent fracture. Methods: the Reykjavik Study fracture registration, drawn from a sample of the Icelandic population (n = 18,872), recorded all fractures of the participants from their entry into the study until December 31, 2012. Medical records for the participants were manually examined and verified. First sentinel fractures were identified. Subsequent fractures, deaths, 10-year probability of fracture and cumulative disutility using multipliers derived from the International Costs and Utilities Related to Osteoporotic fractures Study (ICUROS) were examined as a function of time after fracture, age and sex. Results: over 10 years, subsequent fractures were sustained in 28% of 1498 individuals with a sentinel hip fracture. For other sentinel fractures, the proportion ranged from 35 to 38%. After each sentinel fracture, the risk of subsequent fracture was highest in the immediate post fracture interval and decreased markedly with time. Thus, amongst individuals who sustained a recurrent fracture, 31–45% did so within 1 year of the sentinel fracture. Hazard ratios for fracture recurrence (population relative risks) were accordingly highest immediately after the sentinel fracture (2.6–5.3, depending on the site of fracture) and fell progressively over 10 years (1.5–2.2). Population relative risks also decreased progressively with age. The utility loss during the first 10 years after a sentinel fracture varied by age (less with age) and sex (greater in women). In women at the age of 70 years, the mean utility loss due to fractures in the whole cohort was 0.081 whereas this was 12-fold greater in women with a sentinel hip fracture, and was increased 15-fold for spine fracture, 4-fold for forearm fracture and 8-fold for humeral fracture. Conclusion: high fracture risks and utility loss immediately after fracture suggest that treatment given as soon as possible after fracture would avoid a higher number of new fractures compared with treatment given later. This provides the rationale for very early intervention immediately after a sentinel fracture.

We assessed the impact of hip fracture on health-related quality of life (HRQoL) and costs in Estonia. The mean 18-month HRQoL loss in quality adjusted life years (QALY) was estimated at 0.31, and the average cumulative cost from a societal perspective was 8146 euros per hip fracture patient. The aim of this study is to estimate the impact of hip fracture on HRQoL, resource consumption, and cost over 18 months after the fracture among individuals aged over 50 in Estonia. A cohort of 205 hip fracture patients ≥50 years was followed up for 18 months. HRQoL was estimated before fracture (recall), after fracture, and at 4, 12, and 18 months using the EQ-5D instrument. Health care utilization and costs were obtained from a public health insurance fund database; social, informal, and indirect costs were estimated using patient-reported data. Hip fracture resulted in the mean 18-month HRQoL loss of 0.31 QALYs. The mean 18-months cumulative cost of hip fracture from a societal perspective was estimated at 8146 (95 % CI 6236–10717) euros per patient. Most of the cost was related to health care (56 %) and informal care (33 %), while social care contributed only 5 %. Utilization of outpatient rehabilitation and nursing care was low (8 % of patients). The impact of hip fracture on HRQoL and cost was substantial. Despite appropriate inpatient care, utilization of rehabilitation, nursing care, and social care were low and potentially insufficient to meet the needs of patients with low HRQoL. The shortfall may partially explain a remarkably high use of informal care.

We reviewed all peer-reviewed papers analysing the cost-effectiveness of vertebroplasty and balloon kyphoplasty for osteoporotic vertebral compression fractures. In general, the procedures appear to be cost effective but are very dependent upon model input details. Better data, rather than new models, are needed to answer outstanding questions. Vertebral augmentation procedures ( VAPs ), including vertebroplasty ( VP ) and balloon kyphoplasty ( BKP ), seek to stabilise fractured vertebral bodies and reduce pain. The aim of this paper is to review current literature on the cost-effectiveness of VAPs as well as to discuss the challenges for economic evaluation in this research area. A systematic literature search was conducted to identify existing published studies on the cost-effectiveness of VAPs in patients with osteoporosis. Only peer-reviewed published articles that fulfilled the criteria of being regarded as full economic evaluations including both morbidity and mortality in the outcome measure in the form of quality-adjusted life years ( QALYs ) were included. The search identified 949 studies, of which four ( 0.4 % ) were identified as relevant with one study added later. The reviewed studies differed widely in terms of study design, modelling framework and data used, yielding different results and conclusions regarding the cost-effectiveness of VAPs. Three out of five studies indicated in the base case results that VAPs were cost effective compared to non-surgical management ( NSM ). The five main factors that drove the variations in the cost-effectiveness between the studies were time horizon, quality of life effect of treatment, offset time of the treatment effect, reduced number of bed days associated with VAPs and mortality benefit with treatment. The cost-effectiveness of VAPs is uncertain. In answering the remaining questions, new cost-effectiveness analysis will yield limited benefit. Rather, studies that can reduce the uncertainty in the underlying data, especially regarding the long-term clinical outcomes of VAPs, should be conducted.

The quality of life during the first 4 months after fracture was estimated in 2,808 fractured patients from 11 countries. Analysis showed that there were significant differences in the quality of life (QoL) loss between countries. Other factors such as QoL prior fracture and hospitalisation also had a significant impact on the QoL loss. The International Costs and Utilities Related to Osteoporotic Fractures Study (ICUROS) was initiated in 2007 with the objective of estimating costs and quality of life related to fractures in several countries worldwide. The ICUROS is ongoing and enrols patients in 11 countries (Australia, Austria, Estonia, France, Italy, Lithuania, Mexico, Russia, Spain, UK and the USA). The objective of this paper is to outline the study design of ICUROS and present results regarding the QoL (measured using the EQ-5D) during the first 4 months after fracture based on the patients that have been thus far enrolled ICUROS. ICUROS uses a prospective study design where data (costs and quality of life) are collected in four phases over 18 months after fracture. All countries use the same core case report forms. Quality of life was collected using the EQ-5D instrument and a time trade-off questionnaire. The total sample for the analysis was 2,808 patients (1,273 hip, 987 distal forearm and 548 vertebral fracture). For all fracture types and countries, the QoL was reduced significantly after fracture compared to pre-fracture QoL. A regression analysis showed that there were significant differences in the QoL loss between countries. Also, a higher level of QoL prior to the fracture significantly increased the QoL loss and patients who were hospitalised for their fracture also had a significantly higher loss compared to those who were not. The findings in this study indicate that there appear to be important variations in the QoL decrements related to fracture between countries.

UNLABELLED: This article describes the development of a model for postmenopausal osteoporosis (PMO) based on Swedish data that is easily adaptable to other countries. INTRODUCTION: The aims of the study were to develop and validate a model to describe the current/future burden of PMO in different national settings. METHODS: For validation purposes, the model was developed using Swedish data and provides estimates from 1990. For each year of the study, the "incident cohort" (women experiencing a first osteoporotic fracture) was identified and run through a Markov model using 1-year cycles until 2020. Health states were based on the number of fractures and death. Fracture by site (hip, vertebral, and non-hip non-vertebral) was tracked for each health state. Transition probabilities reflected site-specific risk of death and subsequent fractures. Bone mineral density (BMD) was included as a model output; model inputs included population size and life tables from 1970 to 2020, incidence of fracture, relative risk of subsequent fractures based on prior fracture, relative risk of death following a fracture by site, and BMD by age (mean and standard deviation). RESULTS: Model predictions averaged across age groups estimated the incidence of hip, vertebral, and other osteoporotic fractures within a 5% margin of error versus published data. In Sweden, the number of osteoporotic fractures is expected to rise by 11.5% between 2009 and 2020, with a shift towards more vertebral fractures and multiple fractures. CONCLUSION: The current PMO disease model is easily adaptable to other countries, providing a consistent measure of present and future burden of PMO in different settings.

Hip fracture incidence rates in Austria over a period of 20 years (1989–2008) were assessed. Age-standardized incidence rates increased until 2005 but decreased thereafter. This change in the secular trend was primarily driven by a decrease in hip fracture incidence in women. The aim of the prevailing study was to assess the incidence rates of hip fractures including changes in trend in the Austrian population over a period of 20 years (1989–2008). The number of hip fractures was obtained from the Austrian Hospital Discharge Register for the entire population ≥50 years of age. A correction factor for multiple registrations of the same diagnosis was determined. Incidence rates (cases per 100,000) of hip fracture were calculated in 5-year age intervals. To analyze the overall change in hip fracture for the period, average annual change expressed as incidence rate ratios (IRRs) was calculated. The age-standardized incidence in women increased until 2005, from 493 to 642, and decreased thereafter. In men, it increased at a measured pace until 2006, from 192 to 280, and decreased thereafter with a slight rebound in 2008. The age-standardized incidence in the entire population increased until 2005, from 376 to 496, and decreased thereafter. The IRR for the last 3 years (2006–2008) was significantly below the IRR for the first 17 years (0.94, ρ

The study estimated the cost-effectiveness of risedronate compared to no treatment in UK women using the FRAX algorithm for fracture risk assessment. A Markov cohort model was used to estimate the cost-effectiveness. Risedronate was found cost-effective from the age of 65 years, assuming a willingness to pay for a QALY of 30,000 pounds.The aim of this study was to assess the cost-effectiveness of risedronate for the prevention and treatment in a UK setting using the FRAX algorithm for fracture risk assessment. A further aim was to establish intervention thresholds with risedronate treatment.The cost-effectiveness of risedronate was compared to no treatment in post-menopausal women with clinical risk factors for fracture using a Markov cohort model populated with data relevant for the UK. The model incorporated the features of FRAX (the WHO risk assessment tool). The analysis had a health care perspective and quality adjusted life years was used as the main outcome measure.Treatment was cost-effective from the age of 65 years, assuming a willingness to pay for a QALY of 30,000 pounds. Treatment was also cost-effective at all ages in women who had previously sustained a fragility fracture or in women with a parental history of hip fracture with a bone mineral density set at the threshold of osteoporosis. At the 30,000 pounds threshold value for a QALY, risedronate was on average found to cost-effective below the 10-year probability of a major osteoporotic fractures of 13.0%.Risedronate is a cost-effective agent for the treatment of established osteoporosis (osteoporosis and a prior fragility fracture) in women from the age of 50 years and older and above 65 years in women with osteoporosis alone. The results support the treatment recommendations in recent UK guidelines for osteoporosis.

The purpose of the paper is to update and review the latest developments related to modelling and economic evaluation of osteoporosis in the period 2002–2005 and further to present a reference model for the assessment of the cost-effectiveness of the prevention and treatment of osteoporosis. The reference model is intended to be used for fracture specific interventions affecting the risk of fracture. An interface version and an extensive description of the model is available on the internet ( http://www.healtheconomics.se ) and also accessible via the International Osteoporosis Foundation ( http://www.osteofound.org ). The purpose of the reference model is to improve the quality and comparability of cost-effectiveness analysis in the osteoporosis field and to serve as a tool for validation of present and future cost-effectiveness models. The reference model allows the cost-effectiveness analysis to be carried out from a societal perspective including intervention, morbidity and mortality costs. The model has been extensively tested and calibrated, and meets the properties of good decision analytic modelling. The model is a state transition Markov cohort model, which is characterised by a 50-year time horizon divided into one year cycle lengths. The following health states are included: “healthy”, “hip fracture”, “spine fracture”, “wrist fracture”, “other fracture”, and “dead”. The model is flexible and allows for the estimation of the cost-effectiveness over different ranges for a selected number of variables (e.g., age, fracture risk, cost of intervention).

The aim of this study was to determine the threshold of fracture probability at which interventions became cost-effective in women based on data from the UK. We modelled the effects of an intervention costing pound 350 per year given for 5 years that decreased the risk of all osteoporotic fractures by 35% followed by a waning of effect (offset time) for a further 5 years. Sensitivity analyses included a range of treatment duration (3-10 years), intervention costs (pound 300-400/year) and offset times (0-15 years). Data on costs and risks were from the UK. Costs included direct costs, but excluded indirect costs due to morbidity. A threshold for cost-effectiveness of pound 30,000/QALY gained was used. With the base case ( pound 350 per year; 35% efficacy) treatment in women was cost-effective with a 10-year hip fracture probability that ranged from 1.1% at the age of 50 years to 9.0% at the age of 85 years. Intervention thresholds were sensitive to the assumed costs and offset time. The exclusion of osteoporotic fractures other than hip fracture significantly increased the cost-effectiveness ratio because of the substantial morbidity from such other fractures, particularly at younger ages. Cost-effective scenarios were found for women at the threshold for osteoporosis from the age of 60 years. Treatment of established osteoporosis was cost-effective irrespective of age. We conclude that the inclusion of all osteoporotic fractures has a marked effect on intervention thresholds, that these vary with age and that available treatments can be targeted cost-effectively to individuals from the UK at moderately increased fracture risk.

The diagnosis of osteoporosis is based on the measurement of bone mineral density (BMD). There are a number of clinical risk factors that provide information on fracture risk over and above that given by BMD. The assessment of fracture risk thus needs to be distinguished from diagnosis to take account of the independent value of the clinical risk factors. These include age, a prior fragility fracture, a parental history of hip fracture, smoking, use of systemic corticosteroids, excess alcohol intake and rheumatoid arthritis. The independent contribution of these risk factors can be integrated by the calculation of fracture probability with or without the use of BMD. Treatment can then be offered to those identified to have a fracture probability greater than an intervention threshold.

Randomized, double-blind, controlled studies have shown that treatment with risedronate reduces the risk of vertebral fracture in postmenopausal women with established vertebral osteoporosis. They also show that the drug decreases the risk of non-vertebral fractures in women with osteoporosis. The aim of this study was to investigate the cost-effectiveness of risedronate in postmenopausal women with osteoporosis. A Markov model was applied to a UK setting. Treatment effects were computed by meta-analysis of randomized, controlled trials and given over 5 years to subjects aged between 60 and 80 years. Quality-adjusted life years (QALYs) and life years gained were used as outcome measures. Intervention with risedronate was cost-effective in women aged 60 years and older. Cost savings were also found for postmenopausal women aged 70 years and older with established vertebral osteoporosis (a prior spine fracture and BMD T-scoreor =-2.5 SD). This treatment was cost-effective for women aged 65 years and older who had a prior vertebral fracture and a BMD T-score at the threshold of osteoporosis ( T-score=-2.5 SD), and in women with a T-scoreor =-2.5 SD, but without a prior vertebral fracture. In women aged 60-80 years and at the threshold of osteoporosis ( T-score=-2.5 SD) but without a prior vertebral fracture, treatment exceeded the threshold for cost-effectiveness. However, if an additional, independent risk factor was assumed (e.g., corticosteroid use) treatment became cost-effective.

Risk Of Major Osteoporotic Fracture (Hip, Vertebral, Radius, Humerus [Mof]) After First, Second And Third Fragility Fracture In A Swedish General Population Cohort

Only few studies have been published hitherto on country-specific incidence of distal forearm fracture. In the prevailing study, incidences were estimated, and trend analyses were performed for the entire Austrian population aged ≥50á. Incidence decreased significantly in women, but not in men, over the past 12 years of observation.To estimate incidence of distal forearm fracture and assess incidence trends in the entire Austrian population aged ≥50á from 1989-2010 for inpatient fractures and from 1999 to 2010 for all fractures.The number of inpatient forearm fractures was obtained from the Austrian Hospital Discharge Register (AHDR) for the entire population aged ≥50á from 1989 to 2010. Total number of distal forearm fractures was modeled using patient-level data on 36,327 patients with distal forearm fractures. Crude and age-standardized incidence rates (cases per 100,000) were estimated in 5-year age intervals. To analyze the change in incidence over time, average annual changes expressed as incidence rate ratios (IRR) were calculated.For all distal forearm fractures, age-standardized incidence in women in 1999 and 2009 were estimated at 709 (95 % CI 675-743) and 607 (578-637), respectively. The age-standardized incidences in men the same years were estimated at 171 (156-185) and 162 (151-174), respectively. IRR analyses showed a significant decrease in women (-1.1 %, p 0.01) but not in men (-0.8 %, p 0.05) over the last 12 years (1999-2010).Incidence of distal forearm fracture in the entire Austrian population is comparable to hip fracture incidence which is known to be among the highest worldwide. However, trend analyses reveal a significant decrease for all distal forearm fractures in women, but not in men, over the last 12 years.

The article describes the adaptation of a model to estimate the burden of postmenopausal osteoporosis in women aged 50 years and over in Italy between 2010 and 2020. For this purpose, a validated postmenopausal osteoporosis disease model developed for Sweden was adapted to Italy. For each year of the study, the ‘incident cohort’ (women experiencing a first osteoporotic fracture) was identified and run through a Markov model using 1-year cycles until 2020. Health states were based on the number of fractures and deaths. Fracture by site (hip, clinical vertebral, non-hip non-vertebral) was tracked for each health state. Transition probabilities reflected fracture site-specific risk of death and subsequent fractures. Model inputs specific to Italy included population size and life tables from 1970 to 2020, incidence of hip fracture and BMD by age in the general population (mean and standard deviation). The model estimated that the number of postmenopausal osteoporotic women would increase from 3.3 million to 3.7 million between 2010 and 2020 (+14.3 %). Assuming unchanged incidence rates by age group over time, the model predicted the overall number of osteoporotic fractures to increase from 285.0 to 335.8 thousand fractures between 2010 and 2020 (+17.8 %). The estimated expected increases in hip, vertebral and non-hip non-vertebral fractures were 22.3, 17.2 and 16.3 %, respectively. Due to demographic changes, the burden of fractures is expected to increase markedly by 2020.

Summary\ud \ud The scorecard summarises key indicators of the burden of osteoporosis and its management in each of the member states of the European Union. The resulting scorecard elements were then assembled on a single sheet to provide a unique overview of osteoporosis in Europe.\ud \ud Introduction\ud \ud The scorecard for osteoporosis in Europe (SCOPE) is an independent project 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.\ud \ud Methods\ud \ud The SCOPE panel reviewed the information available on osteoporosis and the resulting fractures for each of the 27 countries of the European Union (EU27). The information researched 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).\ud \ud Results\ud \ud There was a marked difference in fracture risk among the EU27. 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, only a minority of patients at high risk receive treatment for osteoporosis 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 were then assembled on a single sheet to provide a unique overview of osteoporosis in Europe.\ud \ud Conclusions\ud \ud The scorecard will enable healthcare professionals and policy makers to assess their country’s general approach to the disease and provide indicators to inform future provision of healthcare.

The use of glucocorticoids in the treatment of medical disorders can lead to rapid bone loss and increased risk of fragility fracture. Updated clinical guidelines are needed that accommodate recent advances in fracture risk assessment and new pharmacological interventions to reduce fracture risk. This document serves as an appendix to the 2012 IOF–ECTS guidelines for the management of glucocorticoid-induced osteoporosis.

Incidence rates of proximal humeral fractures in Austria over a period of twenty years (1989–2008) were estimated. Age standardized incidence rates increased until 2008, primarily driven by an increase in incidence rates in women. The aim of the prevailing study was to estimate incidence rates of proximal humeral fractures and to assess changes in trend in the Austrian population aged 50 years and above, over a period of 20 years (1989–2008). Number of proximal humeral fractures were obtained from the Austrian Hospital Discharge Register for the entire population >50 years of age. Adjustment factors were determined for multiple registrations of the same diagnosis, and for the fact that not all patients with proximal humeral fractures are treated in an inpatient setting. To analyze the overall change in this type of fracture for the period, average annual changes expressed as incidence rate ratios were calculated. The estimated age-standardized incidence (fractures per 100,000 individuals) of proximal humeral fractures among Austrians >50 years of age increased in men from 112 (95 % CI, 99–124) to 141 (129–153) and in women from 222 (202–241) to 383 (360–406). The increase appeared to be linear with no leveling off towards the end of the study period. While some caution is necessary when interpreting the results given the use of adjustment factors, there appears to have been a rise in the incidence of proximal humeral fractures in Austria in both men and women, with no leveling off in recent years. The reasons for this are not clear, but in the light of previously reported leveling off in the increase in the incidence of hip fractures, a change in the patterns of falls cannot be ruled out.

This study uses data from a previously published randomised trial where balloon kyphoplasty was compared to non-surgical management. Of the improved overall quality of life, 60 % was caused by decreased pain. However, ignoring other dimensions of quality of life would underestimate the procedure's effect.Acute back pain has been viewed as the most important factor lowering quality of life (QoL) for patients suffering vertebral fractures. The objective of this study was to quantify the impact of different health dimensions on overall QoL using patient-reported outcome measurements (PROMs) collected in Fracture Reduction Evaluation (FREE) trial.The analysis was based on patients included in the 2-year-long randomised controlled FREE trial studying the efficacy and safety of balloon kyphoplasty procedure (BKP) compared to non-surgical management (NSM). The PROMs included were EQ-5D, Short Form (SF)-36, visual analogue scale (VAS) pain and the Roland-Morris Disability Questionnaire (RMDQ). The health dimensional contribution to the overall QoL improvements was analysed by isolating the impact of each dimension on QoL in the SF-36 and EQ-5D, respectively. A correlation analysis of the QoL improvement was performed to investigate the relationships between the four instruments.Changes in pain explained 60 % of the quality-adjusted life years (QALY) gained in BKP vs. NSM followed by self-care (17 %), mobility (16 %) and usual activities (10 %) (EQ-5D). Health dimensions capturing the mental state had little impact on the QALY gained. The SF-36 dimensional analysis showed similar results. The correlation analysis showed that the correlation between VAS pain, RMDQ and QALY improvement was fairly weak.Changes in the pain dimension of health are the most important drivers for changes of overall QoL in patients treated with BKP or NSM. However, ignoring the impact of other dimensions would lead to an underestimation of the actual improvement in overall QoL.

UNLABELLED: This paper provides a framework for the development of national guidelines for the management of glucocorticoid-induced osteoporosis in men and women aged 18 years and over in whom oral glucocorticoid therapy is considered for 3 months or longer. INTRODUCTION: The need for updated guidelines for Europe and other parts of the world was recognised by the International Osteoporosis Foundation and the European Calcified Tissue Society, which set up a joint Guideline Working Group at the end of 2010. METHODS AND RESULTS: The epidemiology of GIO is reviewed. Assessment of risk used a fracture probability-based approach, and intervention thresholds were based on 10-year probabilities using FRAX. The efficacy of intervention was assessed by a systematic review. CONCLUSIONS: Guidance for glucocorticoid-induced osteoporosis is updated in the light of new treatments and methods of assessment. National guidelines derived from this resource need to be tailored within the national healthcare framework of each country.

UNLABELLED: This article describes the adaptation of a model assessing the incidence of osteoporotic fractures and prevalence of postmenopausal osteoporosis (PMO) in Germany. PURPOSE: The purpose of this paper is to estimate the epidemiological burden of PMO in Germany from 2010 to 2020. METHODS: For each year of the study, the 'incident cohort' (women experiencing a first osteoporotic fracture) was identified and run through a Markov model using 1-year cycles until 2020. Health states were based on the number of fractures (1, 2 or ≥3) and deaths. Although the fracture site was not explicitly accounted for in the model structure, the site (hip, vertebral, non-hip non-vertebral) was tracked for each health state. Transition probabilities reflected the site-specific risk of death and of subsequent fractures. Model inputs included population size and life tables from 1970 to 2020, incidence of fracture and BMD by age in the general population (mean and standard deviation). RESULTS: In 2010, the number of osteoporotic fractures was estimated at 349,560 in women aged 50 years or more, including 80,177 hip and 48,550 vertebral fractures. By 2020, the population is expected to grow by 13.1 %. As a result, the number of fractures is predicted to increase by 15.2 %. The improvement in life expectancy is predicted to lead to a relatively smaller increase in the number of deaths attributable to fractures (+12.8 %), but also to an increase in the prevalence of women with multiple prior fractures (+25.5 %). CONCLUSION: The PMO disease model, first developed for Sweden, was adapted to Germany. Due to the ageing of the population, the number of osteoporotic fractures is expected to increase markedly by +15.2 % by 2020.

UNLABELLED: This article describes the adaptation of a model estimating the burden of postmenopausal osteoporosis (PMO) to the UK. PURPOSE: The purpose of this study was to estimate the present and future epidemiology of PMO in the UK. METHODS: For each year of the study, the 'incident cohort' (women experiencing a first osteoporotic fracture) was identified and run through a Markov model using 1-year cycles until 2020. Health states were based on the number of fractures and death. Fracture by site was tracked for each health state. Transition probabilities reflected fracture site-specific risk of death and subsequent fractures. RESULTS: Assuming that the rate of incident fractures by age is constant over time, the model estimated the total number of PMO fractures at 224,219 in 2010, including 51,927 hip and 30,994 clinical vertebral fractures. These estimates were predicted to increase by 17.2%, 16.6% and 17.9%, respectively, by 2020. The number of postmenopausal women living with osteoporosis was predicted to increase from 1.8 million in 2010 to 2.1 million in 2020 (+16.5%). A sensitivity analysis demonstrated that the estimated number of fractures is most sensitive to the assumption made on the trends in the rate of incidence. CONCLUSION: The PMO disease model, first developed for Sweden, was adapted to the UK. Due to demographic changes, the burden of osteoporosis is expected to increase by almost a fifth by 2020. Due to the lack of country-specific data, these results rely on several assumptions regarding the incidence of non-hip fractures, trends in BMD and rate of incidence over time.

Introduction The National Osteoporosis Foundation (NOF) recommends considering treatment in women with a 20% or higher 10-year probability of a major fracture. However, raloxifene reduces both the risk of vertebral fractures and invasive breast cancer so that raloxifene treatment may be clinically appropriate and cost-effective in women who do not meet a 20% threshold risk. The aim of this study was to identify cost-effective scenarios of raloxifene treatment compared to no treatment in younger postmenopausal women at increased risk of invasive breast cancer and fracture risks below 20%. Method A micro-simulation model populated with data specific to American Caucasian women was used to quantify the costs and benefits of 5-year raloxifene treatment. The population evaluated was selected based on 10-year major fracture probability as estimated with FRAX® being below 20% and 5-year invasive breast cancer risk as estimated with the Gail risk model ranging from 1% to 5%. Results The cost per QALY gained ranged from US $22,000 in women age 55 with 5% invasive breast cancer risk and 15–19.9% fracture probability, to $110,000 in women age 55 with 1% invasive breast cancer risk and 5–9.9% fracture probability. Raloxifene was progressively cost-effective with increasing fracture risk and invasive breast cancer risk for a given age cohort. At lower fracture risk in combination with lower invasive breast cancer risk or when no preventive raloxifene effect on invasive breast cancer was assumed, the cost-effectiveness of raloxifene worsened markedly and was not cost-effective given a willingness-to-pay of US $50,000. At fracture risk of 15–19.9% raloxifene was cost-effective also in women at lower invasive breast cancer risk. Conclusions Raloxifene is potentially cost-effective in cohorts of young postmenopausal women, who do not meet the suggested NOF 10-year fracture risk threshold. The cost-effectiveness is contingent on their 5-year invasive breast cancer risk. The result highlights the importance of considering a woman's full risk profile when considering anti-osteoporosis treatment.

The cost-effectiveness of strontium ranelate was compared to no treatment in UK women using the FRAX algorithm for fracture risk assessment. At a willingness-to-pay of pound 30,000 per quality-adjusted life-year (QALY), strontium ranelate was generally cost-effective in women with prior fracture at the threshold of osteoporosis from an age of 65 years.The objectives of the study were to estimate the cost-effectiveness of strontium ranelate in the UK for the treatment of osteoporosis and to establish intervention thresholds for treatment using the FRAX tool.The cost-effectiveness of strontium ranelate was compared to no treatment in postmenopausal women with clinical risk factors for fracture using a lifetime simulation model based on Markov cohort methodology that incorporated the features of FRAX.At a threshold of pound 30,000 per QALY, strontium ranelate was generally cost-effective in women from an age of 65 years with prior fracture at the threshold of osteoporosis (i.e., a T-score of -2.5 SD) and in women with a prior fracture (and no information on bone mineral density) from the age of 65 years. At a threshold of pound 20,000, strontium ranelate became cost-effective at a 10-year fracture probability of 25.7% and at 16.9% with a threshold of pound 30,000 for a QALY.Strontium ranelate is a cost-effective agent for the treatment of established osteoporosis in women over the age of 65 years. Cost-effective scenarios were also found for the prevention and treatment of fractures associated with osteoporosis, in younger women with additional clinical risk factors.

Background An important aspect of cost-effectiveness analysis of osteoporosis is to accurately model the fracture risk and mortality related to the patient groups in the analysis. The estimation of fracture risk is based on a number of factors, such as the level of general risk of the normal population, the effect of treatment and the prevalence of clinical risk factors (CRFs) for fracture. Fracture risk has traditionally been calculated with risk adjustments based on age, bone mineral density and prior vertebral fracture. The treatment effect has been derived from clinical trials and, in the absence of subgroup analyses, the same efficacy has been assumed irrespective of the fracture risk of the population. The FRAX ® tool enables the estimation of risk based on a wider range of risk factors, and treatment efficacy that is dependent on the level of risk in the analyzed population. The objective was to describe the implementation of the FRAX ® algorithms into health economic osteoporosis models and to highlight how it differs from traditional risk assessment. Methods The selective estrogen receptor modulator, bazedoxifene, was evaluated in a Swedish setting with traditional and FRAX ® -based risk assessment in a previously developed Markov model that included fractures and thromboembolic events, and also was adapted to accommodate risk-dependent efficacy, which is available for bazedoxifene. Results The traditional approach gave lower ICERs at ages up to 60 years compared to the FRAX ® method when only considering age, BMD and prior fracture. At 70 years and older and when adding more CRFs with the FRAX ® approach, the FRAX ® ICER decreased and fell below the traditional approach. The risk dependant efficacy was the main reason for lower ICERs with FRAX ® in women at higher risk of fracture. Discussion FRAX ® applied in cost-effectiveness analyses is a more granular method for the estimation of fracture risk, mortality and efficacy compared to previous approaches that can also improve case finding. Furthermore, it facilitates the estimation of cost-effectiveness for various types of patients with different combinations of CRFs, which more closely matches patients in clinical practice.

Summary: The cost-effectiveness of bazedoxifene was compared to placebo in France, Germany, Italy, Spain, Sweden and the UK from a healthcare perspective using FRAX® for both fracture risks and for treatment efficacy. Cost/QALY differences were explained to a large extent by differences in fracture risk. Introduction: In cost-effectiveness modelling of osteoporosis treatments, the fracture risk has traditionally been calculated with risk adjustments based on age, bone mineral density and prior fracture. However, knowledge of additional clinical risk factors contributes to fracture risk assessment as demonstrated by the FRAX® tool. Bazedoxifene, a new selective estrogen receptor modulator for the treatment and prevention of osteoporosis, has been shown in a phase III clinical trial to reduce the risk of osteoporotic fractures in women. In an analysis using FRAX®, the efficacy of bazedoxifene was greater in patients with higher fracture risk. Methods: The aim of this study was to evaluate the cost-effectiveness of bazedoxifene compared to placebo in France, Germany, Italy, Spain, Sweden and the UK from a healthcare perspective using FRAX®. A Markov cohort model was adapted to incorporate the FRAX® risk factors. FRAX® produces relative risks for hip fractures and major osteoporotic fractures. Patients were given a 5-year intervention, reducing the risk of fractures in a risk-dependent manner. The effect of treatment on fractures was assumed to decline linearly over 5 years after the intervention. Results: There are large cost/quality-adjusted life year variations between countries in the European setting studied. The base case values ranged from cost saving ( Sweden ) to EUR 105,450 ( Spain ) in 70-year-old women with a T-score of −2.5 SD and a prior fracture. Conclusion: Bazedoxifene can be a cost-effective treatment for postmenopausal osteoporosis. The variability between countries was explained to a large extent by differences in fracture risk, and the estimated cost-effectiveness was highly dependent on the population’s FRAX®-estimated probability of major osteoporotic fracture.

Introduction Longevity has resulted in a greater proportion of the population entering a time of life when increasing bone fragility and falls predispose to fractures, particularly nonvertebral fractures. Women over 80 years of age constitute 10% of the population but contribute 30% of all fractures and 60% of all nonvertebral fractures. Despite this, few studies have examined antifracture efficacy of treatments in this high-risk group and none has provided evidence for benefits beyond 3 years. Materials and methods To determine whether strontium ranelate reduces the risk of vertebral and nonvertebral fractures during 5 years, we analyzed a subgroup of 1489 female patients over 80 years of age (mean 83.5 ± 3.0 years) with osteoporosis from the SOTI (spinal osteoporosis therapeutic intervention) and TROPOS (treatment of peripheral osteoporosis) studies randomized to strontium ranelate 2 g/d or placebo. All received a supplement of calcium plus vitamin D. Results By intention to treat, vertebral fracture risk was reduced by 31% (relative risk, RR = 0.69; 95% confidence interval, CI 0.52-0.92), nonvertebral fracture risk by 27% (RR = 0.73; 95% CI 0.57-0.95), major nonvertebral fracture risk by 33% (RR = 0.67; 95% CI 0.50-0.89) and hip fracture risk by 24% (RR = 0.76; 95% CI 0.50-1.15, not significant). Treatment was cost-saving as it decreased cost and increased QALYs and life-years. Discussion Strontium ranelate safely produced a significant reduction in vertebral and nonvertebral fracture risk during 5 years in postmenopausal women over 80 years of age and was cost saving.

Less than half of patients in Scandinavian societies achieve target cholesterol values established by consensus coronary prevention panels.Using logistic regression analysis, we determined that patients not at consensus cholesterol goals after 3 months of treatment using lipid-lowering medications were significantly more likely to achieve these goals at 12 months if they were treated with an active management strategy (changes in lipid-lowering therapy within 3 months), had a diagnosis of diabetes mellitus, or initiated lipid-lowering more recently, compared with their counterparts without these factors.An active management strategy is associated with a higher probability of achieving treatment goals in patients not at goal after 3 months following treatment initiation.