BACKGROUND: The Multiple Outcomes of Raloxifene Evaluation (MORE) study showed that treatment with raloxifene reduces the risk of vertebral fracture and breast cancer in postmenopausal women with osteoporosis. OBJECTIVE: Based on the MORE study the aim of the present study was to assess the cost effectiveness of raloxifene (compared with no treatment) for the treatment of osteoporosis in postmenopausal women in Sweden. DESIGN: A revised version of a previously developed computer simulation model was used. The impact of the risk-reducing effect of raloxifene on vertebral fractures and breast cancer on cost effectiveness was analysed using a clinical and a morphometric definition of vertebral fracture. Benefits of raloxifene treatment were measured in quality-adjusted life-years (QALYs) and life-years gained. The study estimated the cost effectiveness mainly from a healthcare perspective but the cost effectiveness taking a societal perspective was also analysed. RESULTS: Intervention costs (in Swedish kronor [SEK] and euros [euro], year 2001 values) in postmenopausal women with a relative risk of vertebral fracture of 2 were SEK372000 (euro40000), SEK303000 (euro33000) and SEK263000 (euro28000) per QALY for women aged 60, 70 and 80 years, at start of treatment, respectively, when the clinical vertebral definition was used. The cost effectiveness using a clinical morphometric vertebral fracture definition was similar to the cost effectiveness using a clinical vertebral fracture definition. CONCLUSIONS: In relation to accepted threshold values for cost per QALY in Sweden, this model indicates, with its underlying assumptions and data, that raloxifene (compared with no treatment) is cost effective for the treatment of postmenopausal women at an increased risk of vertebral fracture, from the Swedish healthcare and societal perspectives.
Ten-year fracture risk assessment with the fracture risk assessment system (FRAX) is increasingly used to guide treatment decisions. Osteoporosis pharmacotherapy reduces fracture risk, but the effect is greater than can be explained from the increase in bone mineral density (BMD). Whether this invalidates fracture predictions with FRAX is uncertain. A total of 35,764 women (age =50 years) and baseline BMD testing (1996–2007) had FRAX probabilities retroactively calculated. A provincial pharmacy database was used to identify osteoporosis medication use. Women were categorized as untreated, current high adherence users [medication possession ratio (MPR) =0.80 in the year after BMD testing], current low adherence users (MPR
Comment In: J Bone Miner Res. 2012 Jun;27(6):1240-222605514
Although the optimal requirement of vitamin D for skeletal health in the general community is controversial, vitamin D deficiency impairs bone mineralization and increases bone turnover via secondary hyperparathyroidism, thus accelerating bone loss and increasing fracture risk. Support for a role of vitamin D deficiency in the epidemiology of hip fracture is found in the seasonal variation of hip fracture incidence that is reported in several studies. If the association were causal, then the incidence and amplitude of the seasonal variation in hip fracture risk should vary by latitude. We addressed this hypothesis by examining the incidence of hip fracture in men and women aged 50 years or more from Sweden (latitudes 55 to 69°) between 1987 and 2009. In order to reduce double counting, only one fracture in a period of a year was counted per individual. Men contributed 104,888 fractures in 33,313,065 person years and women 264,362 fractures in 38,387,660 person years. The effects of season and latitude were examined by Poisson regression. As expected, hip fracture rates were higher in women than in men. After adjustment for age, season and population density, hip fracture incidence increased by 3.0% (95% CI: 2.7-3.2%) per degree increase in latitude for men and by 1.9% (95% CI: 1.8-2.1%) for women. There was a marked seasonal variation of hip fracture with the highest risk in February and lower by 37.5% in men and by 23.5% women during the summer. There were significant interactions of amplitude of the seasonal variation with latitude (p
The incidence of hip, forearm and humeral fractures was studied in two cities from the Russian Federation. Fracture rates were used to create a FRAX model for Russia and to estimate the current and future burden of fracture.
There is scant information on the epidemiology of fracture in Russia. The aim of the study was to determine the incidence of major fractures in order to populate a new FRAX model and to characterise the burden and future burden of fractures.
The number of hip, forearm and humeral fractures was determined in two Russian cities with a well-defined catchment population over a 2-3-year period. Incidence rates for the two cities were merged and used to populate a FRAX model for Russia. Incidence rates were also applied to the general population in 2010 and 25 years later in 2035.
A total of 6,012 fractures were documented. For hip fracture, 27 % of cases in Pervouralsk and 1.8 % in Yaroslavl were not registered in the hospital data base. The incidence of index fractures increased with age and was higher in women than in men. The lifetime probability of hip fracture at the age of 50 years was 4 % in men and 7 % in women. The total number of hip fractures estimated in 2010 (112,000) is expected to rise to 159,000 in 2035. The estimated number of major fractures will rise from 590,000 to 730,000 over the same time interval.
Fragility fractures pose a serious health care problem in Russia. Urgent steps are needed to improve the acute management of hip fracture and long-term care of other osteoporotic fractures.
An excess mortality is well described after vertebral fracture. Deaths are in part related to co-morbidity, but could also be due to the fracture event itself, either directly or indirectly. The aim of this study was to examine the quantum and pattern of mortality following vertebral fracture. We identified 16,051 men and women aged 50 years or more with a vertebral fracture that required hospitalization in 28.8 million person years from the patient register of Sweden. Mortality after vertebral fracture was examined using Poisson models applied to fracture patients and compared to that of the general population. At all ages, the risk of death was markedly increased immediately after the event. After a short period of declining risk, the risk increased with age at a rate that was higher than that of the general population and comparable to that 1 year after hip fracture. The latter function was assumed to be due to deaths related to co-morbidity and the residuum assumed to be due to the vertebral fracture. Causally related deaths comprised 28% of all deaths associated with vertebral fracture (depending on age). We conclude that a minority of deaths following hospitalization for vertebral fracture are attributable to the fracture itself under the assumptions we used.
This report provides an overview and a comparison of the burden and management of fragility fractures in the largest five countries of the European Union plus Sweden (EU6). In 2017, new fragility fractures in the EU6 are estimated at 2.7 million with an associated annual cost of €37.5 billion and a loss of 1.0 million quality-adjusted life years.
Osteoporosis is characterized by reduced bone mass and strength, which increases the risk of fragility fractures, which in turn, represent the main consequence of the disease. This report provides an overview and a comparison of the burden and management of fragility fractures in the largest five EU countries and Sweden (designated the EU6).
A series of metrics describing the burden and management of fragility fractures were defined by a scientific steering committee. A working group performed the data collection and analysis. Data were collected from current literature, available retrospective data and public sources. Different methods were applied (e.g. standard statistics and health economic modelling), where appropriate, to perform the analysis for each metric.
Total fragility fractures in the EU6 are estimated to increase from 2.7 million in 2017 to 3.3 million in 2030; a 23% increase. The resulting annual fracture-related costs (€37.5 billion in 2017) are expected to increase by 27%. An estimated 1.0 million quality-adjusted life years (QALYs) were lost in 2017 due to fragility fractures. The current disability-adjusted life years (DALYs) per 1000 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.
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.
The study objective was to determine whether diabetes is a risk factor for incident hip or major osteoporotic fractures independent of the WHO fracture risk assessment tool (FRAX). Men and women with diabetes (n = 3518) and nondiabetics (n = 36,085) aged =50 years at the time of bone mineral density (BMD) testing (1990 to 2007) were identified in a large clinical database from Manitoba, Canada. FRAX probabilities were calculated, and fracture outcomes to 2008 were established via linkage with a population-based data repository. Multivariable Cox proportional hazards models were used to determine if diabetes was associated with incident hip fractures or major osteoporotic fractures after controlling for FRAX risk factors. Mean 10-year probabilities of fracture were similar between groups for major fractures (diabetic 11.1 ± 7.2 versus nondiabetic 10.9 ± 7.3, p = 0.116) and hip fractures (diabetic 2.9 ± 4.4 versus nondiabetic 2.8 ± 4.4, p = 0.400). Diabetes was a significant predictor of subsequent major osteoporotic fracture (hazard ratio [HR] = 1.61, 95% confidence interval [CI] 1.42-1.83) after controlling for age, sex, medication use, and FRAX risk factors including BMD. Similar results were seen after adjusting for FRAX probability directly (HR = 1.59, 95% CI 1.40-1.79). Diabetes was also associated with significantly higher risk for hip fractures (p
Adipocytes and osteoblasts share a common progenitor, and there is, therefore, potential for both autocrine and endocrine effects of adiponectin on skeletal metabolism. The aim of the present study was to determine whether high serum adiponectin was associated with an increased risk of fracture in elderly men. We studied the relationship between serum adiponectin and the risk of fracture in 999 elderly men drawn from the general population and recruited to the Osteoporotic Fractures in Men (MrOS) study in Gothenburg, Sweden. Baseline data included general health questionnaires, lifestyle questionnaires, body mass index (BMI), bone mineral density (BMD), serum adiponectin, osteocalcin, and leptin. Men were followed for up to 7.4 years (average, 5.2 years). Poisson regression was used to investigate the relationship between serum adiponectin, other risk variables and the time-to-event hazard function of fracture. Median levels of serum adiponectin at baseline were 10.4?µg/mL (interquartile range, 7.7-14.3). During follow-up, 150 men sustained one or more fractures. The risk of fracture increased in parallel with increasing serum adiponectin (hazard ratio [HR]/SD, 1.46; 95% confidence interval [CI], 1.23-1.72) and persisted after multivariate-adjusted analysis (HR/SD, 1.30; 95% CI, 1.09-1.55). Serum adiponectin shows graded stepwise association with a significant excess risk of fracture in elderly men that was independent of several other risk factors for fracture. Its measurement holds promise as a risk factor for fracture in men.
A FRAX model for Canada was constructed for prediction of osteoporotic and hip fracture risk using national hip fracture data with and without the use of femoral neck bone mineral density (BMD). Performance of this system was assessed independently in a large clinical cohort of 36,730 women and 2873 men from the Manitoba Bone Density Program database that tracks all clinical dual-energy X-ray absorptiometry (DXA) test results for the Province of Manitoba, Canada. Linkage with other provincial health databases allowed for the direct comparison of fracture risk estimates from the Canadian FRAX model with observed fracture rates to 10 years (549 individuals with incident hip fractures and 2543 with incident osteoporotic fractures). The 10-year Kaplan-Meier estimate for hip fractures in women was 2.7% [95% confidence interval (CI) 2.1-3.4%] with a predicted value of 2.8% for FRAX with BMD, and in men the observed risk was 3.5% (95% CI 0.8-6.2%) with predicted value of 2.9%. The 10-year estimate of osteoporotic fracture risk for all women was 12.0% (95% CI 10.8-13.4%) with a predicted value of 11.1% for FRAX with BMD, and in men, the observed risk was 10.7% (95% CI 6.6-14.9%) with a predicted value of 8.4%. Discrepancies were observed within some subgroups but generally were small. Fracture discrimination based on receiver operating characteristic curve analysis was comparable with published meta-analyses with area under the curve for osteoporotic fracture prediction of 0.694 (95% CI 0.684-0.705) for FRAX with BMD and for hip fractures 0.830 (95% CI 0.815-0.846), both of which were better than FRAX without BMD or BMD alone. Individual risk factors considered by FRAX made significant independent contributions to fracture prediction in one or more of the models. In conclusion, a Canadian FRAX tool calibrated on national hip fracture data generates fracture risk predictions that generally are consistent with observed fracture rates across a wide range of risk categories.