Individual Fracture Risk Research Articles

Medicare Part D's Exclusion of Benzodiazepines and Fracture Risk in Nursing Homes

Medicare Part D excludes benzodiazepine medications from coverage, and some state Medicaid programs also limit coverage. We assessed whether such policies decrease the risk of fractures in elderly individuals living in nursing homes. This is a quasi-experimental study with interrupted time-series estimation and extended Cox proportional hazards models comparing changes in outcomes before and after implementation of Medicare Part D in a nationwide sample of nursing home residents in 48 states. The study included 1 068 104 residents and a subsample of 50 874 residents with fracture data from 1 pharmacy. We assessed monthly prescribing rates of benzodiazepines and potential substitutes from January 1, 2005, through June 30, 2007, and hazard ratios for incident hip fracture and falls, adjusted for age, sex, and race/ethnicity. Estimates were stratified by concurrent Medicaid limits on benzodiazepines: no supplemental coverage (1 state), partial supplemental coverage (6 states), or complete supplemental coverage (41 states). The no-supplemental-coverage policy resulted in an immediate and significant reduction of 10 absolute points in benzodiazepine use (27.0% to 17.0%) after Medicare Part D was implemented (95% confidence interval, -0.11 to -0.09; P < .001). Benzodiazepine use remained stable in the partial-supplemental- and complete-supplemental-coverage states. Hazard ratios for incident hip fracture were 1.60 (95% confidence interval, 1.05 to 2.45; P = .03) in the no-supplemental-coverage state after Medicare Part D implementation and 1.17 (95% confidence interval, 0.93 to 1.46; P = .18) in the partial-supplemental-coverage states, relative to complete-supplemental-coverage states. Supplemental drug coverage exclusion policies affect the medication use of nursing home residents and may not decrease their fracture risk.

Extreme scalability challenges in micro‐finite element simulations of human bone

AbstractCoupling recent imaging capabilities with microstructural finite element (µFE) analysis offers a powerful tool to determine bone stiffness and strength. It shows high potential to improve the individual fracture risk prediction, a tool much needed in the diagnosis and treatment of osteoporosis, that is, according to the World Health Organization (WHO), second only to cardiovascular disease as a leading health‐care problem. We adapted a multilevel preconditioned conjugate gradient method to solve the very large voxel models that arise in the µFE bone structure analysis. The intricate microstructure properties of bone lead to sparse matrices with billions of rows, thus rendering this application to be an ideal candidate for massively parallel architectures such as the BG/L Supercomputer. In this work we present our progress as well as the challenges we were able to identify in our quest to achieve scalability to thousands of BG/L cores. Copyright © 2010 John Wiley &amp; Sons, Ltd.

Pathogenesis of Osteoporosis.

As for most multifactorial disorders, the pathogenesis of osteoporosis is complex, and a different set of mechanisms may be operative in any given individual. However, there are certain common causes of bone loss and increased fracture risk with aging in most people. These include genetic factors contributing to the acquisition of peak bone mass, illnesses affecting skeletal growth and development, sex steroid deficiency following the menopause in women and with aging in men, and intrinsic, age-related changes in bone metabolism. Superimposed on these factors are specific secondary causes of bone loss, such as corticosteroid use or other illnesses affecting bone metabolism that may contribute to fracture risk in individuals exposed to these factors. The past decade has witnessed tremendous advances in our understanding of each of these various causes of bone loss, leading to the development of novel, mechanism-based therapeutic approaches to prevent and treat this important public health disorder.

Evaluation and Management of Osteoporosis and Fragility Fractures in The Elderly

Osteoporosis is characterized by low bone mass and microarchitectural deterioration that leads to increased bone fragility and fracture. The medical, psychosocial and economic burden that fragility fractures have on individuals and society is staggering. As the geriatric segment of the population continues to expand, so to will the magnitude of this epidemic. There are multiple mechanisms influencing bone quality and bone loss with age. Fragility fracture is a composite of multiple intrinsic and extrinsic factors related to the individual and their environment. Fall prevention remains the cornerstone of management in this problem. The FRAX® fracture risk assessment program, which estimates the 10-year probability of a major osteoporotic fracture, is an exciting new tool in assessing risk. Novel therapeutics, including zoledronic acid, strontium and teriparatide, are now available to complement proven osteoporosis treatments and more effectively decrease fracture risk in vulnerable individuals. Agents in Phase III trials, including denosumab and lasofoxifene, will probably increase the armamentarium of tools clinicians can use to combat the growing problem of osteoporosis and its complications.

Timing of Repeat BMD Measurements: Development of an Absolute Risk-Based Prognostic Model

This study attempted to address the following questions: for an individual who is at present nonosteoporotic, given their current age and BMD level, what is the individual's risk of fracture and when is the ideal time to repeat a BMD measurement? Nonosteoporotic women (n = 1008) and men (n = 750) over the age of 60 in 1989 from the Dubbo Osteoporosis Epidemiology Study were monitored until one of the following outcomes occurred: (1) BMD reached "osteoporosis" level (i.e., T-scores < or = -2.5) or (2) an incident fragility fracture. During the follow-up period (average, 7 yr), 346 women (34%) and 160 men (21%) developed osteoporosis or sustained a low-trauma fracture. The risk of osteoporosis or fracture increased with advancing age (women: RR/10 yr, 1.3; 95% CI, 1.1-1.6; men: RR/10 yr, 2.3; 95% CI, 1.7-2.9) and lower BMD levels (women: RR per -0.12 g/cm(2), 3.2; 95% CI, 2.6-4.1; RR per -0.12 g/cm(2), 2.6; 95% CI, 2.0-3.3). Using the predicted risk (of osteoporosis or fracture) of 10% as a cut-off level for repeating BMD measurement, the estimated time to reach the cut-off level varied from 1.5 (for an 80-yr-old woman with a T-score of -2.2) to 10.6 yr (for a 60-yr-old man with a T-score of 0). These results suggest that, based on an individual's current age and BMD T-score, it is possible to estimate the optimal time to repeat BMD testing for the individual. The prognostic model and approach presented in this study may help improve the individualization and management of osteoporosis.

Use of FTIR Spectroscopic Imaging to Identify Parameters Associated With Fragility Fracture

BMD does not entirely explain an individual's risk of fracture. The purpose of this study was to assess whether specific differences in spatially resolved bone composition also contribute to fracture risk. These differences were assessed using Fourier transform infrared spectroscopic imaging (FTIRI) and analyzed through multiple logistic regression. Models were constructed to determine whether FTIRI measured parameters describing mineral content, mineral crystal size and perfection, and collagen maturity were associated with fracture. Cortical and cancellous bone were independently evaluated in iliac crest biopsies from 54 women (32 with fractures, 22 without) who had significantly different spine but not hip BMDs and ranged in age from 30 to 83 yr. The parameters that were significantly associated with fracture in the model were cortical and cancellous collagen maturity (increased with increased fracture risk), cortical mineral/matrix ratio (higher with increased fracture risk), and cancellous crystallinity (increased with increased fracture risk). As expected, because of its correlation with cortical but not cancellous bone density, hip BMD was significantly associated with fracture risk in the cortical but not the cancellous model. This research suggests that additional parameters associated with fracture risk should be targeted for therapies for osteoporosis.

The clinical role of dual energy X-ray absorptiometry

Dual energy X-ray absorptiometry (DXA) measurements of hip and spine bone mineral density (BMD) have an important role in the evaluation of individuals at risk of osteoporosis, and in helping clinicians advise patients about the appropriate use of anti-fracture treatment. Compared with alternative bone densitometry techniques, hip and spine DXA examinations have a number of advantages that include a consensus that BMD results can be interpreted using the World Health Organisation (WHO) T-score definition of osteoporosis, a proven ability to predict fracture risk, proven effectiveness at targeting anti-fracture therapies, and the ability to monitor response to treatment. This review discusses the evidence for these and other clinical aspects of DXA scanning, including its role in the new WHO algorithm for treating patients on the basis of their individual fracture risk.

Fracture prevention in men

The lifetime risk of experiencing a fracture in 50-year-old men is lower (20%) than the risk in women (50%). Consequently, much less research has been carried out on osteoporosis and fracture risk in men. Differences in the risk and incidence of fractures between men and women are related to differences in bone-related and fall-related factors between the sexes. During the past decade, progress has been achieved in case finding and fracture prevention in men. Epidemiology studies have better specified the prevalence and incidence of fractures, and insight into the pathophysiology of osteoporosis and fractures in men has progressed considerably. Case finding for men and women at the highest risk of fracture is now possible using the FRAX algorithm, which includes clinical risk factors, with and without bone mineral density, and allows calculation of an individual's 10-year fracture risk. Although strategies to prevent fractures are much less common in men than in women, several treatment options are now available for this purpose. Bisphosphonates, in particular, consistently demonstrate a positive effect on bone mineral density, and some data also indicate decreased rates of vertebral fractures. For men with severe osteoporosis, treatment with the anabolic agent teriparatide might be an effective option.

Pelvic Organ Prolapse and Relationship with Skeletal Integrity

Health burden related to osteoporotic fractures in an aging female population far exceeds that imposed by other chronic disorders such as cardiovascular disease and breast cancer. Bone mineral density assessment and clinical risk factors provide independent insights into fracture risk in individuals. A finite list of clinical risk factors are identified as prognostic of fracture risk, namely among aging women, including low body mass, compromised reproductive physiology (e.g., prolonged periods of amenorrhea and early menopause), parental and personal histories of fracture, and alcohol and tobacco use. Pelvic organ prolapse is a common gynecologic entity and a contributor to age-related morbidities. The purpose of this review is to communicate data identifying pelvic organ prolapse as another clinical risk factor for fracture risk in postmenopausal women and to increase the caregiver's vigilance in anticipating and instituting preventive care strategies to a population (i.e., postmenopausal women with clinically appreciable pelvic organ prolapse) that may be at an enhanced lifetime risk for skeletal fractures.

Diagnostik der Osteoporose

The diagnostic approach to osteoporosis usually involves an ample risk assessment, a physical examination, a radiograph of the thoracic and lumbar spine, a bone densitometry using dual X-ray absorptiometry, and a basic blood test. The aim of this approach is to assign a person to one of the WHO-based diagnostic categories, and to estimate the ten-year fracture risk of this individual. In countries where available, the individual ten-year fracture risk can now easily be calculated for men and women of forty years of age and above, by using a computer-driven calculation tool, called FRAX, which has been developed by WHO recently.

Österreichischer Leitfaden zur medikamentösen Therapie der postmenopausalen Osteoporose – Update 2009

Osteoporosis is a systemic skeletal disease characterized by diminished bone mass and deterioration of bone microarchitecture, leading to increased fragility and subsequent increased fracture risk. Therapeutic measures therefore aim at reducing individual fracture risk. In Austria, the following drugs, all of which have been proven to reduce fracture risk, are currently registered for the treatment of postmenopausal osteoporosis: alendronate, risedronate, etidronate, ibandronate, raloxifene, teriparatide (1-34 PTH), 1-84 PTH, strontium ranelate and salmon calcitonin. Fluorides are still available, but their role in daily practice has become negligible. Currently, there is no evidence that a combination of two or more of these drugs could improve anti-fracture potency. However, treatment with PTH should be followed by the treatment with an anticatabolic drug such as bisphosphonates. Calcium and vitamin D constitute an important adjunct to any osteoporosis treatment.

Theoretical analysis of alendronate and risedronate effects on canine vertebral remodeling and microdamage

Bisphosphonates suppress bone remodeling activity, increase bone volume, and significantly reduce fracture risk in individuals with osteoporosis and other metabolic bone diseases. The objectives of the current study were to develop a mathematical model that simulates control and 1 year experimental results following bisphosphonate treatment (alendronate or risedronate) in the canine fourth lumbar vertebral body, validate the model by comparing simulation predictions to 3 year experimental results, and then use the model to predict potential long term effects of bisphosphonates on remodeling and microdamage accumulation. To investigate the effects of bisphosphonates on bone volume and microdamage, a mechanistic biological model was modified from previous versions to simulate remodeling in a representative volume of vertebral trabecular bone in dogs treated with various doses of alendronate or risedronate, including doses equivalent to those used for treatment of post-menopausal osteoporosis in humans. Bisphosphonates were assumed to affect remodeling by suppressing basic multicellular unit activation and reducing resorption area. Model simulation results for trabecular bone volume fraction, microdamage, and activation frequency following 1 year of bisphosphonate treatment are consistent with experimental measurements. The model predicts that trabecular bone volume initially increases rapidly with 1 year of bisphosphonate treatment, and continues to slowly rise between 1 and 3 years of treatment. The model also predicts that microdamage initially increases rapidly, 0.5–1.5-fold for alendronate or risedronate during the first year of treatment, and reaches its maximum value by 2.5 years before trending downward for all dosages. The model developed in this study suggests that increasing bone volume fraction with long term bisphosphonate treatment may sufficiently reduce strain and damage formation rate so that microdamage does not accumulate above that which is initiated in the first two years of treatment.

Predicting risk of osteoporotic fracture in men and women in England and Wales: prospective derivation and validation of QFractureScores

Objective To develop and validate two new fracture risk algorithms (QFractureScores) for estimating the individual risk of osteoporotic fracture or hip fracture over 10 years.Design Prospective open cohort study with...

Pharmacogenetics of osteoporosis and the prospect of individualized prognosis and individualized therapy

Description of recent progress in genetics and pharmacogenetics of osteoporosis. Osteoporosis and its consequence of fragility fracture are characterized by highly complex phenotypes, which include bone mineral density, bone strength, bone turnover markers, and nonskeletal traits. Recent developments in the genome-wide studies using high-throughput single-nucleotide polymorphisms have yielded reliable findings. Four genome-wide studies have identified 40 single-nucleotide polymorphisms in various chromosomes that were modestly associated with either bone mineral density or fracture risk. Clinical response, including adverse reactions, to antiosteoporosis therapy (such as bisphosphonates and selective estrogen receptor modulators) is highly variable among treated individuals. Candidate gene studies have found that common polymorphic variations within the collagen I alpha 1 and vitamin D receptor genes were associated with variability in response to antiosteoporosis treatment. Moreover, a recent genome-wide study identified four single-nucleotide polymorphisms that were associated with bisphosphonate-related osteonecrosis of the jaw with relative risk being between 10 and 13. The evaluation of osteoporosis and fracture risk is moving from a risk stratification approach to a more individualized approach, in which an individual's absolute risk of fracture is evaluable as a constellation of the individual's environmental exposure and genetic makeup. Therefore, the identification of gene variants that are associated with osteoporosis phenotypes or response to therapy can eventually help individualize the prognosis, treatment and prevention of fracture and its adverse outcomes.

Mapping translational research into individualized prognosis of fracture risk

AbstractThe assessment of fracture risk has until now been based on the measurement of bone mineral density (BMD) and/or a prior fracture. Individuals with BMD T‐scores &lt; –2.5 (e.g. osteoporosis) or with prior fractures are indicated for treatment. However, recent data have suggested that 55% of women and 74% of men who sustained a fracture did not have osteoporosis. Therefore, the current strategy reduces a small number of fractures in the general population, and new thinking is required for that majority of individuals whose BMD measurements are at or near (both sides) the current threshold of osteoporosis. An individual's absolute risk of fracture can be estimated from the individual risk profile, which includes age, BMD, weight or body mass index, prior fracture, comorbidities, corticosteroid use, lifestyle factors, and falls. Therefore, risk assessment must simultaneously consider all risk factors to which the individual is exposed. A number of prognostic models and predictive nomograms have been developed to estimate an individual's absolute risk of fracture, but they have not been externally validated. Nevertheless, these prognostic models can be effective tools for individualizing short‐term and long‐term risks of fracture, which can help patient counseling and selecting appropriate patients for intervention to maximize the benefit of fracture reduction in the general population.

Ostéoporose postménopausique : le point sur sa prise en charge

The current management of osteoporosis is based on several keypoints. The first critical step is to identify patients at high risk of fragility fracture, especially those who already sustained a first fracture, but still not often treated. Evaluating fracture risk includes not only bone-mineral density measurement and age, which are the two main risk factors, but also other clinical risk factors. Treatment decision is then based on estimated level of absolute fracture risk over 10 years. In fact, the main goal of postmenopausal osteoporosis treatment is to reduce this risk of fragility fracture. Treatment choice is based both on drug properties demonstrated by clinical trials and the specific fracture risks of each patient. In addition, it is important to identify whether patients are at risk of vertebral fractures or else at risk of vertebral and nonvertebral fractures. Duration of treatment is at least four to five years after which individual-fracture risk has to be reevaluated. As in many other chronic disease treatments, adherence to therapy is poor and has to be carefully assessed by all health-care professionals.

Latest news and product developments

AbstractOsteoporosis guidelineA new guideline on the management of osteoporosis in men over 50 and post‐menopausal women has been published by the National Osteoporosis Guideline Group (www.shef.ac.uk/NOGG), a group of organisations representing health professionals and patients, with funding from several pharmaceutical companies.The guideline recommends using the FRAX tool (www.shef.ac.uk/FRAX) to assess the 10‐year fracture risk in individuals with risk factors to facilitate targeting DXA scans to measure bone mineral density. Patients who have already sustained a fragility fracture should be treated without risk assessment. Treatment recommendations are similar to those published in draft NICE guidance on primary and secondary prevention, selecting alendronate as the drug of first choice for most patients.Efalizumab efficacyA multicentred postapproval trial has demonstrated long‐term efficacy and a favourable safety profile for efalizumab (Raptiva) in moderate to severe chronic plaque psoriasis.The CONTROL II study, presented in September at the 17th EADV congress in Paris, was conducted at 170 sites in 18 European countries and involved 1255 patients who had failed to respond to traditional systemic therapies. In this non‐blinded study, 68 per cent of participants achieved the primary efficacy end‐point and showed improvement within the first 12 weeks; control was maintained in responding patients who continued treatment.Adverse effects were graded as mild or moderate and similar to those reported in earlier studies. There was no evidence of an increase in malignancies or infections.New oral anticoagulantRivaroxaban (Xarelto), an oral factor Xa inhibitor, has been introduced for the prevention of venous thrombo‐embolism in patients undergoing elective hip or knee replacement surgery. Compared with the low molecular weight heparin enoxaparin (Clexane), rivaroxaban has been shown to reduce the risk of venous thrombosis by 70 per cent after hip replacement and by 49 per cent after knee replacement; the risk of bleeding was similar.At the recommended dose of 10mg once daily, prophylaxis after hip surgery lasts five weeks and costs £157; prophylaxis after knee surgery lasts two weeks and costs £63.New productsUCB Pharma has introduced lacosamide (Vimpat) as adjunctive treatment of partial‐onset epilepsy with or without secondary generalisation in patients aged 16 and over. A month's treatment at the recommended maintenance dose of 100‐200mg twice daily costs approximately £73‐£140.A new non‐nucleoside reverse transcriptase inhibitor (NNRI) is available for the treatment of HIV‐1 infection in combination with a boosted protease inhibitor (PI) and other antiretrovirals in treatment‐experienced adults. Etravirine (Intelence) costs approximately £320 for one month's treatment at the recommended dose of 200mg twice daily.Voltarol Pain‐Eze (diclofenac) 12.5mg tablets are now available without prescription; a pack of 18 tablets costs £5.99.Atypicals and EPS riskAtypical antipsychotics are not associated with a significantly lower risk of extra‐pyramidal symptoms than first‐generation agents such as perphenazine (Fentazin), a new analysis of the CATIE study has shown (Br J Psychiatry 2008;193:279–88).CATIE was a large trial comparing the efficacy and safety of antipsychotics in the treatment of schizophrenia in which perphenazine was a representative first‐generation agent (Am J Psychiatry 2006;163:611–22). This analysis found no differences in the risk of parkinsonism, dystonia, akathisia or tardive dyskinesia between perphenazine and the newer antipsychotics; use of antiparkinsonian medication was higher with risperidone and lower with quetiapine (Seroquel).Mental health websiteA new website offering information about mental illnesses and drug treatment has been launched by the United Kingdom Psychiatric Pharmacy Group (UKPPG), the College of Mental Health Pharmacists (CMHP), the Pharmaceutical Schizo‐phrenia Initiative (PSI) and the National Institute for Mental Health in England (NIMHE).www.choiceandmedication.org.uk includes information about 17 mental illnesses and a large number of drug treatments. It offers links to other sites offering information and downloadable leaflets, help to identify the local mental health trust and downloadable charts comparing treatments for each indication.

Prediction of the fracture load of whole proximal femur specimens by topological analysis of the mineral distribution in DXA-scan images

Objective To evaluate scanner-generated images of hip specimens obtained from dual energy X-ray absorptiometry (DXA) by quantitative image analysis of bone mineral distribution in the standard regions of interest (ROI), to predict the ultimate mechanical strength, and to compare the predictive potential with standard densitometry. Materials and Methods Femoral bone mineral density (BMD) of 100 hip specimens was obtained by DXA in the total hip, shaft, trochanteric, and neck ROI. Maximum compressive strength (MCS) of the specimens was measured in a mechanical loading device simulating a fall on the greater trochanter. The topology of bone mineral distribution in the scan images was evaluated by image processing methods based on the Minkowski functionals (MF) using the optimized topological parameter MF2D. Correlation and multivariate analysis were employed to assess the statistical potential of BMD and MF2D with respect to predict the mechanical strength of the femur specimens. Results R 2 for the correlation between load-to-failure and BMD varied between 0.73 and 0.79 (exponential curve fit, p < 0.001), being highest in the trochanteric ROI. Correlation between load-to-failure of the specimens with the topological parameter MF2D ranged from R 2 = 0.8 to 0.91 ( p < 0.001). In a multivariate model combining the topological information from all ROIs, correlation with MCS rose to R 2 = 0.94. Conclusion The topological parameter MF2D can be employed to predict the mechanical strength of proximal femur specimens from DXA-generated images. Performance is superior to standard evaluation of DXA. In the future, the proposed image processing method may serve to improve the assessment of an individual's fracture risk.

Fracture Risk From Psychotropic Medications

Selective serotonin reuptake inhibitors (SSRIs), benzodiazepines, and antipsychotics have each been associated with an increased risk of fracture in older individuals. The aim of this study was to better define the magnitude of fracture risk with psychotropic medications and to determine whether a dose-effect relationship exists. Population-based administrative databases were used to examine psychotropic medication exposure and fractures in persons aged 50 years and older in Manitoba between 1996 and 2004. Persons with osteoporotic fractures (vertebral, wrist, or hip [n = 15,792]) were compared with controls (3 controls for each case matched for age, sex, ethnicity, and comorbidity [n = 47,289]). Medications examined included antidepressants (SSRIs vs other monoamines), antipsychotics, lithium, and benzodiazepines. Selective serotonin reuptake inhibitors were associated with the highest adjusted odds of osteoporotic fractures (odds ratio [OR] = 1.45; 95% confidence interval [CI], 1.32-1.59). Other monoamine antidepressants (OR = 1.15; 95% CI, 1.07-1.24) and benzodiazepines (OR = 1.10; 95% CI, 1.04-1.16) were also associated with greater fracture risk, although the relationship was weaker. Lithium was associated with lower fracture risk (OR = 0.63; 95% CI, 0.43-0.93), whereas the relationship with antipsychotics was not significant in the models that adjusted for diagnoses. A dose-effect relationship was seen with SSRIs and benzodiazepines. This study provides novel insight into the relationship between fractures and psychotropic medications in the elderly. Selective serotonin reuptake inhibitors seem to have a greater risk than other psychotropic classes, and higher doses may further increase that risk. Lithium seems to be protective against fractures.

Validation of ten-year fracture risk prediction: A clinical cohort study from the Manitoba Bone Density Program

Introduction Absolute 10-year fracture risk is the preferred method for fracture risk assessment. The validity of applying published fracture rates from one population to another population is uncertain. Methods 20,579 women age 47.5 years or older at the time of baseline femoral neck bone mineral density (BMD) were identified in a database containing all clinical DXA results for the Province of Manitoba, Canada. Individual 10-year fracture risk was predicted from age-only and age plus femoral neck T-score using published 10-year fracture risk for Swedish women. Health service records were assessed for the presence of non-trauma ‘osteoporotic’ fracture codes (hip, clinical spine, wrist, humerus) subsequent to BMD testing (86,447 person- y follow up, 1173 patients with osteoporotic fractures). Fracture rates were derived for subgroups stratified by age (5-year strata) and estimated risk (5% strata). 10-year fracture rates were computed directly by the Kaplan–Meier method (10-year continuous data) and by the actuarial method (two 5-year periods with adjustments for aging, death and expected BMD loss). Results Direct and actuarial methods gave nearly identical point estimates, but the latter were more precise. There was a strong linear correlation between predicted and observed fracture rates based upon age-only ( r = 0.95) and age plus BMD ( r = 0.99). For age strata 50 to 75, and for estimated risk strata from 0–5% to 20–25%, the confidence intervals overlapped the line of identity. For women age >77.5 or estimated risk >25%, observed exceeded estimated fracture rates. This is explained by healthy selection bias whereby elderly women referred for BMD testing have lower mortality than expected, hence more years at risk for fracture. Corrected for survival bias, women age >77.5 had observed fracture rates no different than predicted. Conclusion Swedish 10-year fracture risk data are generally applicable to the Canadian female population referred for clinical BMD testing, though fracture rates were underestimated in the oldest and highest risk subgroups due to healthy selection bias.