Probability Of Major Osteoporotic Fracture Research Articles

Significantly higher estimated 10-year probability of fracture in lupus patients with bone mineral density comparable to that of healthy individuals

This study aimed at comparing the FRAX 10-year fracture risk between SLE patients and demographically- and anthropometrically matched healthy individuals. Consecutive SLE patients aged ≥ 40 were analyzed for the FRAX 10-year probability of major osteoporotic and hip fractures and their risk was compared with healthy controls matched for age, gender and body mass index. Potential determinants associated with higher 10-year fracture probability in the SLE patients were studied by regression models. Ninety subjects (45 SLE patients and 45 healthy controls) were studied. While the bone mineral density (BMD) of the lumbar spine and dominant hip was comparable between the two groups, the FRAX 10-year probability of major and hip fractures was significantly higher in SLE patients. Significantly more SLE patients had high 10-year fracture risk as defined by the National Osteoporosis Foundation compared with healthy controls (16 vs. 2 %, p = 0.026). After controlling for glucocorticoid use and premature menopause which were significant univariate risk factors, the difference in the 10-year fracture risk became insignificant. Amongst SLE patients, increasing age, lower hip BMD and cumulative glucocorticoid dose independently predicted higher 10-year major fracture risk while higher anti-dsDNA level independently predicted higher hip fracture risk in addition to age and lower hip BMD. Chronic glucocorticoid use and premature menopause led to higher 10-year probability of major osteoporotic and hip fractures in SLE patients compared with their healthy counterparts although their BMD was comparable. Advanced age, lower hip BMD, cumulative glucocorticoid and higher anti-dsDNA level independently predicted higher 10-year fracture risk amongst SLE patients.

Prevalence and seasonal variation of hypovitaminosis D and its relationship to bone metabolism in healthy Hungarian men over 50 years of age: the HunMen Study

This study reports a high prevalence of hypovitaminosis D and low bone mineral density (BMD) in a healthy Hungarian male cohort over 50years of age. Men with 25-hydroxyvitamin D levels of <75nmol/L had a significantly higher 10-year hip and major osteoporotic fracture probability using the country-specific fracture risk assessment (FRAX) algorithm. The aim of this study is to characterize the prevalence and seasonal variation of hypovitaminosis D and its relationship to bone metabolism in healthy Hungarian men over 50years of age. We determined levels of 25-hydroxyvitamin D (25-OH-D), PTH, osteocalcin (OC), C-terminal telopeptides of type-I collagen (CTX-I), procollagen type 1 amino-terminal propeptide (PINP), BMD at L1-L4 (LS) and femur neck (FN), daily dietary calcium intake, and the 10-year probability of hip fracture and a major osteoporotic fracture using the country-specific FRAX algorithm in 206 randomly selected ambulatory men. The mean (range) age of the volunteers was 60 (51-81) years. The prevalence of hypovitaminosis D (25-OH-D, <75nmol/L) was 52.9%. The prevalence of low (T-score < -1.0) BMD at the FN and LS was 45% and 35.4%, respectively. The mean (range) FRAX hip fracture and FRAX major osteoporotic fracture was 0.8% (0-9.4%) and 3.8% (1.7-16%), respectively. On comparing the vitamin D sufficient to the insufficient group, there was a statistically significant difference between the FRAX hip fracture and FRAX major osteoporotic fracture indexes. There was significant seasonal variation in the vitamin D levels; the lowest levels were measured in winter and the highest in summer. A high prevalence of hypovitaminosis D and low BMD were observed in the studied Hungarian male population. This is the first study reporting higher 10-year hip and major osteoporotic fracture probability using the country-specific FRAX algorithm in individuals with hypovitaminosis D.

A systematic review of hip fracture incidence and probability of fracture worldwide.

SummaryThe country-specific risk of hip fracture and the 10-year probability of a major osteoporotic fracture were determined on a worldwide basis from a systematic review of literature. There was a greater than 10-fold variation in hip fracture risk and fracture probability between countries.IntroductionThe present study aimed to update the available information base available on the heterogeneity in the risk of hip fracture on a worldwide basis. An additional aim was to document variations in major fracture probability as determined from the available FRAX models.MethodsStudies on hip fracture risk were identified from 1950 to November 2011 by a Medline OVID search. Evaluable studies in each country were reviewed for quality and representativeness and a study (studies) chosen to represent that country. Age-specific incidence rates were age-standardised to the world population in 2010 in men, women and both sexes combined. The 10-year probability of a major osteoporotic fracture for a specific clinical scenario was computed in those countries for which a FRAX model was available.ResultsFollowing quality evaluation, age-standardised rates of hip fracture were available for 63 countries and 45 FRAX models available in 40 countries to determine fracture probability. There was a greater than 10-fold variation in hip fracture risk and fracture probability between countries.ConclusionsWorldwide, there are marked variations in hip fracture rates and in the 10-year probability of major osteoporotic fractures. The variation is sufficiently large that these cannot be explained by the often multiple sources of error in the ascertainment of cases or the catchment population. Understanding the reasons for this heterogeneity may lead to global strategies for the prevention of fractures.

Routine Application of the Korean FRAX Model in Women: a Single-center Study

= Abstract = Objectives: The objective of this study was to assess the efficacy of the Korean fracture-risk assessment tool (FRAX) model for routine application in women who had a general check-up for bone mineral density (BMD). Methods: This retrospective study was conducted at a university hospital and comprised 343 patients, whose BMD and clinical risk factors were assessed for FRAX calculation. The 10-year probabilities of hip and major osteoporotic fractures were compared with the result of the FRAX ® tool (http://www.shef.ac.uk/FRAX, web version 3.5) applied to Korean models developed at the World Health Organization Collaborating Center with or without femoral neck bone mineral density. Results: The T-score gradually decreased with increasing age. Additionally, the 10-year probability of a major osteoporotic fracture increased with age. However, the probability of hip fracture showed no correlation with age if BMD was not included in the estimation. Conclusion: Previous report on patients whose probability of a proximal femoral fracture were calculated using Korean FRAX models produced a higher score than our data because our data involved a general population. A larger general population is needed to confirm the Korean FRAX model. However, our data provide information for physicians to assess the Korean FRAX model in the general female population.

Incidence of Osteoporosis and Falls and Predictors of Fracture Risk in Postmenopausal Women.

The purpose of this study was to investigate the incidence of osteoporosis and falls and their consequences, and to identify predictors of fracture risk in the postmenopausal women. A total of 687 postmenopausal women were recruited through a stratified convenience sampling. A structured questionnaire was used to obtain osteoporosis and fall history and details of their most recent fall. To predict fracture risk factors, we collected demographic and physical health variables related osteoporosis and fall. Fracture risk was measured by FRAX(R) to calculate 10-year probability of major osteoporotic and hip fracture. The prevalence of osteoporosis was 22.1%, and 66.4% of them had treatments for osteoporosis. The incidence of falls during the past year was 19.2% and 38.6% of those who fell suffered consequent fractures. Women with history of osteoporosis and falls were significant predictors of 10-year probability of major osteoporotic and hip fracture. Other significant predictors were history of fracture, chronic disease, surgical menopause, lower BMI, poorer perceived health and no job. It appears that history of osteoporosis and falls are main predictors of fracture risk. Nursing assessment should be performed by detail history taking for osteoporosis, fall, chronic disease, and fracture to screen fracture risk group among postmenopausal women.

Feasibility of FRAX for Prediction of Osteoporotic Vertebral Fractures in Korea

Study DesignRetrospective study.PurposeTo assess the feasibility and limitations of fracture risk assessment tool (FRAX) for osteoporotic vertebral fractures in the Korean population.Overview of LiteratureThe FRAX algorithm is country specific and uses clinical risk factor data to calculate an individual patient's 10-year probability of hip fracture and 10-year probability of major osteoporotic fracture. However, it has not been adequately investigated for Korean.MethodsOne hundred ninety four patients who had all risk factor data for the calculation of FRAX were divided into two groups depending on the existence of vertebral fractures: the fracture group was comprised of 88 patients and the non-facture group comprised of 105 patients. We analyzed prediction of the fracture by applying respectively the Korean, Japanese, USA and UK model, and compared their FRAX results by calculating lumbar bone mineral density (BMD) instead of femoral neck BMD.ResultsThe prediction of vertebral fracture using FRAX was 10.9 ± 6.2% in the fracture group, 9.5 ± 5.5% of the non-fracture group in the Korean model (p = 0.108); 17.9 ± 10.2% in the fracture group, 14.6 ± 9.0% in the non-fracture group in the Japanese model (p = 0.017). Only the Japanese model exhibited significant difference in vertebral fracture risk. The prediction of vertebral fracture using lumbar BMD instead of femoral neck BMD was 19.5 ± 12.1% in the fracture group, 16.0 ± 10.3% in the non-fracture group in the Korean model (p = 0.029). All models had statistically significant differences for the prediction of osteoporotic vertebral fracture.ConclusionsThe 10-year probability of osteoporotic vertebral fracture had underestimation of the risk considering treatment eligibility based on the National Osteoporosis Foundation guidelines. BMD that accurately reflects the contribution of each result to fracture risk should be preferred for the prediction of fracture using FRAX, when lumbar spine and hip BMD measurements are both performed for clinical purposes in Korean.

FRAX® probabilities and risk of major osteoporotic fracture in France

The incidence of hip fracture, death and the estimated incidence of major osteoporotic fracture in France were used to determine the lifetime and 10-year probability of fracture and incorporated into a probability model (FRAX®) calibrated to the French population. Fracture probabilities in the French population have not been determined. Our aim was to determine the incidence of hip fracture in France and the estimated 10-year probabilities of hip and major osteoporotic fractures. The study population included adults over 50years living in France in 2004. Incident hip fracture cases were identified from the French PMSI database. Incidence of the other major osteoporotic fractures was imputed from the relationship between hip fracture incidence and other major fracture in Sweden. These data were used to calculate population-based fracture probabilities according to age and BMD using cutoff values for femoral neck T-scores from the NHANES III data in Caucasian women. The probability model (FRAX®) calibrated to the French population was used to compute individual fracture probabilities according to specific clinical risk factors. We identified 15,434 men and 51,469 women with an incident hip fracture. The remaining lifetime probability of hip fracture at 50years was approximately 10 and 30% respectively. With a femoral neck T-score of -2 SD, one in two women and one in five men would sustain a major osteoporotic fracture in their lifetime. The 10-year probability of other major osteoporotic fractures increased with declining T-score and increasing age. Low body mass index and other clinical risk factors had an independent effect on fracture probability whether or not BMD was included in the FRAX® model. This analysis provides detailed estimation on the risk of fracture in the French population and may help to define therapeutic guidelines.

Calibration of FRAX ® 3.1 to the Dutch population with data on the epidemiology of hip fractures.

SummaryThe FRAX tool has been calibrated to the entire Dutch population, using nationwide (hip) fracture incidence rates and mortality statistics from the Netherlands. Data used for the Dutch model are described in this paper.IntroductionRisk communication and decision making about whether or not to treat with anti-osteoporotic drugs with the use of T-scores are often unclear for patients. The recently developed FRAX models use easily obtainable clinical risk factors to estimate an individual's 10-year probability of a major osteoporotic fracture and hip fracture that is useful for risk communication and subsequent decision making in clinical practice. As of July 1, 2010, the tool has been calibrated to the total Dutch population. This paper describes the data used to develop the current Dutch FRAX model and illustrates its features compared to other countries.MethodsAge- and sex-stratified hip fracture incidence rates (LMR database) and mortality rates (Dutch national mortality statistics) for 2004 and 2005 were extracted from Dutch nationwide databases (patients aged 50+ years). For other major fractures, Dutch incidence rates were imputed, using Swedish ratios for hip to osteoporotic fracture (upper arm, wrist, hip, and clinically symptomatic vertebral) probabilities (age- and gender-stratified). The FRAX tool takes into account age, sex, body mass index (BMI), presence of clinical risk factors, and bone mineral density (BMD).ResultsFracture incidence rates increased with increasing age: for hip fracture, incidence rates were lowest among Dutch patients aged 50–54 years (per 10,000 inhabitants: 2.3 for men, 2.1 for women) and highest among the oldest subjects (95–99 years; 169 of 10,000 for men, 267 of 10,000 for women). Ten-year probability of hip or major osteoporotic fracture was increased in patients with a clinical risk factor, lower BMI, female gender, a higher age, and a decreased BMD T-score. Parental hip fracture accounted for the greatest increase in 10-year fracture probability.ConclusionThe Dutch FRAX tool is the first fracture prediction model that has been calibrated to the total Dutch population, using nationwide incidence rates for hip fracture and mortality rates. It is based on the original FRAX methodology, which has been externally validated in several independent cohorts. Despite some limitations, the strengths make the Dutch FRAX tool a good candidate for implementation into clinical practice.

Riesgo de fractura osteoporótica y de cadera en pacientes con enfermedad pulmonar obstructiva crónica

Aim Osteoporosis is a frequent comorbidity in patients with chronic obstructive pulmonary disease (COPD). We have studied the risk of major osteoporotic fracture and hip fracture in patients with COPD. Patients and methods A multicenter cross-sectional study was performed in Spain in 26 hospitals of 16 regional communities. Patients diagnosed with COPD who required admission to the Internal Medicine Service due to exacerbation of their respiratory disease were enrolled. COPD was confirmed by post-bronchodilator spirometry in stable state: maximum expiratory volume in the first second (FEV 1) < 80% of the theoretical value and quotient FEV 1/FVC < 0.70 and percent predicted after the administration of a bronchodilator. Dyspnea was evaluated with the modified Medical Research Council (mMRC) dyspnea scale. The principal variable was the likelihood of fracture evaluated with the FRAX ® tool for the Spanish population. Results Three hundred and ninety two patients, 347 (88%) men, with a mean (SD) age of 73.7 (8.9) years and a mean FEV 1 of 1.23 liters (43.3% of predicted) were enrolled. Only 37 patients (9.4%), 27 men and 10 women had been diagnosed previously of osteoporosis. Overall, 1.8% (95% CI: 0.9-3.6) had a 10-year probability of major osteoporotic fracture ≥ 20% and 49.7% (95% CI: 44.8-54.7) had a probability of hip fracture ≥ 3%. No relationship was observed between the probability of fracture and GOLD stage or mMRC dyspnea scale. Conclusions The diagnosis of osteoporosis is uncommon in our COPD patients. However, half of them have a high probability of a hip fracture in the next 10 years.

Fracture risk assessment without bone density measurement in routine clinical practice

Fracture probability assessed without bone mineral density (BMD) could potentially be sufficient for clinical decision making in many individuals categorized as low or high fracture risk. For individuals falling in a moderate risk range, there is incremental value in using BMD in the probability calculation as this appropriately reclassifies risk in over one third of the individuals. A new fracture risk assessment tool from the World Health Organization (FRAX) estimates 10-year major osteoporotic and hip fracture probabilities from multiple clinical risk factors with or without hip BMD. The objective of this study is to determine whether fracture probability derived without BMD can be used to identify individuals who would be designated for treatment. A historical cohort of 36,730 women and 2,873 men aged 50 years and older drawn from the Manitoba Bone Density Program database, which contains clinical BMD results for the Province of Manitoba, Canada, was included in the study. When 10-year probability for major osteoporotic fracture estimated without knowledge of BMD was high (≥ 20%), the vast majority (92.8%) qualified for intervention under the National Osteoporosis Foundation (NOF) guidelines, whereas among those at low risk (<10%), the vast majority (80.5%) did not satisfy any NOF intervention criteria. The benefit of including BMD in the risk assessment was greatest among those initially at moderate risk (10-19%) when fracture probability was derived without BMD, but this represented only 29.4% of the cohort (9.3% of those aged < 65 years and 48.7% of those ≥ 65 years). Fracture probability derived without BMD is able to risk stratify women in terms of future fracture risk and could potentially be sufficient for clinical decision making in many of those designated at low or high fracture risk.

Evaluation of fracture risk in osteoporosis

Osteoporotic fractures are associated with excess mortality. Effective treatment options are available, which reduce the risk of vertebral and non-vertebral fractures, but the identification of patients with high fracture risk is problematic. Low bone mineral density (BMD)--the basis for the diagnosis of osteoporosis--is an important, but not the only determinant of fracture risk. Several clinical risk factors are know that operate partially or completely independently of BMD, and affect the fracture risk. These include age, a prior fragility fracture, a parental history of hip fracture, use of corticosteroids, excess alcohol intake, rheumatoid arthritis, and different types of diseases which can cause secondary bone loss. The FRAX® tool integrates the weight of above mentioned clinical risk factors for fracture risk assessment with or without BMD value, and calculates the 10-year absolute risk of hip and major osteoporotic (hip, vertebral, humerus and forearm together) fracture probabilities. Although the use of data is not yet uniform, the FRAX® is a promising opportunity to identify individuals with high fracture risk. The accumulation of experience with FRAX® is going on and it can modify current diagnostic and therapeutic recommendations in Hungary as well.

Spine-Hip T-Score Difference Predicts Major Osteoporotic Fracture Risk Independent of FRAX ®: A Population-Based Report From CAMOS

The WHO fracture risk assessment tool (FRAX ®) estimates an individual’s 10-yr major osteoporotic and hip fracture probabilities. When bone mineral density (BMD) is included in the FRAX calculation, only the femoral neck measurement can be used. Recently, a procedure was reported for adjusting major osteoporotic fracture probability from FRAX with femoral neck BMD based on the difference (offset) between the lumbar spine and the femoral neck T-score values. The objective of the current analysis was to independently evaluate this algorithm in a population-based cohort of 4575 women and 1813 men aged 50 yr and older from the Canadian Multicentre Osteoporosis Study. For women and men combined, there was a 15% (95% confidence interval 7–24%) increase in major osteoporotic fracture risk for each offset T-score after adjusting for FRAX probability calculated with femoral neck BMD. The effect was stronger in women than men, but a significant sex interaction was not detected. Among the full cohort, 5.5% had their risk category reclassified after using the offset adjustment. Sex- and age-dependent offsets (equivalent to an offset based on Z-scores) showed improved risk classification among individuals designated to be at moderate risk with the conventional FRAX probability measurement. In summary, the T-score difference between the lumbar spine and femoral neck is an independent risk factor for major osteoporotic fractures that is independent of the FRAX probability calculated with femoral neck BMD.

Effects of FRAX ® Model Calibration on Intervention Rates: A Simulation Study

The WHO fracture risk assessment tool (FRAX ®) estimates an individual’s 10-yr major osteoporotic and hip fracture probabilities using a tool customized to the fracture epidemiology of a specific population. Incorrect model calibration could therefore affect performance of the model in clinical practice. The current analysis was undertaken to explore how simulated miscalibration in the FRAX ® tool would affect the numbers of individuals meeting specific intervention criteria (10-yr major osteoporotic fracture probability ≥20%, 10-yr hip fracture probability ≥3%). The study cohort included 36,730 women and 2873 men aged 50 yr and older with FRAX ® probability estimates using femoral neck bone mineral density. We simulated relative miscalibration error in 10% increments from −50% to +50% relative to a correctly calibrated FRAX ® model. We found that small changes in model calibration (even on the order of 10%) had large effects on the number of individuals qualifying for treatment. There was a steep gradient in the relationship between relative change in calibration and relative change in intervention rates: for every 1% change in calibration, there was a 2.5% change in intervention rates for women and 4.1% for men. For hip fracture probability, the gradient of the relationship was closer to unity. These results highlight the importance of FRAX ® model calibration, and speak to the importance of using high-quality fracture epidemiology in constructing FRAX ® tools.

FRAX ® Bone Mineral Density Task Force of the 2010 Joint International Society for Clinical Densitometry & International Osteoporosis Foundation Position Development Conference

FRAX ® is a fracture risk assessment algorithm developed by the World Health Organization in cooperation with other medical organizations and societies. Using easily available clinical information and femoral neck bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA), when available, FRAX ® is used to predict the 10-year probability of hip fracture and major osteoporotic fracture. These values may be included in country specific guidelines to aid clinicians in determining when fracture risk is sufficiently high that the patient is likely to benefit from pharmacological therapy to reduce that risk. Since the introduction of FRAX ® into clinical practice, many practical clinical questions have arisen regarding its use. To address such questions, the International Society for Clinical Densitometry (ISCD) and International Osteoporosis Foundations (IOF) assigned task forces to review the best available medical evidence and make recommendations for optimal use of FRAX ® in clinical practice. Questions were identified and divided into three general categories. A task force was assigned to investigating the medical evidence in each category and developing clinically useful recommendations. The BMD Task Force addressed issues that included the potential use of skeletal sites other than the femoral neck, the use of technologies other than DXA, and the deletion or addition of clinical data for FRAX ® input. The evidence and recommendations were presented to a panel of experts at the ISCD-IOF FRAX ® Position Development Conference, resulting in the development of ISCD-IOF Official Positions addressing FRAX ®-related issues.

Official Positions for FRAX ® Bone Mineral Density and FRAX ® Simplification : From Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX ®

Tools to predict fracture risk are useful for selecting patients for pharmacological therapy in order to reduce fracture risk and redirect limited healthcare resources to those who are most likely to benefit. FRAX ® is a World Health Organization fracture risk assessment algorithm for estimating the 10-year probability of hip fracture and major osteoporotic fracture. Effective application of FRAX ® in clinical practice requires a thorough understanding of its limitations as well as its utility. For some patients, FRAX ® may underestimate or overestimate fracture risk. In order to address some of the common issues encountered with the use of FRAX ® for individual patients, the International Society for Clinical Densitometry (ISCD) and International Osteoporosis Foundation (IOF) assigned task forces to review the medical evidence and make recommendations for optimal use of FRAX ® in clinical practice. Among the issues addressed were the use of bone mineral density (BMD) measurements at skeletal sites other than the femoral neck, the use of technologies other than dual-energy X-ray absorptiometry, the use of FRAX ® without BMD input, the use of FRAX ® to monitor treatment, and the addition of the rate of bone loss as a clinical risk factor for FRAX ®. The evidence and recommendations were presented to a panel of experts at the Joint ISCD-IOF FRAX ® Position Development Conference, resulting in the development of Joint ISCD-IOF Official Positions addressing FRAX ®-related issues.

Fracture Burden in Relation to Low Bone Mineral Density and FRAX ® Probability

Although the risk of fracture increases exponentially with declining bone mineral density, most fragility fractures have been shown to occur in individuals who do not meet the conventional densitometric definition for osteoporosis. The World Health Organization fracture risk assessment tool (FRAX ®) estimates individual 10-yr major osteoporotic and hip fracture probabilities. Intervention criteria based on risk assessment have been proposed by several groups, including the National Osteoporosis Foundation (NOF). We determined the relationship between 10-yr fracture probability and subsequent fracture burden in 36,730 women and 2873 men aged 50 yr and older. Using a major fracture probability cutoff of 20%, 29.4% of major osteoporotic fractures were identified in women and 4.9% in men. Based on a hip fracture probability cutoff of 3%, 54.1% of major osteoporotic fractures were detected in women and 53.4% in men. Using all NOF criteria, 65.9% of major osteoporotic fractures were detected in women and 69.3% in men. We conclude that men and women with FRAX probabilities below the high-risk NOF cutoffs have a high burden of major osteoporotic fractures. Strategies to enhance risk stratification in this group should be developed through international collaborations.

The Fracture Risk Assessment Tool (FRAX®): Applications in Clinical Practice

Osteoporosis is a serious health concern affecting millions of Americans, with many patients going undiagnosed and untreated. Fractures due to osteoporosis and fracture-related complications are the most clinically relevant and costly consequences of this disorder. The Fracture Risk Assessment Tool (FRAX®), released by the World Health Organization (WHO) in February 2008, is a major achievement in helping determine which patients may be candidates for pharmacological therapy for osteoporosis. This Web-based algorithm, which has been incorporated into some dual x-ray absorptiometry (DXA) reporting software, calculates the 10-year probability of major osteoporotic fracture (clinical vertebral, hip, forearm, or humerus) and the 10-year probability of hip fracture in men and women based on easily obtained clinical risk factors and bone mineral density (BMD) of the femoral neck (optional). The National Osteoporosis Foundation updated its U.S. guidelines in February 2008 to incorporate FRAX and recommends that all postmenopausal women and men aged ≥50 years with a hip or vertebral fracture, a T-score ≤-2.5 at the femoral neck or spine (excluding secondary causes), or low bone mass (T-score between -1.0 and -2.5) and a 10-year probability of hip fracture ≥3% or of major osteoporosis-related fracture ≥20% (based on FRAX) should be considered candidates for drug therapy. Despite its demonstrated clinical utility, FRAX has limitations and should not be used in all situations. Acceptance and clinical use of FRAX may help identify men and women at increased risk for osteoporotic fracture, but implementing the tool into clinical practice may be a challenge for busy physicians.

High fracture probability with FRAX® usually indicates densitometric osteoporosis: implications for clinical practice

Most patients designated as high risk of fracture using fracture risk assessment tool (FRAX) with femoral neck bone mineral density (BMD) (i.e., 10-year major osteoporotic fracture probability exceeding 20% or hip fracture exceeding 3%) have one or more T-scores in the osteoporotic range; conversely, almost no high risk patients have normal T-scores at all bone mineral density measurement sites. We determined the agreement between a FRAX designation of high risk of fracture [defined as 10-year major osteoporotic fracture probability (≥ 20%) or hip fracture probability (≥ 3%)] and the WHO categorizations of bone mineral density according to T-score. Ten-year FRAX probabilities calculated with femoral neck BMD were derived using both Canadian and US white tools for a large clinical cohort of 36,730 women and 2,873 men age 50 years and older from Manitoba, Canada. Individuals were classified according to FRAX fracture probability and BMD T-scores alone. Most individuals designated by FRAX as high risk of major osteoporotic fracture had a T-score in the osteoporotic range at one or more BMD measurement sites (85% with Canadian tool and 83% with US white tool). The majority of individuals deemed at high risk of hip fracture had one or more T-scores in the osteoporotic range (66% with Canadian tool and 64% with US white tool). Conversely, there were extremely few individuals (<1%) who were at high risk of major osteoporotic or hip fracture with normal T-scores at all BMD measurement sites. A FRAX designation of high risk of fracture is usually associated with a densitometric diagnosis of osteoporosis.

A meta-analysis of the effect of strontium ranelate on the risk of vertebral and non-vertebral fracture in postmenopausal osteoporosis and the interaction with FRAX®

The aim of the present study was to determine the efficacy of strontium ranelate as a function of baseline fracture risk. Treatment with strontium ranelate was associated with a significant 31% decrease in all clinical osteoporotic fractures (vertebral fractures included). Hazard ratios for the effect of strontium ranelate on the fracture outcome did not change significantly with increasing fracture probability. Two previous studies have suggested that the efficacy of intervention may be greater in the segment of the population at highest fracture risk as assessed by the FRAX(®) algorithms. The aim of the present study was to determine whether the anti-fracture efficacy of strontium ranelate was dependent of the level of fracture risk. The primary data of the two phase III studies (SOTI and TROPOS) of the effects of strontium ranelate in postmenopausal osteoporosis were combined. Country-specific probabilities were computed using the FRAX(®) tool (version 2.0). The primary outcome variable comprised all clinical osteoporotic fractures (including clinical vertebral fractures). Interactions between fracture probability and efficacy were explored by Poisson regression. The 10-year probability of major osteoporotic fractures (with BMD) ranged from 2.5% to 90.8%. FRAX(®)-based hip fracture probabilities ranged from 0.1% to 90.3%. The incidence of clinical osteoporotic fractures (vertebral fractures excluded) and morphometric vertebral fractures increased with increasing baseline fracture probabilities. Treatment with strontium ranelate was associated with a 31% (95% CI = 20-39%) decrease in osteoporotic clinical fractures and a 40% decrease in vertebral fractures assessed by semiquantitative morphometry (95% CI = 31-48%) Hazard ratios for the effect of strontium ranelate on the fracture outcomes did not change significantly with increasing fracture probability. Strontium ranelate significantly decreased the risk of osteoporotic clinical fractures, non vertebral fractures and morphometric vertebral fractures in women. Overall, the efficacy of strontium ranelate was not dependent of the level of fracture risk assessed by FRAX.

Construction of a FRAX® model for the assessment of fracture probability in Canada and implications for treatment

We describe the creation of a FRAX® model for the assessment of fracture probability in Canadian men and women, calibrated from national hip fracture and mortality data. This FRAX tool was used to examine possible thresholds for therapeutic intervention in Canada in two large complementary cohorts of women and men. To evaluate a Canadian World Health Organization (WHO) fracture risk assessment (FRAX®) tool for computing 10-year probabilities of osteoporotic fracture. Fracture probabilities were computed from national hip fracture data (2005) and death hazards (2004) for Canada. Probabilities took account of age, sex, clinical risk factors (CRFs), and femoral neck bone mineral density (BMD). Treatment implications were studied in two large cohorts of individuals age 50years and older: the population-based Canadian Multicentre Osteoporosis Study (4,778 women and 1,919 men) and the clinically referred Manitoba BMD Cohort (36,730 women and 2,873 men). Fracture probabilities increased with age, decreasing femoral neck T-score, and number of CRFs. Among women, 10.1-11.3% would be designated high risk based upon 10-year major osteoporotic fracture probability exceeding 20%. A much larger proportion would be designated high risk based upon 10-year hip fracture probability exceeding 3% (25.7-28.0%) or osteoporotic BMD (27.1-30.9%), and relatively few from prior hip or clinical spine fracture (1.6-4.2%). One or more criteria for intervention were met by 29.2-34.0% of women excluding hip fracture probability (35.3-41.0% including hip fracture probability). Lower intervention rates were seen among CaMos (Canadian Multicentre Osteoporosis Study) men (6.8-12.9%), but in clinically referred men from the Manitoba BMD Cohort, one or more criteria for high risk were seen for 26.4% excluding hip fracture probability (42.4% including hip fracture probability). The FRAX tool can be used to identify intervention thresholds in Canada. The FRAX model supports a shift from a dual X-ray absorptiometry (DXA)-based intervention strategy, towards a strategy based on fracture probability for a major osteoporotic fracture.