Independent clinical validation of a Canadian FRAX tool: Fracture prediction and model calibration

Self Cite

115

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)(1997)(1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(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 <0.80), and past users. Fractures outcomes to 10 years were established form a population-based health data repository. FRAX and femoral neck BMD alone stratified major osteoporotic and hip fracture risk within untreated and each treated subgroup (all p-values <0.001) with similar area under the receiver operating characteristic curve. In untreated and each treated subgroup, a stepwise gradient in observed 10-year major osteoporotic and hip fracture incidence was found as a function of the predicted probability tertile (all p-values <0.001 for linear trend). Concordance (calibration) plots for major osteoporotic fractures and hip fractures showed good agreement between the predicted and observed 10-year fracture incidence in untreated women and each treated subgroup. Only in the highest risk tertile of women highly adherent to at least 5 years of bisphosphonate use was observed hip fracture risk significantly less than predicted, though major osteoporotic fracture risk was similar to predicted. In summary, this work suggests that the FRAX tool can be used to predict fracture probability in women currently or previously treated for osteoporosis. Although FRAX should not be used to assess the reduction in fracture risk in individuals on treatment, it may still have value for guiding the need for continued treatment or treatment withdrawal. ß

Section: Discussionmentioning

confidence: 53%

Section: Bone Density Measurementsmentioning

confidence: 99%

Does osteoporosis therapy invalidate FRAX for fracture prediction?

Leslie

Lix

Johansson

et al. 2012

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115

“…Proxies were used for smoking (chronic obstructive pulmonary disease [COPD] diagnosis) and high alcohol intake (alcohol or substance abuse diagnosis) over the same time frame. (9) Prolonged glucocorticoid use was defined as greater than 90 days dispensed in the year before DXA testing. We adjusted for the effect of missing parental hip fracture information on FRAX probability estimates before 2005 using age-and sex-specific adjustment factors derived from 2005 to 2008 parental hip fracture responses as described.…”

Section: Calculation Of Frax Probabilitymentioning

confidence: 99%

“…FRAX used with BMD has been demonstrated to more accurately predict 10-year fracture probability than BMD or clinical risk factors alone in both men and women over age 50 years of age. (8,9) The clinical risk factors included in the calculation of the FRAX probability include age, sex, body mass index (BMI), prolonged use of glucocorticoids, parental hip fracture, current smoking, alcohol intake !3 units per day, rheumatoid arthritis, prior fragility fracture, and femoral neck BMD. FRAX can be used to estimate fracture risk in situations where the femoral neck BMD is not known (clinical FRAX).…”

Section: Introductionmentioning

confidence: 99%

Inflammatory bowel disease and the risk of fracture after controlling for FRAX

Targownik

Bernstein

Nugent

et al. 2012

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Subjects with inflammatory bowel disease (IBD) are at increased risk for hip and other major osteoporotic fractures. However, previous analyses have not fully accounted for differences in bone mineral density (BMD) and other clinical factors that affect the risk of fracture. The World Health Organization Fracture Risk Assessment tool (FRAX) can be used to predict the 10-year fracture risk from BMD and clinical risk factors. A population-based database containing clinical information on all IBD subjects in the province of Manitoba, Canada, was linked with the Manitoba Bone Mineral Density Database, which contains results of all dual X-ray absorptiometry (DXA) scans in the province. FRAX probabilities were calculated for all subjects aged 50 years or more undergoing baseline DXA testing. Subjects were followed for occurrence of major osteoporotic fractures (MOF; hip, clinical spine, wrist, humerus). Cox proportional hazards models were used to determine whether IBD was independently predictive of MOF or hip fracture. After controlling for FRAX fracture probability computed with BMD, IBD was not associated with a significantly increased risk for MOF (hazard ratio [HR] ¼ 1.12, 95% confidence interval [CI], 0.83-1.55) but was associated with an increased risk for hip fracture (HR ¼ 2.14; 95% CI, 1.26-3.65). The addition of femoral neck T-score to FRAX probability without knowledge of BMD had a negligible effect on the estimated HRs for IBD, suggesting that IBD mediates any effect on fracture risk independently of femoral neck BMD. After controlling for FRAX probability, subjects with IBD are not at an increased risk for overall MOF, but may be at increased risk of hip fracture. ß

“…In the United States and Europe, FRAX accurately predicts the 10-year probability of major osteoporotic fracture and hip fracture in patients with characteristics like the study subjects. (4,5) Importantly, because FRAX was designed to identify patients for whom treatment would be beneficial, analyses of clinical trials with different classes of osteoporosis treatments have documented that this is true. (6)(7)(8)(9) Since its availability in 2008, FRAX estimates of fracture probability have been incorporated, albeit in various ways, into clinical guidelines of several national societies including the NOF.…”

mentioning

confidence: 99%

To FRAX or not to FRAX

McClung

2012

T he WHO Fracture Risk Assessment Tool (FRAX) calculator is the most thoroughly studied and widely used tool of fracture risk assessment. (1) FRAX is now available in 39 countries and is increasingly being used as a guide for clinical decision-making. The specific objective of developing FRAX was to aid clinicians in identifying the most appropriate patients to receive pharmacologic therapy to reduce fracture risk. Prior to FRAX, treatment decisions were based primarily on bone mineral density (BMD) values with the threshold at which treatment was recommended being modified crudely by the simple presence of absence of other clinical risk factors. For example, the 1998 National Osteoporosis Foundation (NOF) guidelines suggested treating all postmenopausal women with a BMD T-score of À2 or lower and all women with a T-score of À1.5 or lower who had one of several risk factors, including being thin, having a fragility fracture as an adult or a family history of fragility fracture. (2) These guidelines identified for therapy almost all patients at high risk for fracture (sensitivity of the approach was good) but enfranchised therapy for many younger postmenopausal women with low bone density but who were at modest or even low fracture risk (poor specificity). Understanding this, clinicians asked themselves ''Which patients who do not have osteoporosis should be treated?'' FRAX was specifically developed to answer that question.After the 1998 NOF guidelines were released, we recognized that individuals could be stratified into gradations of fracture risk more effectively if BMD was combined with other independent clinical risk factors for fracture than could be accomplished by using individual risk factors for such as age, BMD, or fracture history alone. (3) The FRAX tool was derived by evaluating the relationships between BMD, clinical risk factors, and fracture risk using individual patient data comprising almost 250,000 patient-years of observation in nine large observational studies performed in different parts of the world. (1) Subjects in those studies were generally healthy older adults who were not on osteoporosis treatment. In the United States and Europe, FRAX accurately predicts the 10-year probability of major osteoporotic fracture and hip fracture in patients with characteristics like the study subjects. (4,5) Importantly, because FRAX was designed to identify patients for whom treatment would be beneficial, analyses of clinical trials with different classes of osteoporosis treatments have documented that this is true. (6)(7)(8)(9) Since its availability in 2008, FRAX estimates of fracture probability have been incorporated, albeit in various ways, into clinical guidelines of several national societies including the NOF. (10)(11)(12) The fracture risk thresholds at which treatment is recommended in the NOF guidelines were based on clinical and health economic considerations. (13) Despite the scientific basis of FRAX and its strengths, several limitations are recognized. FRAX treats all risk factors as ca...