Ten-year fracture probability identifies women who will benefit from clodronate therapy—additional results from a double-blind, placebo-controlled randomised study

McCloskey, Eugène; Johansson, Helena; Odén, Anders; Vasireddy, Sreekanth; Kayan, Karthik; Pande, Ketan C; Jalava, Taina; Kanis, John А.

doi:10.1007/s00198-008-0786-9

Cited by 133 publications

(94 citation statements)

References 36 publications

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“…Although the provincial retail database system is highly complete and accurate for prescribed medications, nonprescription drug use (eg, calcium and vitamin D), nonpharmacological interventions (eg, falls prevention and exercise), and patient behavior (eg, following the correct procedure for medication administration) cannot be assessed. We also combined all forms of osteoporosis therapy, whereas these may differ in terms of vertebral and non-vertebral fraction prevention (5,6) and FRAX probability dependency (39)(40)(41)(42) for specific classes and agents. Some treatments appear to show efficacy in those at highest risk with little or no efficacy in those at lower fracture risk (such as clodronate, (39) bazedoxifene, (40) and denosumab (43) ), whereas others show antifracture effect that is independent of baseline fracture risk (such as raloxifene (41) and strontium (42) ).…”

Section: Discussionmentioning

confidence: 99%

Does osteoporosis therapy invalidate FRAX for fracture prediction?

Leslie

Lix

Johansson

et al. 2012

Journal of Bone and Mineral Research

114

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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

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Section: Discussionmentioning

confidence: 99%

Does osteoporosis therapy invalidate FRAX for fracture prediction?

Leslie

Lix

Johansson

et al. 2012

Journal of Bone and Mineral Research

114

View full text Add to dashboard Cite

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“…However, there was not a significant interaction between FRAX with BMD and treatment (p ¼ 0.10). (3) There was also no significant interaction between FN BMD and treatment. (12) Kanis and colleagues (5) examined the interaction between treatment with bazedoxifene and FRAX for clinical fractures (including clinical spine).…”

Section: Discussionmentioning

confidence: 86%

“…For clodronate, there was a significant interaction between treatment and BMI. (3) Among women with a BMI of 30 kg/m 2 (75th percentile) the reduction in fracture risk was 10% (HR 0.90; 95% CI, 0.69-1.17), whereas with a BMI of 21 (10th percentile) the reduction in fracture risk was 40% (HR 0.60; 95% CI, 0.45-0.81).…”

Section: Discussionmentioning

confidence: 99%

“…McCloskey and colleagues (3) examined the interaction between treatment with clodronate and FRAX for osteoporotic clinical fractures. Overall, clodronate was associated with a hazard ratio (HR) of 0.76 (95% CI, 0.63-0.93) for osteoporotic clinical fractures.…”

Section: Discussionmentioning

confidence: 99%

“…Four recent post hoc analyses of data from placebo controlled randomized trials have examined for evidence of an interaction between the 10-year probability of fracture as calculated by FRAX and specific pharmacologic treatment (clodronate, (3) bazedoxifene, (4) raloxifene, (5) strontium ranelate (6) ) on fracture incidence. For both clodronate and bazedoxifene, the authors concluded that their results provided some evidence that higher ORIGINAL ARTICLE J JBMR FRAX score at baseline was associated with a greater relative reduction in risk of clinical fractures.…”

Section: Introductionmentioning

confidence: 99%

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Effect of alendronate for reducing fracture by FRAX score and femoral neck bone mineral density: The fracture intervention trial

Donaldson

Palermo

Ensrud

et al. 2012

Journal of Bone and Mineral Research

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The WHO Fracture Risk Assessment Tool (FRAX; http://www.shef.ac.uk/FRAX) estimates the 10-year probability of major osteoporotic fracture. Clodronate and bazedoxifene reduced nonvertebral and clinical fracture more effectively on a relative scale in women with higher FRAX scores. We used data from the Fracture Intervention Trial (FIT) to evaluate the interaction between FRAX score and treatment with alendronate. We combined the Clinical Fracture (CF) arm and Vertebral Fracture (VF) arm of FIT. The CF and VF arm of FIT randomized 4432 and 2027 women, respectively, to placebo or alendronate for 4 and 3 years, respectively. FRAX risk factors were assessed at baseline. FRAX scores were calculated by WHO. We used Poisson regression models to assess the interaction between alendronate and FRAX score on the risk of nonvertebral, clinical, major osteoporotic, and radiographic vertebral fractures. Overall, alendronate significantly reduced the risk of nonvertebral fracture (incidence rate ratio [IRR] 0.86; 95% confidence interval [CI], 0.75-0.99), but the effect was greater for femoral neck (FN) bone mineral density (BMD) T-score À2.5 (IRR 0.76; 95% CI, 0.62-0.93) than for FN T-score > À2.5 (IRR 0.96; 95% CI, 0.80-1.16) (p ¼ 0.02, interaction between alendronate and FN BMD). However, there was no evidence of an interaction between alendronate and FRAX score with FN BMD for risk of nonvertebral fracture (interaction p ¼ 0.61). The absolute benefit of alendronate was greatest among women with highest FRAX scores. Results were similar for clinical fractures, major osteoporotic fractures, and radiographic vertebral fractures and whether or not FRAX scores included FN BMD. Among this cohort of women with low bone mass there was no significant interaction between FRAX score and alendronate for nonvertebral, clinical or major osteoporotic fractures, or radiographic vertebral fractures. These results suggest that the effect of alendronate on a relative scale does not vary by FRAX score. A randomized controlled trial testing the effect of antifracture agents among women with high FRAX score but without osteoporosis is warranted. ß

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A Comparison of Prediction Models for Fractures in Older Women

Ensrud¹

2009

Arch Intern Med

158

101

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Background A web-based risk assessment tool (FRAX®) using clinical risk factors with and without femoral neck bone mineral density (BMD) has been incorporated into clinical guidelines regarding treatment to prevent fractures. Our objective is to determine whether prediction with FRAX® models is superior to that based on parsimonious models. Methods We conducted a prospective cohort study in 6252 women aged ≥65 years and compared the value of FRAX® models that include BMD to parsimonious models based on age and BMD alone for prediction of fractures. We also compared FRAX® models without BMD to simple models based on age and fracture history alone. Fractures (hip, major osteoporotic [hip, clinical vertebral, wrist, or humerus], and any clinical fracture) were ascertained during 10 years of follow-up. Area under the curve (AUC) statistics from receiver operating characteristic (ROC) curve analysis were compared between FRAX® models and simple models. Results AUC comparisons revealed no differences between FRAX® models with BMD versus simple models with age and BMD alone in discriminating hip (AUC=0.75 for FRAX® model and 0.76 for simple model, p=0.26); major osteoporotic (AUC=0.68 for FRAX® model and 0.69 for simple model, p=0.51); or clinical fracture (AUC=0.64 for FRAX® model and 0.63 for simple model, p=0.16). Similarly, performance of parsimonious models containing age and fracture history alone was nearly identical to that of FRAX® models without BMD. The proportion of women in each quartile of predicted risk who actually experienced a fracture outcome did not differ between FRAX® and simple models (p≥0.16). Conclusions Simple models based on age and BMD alone or age and fracture history alone predicted 10-year risk of hip, major osteoporotic, and clinical fracture as well as more complex FRAX® models.

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Ten-year fracture probability identifies women who will benefit from clodronate therapy—additional results from a double-blind, placebo-controlled randomised study

Abstract: The estimation of an individual's 10-year probability of fracture by the FRAX algorithm identifies patients at high risk of fracture who will respond to bisphosphonate therapy.

Cited by 133 publications

References 36 publications

Does osteoporosis therapy invalidate FRAX for fracture prediction?

Does osteoporosis therapy invalidate FRAX for fracture prediction?

Effect of alendronate for reducing fracture by FRAX score and femoral neck bone mineral density: The fracture intervention trial

A Comparison of Prediction Models for Fractures in Older Women

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