When the FRAX® test is applied to controlled clinical trials
ABSTRACT FRAX(®) is a computer-based algorithm developed by the World Health Organization Collaborating Centre for Metabolic Bone Diseases in Sheffield (UK). This algorithm calculates fracture probability from easily obtained clinical risk factors in men and women: age, sex, body mass index and dichotomized variables comprising prior fragility fracture, parental history of hip fracture, current tobacco smoking, use of long-term oral glucocorticoid, rheumatoid arthritis, other causes of secondary osteoporosis and high alcohol consumption (femoral neck bone mineral density can be optionally input to enhance fracture risk prediction). The output of FRAX(®) is the 10-year probability of a major osteoporotic fracture (hip, clinical spine, humerus or wrist fracture) and the 10-year probability of hip fracture.Recently various Authors have re-evaluated the effectiveness of drugs approved for postmenopausal osteoporosis to test whether they are more effective in women with higher FRAX(®) probabilities.
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ABSTRACT: Prevalent vertebral fractures and baseline bone mineral density (BMD) predict subsequent fracture risk. The objective of this analysis is to examine whether baseline vertebral fracture severity can predict new vertebral and nonvertebral fracture risk. In the randomized, double-blind 3-year Multiple Outcomes of Raloxifene Evaluation (MORE) trial, 7705 postmenopausal women with osteoporosis (low BMD or prevalent vertebral fractures) were randomly assigned to placebo, raloxifene 60 mg/day, or raloxifene 120 mg/day. Post hoc analyses studied the association between baseline fracture severity and new fracture risk in the placebo group and the effects of placebo, raloxifene 60 mg/day, and raloxifene 120 mg/day on new fracture risk in women with the most severe prevalent vertebral fractures (n = 614). Vertebral fracture severity was visually assessed using semiquantitative analysis of radiographs and categorized by estimated decreases in vertebral heights. Reported new nonvertebral fractures were radiographically confirmed. Baseline vertebral fracture severity predicted vertebral and nonvertebral fracture risk at 3 years. In women without prevalent vertebral fractures, 4.3 and 5.5% had new vertebral and nonvertebral fractures, respectively. In women with mild, moderate, and severe prevalent vertebral fractures, 10.5, 23.6, and 38.1% respectively had new vertebral fractures, whereas 7.2, 7.7, and 13.8% respectively experienced new nonvertebral fractures. Number of prevalent vertebral fractures and baseline BMD also predicted vertebral fracture risk, but the severity of prevalent vertebral fractures was the only predictor of nonvertebral fracture risk and remained a significant predictor after adjustment for baseline characteristics, including baseline BMD. In patients with severe baseline vertebral fractures, raloxifene 60 mg/day decreased the risks of new vertebral [RR 0.74 (95% Cl 0.54, 0.99); P = 0.048] and nonvertebral (clavicle, humerus, wrist, pelvis, hip, and leg) fractures [RH 0.53 (95% CI 0.29, 0.99); P = 0.046] at 3 years. To prevent one new fracture at 3 years in women with severe baseline vertebral fractures with raloxifene 60 mg/day, the number needed to treat (NNT) was 10 for vertebral and 18 for nonvertebral fractures. Similar results were observed in women receiving raloxifene 120 mg/day. In summary, baseline vertebral fracture severity was the best independent predictor for new vertebral and nonvertebral fracture risk. Raloxifene decreased new vertebral and nonvertebral fracture risk in the subgroup of women with severe vertebral fractures at baseline. These fractures may reflect architectural deterioration, independent of BMD, leading to increased skeletal fragility.Bone 11/2003; 33(4):522-32. DOI:10.1016/S8756-3282(03)00241-2 · 3.97 Impact Factor
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ABSTRACT: Osteoporotic structural damage and bone fragility result from reduced bone formation and increased bone resorption. In a phase 2 clinical trial, strontium ranelate, an orally active drug that dissociates bone remodeling by increasing bone formation and decreasing bone resorption, has been shown to reduce the risk of vertebral fractures and to increase bone mineral density. To evaluate the efficacy of strontium ranelate in preventing vertebral fractures in a phase 3 trial, we randomly assigned 1649 postmenopausal women with osteoporosis (low bone mineral density) and at least one vertebral fracture to receive 2 g of oral strontium ranelate per day or placebo for three years. We gave calcium and vitamin D supplements to both groups before and during the study. Vertebral radiographs were obtained annually, and measurements of bone mineral density were performed every six months. New vertebral fractures occurred in fewer patients in the strontium ranelate group than in the placebo group, with a risk reduction of 49 percent in the first year of treatment and 41 percent during the three-year study period (relative risk, 0.59; 95 percent confidence interval, 0.48 to 0.73). Strontium ranelate increased bone mineral density at month 36 by 14.4 percent at the lumbar spine and 8.3 percent at the femoral neck (P<0.001 for both comparisons). There were no significant differences between the groups in the incidence of serious adverse events. Treatment of postmenopausal osteoporosis with strontium ranelate leads to early and sustained reductions in the risk of vertebral fractures.New England Journal of Medicine 02/2004; 350(5):459-68. DOI:10.1056/NEJMoa022436 · 55.87 Impact Factor
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ABSTRACT: Fracture risk prediction can be enhanced by the concurrent assessment of other clinical risk factors. This study demonstrates that 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. Treatments for osteoporosis are targeted largely to patients with low bone density (BMD) or a prior fragility fracture. Fracture risk prediction can be enhanced by the concurrent assessment of other clinical risk factors, but it is important to determine whether the risk so identified can be reduced by intervention. We determined the effect of a bisphosphonate on fracture rates when risk was calculated using a new risk algorithm (FRAX). Women aged 75 years or more were recruited to a randomised, double-blind controlled trial of 800 mg oral clodronate (Bonefos) daily over 3 years. Baseline clinical risk factors were entered in the FRAX model to compute the 10-year probability of major osteoporotic fractures with or without input of femoral neck BMD. The interaction between fracture probability and treatment efficacy was examined by Poisson regression. In 3,974 women, the interaction between fracture probability and treatment efficacy was significant when probability was assessed without BMD (p = 0.043), but not when BMD was included (p = 0.10). Efficacy was more evident in those deemed at highest risk. For example women lying at the 75th percentile of fracture probability in the absence of BMD (10-year probability 24%) treatment reduced fracture risk by 27% (HR 0.73, 95%CI 0.58-0.92). In those with a fracture probability of 30% (90th percentile), the fracture risk reduction was 38% (HR 0.62, 0.46-0.84). 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.Osteoporosis International 12/2008; 20(5):811-7. DOI:10.1007/s00198-008-0786-9 · 4.17 Impact Factor