; for the Fracture Intervention Trial Research Group Context.-Alendronate sodium reduces fracture risk in postmenopausal women who have vertebral fractures, but its effects on fracture risk have not been studied for women without vertebral fractures. Objective.-To test the hypothesis that 4 years of alendronate would decrease the risk of clinical and vertebral fractures in women who have low bone mineral density (BMD) but no vertebral fractures. Design.-Randomized, blinded, placebo-controlled trial. Setting.-Eleven community-based clinical research centers. Subjects.-Women aged 54 to 81 years with a femoral neck BMD of 0.68 g/cm 2 or less (Hologic Inc, Waltham, Mass) but no vertebral fracture; 4432 were randomized to alendronate or placebo and 4272 (96%) completed outcome measurements at the final visit (an average of 4.2 years later). Intervention.-All participants reporting calcium intakes of 1000 mg/d or less received a supplement containing 500 mg of calcium and 250 IU of cholecalciferol. Subjects were randomly assigned to either placebo or 5 mg/d of alendronate sodium for 2 years followed by 10 mg/d for the remainder of the trial. Main Outcome Measures.-Clinical fractures confirmed by x-ray reports, new vertebral deformities detected by morphometric measurements on radiographs, and BMD measured by dual x-ray absorptiometry. Results.-Alendronate increased BMD at all sites studied (PϽ.001) and reduced clinical fractures from 312 in the placebo group to 272 in the intervention group, but not significantly so (14% reduction; relative hazard [RH], 0.86; 95% confidence interval [CI], 0.73-1.01). Alendronate reduced clinical fractures by 36% in women with baseline osteoporosis at the femoral neck (Ͼ2.5 SDs below the normal young adult mean; RH, 0.64; 95% CI, 0.50-0.82; treatment-control difference, 6.5%; number needed to treat [NNT], 15), but there was no significant reduction among those with higher BMD (RH, 1.08; 95% CI, 0.87-1.35). Alendronate decreased the risk of radiographic vertebral fractures by 44% overall (relative risk, 0.56; 95% CI, 0.39-0.80; treatment-control difference, 1.7%; NNT, 60). Alendronate did not increase the risk of gastrointestinal or other adverse effects. Conclusions.-In women with low BMD but without vertebral fractures, 4 years of alendronate safely increased BMD and decreased the risk of first vertebral deformity. Alendronate significantly reduced the risk of clinical fractures among women with osteoporosis but not among women with higher BMD.

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There was no evidence of synergy between parathyroid hormone and alendronate. Changes in the volumetric density of trabecular bone, the cortical volume at the hip, and levels of markers of bone turnover suggest that the concurrent use of alendronate may reduce the anabolic effects of parathyroid hormone. Longer-term studies of fractures are needed to determine whether and how antiresorptive drugs can be optimally used in conjunction with parathyroid hormone therapy.

Context Type 2 diabetes is associated with higher bone density (BMD) and, paradoxically, with increased fracture risk. It is not known if low BMD, central to fracture prediction in older adults, identifies fracture risk in diabetic patients. Objective Determine if femoral neck (FN) BMD T-score and FRAX score are associated with fracture in older diabetic adults. Design Three observational studies: Study of Osteoporotic Fractures, Osteoporotic Fractures in Men, and Health, Aging and Body Composition study. Setting Older community-dwelling adults in U.S. Participants 9,449 women; 7,436 men. Main outcome measure(s) Self-reported incident fractures, verified by radiology reports. Results Of 770 diabetic women, 84 experienced a hip and 262 a non-spine fracture during mean (SD) follow-up of 12.6 (5.3) years. Of 1,199 diabetic men, 32 experienced a hip and 133 a non-spine fracture during mean follow-up of 7.9 (2.5) years. Age-adjusted hazard ratios (HR) for one unit decrease in FN BMD T-score in diabetic women were 1.88 (95% confidence interval [CI], 1.43–2.48) for hip and 1.52 (95% CI, 1.31–1.75) for non-spine fracture. HRs in diabetic men were 5.71 (95% CI, 3.42–9.53) for hip and 2.17 (95% CI, 1.75–2.69) for non-spine fracture. FRAX score was also associated with fracture risk in diabetic participants. However, for a given T-score and age or FRAX score, diabetic participants had a higher fracture risk than those without diabetes. For a similar hip fracture risk, diabetic participants had a higher T-score than non-diabetic participants. The difference in T-score was 0.59 (95% CI, 0.31–0.87) for women and 0.38 (95% CI, 0.09–0.66) for men. Conclusions Among older adults with type 2 diabetes, FN BMD T-score and FRAX score were associated with hip and non-spine fracture risk. However, in these patients, compared with participants without diabetes, fracture risk was higher for a given T-score and age or a given FRAX score.

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