Effect of Alendronate on Risk of Fracture in Women With Low Bone Density but Without Vertebral Fractures<SUBTITLE>Results From the Fracture Intervention Trial</SUBTITLE>

Abstract

; 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.

Effect of denosumab treatment on the risk of fractures in subgroups of women with postmenopausal osteoporosis

“…Similar consistency of treatment effect among subgroups has been observed with alendronate, risedronate, and strontium ranelate. (4)(5)(6)8,12) We did not observe different effects on new vertebral fracture risk in patients stratified by BMI or renal function as was seen with zoledronic acid. (7) As has been observed in studies with some bisphosphonates, the effect of denosumab therapy on nonvertebral fracture risk was influenced by baseline BMD.…”

“…In a preplanned analysis, alendronate reduced the risk of nonvertebral fractures among women with a femoral neck BMD T-score À2.5 but not in those with a T-score > À2.5. (8) In post hoc analyses, ibandronate and bazedoxifene appeared to reduce nonvertebral fracture risk in patients with low femoral neck BMD T-scores but not in women with higher BMD values. (9,10) Similarly, strontium ranelate was shown to reduce hip fracture risk in a post hoc analysis of a high-risk subgroup but not in the overall study population.…”

The potential value of monitoring bone turnover markers among women on alendronate

“…(16) The trial had two arms: the Vertebral Fracture Arm, which included 2027 women who had vertebral fractures identified on radiographs at baseline, (1) and the Clinical Fracture Arm, which included 4432 women without baseline vertebral fractures. (2) Patients for both arms were recruited between May 1992 and May 1993. A random sample of women in FIT (n ¼ 1304 of 6459; 20.2%) had serial measurements of biochemical markers of bone turnover, comprising 392 women from the Vertebral Fracture Arm (1) and 912 women from the Clinical Fracture Arm.…”

“…A random sample of women in FIT (n ¼ 1304 of 6459; 20.2%) had serial measurements of biochemical markers of bone turnover, comprising 392 women from the Vertebral Fracture Arm (1) and 912 women from the Clinical Fracture Arm. (2) Subjects were randomly allocated to daily alendronate or placebo. The dose of alendronate was initially 5 mg/day for 2 years but was increased to 10 mg/d at the second annual visit because other trials suggested that 10 mg/d had greater effects on bone mineral density.…”

“…A lendronate and other N-containing bisphosphonates are effective therapies (1,2) that are widely used for prevention of fragility fractures in postmenopausal women with osteoporosis. After starting a patient on alendronate, clinicians often monitor the response to make sure treatment is working as expected.…”