Fracture Risk Reduction with Alendronate in Women with Osteoporosis: The Fracture Intervention Trial

Abstract

We examined the effect of alendronate treatment for 3-4 yr on risk of new fracture among 3658 women with osteoporosis enrolled in the Fracture Intervention Trial. This cohort included women with existing vertebral fracture and those with osteoporosis as defined by T score of less than -2.5 at the femoral neck but without vertebral fracture. All analyses were prespecified in the data analysis plan. The magnitudes of reduction of fracture incidence with alendronate were similar in both groups. The two groups were, therefore, pooled to obtain a more precise estimate of the effect of alendronate on relative risk of fracture (relative risk, 95% confidence interval): hip (0.47, 0.26-0.79), radiographic vertebral (0.52, 0.42-0.66), clinical vertebral (0.55, 0.36-0.82), and all clinical fractures (0.70, 0.59-0.82). Reductions in risk of clinical fracture were statistically significant by 12 months into the trial. We conclude that reductions in fracture risk during treatment with alendronate are consistent in women with existing vertebral fractures and those without such fractures but with bone mineral density in the osteoporotic range. Furthermore, reduction in risk is evident early in the course of treatment. This pooled analysis provides a more precise estimate of the antifracture efficacy of alendronate in women with osteoporosis than that in prior reports.

Anti-Osteoporosis Medication Prescriptions and Incidence of Subsequent Fracture Among Primary Hip Fracture Patients in England and Wales: An Interrupted Time-Series Analysis

“…Therapy recommendations contained within NICE TA 87 were based on data from 39 published RCTs, (8) with reference made to the Fracture Intervention Trial where the relative risk (RR) between alendronate versus placebo arms for subsequent "any clinical" or hip fracture was 0.74 (95% CI, 0.59 to 0.92) and 0.49 (95% CI, 0.23 to 0.99), respectively, among women with an existing vertebral fracture. (16) Our use of an interrupted time series approach that controls for baseline level and trend is considered a strong quasi-experimental modeling strategy, allowing for "real world" estimation of longitudinal effects when an RCT is unfeasible. (10,12) The reverse of this ecological correlation has also been previously demonstrated, ie, recent increases in hip fracture incidence alongside a reduction in bisphosphonate use, (17) itself likely due to reports of atypical femoral fractures associated with long-term bisphosphonate use.…”

Canadian Consensus Conference on Osteoporosis, 2006 Update

“…98 In a post hoc pooled analysis of the vertebral fracture and clinical fracture arms of FIT, alendronate reduced the relative risk of hip fracture by 53% (P = 0.005) over 3 to 4 years in postmenopausal women with a prevalent vertebral fracture or a femoral neck BMD T-score of −2.5 or less. 99 In this post hoc analysis, alendronate has been found to reduce fractures both in high risk women with vertebral fractures and those with osteopenia. 99 Furthermore, clinical vertebral fracture rate reduction (59%; P < 0.001) was demonstrated as early as one year into the study.…”

“…99 In this post hoc analysis, alendronate has been found to reduce fractures both in high risk women with vertebral fractures and those with osteopenia. 99 Furthermore, clinical vertebral fracture rate reduction (59%; P < 0.001) was demonstrated as early as one year into the study. 99 In a more recent post hoc analysis of a subgroup of women who had T-scores of −1.6 to −2.5, there was a relative risk reduction in clinical and radiographic fractures of 60 (P = 0.005) and 43% (P = 0.002) respectively, compared with placebo with 3 years of therapy.…”

Effect of alendronate and vitamin D3 on fractional calcium absorption in a double-blind, randomized, placebo-controlled trial in postmenopausal osteoporotic women

“…(8) Bisphosphonates inhibit osteoclast-mediated bone resorption, increase bone mineral density (BMD), and decrease the risk of vertebral, hip, and other nonvertebral fractures. (12) Theoretically, bisphosphonates might increase FCA indirectly by increasing serum PTH and 1,25(OH) 2 D 3 levels. (13,14) Bisphosphonates are approved in the prevention and treatment of osteoporosis.…”