Efficacy of continued alendronate for fractures in women with and without prevalent vertebral fracture: The FLEX Trial

Abstract

In the Fracture Intervention Trial (FIT) Long Term Extension (FLEX) Trial, 10 years of alendronate (ALN) did not significantly reduce the risk of nonvertebral fractures (NVFs) compared with 5 years of ALN. Continuing ALN reduced the risk of clinical but not morphometric vertebral fractures regardless of baseline vertebral fracture status. In previous studies, ALN efficacy for NVF prevention in women without prevalent vertebral fracture was limited to those with femoral neck (FN) T-scores of À2.5 or less. To determine whether the effect of longterm ALN on fracture differs by vertebral fracture status and femoral neck (FN) T-score, we performed a post hoc analysis using FLEX data, a randomized, double-blind, placebo-controlled trial among 1099 postmenopausal women originally randomized to ALN in the FIT with mean ALN use of 5 years. In the FLEX Trial, women were randomized to placebo (40%) or ALN 5 mg/day (30%) or ALN 10 mg/day (30%) for an additional 5 years. Among women without vertebral fracture at FLEX baseline (n ¼ 720), continuation of ALN reduced NVF in women with FLEX baseline FN T-scores of À2.5 or less [relative risk (RR) ¼ 0.50, 95% confidence interval (CI) 0.26-0.96] but not with T-scores of greater than À2.5 and À2 or less (RR 0.79, 95% CI 0.37-1.66) or with T-scores of greater than À2 (RR 1.41, 95% CI 0.75-2.66; p for interaction ¼ .019). Continuing ALN for 10 years instead of stopping after 5 years reduces NVF risk in women without prevalent vertebral fracture whose FN T-scores, achieved after 5 years of ALN, are À2.5 or less but does not reduce risk of NVF in women whose T-scores are greater than À2. ß

Atypical subtrochanteric and diaphyseal femoral fractures: Report of a task force of the american society for bone and mineral Research

“…In the FLEX trial, the incidence of clinical (but not morphometric) vertebral fractures was significantly lower in those on 10 years of continued alendronate versus those who stopped after 5 years (162) ; reduction in nonvertebral fracture incidence was limited to women without a fracture history but with femoral neck T-scores that were -2.5 or less. (165) While conclusions from this trial need to be tempered by its limitations, primarily the small study sample, these are the only long-term fracture data available with alendronate treatment. With regard to risedronate, 7 years of therapy did not further reduce the incidence of vertebral fractures below that observed with 3 and 5 years of therapy.…”

Proportion of osteoporotic women remaining at risk for fracture despite adherence to oral bisphosphonates

“…The occurrence of one or more fractures is a risk factor for additional future fractures in both untreated patients [13], and in those treated with bisphosphonates [14]. Furthermore persistence of osteoporotic T-scores or further decrease in BMD after treatment indicates a higher risk of subsequent fracture compared to those with higher post treatment T-scores, and potential to benefit from additional treatment [15]. Thus the outcomes of fracture, or the surrogate outcomes of decline in BMD or persistent low BMD, are often used by practitioners to guide decisions regarding continuing or switching therapies, because the occurrence of each of these is associated with an elevated risk of fracture relative to other treated patients [16,17].…”

Postmenopausal osteoporosis treatment with antiresorptives: Effects of discontinuation or long-term continuation on bone turnover and fracture risk—a perspective

“…(52) The risk of clinical vertebral fracture was significantly reduced in those who received active treatment for 10 years. A post hoc analysis of the FLEX data indicated that among patients with no prevalent vertebral fracture, continued alendronate therapy provided protection from nonvertebral fractures in women with a femoral neck T-score of À2.5 but not those with a T-score > À2, (54) suggesting that BMD measurements after 5 years of therapy might therefore be useful in identifying those most likely to benefit from continued bisphosphonate therapy.…”