Randomized controlled trials Black et al. recently reported an analysis of subtrochanteric and diaphyseal
fractures in the Fracture Intervention Trial (FIT) of alendronate and its extension [1, 2, 5, 68] and the HORIZON Pivotal Fracture Trial (PFT) of zoledronic acid 5 mg . Twelve fractures in ten patients were documented in the subtrochanteric or diaphyseal region (Table 3) a combined rate of 2.3 per 10,000 patient-years . However, radiographs were not available to confirm typical vs atypical radiographic Peptide 17 features. There was no significant increase over placebo in the risk of subtrochanteric/diaphyseal fractures during the FIT, FIT Long-Term Extension (FLEX) or HORIZON-PFT trials. Compared with
placebo, the relative hazard was 1.03 (95% CI 0.1–16.5) for alendronate use in the FIT trial, 1.5 (95% CI 0.3–9.0) for zoledronic acid in the HORIZON-PFT and 1.3 (95% CI 0.1–14.7) for continued alendronate use in the FLEX trial. The interpretation of this analysis is limited by the small number of AZD6244 clinical trial events and the large confidence intervals. Table 3 Characteristics of ten patients with 12 low-trauma subtrochanteric or femoral diaphyseal fractures in the FIT, FLEX and HORIZON-PFT trials (adapted from Black et al. ) Study Age (years) Study medication Time from randomization to fracture (days [years]) Bilateral? ID-8 Prodromal symptoms Compliance Concomitant therapy FIT 75 Placebo 962 (2.6) >75% None FIT 69 Alendronate 1,682 (4.6) >75% None EPZ015938 purchase FLEX 79 Alendronate (first fracture) 1,250 (3.4) Stopped 3 years before first fracture Alendronate, 6 years (in FIT before FLEX) Alendronate (second fracture) 1,369 (3.8) FLEX 80 Alendronate/placebo 1,257 (3.4) Stopped 3 years before fracture Alendronate, 6 years (in FIT before FLEX) FLEX 83 Alendronate/alendronate 1,006 (2.8) >75% Alendronate, 5 years (in FIT before FLEX) HORIZON 65 Zoledronic acid 454 (1.2)
Hip pain 100% Raloxifene HORIZON 78 Placebo 1,051 (2.9) Hip pain 100% None HORIZON 65 Zoledronic acid 732 (2.0) 100% None HORIZON 72 Placebo 321 (0.9) 100% Calcitonin HORIZON 71 Zoledronic acid (2 fractures) 934 (2.6) Yes Bone pain 100% Bisphosphonate and hormone replacement therapy, both before study Bilezikian et al. reported the incidence of subtrochanteric fractures in the randomized, placebo-controlled phase III studies of risedronate in post-menopausal osteoporosis, which enrolled more than 15,000 patients. In trials of up to 3 years duration, the mean incidence of subtrochanteric fractures was 0.14% in risedronate 2.5-mg treated patients (n = 4,998), 0.13% in risedronate 5-mg treated patients (n = 5,395) and 0.17% in placebo-treated patients (n = 5,363) .