Fractures are frequent in patients receiving
hemodialysis. We tested the hypothesis that
cinacalcet would reduce the rate of clinical fractures in patients receiving
hemodialysis using data from the Evaluation of
Cinacalcet HCl
Therapy to Lower Cardiovascular Events trial, a placebo-controlled trial that randomized 3883
hemodialysis patients with
secondary hyperparathyroidism to receive
cinacalcet or placebo for ≤64 months. This study was a prespecified secondary analysis of the trial whose primary end point was all-cause mortality and non-fatal cardiovascular events, and one of the secondary end points was first clinical fracture event. Clinical fractures were observed in 255 of 1935 (13.2%) patients randomized to placebo and 238 of 1948 (12.2%) patients randomized to
cinacalcet. In an unadjusted intention-to-treat analysis, the relative hazard for fracture (
cinacalcet versus placebo) was 0.89 (95% confidence interval [95% CI], 0.75 to 1.07). After adjustment for baseline characteristics and
multiple fractures, the relative hazard was 0.83 (95% CI, 0.72 to 0.98). Using a prespecified lag-censoring analysis (a measure of actual drug exposure), the relative hazard for fracture was 0.72 (95% CI, 0.58 to 0.90). When participants were censored at the time of cointerventions (
parathyroidectomy, transplant, or provision of commercial
cinacalcet), the relative hazard was 0.71 (95% CI, 0.58 to 0.87). Fracture rates were higher in older compared with younger patients and the effect of
cinacalcet appeared more pronounced in older patients. In conclusion, using an unadjusted intention-to-treat analysis,
cinacalcet did not reduce the rate of clinical fracture. However, when accounting for differences in baseline characteristics,
multiple fractures, and/or events prompting discontinuation of study drug,
cinacalcet reduced the rate of clinical fracture by 16%-29%.