Effects of Cinacalcet on Fracture Events in Patients Receiving Hemodialysis

Abstract

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%. 26: 146626: -147526: , 201526: . doi: 10.1681 Patients with end stage renal disease (ESRD) on dialysis have increased risk of fractures compared with the general population. 1 Fracture incidence rates vary by geographic region, although rates are consistently higher in patients with CKD than matched controls from the same country. [2][3][4][5][6] Depending on the study, 10%-52% of patients receiving dialysis J Am Soc Nephrol

Fractures in patients with CKD—diagnosis, treatment, and prevention: a review by members of the European Calcified Tissue Society and the European Renal Association of Nephrology Dialysis and Transplantation

“…This has been reported to be low, ranging from 7% to 20%, 35,36 and only 1% of patients had vertebral fractures based on clinical diagnosis in 1 clinical trial. 37 This may be an underestimation because radiographic imaging is not systematically performed. In case-control studies with a small number of dialysis patients, low BMD at the lumbar spine was associated with vertebral and prevalent or self-reported peripheral fractures.…”

“…Indeed, cinacalcet was found to efficiently reduce fracture rates in elderly dialysis patients with secondary hyperparathyroidism. 37 We recommend lowering PTH as a first action to reduce cortical bone loss and to limit the risk of peripheral fractures. Because of the lack of data on denosumab in high PTH conditions, 139 its use would be considered when PTH has been normalized.…”

Efficacy of low-dose cinacalcet on alternate days for the treatment of secondary hyperparathyroidism in hemodialysis patients: a single-center study

“…[12][13][14][15][16][17][18][19] Moreover, treatment with cinacalcet decreases the incidence of vascular calcification 20 and bone fractures. 21 In Thailand, however, the…”

Novel treatment options for secondary hyperparathyroidism in end-stage kidney disease patients on hemodialysis therapy

“…В крупных клинических исследованиях доказана способность препа-рата снижать частоту переломов бедренной кости на 54% у диализных пациентов, в сравнении с группой плацебо на 92 % реже применять паратиреоидэктомию и снижать НАУЧНЫЙ ОБЗОР число госпитализаций, связанное с сердечно-сосудистой заболеваемостью на 39% [17,19,20].…”