Bone mineral density changes following discontinuation of ronacaleret treatment: Off-treatment extension of a randomized, dose-finding phase II trial

Context: Parathyroidectomy in patients with hyperparathyroidism can produce subsequent increases in bone mineral density (BMD). Ronacaleret, a selective calcium-sensing receptor antagonist that stimulates endogenous parathyroid hormone release, induced mild hyperparathyroidism. Objective: The aim of this study is to evaluate whether BMD changes after cessation of ronacaleret treatment. Design: Observational, off-treatment, extension of a randomized, placebo-controlled, dose-ranging phase II trial. Setting: Fifteen academic centers in seven countries. Patients: Postmenopausal women with low BMD; 171 out of 569 women in the parent study were enrolled in the extension study. Interventions: Subjects were treated with ronacaleret 100 mg (n = 16), 200 mg (n = 38), 300 mg (n = 35), or 400 mg (n = 32) once daily, alendronate 70 mg (n = 17) once weekly, or matching placebo (n = 33) for 1012 months; BMD was measured after discontinuation of ronacaleret or alendronate treatment. Main outcome measure: Mean percent change in lumbar spine areal BMD by dual-energy X-ray absorptiometry at 6-12 months after discontinuing ronacaleret or alendronate compared with the 10- to 12-month BMD measurement of the parent study. Results: At the lumbar spine, all doses of ronacaleret resulted in gains in BMD while on treatment. These increases in BMD were maintained or increased after discontinuation of ronacaleret All doses of ronacaleret caused bone loss at the total hip while on active treatment However, there was an attenuation of this loss in the off-treatment extension study. Conclusion: The gain in BMD at the lumbar spine was maintained post-treatment and the loss of BMD at the total hip was attenuated. We hypothesize that there may have been some bone remineralization after cessation of ronacaleret. (C) 2014 Elsevier Inc. All rights reserved.