ronacaleret and Osteoporosis--Postmenopausal

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.. The aim of this study is to evaluate whether BMD changes after cessation of ronacaleret treatment.. Observational, off-treatment, extension of a randomized, placebo-controlled, dose-ranging phase II trial.. Fifteen academic centers in seven countries.. Postmenopausal women with low BMD; 171 out of 569 women in the parent study were enrolled in the extension study.. Subjects were treated with ronacaleret 100mg (n=16), 200mg (n=38), 300mg (n=35), or 400mg (n=32) once daily, alendronate 70mg (n=17) once weekly, or matching placebo (n=33) for 10-12months; BMD was measured after discontinuation of ronacaleret or alendronate treatment.. Mean percent change in lumbar spine areal BMD by dual-energy X-ray absorptiometry at 6-12months after discontinuing ronacaleret or alendronate compared with the 10- to 12-month BMD measurement of the parent study.. 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.. 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.

Topics: Aged; Bone Density; Female; Follow-Up Studies; Humans; Indans; Lumbar Vertebrae; Middle Aged; Osteoporosis, Postmenopausal; Phenylpropionates; Receptors, Calcium-Sensing

Ronacaleret, a calcium-sensing receptor antagonist that stimulates PTH release from the parathyroid glands, was evaluated as an oral osteoanabolic agent for the treatment of osteoporosis.. Our objective was to compare the effects of ronacaleret, teriparatide, and alendronate on bone mineral density (BMD) and markers of bone turnover.. In this randomized, placebo-controlled, dose-ranging trial, spine and hip BMD were assessed by dual-energy x-ray absorptiometry and bone turnover markers were measured.. Patients included 569 postmenopausal women with low BMD.. Subjects were offered open-label 20 μg teriparatide sc once daily or were randomized to 100, 200, 300, or 400 mg oral ronacaleret once daily, 70 mg alendronate once weekly, or placebo and were followed for up to 12 months.. Percentage change from baseline in lumbar spine BMD was assessed at month 12.. With ronacaleret, the increases in lumbar spine BMD at 12 months (0.3-1.6%) were significantly lower than those attained with teriparatide (9.1%) or alendronate (4.5%). There were small decreases in total hip, femoral neck, and trochanter BMD at month 12 with ronacaleret compared with increases in the teriparatide and alendronate arms. Bone turnover markers increased in the ronacaleret and teriparatide arms and decreased in the alendronate arm. PTH elevations with ronacaleret were prolonged relative to those previously reported with teriparatide.. The densitometric findings in the context of prolonged PTH elevation and increased bone turnover suggest ronacaleret induces mild hyperparathyroidism. Ronacaleret only modestly increased lumbar spine BMD and decreased BMD at hip sites.

Topics: Administration, Oral; Aged; Alendronate; Biomarkers; Bone Density; Bone Density Conservation Agents; Bone Remodeling; Calcium; Female; Humans; Indans; Middle Aged; Osteoporosis, Postmenopausal; Parathyroid Hormone; Patient Compliance; Phenylpropionates; Receptors, Calcium-Sensing; Teriparatide