Ronacaleret, a calcium-sensing receptor antagonist, increases trabecular but not cortical bone in postmenopausal women.
Author(s): Fitzpatrick LA, Dabrowski CE, Cicconetti G, Gordon DN, Fuerst T, Engelke KA, Genant HK
Affiliation(s): GlaxoSmithKline, King of Prussia, PA 19406. firstname.lastname@example.org.
Publication date & source: 2011-11-02, J Bone Miner Res., [Epub ahead of print]
CONTEXT: Intermittent injections of parathyroid hormone have osteoanabolic effects that increase bone mineral density (BMD). Ronacaleret is an orally administered calcium-sensing receptor antagonist that stimulates endogenous parathyroid hormone release from the parathyroid glands. OBJECTIVE: Our objective was to compare the effects of ronacaleret and teriparatide on volumetric BMD (vBMD) measured by quantitative computed tomography (QCT). DESIGN AND SETTING: We conducted a randomized, placebo-controlled, dose-ranging trial at 45 academic centers with 31 sites participating in the sub-study. PATIENTS: Patients included 569 postmenopausal women with low bone mineral density; vBMD was assessed at the spine and hip in a subset of 314 women. INTERVENTIONS: Patients were treated for up to 12 months with open-label teriparatide 20 microg subcutaneously once daily or randomly assigned in a double-blind manner to ronacaleret 100 mg, 200 mg, 300 mg or 400 mg once daily, alendronate 70 mg once weekly or matching placebos. RESULTS: Ronacaleret increased spine integral (0.49% to 3.9%) and trabecular (1.8% to 13.3%) vBMD compared to baseline although the increments were at least 2-fold lower than that attained with teriparatide (14.8% and 24.4%, respectively) but similar or superior to that attained with alendronate (5.0% and 4.9%, respectively). There were small non-dose-dependent decreases in integral vBMD of the proximal femur with ronacaleret (-0.1 to -0.8%) compared with increases in the teriparatide (3.9%) and alendronate (2.7%) arms. PTH elevations with ronacaleret were prolonged relative to that seen historically with teriparatide. CONCLUSION: Ronacaleret preferentially increased vBMD of trabecular bone that is counterbalanced by small decreases in BMD at cortical sites. The relative preservation of trabecular bone and loss at cortical sites are consistent with the induction of mild hyperparathyroidism with ronacaleret therapy (ClinicalTrials.gov number, NCT00471237). (c) 2011 American Society for Bone and Mineral Research. Copyright (c) 2011 American Society for Bone and Mineral Research.