Ronacaleret, a calcium-sensing receptor antagonist, has no significant effect on radial fracture healing time: Results of a randomized, double-blinded, placebo-controlled Phase II clinical trial

BackgroundFractures cause significant morbidity, mortality, and use of health care resources. An oral agent that enhances fracture healing could reduce costs and prevent future disabilities. In Phase I studies, ronacaleret, a novel calcium-sensing receptor antagonist, stimulated parathyroid hormone (PTH) release and increased bone formation markers, suggesting that it may act as an effective oral anabolic agent to enhance fracture healing.MethodsThis was a randomized, double-blind, placebo-controlled, parallel-group, clinical trial in 85 male and female subjects who had sustained a closed, unilateral, extra-articular fracture of the distal radius and were receiving conservative treatment. Subjects were randomly assigned in a double-blind manner to ronacaleret 200 mg twice daily, ronacaleret 400 mg once daily or matching placebo and followed for 12 weeks. Fracture healing was assessed by radiographs and quantitative computed tomography (CT), and bone turnover markers were measured. The study was terminated early for futility based on the results of an unplanned interim analysis.ResultsThere were no significant differences between treatment groups in time to radiographic fracture healing (74, 65 and 68 days for placebo, 200 mg twice daily and 400 mg once daily dose groups, respectively), cortical bridging, grip strength, pain and swelling, time to cast removal, or range of motion. Markers of bone formation and levels of whole PTH, intact PTH and serum calcium increased following treatment with ronacaleret.ConclusionRonacaleret had no significant effect on duration of healing by radiograph or CT scan, time to cast removal, clinical symptoms, grip strength, or range of motion.

► Fractures result in significant morbidity, mortality and healthcare costs. ► An oral agent that enhances fracture healing could reduce future disabilities. ► Fracture healing was assessed in 170 subjects randomly assigned to a novel calcium-sensing receptor antagonist or placebo. ► The study was terminated for futility based on the results of an unplanned interim analysis. ► Ronacaleret had no significant effect on duration of healing, time to cast removal, grip strength or range of motion.