title: 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.
abstract: BACKGROUND
  Fractures 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.
  
  
  METHODS
  This 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.
  
  
  RESULTS
  There 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.
  
  
  CONCLUSIONS
  Ronacaleret 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.
authors: Medicines Development Center, GlaxoSmithKline, King of Prussia, PA 19406, USA. lorraine.a.fitzpatrick@gsk.com
authors: Lorraine A
authors: LA
authors: Fitzpatrick
authors: Phillipa L
authors: PL
authors: Smith
authors: Trish A
authors: TA
authors: McBride
authors: Michael A
authors: MA
authors: Fries
authors: Mohammad
authors: M
authors: Hossain
authors: Christine E
authors: CE
authors: Dabrowski
authors: David N
authors: DN
authors: Gordon
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D016723:Bone Remodeling / Q000187:drug effects; D002118:Calcium / Q000097:blood / Q000652:urine; D003710:Demography; D004311:Double-Blind Method; D005260:Female; D017102:Fracture Healing / Q000187:drug effects*; D006801:Humans; D007189:Indans / Q000494:pharmacology* / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D010666:Phenylpropionates / Q000494:pharmacology* / Q000627:therapeutic use*; D010919:Placebos; D011859:Radiography; D011885:Radius Fractures / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology*; D044169:Receptors, Calcium-Sensing / Q000037:antagonists & inhibitors*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D007189:Indans; D010281:Parathyroid Hormone; D010666:Phenylpropionates; D010919:Placebos; D044169:Receptors, Calcium-Sensing; C561716:ronacaleret; D002118:Calcium