title: The effects of ronacaleret, a calcium-sensing receptor antagonist, on bone mineral density and biochemical markers of bone turnover in postmenopausal women with low bone mineral density.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  Our objective was to compare the effects of ronacaleret, teriparatide, and alendronate on bone mineral density (BMD) and markers of bone turnover.
  
  
  METHODS
  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.
  
  
  METHODS
  Patients included 569 postmenopausal women with low BMD.
  
  
  METHODS
  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.
  
  
  METHODS
  Percentage change from baseline in lumbar spine BMD was assessed at month 12.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: GlaxoSmithKline, Biopharm Development Unit, 709 Swedeland Road, UM2291, King of Prussia, Pennsylvania 19406, USA. lorraine.a.fitzpatrick@gsk.com
authors: Lorraine A
authors: LA
authors: Fitzpatrick
authors: Christine E
authors: CE
authors: Dabrowski
authors: Gregory
authors: G
authors: Cicconetti
authors: David N
authors: DN
authors: Gordon
authors: Socrates
authors: S
authors: Papapoulos
authors: Henry G
authors: HG
authors: Bone
authors: John P
authors: JP
authors: Bilezikian