title: Bone mineral density changes following discontinuation of ronacaleret treatment: off-treatment extension of a randomized, dose-finding phase II trial.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  The aim of this study is to evaluate whether BMD changes after cessation of ronacaleret treatment.
  
  
  METHODS
  Observational, off-treatment, extension of a randomized, placebo-controlled, dose-ranging phase II trial.
  
  
  METHODS
  Fifteen academic centers in seven countries.
  
  
  METHODS
  Postmenopausal women with low BMD; 171 out of 569 women in the parent study were enrolled in the extension study.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: GlaxoSmithKline, King of Prussia, PA 19406, USA. Electronic address: lorraine.a.fitzpatrick@gsk.com.
authors.forename: Lorraine A
authors.initials: LA
authors.lastname: Fitzpatrick
authors.affiliation: GlaxoSmithKline, King of Prussia, PA 19406, USA.
authors.forename: Margaret
authors.initials: M
authors.lastname: Wooddell
authors.affiliation: GlaxoSmithKline, King of Prussia, PA 19406, USA.
authors.forename: Christine E
authors.initials: CE
authors.lastname: Dabrowski
authors.affiliation: GlaxoSmithKline, King of Prussia, PA 19406, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Cicconetti
authors.affiliation: GlaxoSmithKline, King of Prussia, PA 19406, USA.
authors.forename: David N
authors.initials: DN
authors.lastname: Gordon
mesh_terms: D000368:Aged; D015519:Bone Density / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007189:Indans / Q000009:adverse effects*; D008159:Lumbar Vertebrae / Q000187:drug effects; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000139:chemically induced; D010666:Phenylpropionates / Q000009:adverse effects*; D044169:Receptors, Calcium-Sensing / Q000037:antagonists & inhibitors
chemical_list: D007189:Indans; D010666:Phenylpropionates; D044169:Receptors, Calcium-Sensing; C561716:ronacaleret
keywords: Bone mineral density; Calcium-sensing receptor antagonist; Hyperparathyroidism; Osteoporosis