title: Effects of denosumab treatment and discontinuation on bone mineral density and bone turnover markers in postmenopausal women with low bone mass.
abstract: BACKGROUND
  Denosumab treatment for 24 months increased bone mineral density (BMD) and reduced bone turnover markers (BTM) in postmenopausal women.
  
  
  OBJECTIVE
  The aim was to determine the effects of prior denosumab or placebo injections on BMD, BTM, and safety over 24 months after treatment discontinuation.
  
  
  METHODS
  We conducted an off-treatment extension of a phase 3, randomized, double-blind, parallel-group study.
  
  
  METHODS
  A total of 256 postmenopausal women with a mean age of 59 yr and a mean lumbar spine T-score of -1.61 at randomization participated in the study.
  
  
  METHODS
  Participants received placebo or 60 mg denosumab every 6 months for 24 months, followed by 24 months off treatment.
  
  
  METHODS
  We measured the percentage changes in BMD and BTM, and evaluated safety.
  
  
  RESULTS
  Of the 256 participants enrolled in the posttreatment phase, 87% completed the study. During 24 months of denosumab treatment, BMD increased (lumbar spine, 6.4%; total hip, 3.6%; 1/3 radius, 1.4%), and BTM decreased (serum C-terminal telopeptide of type 1 collagen, 63%; and N-terminal propeptide of type 1 procollagen, 47%), compared with placebo. After discontinuation, BMD declined, but the previously treated denosumab group maintained higher BMD than the previously treated placebo group at these sites (P ≤ 0.05). Final BMD at month 48 strongly correlated with month 0 BMD. After denosumab discontinuation, BTM increased above baseline within 3 months (serum C-terminal telopeptide of type 1 collagen) or 6 months (N-terminal propeptide of type 1 procollagen) and returned to baseline by month 48. Adverse event rates during the off-treatment phase were similar between groups.
  
  
  CONCLUSIONS
  In postmenopausal women with low BMD, the effects of 60 mg denosumab treatment for 24 months on BMD and BTM are reversible upon discontinuation, reflecting its biological mechanism of action. Residual BMD measurements remained above those of the group previously treated with placebo.
authors.affiliation: Michigan Bone and Mineral Clinic, Detroit, Michigan 48236, USA. hgbone.md@att.net
authors.forename: Henry G
authors.initials: HG
authors.lastname: Bone
authors.forename: Michael A
authors.initials: MA
authors.lastname: Bolognese
authors.forename: Chui Kin
authors.initials: CK
authors.lastname: Yuen
authors.forename: David L
authors.initials: DL
authors.lastname: Kendler
authors.forename: Paul D
authors.initials: PD
authors.lastname: Miller
authors.forename: Yu-Ching
authors.initials: YC
authors.lastname: Yang
authors.forename: Luanda
authors.initials: L
authors.lastname: Grazette
authors.forename: Javier
authors.initials: J
authors.lastname: San Martin
authors.forename: J Christopher
authors.initials: JC
authors.lastname: Gallagher
mesh_terms: D000368:Aged; D000465:Algorithms; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers / Q000032:analysis* / Q000097:blood; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D016723:Bone Remodeling / Q000187:drug effects*; D000069448:Denosumab; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D050723:Fractures, Bone / Q000453:epidemiology / Q000517:prevention & control; D006801:Humans; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000188:drug therapy*; D010919:Placebos; D053245:RANK Ligand / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D028761:Withholding Treatment
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D050071:Bone Density Conservation Agents; D010919:Placebos; D053245:RANK Ligand; D000069448:Denosumab