title: Two-year treatment with denosumab (AMG 162) in a randomized phase 2 study of postmenopausal women with low BMD.
abstract: Denosumab is a monoclonal antibody to RANKL. In this randomized, placebo-controlled study of 412 postmenopausal women with low BMD, subcutaneous denosumab given every 3 or 6 mo was well tolerated, increased BMD, and decreased bone resorption markers for up to 24 mo. Continued study of denosumab is warranted in the treatment of low BMD in postmenopausal women.
  
  
  BACKGROUND
  Denosumab is a fully human monoclonal antibody that inhibits RANKL, a key mediator of osteoclastogenesis and bone remodeling. This prespecified exploratory analysis evaluated the efficacy and safety of denosumab through 24 mo in the treatment of postmenopausal women with low BMD.
  
  
  METHODS
  Four hundred twelve postmenopausal women with lumbar spine BMD T-scores of -1.8 to -4.0 or femoral neck/total hip T-scores of -1.8 to -3.5 were randomly assigned to receive double-blind, subcutaneous injections of placebo; denosumab 6, 14, or 30 mg every 3 mo; denosumab 14, 60, 100, or 210 mg every 6 mo; or open-label oral alendronate 70 mg once weekly. Outcome measures included BMD at the lumbar spine, total hip, distal one-third radius, and total body; bone turnover markers; and safety.
  
  
  RESULTS
  Denosumab increased BMD at all measured skeletal sites and decreased concentrations of bone turnover markers compared with placebo at 24 mo. At the lumbar spine, BMD increases with denosumab ranged from 4.13% to 8.89%. BMD changes with denosumab 30 mg every 3 mo and > or =60 mg every 6 mo were similar to, or in some cases greater than, with alendronate. The incidence of adverse events was similar in the placebo, denosumab, and alendronate treatment groups. Exposure-adjusted adverse events over 2 yr of treatment were similar to those reported during the first year of treatment.
  
  
  CONCLUSIONS
  In these postmenopausal women with low BMD, treatment with denosumab for 2 yr was associated with sustained increases in BMD and reductions in bone resorption markers compared with placebo.
authors: New Mexico Clinical Research & Osteoporosis Center, Albuquerque, NM 87106, USA. lewiecki@aol.com
authors: E Michael
authors: EM
authors: Lewiecki
authors: Paul D
authors: PD
authors: Miller
authors: Michael R
authors: MR
authors: McClung
authors: Stanley B
authors: SB
authors: Cohen
authors: Michael A
authors: MA
authors: Bolognese
authors: Yu
authors: Y
authors: Liu
authors: Andrea
authors: A
authors: Wang
authors: Suresh
authors: S
authors: Siddhanti
authors: Lorraine A
authors: LA
authors: Fitzpatrick
mesh_terms: D000368:Aged; D019386:Alendronate / Q000008:administration & dosage / Q000009:adverse effects; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000276:immunology; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects* / Q000276:immunology; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D001862:Bone Resorption / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D000069448:Denosumab; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D017698:Postmenopause; D053245:RANK Ligand / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000276:immunology; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D050071:Bone Density Conservation Agents; D053245:RANK Ligand; C505688:TNFSF11 protein, human; D000069448:Denosumab; D019386:Alendronate