title: Effect of denosumab on bone mineral density and biochemical markers of bone turnover: six-year results of a phase 2 clinical trial.
abstract: BACKGROUND
  This is a study extension to evaluate the efficacy and safety of long-term treatment with denosumab in postmenopausal women with low bone mass.
  
  
  OBJECTIVE
  Our objective was to describe changes in bone mineral density (BMD) and bone turnover markers as well as safety with 6 yr of denosumab treatment.
  
  
  METHODS
  We conducted an ongoing 4-yr, open-label, single-arm, extension study of a dose-ranging phase 2 trial. This paper reports a 2-yr interim analysis representing up to 6 yr of continuous denosumab treatment.
  
  
  METHODS
  This multicenter study was conducted at 23 U.S. centers.
  
  
  METHODS
  Of the 262 subjects who completed the parent study, 200 enrolled in the study extension and 178 (89%) completed the first 2 yr.
  
  
  METHODS
  All subjects received denosumab 60 mg sc every 6 months.
  
  
  METHODS
  We evaluated BMD at the lumbar spine, total hip, femoral neck, and one third radius; biochemical markers of bone turnover; and safety, reported as adverse events.
  
  
  RESULTS
  Over a period of 6 yr, continuous treatment with denosumab resulted in progressive gains in BMD in postmenopausal women with low bone mass. Reduction in bone resorption was sustained over the course of continuous treatment. Independent of past treatment and discontinuation period, subjects demonstrated responsiveness to denosumab therapy as measured by BMD and bone turnover markers. The safety profile of denosumab did not change over time.
  
  
  CONCLUSIONS
  In this study, denosumab was well tolerated and effective through 6 yr of continuous treatment in postmenopausal women with low bone mass.
authors.affiliation: Colorado Center for Bone Research, 3190 South Wadsworth Boulevard, Ste 250, Lakewood, Colorado 80227, USA. millerccbr@aol.com
authors.forename: Paul D
authors.initials: PD
authors.lastname: Miller
authors.forename: Rachel B
authors.initials: RB
authors.lastname: Wagman
authors.forename: Munro
authors.initials: M
authors.lastname: Peacock
authors.forename: E Michael
authors.initials: EM
authors.lastname: Lewiecki
authors.forename: Michael A
authors.initials: MA
authors.lastname: Bolognese
authors.forename: Richard L
authors.initials: RL
authors.lastname: Weinstein
authors.forename: Beiying
authors.initials: B
authors.lastname: Ding
authors.forename: Javier
authors.initials: J
authors.lastname: San Martin
authors.forename: Michael R
authors.initials: MR
authors.lastname: McClung
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019386:Alendronate / Q000627:therapeutic use; D000469:Alkaline Phosphatase / Q000097:blood; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001842:Bone and Bones / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D015331:Cohort Studies; D000069448:Denosumab; D005260:Female; D006615:Hip / Q000000981:diagnostic imaging; D006801:Humans; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy* / Q000473:pathology; D053245:RANK Ligand / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D011859:Radiography; D011884:Radius / Q000000981:diagnostic imaging; D013131:Spine / Q000000981:diagnostic imaging
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D050071:Bone Density Conservation Agents; D053245:RANK Ligand; D000069448:Denosumab; D000469:Alkaline Phosphatase; D019386:Alendronate