title: A 24-month study evaluating the efficacy and safety of denosumab for the treatment of men with low bone mineral density: results from the ADAMO trial.
abstract: BACKGROUND
  One in 4 men in the United States aged >50 years will have an osteoporosis-related fracture. Fewer data are available on osteoporosis treatment in men than in women.
  
  
  OBJECTIVE
  The purpose of this study was to evaluate denosumab therapy in men with low bone mineral density (BMD).
  
  
  METHODS
  This was a phase 3 study with 2 treatment periods: a previously reported 12-month double-blind, placebo-controlled phase and a 12-month open-label phase.
  
  
  METHODS
  This was a multicenter study conducted in North America and Europe.
  
  
  METHODS
  A total of 228 men entered the open-label phase and 219 completed the study.
  
  
  METHODS
  Men from the original denosumab (long-term) and placebo (crossover) groups received 60 mg of denosumab sc every 6 months.
  
  
  METHODS
  BMD, serum collagen type I C-telopeptide, and safety were measured.
  
  
  RESULTS
  During the open-label phase, continued BMD increases occurred with long-term denosumab treatment (2.2% lumbar spine, 0.9% total hip, 1.3% femoral neck, 1.3% trochanter, and 0.2% 1/3 radius), resulting in cumulative 24-month gains from baseline of 8.0%, 3.4%, 3.4%, 4.6%, and 0.7%, respectively (all P < .01). The crossover group showed BMD gains after 12 months of denosumab treatment similar to those of the long-term denosumab group during the first treatment year. Significant reductions in serum collagen type I C-teleopeptide were observed after denosumab administration. Adverse event rates were similar between groups, and no new safety signals were identified.
  
  
  CONCLUSIONS
  In men with low BMD, denosumab treatment for a second year continued to increase BMD, maintained reductions in bone resorption, and was well tolerated. BMD increased in men initiating denosumab during the second year. These effects were similar to those previously seen in postmenopausal women with osteoporosis and in men with prostate cancer receiving androgen deprivation therapy.
authors.affiliation: Aarhus University Hospital (B.L.L.), DK-8000 Aarhus, Denmark; Center for Clinical and Basic Research (C.S.T.), 2750 Ballerup, Denmark; Amgen Inc. (P.-R.H., Y.-C.Y., R.B.W., F. M., S.S.), Thousand Oaks, California 91320; INSERM UMR 1033 (R.C.), Université de Lyon, Hôpital Edouard Herriot, F-69437, Lyon, France; Krakow Medical Center (E.C.), Krakow, 31-501 Poland; University of British Columbia (D.L.K.), Vancouver, British Columbia V6T 1Z4, Canada; University of Liège (J.-Y.R.), 4000 Liège, Belgium; Altoona Center for Clinical Research (A.K.), Duncansville, Pennsylvania 16635; New Mexico Clinical Research and Osteoporosis Center (E.M.L.), Albuquerque, New Mexico 87106; Colorado Center for Bone Research (P.D.M.), Lakewood, Colorado 80227; Bethesda Health Research Center (M.A.B.), Bethesda, Maryland 20817; Oregon Osteoporosis Center (M.R.M.), Portland, Oregon 97213; Michigan Bone and Mineral Clinic (H.G.B.), Detroit, Michigan 48236; Uppsala University (Ö.L.), 751 05 Uppsala, Sweden; University of Southern Denmark and Glostrup Hospital (B.A.), DK-5000 Odense and Copenhagen, Denmark; Dallas Veterans Affairs Medical Center and University of Texas Southwestern (U.G.), Dallas, Texas 75390; and Oregon Health and Science University (E.O.), Portland, Oregon 97239.
authors.forename: Bente L
authors.initials: BL
authors.lastname: Langdahl
authors.forename: Christence Stubbe
authors.initials: CS
authors.lastname: Teglbjærg
authors.forename: Pei-Ran
authors.initials: PR
authors.lastname: Ho
authors.forename: Roland
authors.initials: R
authors.lastname: Chapurlat
authors.forename: Edward
authors.initials: E
authors.lastname: Czerwinski
authors.forename: David L
authors.initials: DL
authors.lastname: Kendler
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Reginster
authors.forename: Alan
authors.initials: A
authors.lastname: Kivitz
authors.forename: E Michael
authors.initials: EM
authors.lastname: Lewiecki
authors.forename: Paul D
authors.initials: PD
authors.lastname: Miller
authors.forename: Michael A
authors.initials: MA
authors.lastname: Bolognese
authors.forename: Michael R
authors.initials: MR
authors.lastname: McClung
authors.forename: Henry G
authors.initials: HG
authors.lastname: Bone
authors.forename: Östen
authors.initials: Ö
authors.lastname: Ljunggren
authors.forename: Bo
authors.initials: B
authors.lastname: Abrahamsen
authors.forename: Ugis
authors.initials: U
authors.lastname: Gruntmanis
authors.forename: Yu-Ching
authors.initials: YC
authors.lastname: Yang
authors.forename: Rachel B
authors.initials: RB
authors.lastname: Wagman
authors.forename: Faisal
authors.initials: F
authors.lastname: Mirza
authors.forename: Suresh
authors.initials: S
authors.lastname: Siddhanti
authors.forename: Eric
authors.initials: E
authors.lastname: Orwoll
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000069448:Denosumab; D005272:Femur Neck / Q000000981:diagnostic imaging / Q000187:drug effects; D050723:Fractures, Bone / Q000453:epidemiology; D006801:Humans; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000453:epidemiology; D011859:Radiography; D011884:Radius / Q000000981:diagnostic imaging / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D050071:Bone Density Conservation Agents; D000069448:Denosumab