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

J Clin Endocrinol Metab. 2015 Apr;100(4):1335-42. doi: 10.1210/jc.2014-4079. Epub 2015 Jan 21.

Abstract

Context: 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).

Design: 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.

Setting: This was a multicenter study conducted in North America and Europe.

Participants: A total of 228 men entered the open-label phase and 219 completed the study.

Intervention: Men from the original denosumab (long-term) and placebo (crossover) groups received 60 mg of denosumab sc every 6 months.

Main outcome measures: 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.

Trial registration: ClinicalTrials.gov NCT00980174.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Biomarkers / metabolism
  • Bone Density / drug effects
  • Bone Density Conservation Agents / adverse effects
  • Bone Density Conservation Agents / therapeutic use*
  • Denosumab
  • Femur Neck / diagnostic imaging
  • Femur Neck / drug effects
  • Fractures, Bone / epidemiology
  • Humans
  • Lumbar Vertebrae / diagnostic imaging
  • Lumbar Vertebrae / drug effects
  • Male
  • Middle Aged
  • Osteoporosis / diagnostic imaging
  • Osteoporosis / drug therapy*
  • Osteoporosis / epidemiology
  • Radiography
  • Radius / diagnostic imaging
  • Radius / drug effects
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Biomarkers
  • Bone Density Conservation Agents
  • Denosumab

Associated data

  • ClinicalTrials.gov/NCT00980174