Efficacy and safety of denosumab in postmenopausal women with osteopenia or osteoporosis: a systematic review and a meta-analysis

Horm Metab Res. 2009 Oct;41(10):721-9. doi: 10.1055/s-0029-1224109. Epub 2009 Jun 17.


Receptor activator of nuclear factor-kappaB ligand (RANKL) is a cytokine essential for osteoclast differentiation, activation, and survival. Denosumab, a human monoclonal antibody against RANKL, constitutes a promising antiresorptive agent for osteoporosis. We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), and other trial registries through January 2009. We selected randomized controlled trials (RCTs) of denosumab in women with low bone mass that described the changes on bone markers and bone mineral density (BMD) as well as the adverse events including fracture risk. We analyzed data from nine RCTs involving 10 329 participants. Although denosumab universally decreased bone markers and increased lumbar and hip BMD, the efficacy evaluation based on percentage (%) mean change from the baseline was not possible due to missing data. Denosumab was not associated with a significant reduction in fracture risk [OR (95% CI) 0.74 (0.33 to 1.64), p=0.45]. Increased risk of serious adverse events [OR (95% CI) 1.83 (1.10 to 3.04), p=0.02] and serious infections [OR (95% CI) 4.45 (1.15 to 17.14), p=0.03] were evident. In conclusion, although effective as an antiresorptive agent, denosumab has not yet proved its efficacy on fracture risk reduction while increased infection risk questions its safety.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Bone Density / drug effects
  • Bone Density / immunology*
  • Bone Remodeling / immunology
  • Denosumab
  • Female
  • Fractures, Bone / immunology
  • Fractures, Bone / prevention & control
  • Humans
  • Osteoporosis, Postmenopausal / drug therapy
  • Osteoporosis, Postmenopausal / immunology*
  • RANK Ligand / adverse effects
  • RANK Ligand / immunology*
  • RANK Ligand / pharmacology*
  • RANK Ligand / therapeutic use


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • RANK Ligand
  • TNFSF11 protein, human
  • Denosumab