The use of denosumab in osteoporosis - an update on efficacy and drug safety

Expert Opin Drug Saf. 2024 Sep;23(9):1069-1077. doi: 10.1080/14740338.2024.2386365. Epub 2024 Sep 11.

Abstract

Introduction: Denosumab (Prolia) is a fully human monoclonal antibody against the receptor activator of the nuclear factor kappaB ligand. It is a potent antiresorptive agent that reduces osteoclastogenesis.

Areas covered: Denosumab has been shown to improve bone mineral density and reduce the incidence of new fractures in postmenopausal women and men. It is also used in the treatment of glucocorticoid-induced osteoporosis, as well as for the prevention of bone loss and reduction of fracture risk in men receiving androgen deprivation therapy for non-metastatic prostate cancer and women receiving adjuvant aromatase inhibitor therapy for breast cancer. Initial safety concerns included infections, cancer, skin reactions, cardiovascular disease, hypocalcemia, osteonecrosis of the jaw, and atypical femur fractures; however, further study and experience provide reassurance on these issues. Anecdotal reports have raised concerns about an increased risk of multiple vertebral fractures following discontinuation of denosumab.

Expert opinion: Although bisphosphonates are often selected as initial therapy for osteoporosis, denosumab may be an appropriate initial therapy in patients at high risk for fracture, including older patients who have difficulty with the dosing requirements of oral bisphosphonates, as well as patients who are intolerant of, unresponsive to, or have contraindications to other therapies. Additional data is needed to address questions regarding treatment duration and discontinuation.

Keywords: Denosumab; efficacy; fractures; osteoporosis; safety.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Bone Density / drug effects
  • Bone Density Conservation Agents* / administration & dosage
  • Bone Density Conservation Agents* / adverse effects
  • Denosumab* / administration & dosage
  • Denosumab* / adverse effects
  • Diphosphonates / administration & dosage
  • Diphosphonates / adverse effects
  • Female
  • Fractures, Bone / chemically induced
  • Fractures, Bone / prevention & control
  • Humans
  • Male
  • Osteoporosis* / chemically induced
  • Osteoporosis* / drug therapy
  • RANK Ligand / administration & dosage
  • RANK Ligand / adverse effects
  • RANK Ligand / antagonists & inhibitors

Substances

  • Denosumab
  • Bone Density Conservation Agents
  • Antibodies, Monoclonal, Humanized
  • RANK Ligand
  • Diphosphonates