Denosumab for the treatment of osteoporosis

Abstract

Introduction: Low trauma fractures due to osteoporosis are a major health concern worldwide. Despite the availability of many therapeutic compounds to reduce fracture risk, osteoporosis remains undertreated and the burden of osteoporotic fractures remains high. Denosumab is a novel agent that acts to reduce bone turnover, improve bone mineral density, and reduce fracture risk, offering a favorable efficacy and safety profile.

Areas covered: This review covers the pharmacology and major clinical trials with extension/post-marketing follow-up, including trials for all FDA-approved indications of denosumab to date.

Expert opinion: Denosumab is an efficacious and safe osteoporosis treatment option, with current data from up to 8 years of continued use showing continued improvement in bone density with sustained fracture risk reduction. Safety profiles overall are similar to placebo, with no new safety concerns in extension trials, though a theoretical increased risk of infection exists with RANKL inhibition. Future considerations include safety of prolonged treatment beyond 8 years, and efficacy/fracture risk after discontinuation or with non-adherence, given the characteristic pharmacodynamic profile of denosumab.

Keywords:

• denosumab
• mAb
• osteoporosis
• receptor activator of nuclear factor kappa-B ligand
• treatment

Declaration of interest

M LeBoff has stock ownership of Amgen. She serves on the Board of Trustees of the National Osteoporosis Foundation (no monetary remuneration). EM Lewiecki has received institutional grant/research support from Amgen, Merck, and Eli Lilly; he has served on scientific advisory boards for Amgen, Merck, Eli Lilly, Radius Health, AgNovos Healthcare, and Alexion. He serves on the Board of Trustees of the National Osteoporosis Foundation (no monetary remuneration). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.