Long-term treatment of osteoporosis: safety and efficacy appraisal of denosumab

Athanasios D Anastasilakis,1 Konstantinos A Toulis,1 Stergios A Polyzos,2 Chrysostomos D Anastasilakis,3 Polyzois Makras41Department of Endocrinology, 424 General Military Hospital, 2Second Medical Clinic, Medical School, Aristotle University of Thessaloniki, Ippokration Hospital, 3Department of Pharmacology, 424 General Military Hospital, Thessaloniki; 4Department of Endocrinology and Diabetes, 251 Hellenic Air Force and VA General Hospital, Athens, GreeceAbstract: Denosumab is a fully human monoclonal antibody to the receptor activator of nuclear factor-κB ligand (RANKL), a member of the tumor necrosis factor receptor superfamily essential for osteoclastogenesis. Denosumab treatment is associated with a rapid, sustained, and reversible reduction in bone turnover markers, a continuous marked increase in bone mineral density at all sites, and a marked decrease in the risk of vertebral, hip, and nonvertebral fractures in women with postmenopausal osteoporosis. Therefore, it could be considered as an effective alternative to previous bisphosphonate treatment as well as first-line treatment of severe osteoporosis. Cost-effectiveness studies support this suggestion. In addition, denosumab seems to be the safest treatment option in patients with impaired renal function. Denosumab is characterized by reversibility of its effect after treatment discontinuation, in contrast with bisphosphonates. Large-scale clinical trials, including the extension of FREEDOM trial for up to 5 years, are reassuring for its safety. However, given its brief post-market period, vigilance regarding adverse events related to putative RANKL inhibition in tissues other than bone, as well as those related to bone turnover oversuppression, is advised.Keywords: adverse event, denosumab, efficacy, fracture, osteoporosis, safet