Recent Update on RANKL Inhibitor

Choi, Han Seok

Abstract

The prevalence of osteoporosis is continuing to increase with growing elderly population. A variety of anti-osteoporotic agents have been used for the prevention and treatment of osteoporosis and osteoporotic fractures. Novel therapeutic agents based on the newly discovered mechanisms in bone biology have been recently introduced. Denosmab, a fully human monoclonal antibody to the receptor activator of nuclear factor-ÎºB ligand, is a new therapeutic agent that inhibits osteoclast differentiation, activity, and survival. In the fracture reduction evaluation of denosumab in osteoporosis every 6 months (FREEDOM) trial, denosumab treatment for 36 months significantly increased bone mineral density at all skeletal sites evaluated, thereby resulting in a significant reduction in the risk of vertebral, nonvertebral, and hip fractures. In the FREEDOM Extension study, in which denosumab treatment was continued for up to 10 years, denosumab showed a continued improvement in bone mineral density and a consistently low fracture risk similar to rates observed in the denosumab group during the FREEDOM trial. Denosumab also offered a favorable safety profile with generally low and stable adverse event rates. Denosumab was indicated for treatment of postmenopausal women with osteoporosis at high risk for fracture, treatment to increase bone mass in men with osteoporosis, treatment of bone loss in men receiving androgen deprivation therapy for prostate cancer, and treatment of bone loss in women receiving adjuvant aromatase inhibitor therapy for breast cancer. For these patients, denosumab is an important option for the prevention and treatment of osteoporosis and osteoporotic fractures.