Denosumab prevents the binding of receptor activator of nuclear factor-kB ligand (RANKL) to receptor activator of nuclear factor-kB (RANK) on the cells of the osteoclastic lineage. RANKL binds to RANK and stimulates osteoclast differentiation, activation and survival.

Denosumab is a fully human monoclonal antibody that binds to RANKL with high affinity and specificity. It blocks the interaction of RANKL with RANK and inhibits bone resorption. In postmenopausal women with low BMD, denosumab administered subcutaneously 60 mg every 6 months increased BMD by 1 to 7 % according to the skeletal site [1].

It inhibits bone resorption strongly and rapidly, e.g. serum CTX-I decreases by more than 80 % one week after denosumab injection. In postmenopausal osteoporotic women, denosumab decreased the risk of vertebral fracture by 70 % (including a 60% decrease in the incidence of multiple vertebral fractures) and the risk of non-spine fractures by 20 % (including a 40 % decrease in the incidence of hip fracture) [2].

Also in older men receiving androgen-deprivation therapy for prostate cancer, denosumab slowed bone turnover, increased BMD by 4 to 7 % as well as decreased the incidence of vertebral fractures by 60 % and the incidence of multiple fractures by 70 % [3].



1. McClung MR, Lewiecki EM, Cohen SB, Bolognese MA, Woodson GC, Moffett AH, Peacock M, Miller PD, Lederman SN, Chesnut CH, Lain D, Kivitz AJ, Holloway DL, Zhang C, Peterson MC, Bekker PJ 2006 Denosumab in postmenopausal women with low bone mineral density. N Engl J Med 354:821-831
2. Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, Delmas P, Zoog HB, Austin M, Wang A, Kutilek S, Adami S, Zanchetta J, Libanati C, Siddhanti S, Christiansen C 2009 Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 361:756-765
3. Smith MR, Egerdie B, Hernández Toriz N, Feldman R, Tammela TL, Saad F, Heracek J, Szwedowski M, Ke C, Kupic A, Leder BZ, Goessl C 2009 Denosumab in men receiving androgen-deprivation therapy for prostate cancer. N Engl J Med 361:745-755