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Endocrine Abstracts (2014) 35 S19.2 | DOI: 10.1530/endoabs.35.S19.2

ECE2014 Symposia Osteoporosis - An update (3 abstracts)

Denosumab: current perspectives

Karine Briot


Rheumatology Department, Cochin Hospital, Paris, France.


The interaction of RANKL with RANK is critical for the formation and function of bone-resorbing osteoclasts. Denosumab, a fully human MAB against RANKL, is an anti-resorptive drug that acts by preventing RANKL from interacting with RANK on the osteoclast precursor cells. Twice-yearly denosumab treatment is associated with markedly improved bone mineral density (BMD) and cortical and trabecular bone strength, and significantly reduced osteoporotic fracture. In clinical studies, denosumab has been shown to decrease the risk for vertebral, hip and nonvertebral fractures in women with postmenopausal osteoporosis and the risk for new vertebral fractures in men with nonmetastatic prostate cancer receiving androgen deprivation therapy, with a rate of side effects similar to placebo. Although clinical effectiveness was maintained for up to 6 months following a single injection of denosumab, cessation of treatment was associated with a more rapid reduction in BMD because the denosumab is not incorporated into the structure of the bone itself. Safety concerns include infections, skin reactions, hypocalcemia, osteonecrosis of the jaw and atypical femur fractures. Placebo-controlled and open-label extension studies showed similar adverse event (AE) and serious AE rates, relative to placebo, over up to 7 years. Data indicate that denosumab offers an effective alternative therapeutic approach for the treatment of severe osteoporosis, with positive effects on BMD and reduction of fragility fractures risk, and a potential advantage on patient adherence.

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