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Denosumab: Mechanisms and Therapeutic Effects in the Treatment of Osteoporosis

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Osteoporosis

Part of the book series: Contemporary Endocrinology ((COE))

Abstract

Denosumab is a fully human monoclonal antibody to receptor activator of nuclear factor kappa-B ligand (RANKL), the principal regulator of osteoclastic bone resorption. By binding and neutralizing RANKL, it is a potent inhibitor of osteoclast differentiation, activity, and survival. For postmenopausal women with osteoporosis, treatment with 60 mg denosumab subcutaneously every 6 months for up to 10 years is associated with continuing increases in bone mineral density (BMD). Denosumab reduces the risk of vertebral fractures, nonvertebral fractures, and hip fractures with a generally favorable safety profile. Larger increases in total hip BMD are associated with greater reductions in the risk of new or worsening vertebral fractures. Atypical femur fractures and osteonecrosis of the jaw have been reported in patients treated with denosumab. There is no evidence that denosumab impairs fracture healing. BMD increases with denosumab are greater than with bisphosphonates. Discontinuation of denosumab is followed by a rapid decrease in BMD, a rise in bone turnover marker levels to above baseline, and a return of vertebral fracture risk to baseline with an apparent increase in the risk of multiple vertebral fractures. Patients who stop denosumab should be continued on treatment with another antiresorptive agent. Teriparatide after denosumab has been associated with bone loss. The combination of denosumab and teriparatide increases BMD more than either agent alone.

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Disclosure

The author has received institutional grant/research support from Amgen, PFEnex, and Mereo; he has served on scientific advisory boards for Amgen, Radius, Shire, Alexion, Ultragenyx, and Sandoz; he serves on the speakers’ bureau for Shire, Alexion, and Radius; he is a board member of the National Osteoporosis Foundation, International Society for Clinical Densitometry, and Osteoporosis Foundation of New Mexico.

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  1. New Mexico Clinical Research & Osteoporosis Center, Albuquerque, NM, USA

    E. Michael Lewiecki

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  1. Massachusetts General Hospital, Boston, MA, USA

    Benjamin Z. Leder

  2. Massachusetts General Hospital, Boston, MA, USA

    Marc N. Wein

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Lewiecki, E.M. (2020). Denosumab: Mechanisms and Therapeutic Effects in the Treatment of Osteoporosis. In: Leder, B., Wein, M. (eds) Osteoporosis. Contemporary Endocrinology. Humana, Cham. https://doi.org/10.1007/978-3-319-69287-6_15

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