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Journal of Bone and Mineral Metabolism

Erschienen in:

15.10.2020 | Invited Review

RANKL as a target for the treatment of osteoporosis

verfasst von: Toshio Matsumoto, Itsuro Endo

Erschienen in: Journal of Bone and Mineral Metabolism | Ausgabe 1/2021

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Abstract

Osteoporosis is characterized by compromised bone strength, predisposing to an increased risk of fracture. Because bone is constantly remodeled, and bone mass and structure are determined by the balance between bone resorption and bone formation, it is important to maintain normal bone turnover. Therefore, therapies that reduce bone resorption have been the mainstream of osteoporosis treatment. Receptor activator of nuclear factor-kappa B ligand (RANKL)-RANK signaling was found to play a pivotal role in the regulation of osteoclastic bone resorption, and inhibition of RANKL-RANK system has become an important therapeutic target for the treatment of osteoporosis. Denosumab, a fully human monoclonal anti-RANKL neutralizing antibody, is developed as a drug for the treatment of osteoporosis. This review summarized pharmacokinetic and pharmacodynamic properties of denosumab, clinical studies including phase 2 dose-ranging and its extension study, phase 3 fracture prevention study (FREEDOM) with extension up to 10 years, studies on male osteoporosis (ADAMO study), and on glucocorticoid-induced osteoporosis, along with relevant clinical studies in Japan. In addition, mechanism of denosumab action that can explain its long-term sustained effects, combination and sequential treatment as well as the problems in discontinuation of denosumab, and finally safety of denosumab therapy is discussed.

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Titel: RANKL as a target for the treatment of osteoporosis
verfasst von: Toshio Matsumoto
Itsuro Endo
Publikationsdatum: 15.10.2020
Verlag: Springer Singapore
Erschienen in: Journal of Bone and Mineral Metabolism / Ausgabe 1/2021
Print ISSN: 0914-8779
Elektronische ISSN: 1435-5604
DOI: https://doi.org/10.1007/s00774-020-01153-7

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