期刊
JOURNAL OF CLINICAL MEDICINE
卷 10, 期 4, 页码 -出版社
MDPI
DOI: 10.3390/jcm10040787
关键词
sclerostin; wnt signaling; osteoblast; osteoclast; osteoporosis; romosozumab
资金
- German Research Foundation [SPP 2084, FOR5146]
- Elsbeth Bonhoff-Foundation
- Fritz-ThyssenFoundation
Osteoporosis is a common disease characterized by reduced bone mass, and Romosozumab, as a novel monoclonal antibody against sclerostin, has a dual mode of action that enhances bone formation and suppresses bone resorption simultaneously, offering potential as a new effective treatment for patients at high fracture risk.
Osteoporosis is characterized by reduced bone mass and disruption of bone architecture, resulting in increased risk of fragility fractures and significant long-term disability. Although both anti-resorptive treatments and osteoanabolic drugs, such as parathyroid hormone analogues, are effective in fracture prevention, limitations exist due to lack of compliance or contraindications to these drugs. Thus, there is a need for novel potent therapies, especially for patients at high fracture risk. Romosozumab is a monoclonal antibody against sclerostin with a dual mode of action. It enhances bone formation and simultaneously suppresses bone resorption, resulting in a large anabolic window. In this opinion-based narrative review, we highlight the role of sclerostin as a critical regulator of bone mass and present human diseases of sclerostin deficiency as well as preclinical models of genetically modified sclerostin expression, which led to the development of anti-sclerostin antibodies. We review clinical studies of romosozumab in terms of bone mass accrual and anti-fracture activity in the setting of postmenopausal and male osteoporosis, present sequential treatment regimens, and discuss its safety profile and possible limitations in its use. Moreover, an outlook comprising future translational applications of anti-sclerostin antibodies in diseases other than osteoporosis is given, highlighting the clinical significance and future scopes of Wnt signaling in these settings.
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