Osteoporosis Treatment with Anti-Sclerostin Antibodies—Mechanisms of Action and Clinical Application

Abstract

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.

Efficacy Evaluation of Modified Siwu Decoction to Treat Osteoporosis in Patients with Poststroke Hemiplegia by Using the Magnetic Resonance Imaging Features

“…A small portion of it comes from food or supplements and has an important role in the human skeleton. BGP is an active polypeptide synthesized and secreted by osteoblasts and plays an important role in regulating bone metabolism, and its level reflects osteoblast activity [22,23]. In this work, the analysis of bone metabolism indicators showed that the 25- OH-VD and BGP of the observation group were significantly higher than those of the control group at 180 days after treatment, with statistically significant differences (P < 0.05).…”

The current situation in the approach to osteoporosis in older adults in Turkey: areas in need of improvement with a model for other populations

“…It has been reported to reduce the risk of vertebral and clinical fractures and increase BMD in women with postmenopausal OP. It is contraindicated in those with a history of myocardial infarction or ischemic stroke but has a manageable tolerability profile [91,92]. The availability and reimbursement of romosozumab have the potential to improve the management of OP in the country.…”

Suppression of sost/sclerostin and dickkopf-1 promote intervertebral disc structure in mice

“…Activation of wnt signaling is known to promote the inflammatory response in the IVD. 44 However, with both administration of scl-Ab and in the KO, while Wnt signaling is activated, heat shock protein gene expression is decreased. Because there was no difference in heat shock protein expression from the dkk1-Ab injection, and despite Wnt signaling being activated, we believe that heat shock protein expression in the IVD is controlled by sclerostin and not by Wnt signaling itself.…”

“…This may be of little concern in humans as IVD degeneration begins as early as 20 years of age 4 and anti-sclerostin antibody is administered in postmenopausal women at high risk for fracture, which commonly occurs later in age. 44 Difference in scl-ab and dkk, Hsp, immune, and wnt signaling…”