Romosozumab (sclerostin monoclonal antibody) for the treatment of osteoporosis in postmenopausal women: A review

Abstract

Romosozumab (ROMO) is a recently approved monoclonal antibody (approved by the U.S. Food and Drug Administration [FDA] in April 2019 and Health Canada in June 2019) for the treatment of osteoporosis in postmenopausal women. ROMO works by selectively inhibiting sclerostin-a glycoprotein that inhibits osteoblasts and further promotes bone resorption. The authors reviewed three phase III clinical trials (Fracture Study in Postmenopausal Women with Osteoporosis [FRAME], Active-Controlled Fracture Study in Postmenopausal Women with Osteoporosis at High Risk [ARCH], and STudy evaluating the effect of RomosozUmab Compared with Teriparatide in postmenopaUsal women with osteoporosis at high risk for fracture pReviously treated with bisphosphonatE therapy [STRUCTURE]) that demonstrated ROMO's ability to increase bone mineral density (BMD) at the lumbar spine and hip and the risk of vertebral and clinical fractures. Additionally, clinical trials demonstrated the risk for serious cardiovascular events among patients that received ROMO, and these severe adverse reactions deserve further investigation. Although ROMO presents as a potentially exciting therapeutic with serious clinical implications, the authors recommend further analysis using real-world evidence (RWE) studies to fully elucidate the cardiovascular event risk associated with ROMO administration.

Resveratrol can enhance osteogenic differentiation and mitochondrial biogenesis from human periosteum-derived mesenchymal stem cells

“…Thus, PO-MSCs were expected to play a more critical role in bone healing than BM-MSCs [12,63]. Recently, several studies have found that the sclerostin antibody has clinical implications for the treatment of osteoporosis [64,65]. Thompson et al [66] reported that systemic administration of sclerostin antibody in geriatric mice can enhance the proliferation of osteogenic cells in the periosteum of geriatric mice and can contribute to an increase in cortical bone thickness.…”

Osteoclasts and Microgravity

“…Clinical trials have shown that monthly subcutaneous injections of romosozumab are effective in increasing bone formation and density and decreasing bone resorption—results in keeping with the known effects of sclerostin on bone homeostasis [ 73 ]. However, there is some concern about the potential cardiotoxicity of romosozumab, prompting the need for further observations [ 74 ]. In addition, there is evidence in experimental animals that sclerostin generated in response to TNF-α and IL-1β improves post-traumatic osteoarthritis by inhibiting the activity of proteolytic enzymes involved in cartilage degradation [ 75 ].…”

Osteoclasts and Microgravity

“…Clinical trials have shown that monthly subcutaneous injections of romosozumab is effective in increasing bone formation and density and decreasing bone resorption, results in keeping with the known effects of sclerostin on bone homeostasis [72]. However, there is some concern about potential cardiotoxicity of romosozumab, prompting the need for further observations [73]. Osteoprotegerin-Fc given subcutaneously to mice flown for 12 days in space produced a sustained suppression of bone resorption and, thus, deserves further study [74].…”