Archives of osteoporosis · 2025
Role of denosumab in lipid metabolism disorders: clinical significance and potential mechanisms.
СтатьяОбзорПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Lou Yuan, Chen Huan, Fei Sijia, Chen Xinda, Guo Lixin, Pan Qi
Аннотация
PURPOSE: Lipid metabolism disorders, characterized by abnormal blood lipid levels, are central to the pathogenesis of obesity, nonalcoholic fatty liver disease (NAFLD), and atherosclerosis. These conditions increase the risk of type 2 diabetes, cardiovascular diseases (CVD), and stroke, highlighting the need for novel therapeutic approaches. Emerging evidence suggests a complex interplay between bone and lipid metabolism, with RANKL playing a key role. This review explores the potential of denosumab, a RANKL-targeting monoclonal antibody, in modulating lipid metabolism and its broader metabolic implications.
METHODS: We conducted a comprehensive literature review to analyze the molecular mechanisms by which denosumab influences lipid metabolism, with a focus on the OPG/RANKL/RANK signaling pathway. Additionally, we examined the roles of immune modulation, bone marrow adipose tissue, and gut microbiota in metabolic diseases.
RESULTS: Denosumab, primarily known for its anti-resorptive effects in osteoporosis, may also exert beneficial effects on lipid metabolism. Preclinical and clinical studies suggest its potential in ameliorating obesity, NAFLD, and atherosclerosis. The OPG/RANKL/RANK axis appears to mediate crosstalk between bone and metabolic pathways, while immune regulation and gut microbiota may further contribute to these effects.
CONCLUSION: Denosumab shows promise as a therapeutic agent for lipid metabolism disorders, though long-term metabolic effects remain unclear. Further research is needed to validate its efficacy and elucidate underlying mechanisms, which could pave the way for novel treatments targeting metabolic diseases.
METHODS: We conducted a comprehensive literature review to analyze the molecular mechanisms by which denosumab influences lipid metabolism, with a focus on the OPG/RANKL/RANK signaling pathway. Additionally, we examined the roles of immune modulation, bone marrow adipose tissue, and gut microbiota in metabolic diseases.
RESULTS: Denosumab, primarily known for its anti-resorptive effects in osteoporosis, may also exert beneficial effects on lipid metabolism. Preclinical and clinical studies suggest its potential in ameliorating obesity, NAFLD, and atherosclerosis. The OPG/RANKL/RANK axis appears to mediate crosstalk between bone and metabolic pathways, while immune regulation and gut microbiota may further contribute to these effects.
CONCLUSION: Denosumab shows promise as a therapeutic agent for lipid metabolism disorders, though long-term metabolic effects remain unclear. Further research is needed to validate its efficacy and elucidate underlying mechanisms, which could pave the way for novel treatments targeting metabolic diseases.