Role of denosumab in lipid metabolism disorders: clinical significance and potential mechanisms

Abstract

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.