Effects of the glucagon-like peptide-1 receptor agonist PEG-Loxe on diabetic osteoporosis: a mechanistic study

BACKGROUND: Diabetic osteoporosis is characterized by disrupted bone remodeling involving impaired osteogenesis and excessive osteoclastic activity. Although glucagon-like peptide-1 receptor agonists (GLP-1RAs) have hypoglycemic benefits, their effects on bone metabolism remain unclear. This study investigates the osteoprotective potential of polyethylene glycol loxenatide (PEG-Loxe), a GLP-1RA hypoglycemic drug. METHODS: mice were treated with PEG-Loxe. We examined serum markers (CTX, HMGB-1, TNF-α, and IL-1β) and performed micro-CT and histomorphometric analyses.In clinical research,serum markers and BMD were analysed. RESULTS: mice, PEG-Loxe increased osteoblasts and reduced osteoclasts. RAGE, HMGB-1, TNF-α, and IL-1β were reduced to varying degrees (p<0.05; p<0.01; p<0.01; p<0.01). Micro CT scanning of 3D images of mouse femurs showed that PEG-Loxe can increase femoral tissue and reduce porosity. In clinical research,CTX, HMGB-1, TNF-α, and IL-1β were significantly reduced in the PEG-Loxe group compared to the Non-PEG-Loxe group (p<0.05). There was no significant difference in BMD between the two groups. CONCLUSIONS: PEG-Loxe exerts comprehensive osteoprotective effects in type 2 diabetes by simultaneously promoting osteogenesis and suppressing osteoclastogenesis, through modulation of HMGB-1 signaling. PEG-Loxe can significantly improve bone turnover status and reduce bone resorption levels, with potential osteoprotective effects.