Capsaicin counteracts dexamethasone-induced osteoporosis and metabolic disturbances in rats: role of AMPK/SIRT1/β-catenin/RUNX2 pathway.

Given their potent immunosuppressive and anti-inflammatory effects, long-term glucocorticoid therapy (GCs) is a common cause of bone fractures and secondary osteoporosis. Transient receptor potential vanilloid 1 (TRPV1) has been shown to play a role in preserving bone homeostasis and preventing bone disorders. The chili pepper is a naturally occurring source of capsaicin, a TRPV1 agonist. For this reason, this study compared the anti-resorptive properties of capsaicin with alendronate, the conventional treatment for osteoporosis, using a rat model of osteoporosis induced by dexamethasone (Dexa). Over six weeks, five groups of rats received the vehicle, Dexa alone (0.1 mg/kg, Sc), or Dexa plus either alendronate (1 mg/kg, orally) or capsaicin (1 or 2.5 mg/kg, orally). After the experiment, osteocalcin, RANKL, phosphorus, calcium, alkaline phosphatase (ALP), and metabolic parameters were measured. Furthermore, AMPK levels and the relative expression of Bax, Bcl-2, SIRT1, β-catenin, and RUNX2 were assessed in bone, and tissues from the femur were evaluated histologically. Capsaicin's effectiveness in alleviating the bone-damaging effect of dexamethasone was evident through a dose-dependent reduction in ALP, RANKL, and Bax, a rise in osteocalcin and Bcl-2, and a higher expression of AMPK, SIRT1, β-catenin, and RUNX2. Additionally, capsaicin improved bone architecture and effectively mitigated Dexa's detrimental metabolic impact on blood glucose and lipid profile. By upregulating the AMPK/SIRT1/β-catenin/RUNX2 pathway, capsaicin exhibits dose-dependent bone-stimulant effects in a dexamethasone-induced osteoporosis model in rats.