Therapeutic potential of hydroxybenzoic acid and lentinan in mitigating glucocorticoid-induced osteoporosis: an experimental study

Introduction The present study aimed to elucidate the therapeutic efficacy and mechanistic roles of Hydroxybenzoic Acid and Lentinan in counteracting glucocorticoid-induced osteoporosis (GIOP) in mice, with a focus on bone metabolism, inflammation, and oxidative stress pathways. Methods Sixty-eight male Swiss Albino mice were randomly assigned to seven groups: Healthy Control, Osteoporosis (methylprednisolone 10 mg/kg), Teriparatide (3 μg/kg), Low-Dose Lentinan (200 mg/kg), High-Dose Lentinan (400 mg/kg), Low-Dose HBA (50 μg/kg), and High-Dose HBA (100 μg/kg). In the study, all treatments were administered daily for a duration of 10 weeks. Results and Discussion Methylprednisolone administration resulted in marked deterioration of bone quality, with significant reductions in 25(OH)D3, IGF-1, and increased osteocalcin, TNF-α, IL-1β, HSP-27, RANK, and RANKL expression, accompanied by severe trabecular bone loss, all treatment groups showed notable recovery, with the most pronounced restoration in teriparatide and high-dose hydroxybenzoic acid groups. Mechanistically, hydroxybenzoic acid exerted potent anti-osteoclastic effects through RANK/RANKL pathway suppression, while Lentinan enhanced osteoblastic activity and mitigated inflammatory damage. In conclusion, these results provide preclinical evidence that HBA and lentinan warrant further investigation as potential adjuncts to established anti-osteoporotic therapy in the setting of long-term glucocorticoid use.