Antiosteoporosis effect of Tempol against bone loss in ovariectomized rats, halting oxidative stress, inflammation, and apoptosis

Aim Osteoporosis, often resulting from estrogen deficiency, is marked by progressive bone loss, oxidative stress, inflammation, and increased cellular apoptosis. This study evaluated the therapeutic efficacy of Tempol, a superoxide dismutase mimetic, in mitigating osteoporotic changes in an ovariectomized (OVX) rat model. Methods Thirty Female Sprague–Dawley rats were assigned to three groups: Sham, OVX, and OVX treated with Tempol (100 mg/kg/day) for 12 weeks via intraperitoneal injection. Results Histological analysis of femoral tissue revealed significant trabecular thinning, increased separation, and reduced osteocyte numbers in the OVX group. These structural impairments were accompanied by decreased serum levels of bone formation markers—alkaline phosphatase (ALP) and osteocalcin—and elevated bone resorption indicators CTX and TRACP-5b. Temporal treatment reversed these changes, improving trabecular architecture and restoring osteocyte density, while normalizing bone turnover markers. Biochemical assays showed that OVX rats had diminished levels of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), indicating heightened oxidative stress. Tempol significantly elevated these enzymes, suggesting enhanced antioxidant defense. Furthermore, Tempol suppressed inflammatory cytokines (TNF-α, IL-6, IL-1β) and pro-apoptotic proteins (Bax, caspase-3) and upregulated the anti-apoptotic marker Bcl-2. Conclusion Overall, Tempol demonstrated a protective role against osteoporosis by improving bone structure, enhancing antioxidant capacity, and modulating inflammatory and apoptotic pathways. These findings support Tempol as a promising candidate for the prevention and treatment of postmenopausal osteoporosis.