<i>N</i> -acetylcysteine Attenuates Osteoporosis Through Improving Bone Mineral Content and Mitigating Oxidative Stress and Inflammation in Rat Models

Background Osteoporosis is a progressive skeletal disorder characterized by decreased bone mass and structural deterioration, often exacerbated by oxidative stress and inflammation. Purpose This study aimed to evaluate the protective effect of N -acetylcysteine (NAC), a potent antioxidant, in a glucocorticoid-induced osteoporosis model in female Wistar rats. Materials and Methods Thirty rats were randomly divided into three groups: control, osteoporosis, and osteoporosis + NAC. Osteoporosis was induced by daily dexamethasone injections for 5 days. NAC (60 mg/kg) was administered orally for 12 weeks. Body weight progression, organ weights (femur, uterus, and vagina), bone biochemical markers, lipid profiles, oxidative stress indicators, and pro-/anti-inflammatory cytokines were measured at the endpoint. Results Rats in the osteoporosis group showed significant reductions in bone mineral density, bone mineral content, and body weights, along with decreased levels of calcium, phosphorus, magnesium, and vitamin D ( p &lt; .001). Estradiol (E2) levels, osteocalcin, and antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase, reduced glutathione) were also significantly reduced, while malondialdehyde (MDA) and inflammatory cytokines (interleukin-6, tumor necrosis factor alpha, interleukin-1 beta) were elevated. NAC supplementation restored these parameters toward normal, significantly improving bone biochemical markers, mineral levels, lipid profiles, and reducing oxidative and inflammatory stress. Interleukin-10 and E2 levels were notably increased in NAC-treated rats compared to the osteoporosis group ( p &lt; .01). Conclusion NAC exerts a protective effect against glucocorticoid-induced osteoporosis through its antioxidant and anti-inflammatory actions, mineral homeostasis support, and partial hormonal restoration. These findings highlight NAC’s potential as an adjunctive therapy for osteoporosis management.