Thymoquinone-Coenzyme Q10 Combination Therapy Ameliorates Post-Spinal Cord Injury Osteoporosis Through Enhanced Wnt/β-Catenin Signaling and Antioxidant Defense.

Spinal cord injury (SCI) results in rapid bone loss and osteoporosis development. This study investigated the synergistic effects of a combination of thymoquinone (TQ) and coenzyme Q10 (CoQ10) on SCI-induced osteoporosis. Thirty male Wistar rats underwent complete spinal cord transection at T10 and were divided into five groups: sham, untreated SCI, TQ-treated (100 mg/kg/day), CoQ10-treated (10 mg/kg/day), and combination therapy (TQ + CoQ10). After 21 days of treatment, combination therapy significantly improved BBB locomotor scores (12.1 ± 0.7 vs. 2.1±0.4 in untreated SCI; p < 0.001) and increased femoral BMD and BMC by 32.8% and 37.9%, respectively. Micro-CT analysis revealed 45.2% higher bone volume/total volume ratio and enhanced trabecular architecture. The combination therapy significantly downregulated SOST expression (76.2% reduction) while upregulating periostin (184.7% increase). Osteoclast markers decreased (CTR: 57.3%, cathepsin K: 63.1%) while osteoblast markers increased (ALP: 143.8%, osterix: 127.4%). Oxidative stress markers improved substantially, with 47.3% lower MDA levels and 86.5% higher SOD activity. TQ + CoQ10 combination therapy produces both synergistic and additive effects that ameliorates SCI-induced osteoporosis in association with altered expression of Wnt/β-catenin signaling components, enhancing bone formation, and reducing oxidative stress, demonstrating superior therapeutic efficacy compared to monotherapies.