Additive effects of curcumin and glucosamine on knee function, cartilage protection, and subchondral bone preservation in a posttraumatic osteoarthritis rat model

Objective: Investigate the combined effects of curcumin and glucosamine on knee function, subchondral bone preservation, and cartilage protection in posttraumatic osteoarthritis (OA) rats. Background: OA increasingly become a global public health concern. Curcumin and glucosamine, both widely used as dietary supplements for OA, have shown distinct therapeutic effects. However, curcumin’s low bioavailability and the debated efficacy of glucosamine limit their broader clinical use. Methods: Posttraumatic OA was induced in Lewis rats through medial meniscus transection surgery. Rats were treated for 8 weeks with curcumin phospholipid liposome (C, 120 mg/kg/d), glucosamine (G, 190 mg/kg/d), or a combination of both (CG, C: G = 1:3, 63/190 mg/kg/d). Knee width was measured weekly, and weight-bearing was assessed twice weekly. Subchondral bone and cartilage changes were analyzed using micro-CT, toluidine blue staining, and the Osteoarthritis Research Society International (OARSI) score. Collagen II expression in cartilage was evaluated by immunohistochemistry. Results: Curcumin phospholipid liposomes significantly reduced joint swelling by up to 4.1% ( P < 0.001) and improved weight-bearing force by 24.2% at week 2 ( P < 0.01) and 14.9% at week 8 ( P < 0.05) in comparison with the medial meniscus transection group. Analysis of micro-CT indicated an increase in bone volume (BV; 11.6%) and bone mineral content (BMC; 13.0%) ( P < 0.05). Histologic analysis showed a 28.8% reduction in OARSI scores ( P < 0.01) and a 53.1% increase in collagen II expression ( P < 0.005). Glucosamine treatment reduced joint swelling by up to 5.7% ( P < 0.0001), improved weight-bearing by 31.6% ( P < 0.001) at week 2, and significantly increased BV (30.4%) and BMC (29.9%; P < 0.05). The combined treatment further reduced swelling by up to 6.6% ( P < 0.0001) and improved the R/L weight-bearing ratio by 24.7% ( P < 0.0001) at week 8. It also enhanced BV (28.6%), BMC (29.7%), and anisotropy degree (59.3%; P < 0.05). In addition, the combination therapy decreased OARSI scores by 27.1% ( P < 0.01) and enhanced the expression of collagen II by 54.2% ( P < 0.005), indicating enhanced cartilage and subchondral bone protection. Conclusion: Curcumin showed superior protection for cartilage, while glucosamine mainly benefited subchondral bone. Combined treatment demonstrated additive effects, improving both knee structure and physical function in OA, offering enhanced pain relief, anti-inflammatory action, and joint preservation.