Pharmacological Perspectives on Curcumin in Osteomyelitis: Molecular Mechanisms, Antibacterial Synergy, and Bone-Regenerative Potential

Osteomyelitis is difficult to treat due to biofilm persistence, limited antibiotic penetration, and increasing resistance. Curcumin, a pleiotropic polyphenol from Curcuma longa, shows convergent activity relevant to bone infection: (i) anti-biofilm and quorum-sensing inhibition, (ii) antibiotic synergy via efflux-pump modulation and membrane permeabilization, (iii) suppression of inflammatory pathways that drive osteoclastogenesis, and (iv) pro-osteogenic effects that support repair. In preclinical models, curcumin and select nanoformulations enhance bacterial clearance, reduce inflammatory osteolysis, and improve osteoblast function; device-related infection models also report decreased biofilm burden when curcumin is combined with standard antibiotics. Pharmacokinetic limitations of free curcumin are mitigated by nanocarriers, surface coatings, and bone-affine composites, though clinical translation remains unproven. This review synthesizes molecular mechanisms, evidence tiers (in vitro to in vivo), and delivery strategies, and distinguishes preventive (coatings/prophylaxis) from therapeutic (adjuvant post-debridement) use cases. Curcumin is a promising adjunct-not a stand-alone therapy-pending standardized biofilm models, bone-level PK/PD, and controlled clinical trials that test defined formulations, doses, and endpoints.