Nutraceuticals in orthopedic implant osseointegration: Mechanisms, evidence, and clinical perspectives

Total joint replacement is one of the most successful interventions in modern orthopedics, but long-term outcomes depend on effective osseointegration. Pharmacological strategies such as bisphosphonates, estrogens, and monoclonal antibodies can enhance bone-implant integration, but their clinical use is limited by adverse effects. Nutraceuticals, including polyphenols, carotenoids, and polyunsaturated fatty acids, have emerged as promising adjuncts to support bone health and osseointegration, thanks to their safety profile and biological activity. This review summarizes the molecular mechanisms involved in osseointegration, analyzes preclinical and clinical evidence on nutraceuticals, and critically assesses their translational potential. These compounds promote osteoblastogenesis, inhibit osteoclast differentiation, and mitigate oxidative stress, thereby improving peri-implant bone stability. Despite encouraging results, the clinical translation of nutraceuticals remains limited. Most available data are preclinical or based on surrogate endpoints such as bone mineral density, whereas true clinical success is determined by bone-to-implant contact and implant survival, which are rarely investigated in randomized controlled trials (RCTs). Advances in bioavailability strategies (liposomes, nanoemulsions, nanostructured lipid carriers) may improve systemic exposure, but future research must standardize dosages and provide high-quality RCTs to clarify the role of nutraceuticals as complementary tools in orthopedic implant surgery.