Abstract
Impaired clinical fracture healing remains a major challenge, with surgical treatment often insufficient in patients with metabolic disorders or comorbidities such as diabetes and osteoporosis. Recent advances in metabolomics have brought the Sirtuin protein family to the forefront of bone regeneration research. These NAD⁺-dependent deacetylases exhibit cell-specific expression and regulate critical processes in osteoblasts and osteoclasts, linking glucose metabolism with bone remodeling. Sirtuins influence key pathways such as Wnt/β-catenin, AMPK, and mTOR, offering novel insights into the mechanisms of fracture healing. Emerging pharmacological strategies targeting Sirtuins show promising results in preclinical models. This review highlights the potential of Sirtuin-based interventions as therapeutic targets in the metabolic regulation of bone repair.