Yun Ding,1,* Yu Gao,2,* Jianjun Sun,1 Zhigang Cai1 

1Department of Cardiothoracic Surgery, Naval Medical Center, Naval Medical University (Second Military Medical University), Shanghai, 200052, People’s Republic of China; 2Department of Gastroenterology, Naval Medical Center, Naval Medical University (Second Military Medical University), Shanghai, 200052, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Zhigang Cai, Department of Cardiothoracic Surgery, Naval Medical Center, Naval Medical University (Second Military Medical University), No. 338, West Huaihai Road, Changning District, Shanghai, 200052, People’s Republic of China, Tel +86-21-81815166, Email Xhtx06@hotmail.com

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.

Keywords: Sirtuins, bone repair, osteoblasts, osteoclasts, glucose metabolism