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  3. Maltol induces diabetic fragility fractures by disrupting the balance of bone remodeling

Maltol induces diabetic fragility fractures by disrupting the balance of bone remodeling

  • Cell Metab. 2026 Mar 27:S1550-4131(26)00095-1. doi: 10.1016/j.cmet.2026.03.001.
Jinyang Wang 1,  Ziyuan Wang 2,  Jinyi Feng 3,  Ying Zhang 2,  Lizheng Yao 2,  Yiran Zhang 2,  Ruijie Zhang 4,  Jingyi Cai 3,  Hao Yu 2,  Songhan Deng 2,  Xinrui Chen 2,  Rui Liang 5,  Caoxin Huang 3,  Jia Li 6,  Xuejun Li 7,  Qinxi Li 8,  Xiulin Shi 9
Affiliations

Affiliations

  • 1 State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen 361102, China; State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Fujian Engineering Research Center of Molecular Theranostic Technology, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, Fujian 361102, China.
  • 2 State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen 361102, China.
  • 3 Department of Endocrinology and Diabetes, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
  • 4 State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Fujian Engineering Research Center of Molecular Theranostic Technology, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, Fujian 361102, China.
  • 5 Chongqing Academy of Chinese Materia Medica, Chongqing 400065, China.
  • 6 Xiamen Meliomics Technology Co., Ltd., Xiamen, Fujian 361028, China.
  • 7 Department of Endocrinology and Diabetes, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China. Electronic address: xmlixuejun@163.com.
  • 8 State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen 361102, China. Electronic address: liqinxi@xmu.edu.cn.
  • 9 Department of Endocrinology and Diabetes, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China. Electronic address: shixiulin2002@163.com.
PMID: 41903530 DOI: 10.1016/j.cmet.2026.03.001
Abstract

Type 2 diabetes is a major risk factor for fragility fractures, yet the contributors to skeletal fragility remain unclear. Through integrated clinical metabolomics, in vivo, and in vitro analyses, we identify maltol-a widely used food additive-as a previously unrecognized risk factor for hyperglycemia-associated bone fragility. Metabolomic profiling of femoral neck tissue from individuals with fragility fractures showed diabetes-associated maltol accumulation, and elevated circulating maltol levels correlated with increased fracture incidence. Mechanistically, maltol inhibits osteoblast differentiation via Wnt/β-catenin and promotes osteoclast maturation through nuclear factor κB (NF-κB) signaling, disrupting bone remodeling. These effects are amplified under hyperglycemia, while Insulin reversal of glucose levels mitigates maltol-induced skeletal deterioration in mouse models. Given the widespread use of maltol in processed foods, these findings suggest that food additive safety should consider metabolic context and call for disease-specific dietary exposure guidelines to reduce fracture risk in diabetes.

Keywords

bone remodeling; diabetes mellitus; fragility fractures; maltol.

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