Upadhyay Prabhat, Kumar Sudhir
Vincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Department of Microbiology and Immunology, Emory University, Atlanta, Georgia, USA.
Diabetes Metab Res Rev. 2025 Jul;41(5):e70062. doi: 10.1002/dmrr.70062.
Diabetic bone disease, a form of secondary osteoporosis, is characterised by reduced bone strength and increased fracture risk, particularly in patients with type 2 diabetes (T2D). Over 35% of T2D patients experience bone loss, with approximately 20% meeting diagnostic criteria for osteoporosis. This review highlights the complex mechanisms underlying diabetic bone disease, emphasising the need to reduce fracture risk and improve clinical outcomes. Key factors such as hyperglycemia, insulin resistance, insulin-like growth factors (IGFs), advanced glycation end products (AGEs), and proinflammatory cytokines disrupt bone turnover by impairing osteoblast and osteoclast function, leading to imbalanced bone formation and resorption. We explore the role of bone turnover and mineralisation in both cortical and trabecular bone, and the impact of microvascular complications on bone microarchitecture. Gut hormones, including Glucagon-like peptide-1 (GLP-1), Glucose-dependent insulinotropic polypeptide (GIP), and Parathyroid hormone (PTH), and the gut microbiota also play crucial roles in the pathogenesis of diabetic bone disease. Specific bacterial species, such as Akkermansia muciniphila and Bacteroides fragilis, are implicated in modulating the gut-bone axis through short-chain fatty acids (SCFAs) and other signalling pathways. These changes, along with altered gut hormone responses, affect bone density, microstructure, and material properties. Despite normal or increased bone mineral density (BMD) in some T2D patients, the material quality of bone is compromised, leading to greater fragility. This review integrates current knowledge of molecular, hormonal, and microbial interactions that contribute to diabetic bone disease, offering insights into potential therapeutic strategies and improving patient care.
糖尿病性骨病是继发性骨质疏松症的一种形式，其特征是骨强度降低和骨折风险增加，尤其是在2型糖尿病（T2D）患者中。超过35%的T2D患者存在骨质流失，约20%符合骨质疏松症的诊断标准。本综述强调了糖尿病性骨病背后的复杂机制，强调了降低骨折风险和改善临床结局的必要性。高血糖、胰岛素抵抗、胰岛素样生长因子（IGFs）、晚期糖基化终产物（AGEs）和促炎细胞因子等关键因素通过损害成骨细胞和破骨细胞功能来破坏骨转换，导致骨形成和吸收失衡。我们探讨了骨转换和矿化在皮质骨和小梁骨中的作用，以及微血管并发症对骨微结构的影响。肠道激素，包括胰高血糖素样肽-1（GLP-1）、葡萄糖依赖性促胰岛素多肽（GIP）和甲状旁腺激素（PTH），以及肠道微生物群在糖尿病性骨病的发病机制中也起着关键作用。特定的细菌种类，如嗜黏蛋白阿克曼氏菌和脆弱拟杆菌，通过短链脂肪酸（SCFAs）和其他信号通路参与调节肠-骨轴。这些变化，连同肠道激素反应的改变，会影响骨密度、微结构和材料特性。尽管一些T2D患者的骨矿物质密度（BMD）正常或增加，但骨的材料质量受损，导致更大的脆性。本综述整合了目前关于导致糖尿病性骨病的分子、激素和微生物相互作用的知识，为潜在的治疗策略提供了见解，并改善了患者护理。
