Cuttone Alessandro, Xourafa Anastasia, Morace Carmela, Cannavò Vittorio, Bueti Francesca Maria, Mandraffino Giuseppe, Squadrito Giovanni, Basile Giorgio, Gaudio Agostino, Catalano Antonino, Russo Giuseppina Tiziana, Bellone Federica
Unit of Internal Medicine, Department of Clinical and Experimental Medicine, University Hospital G. Martino, University of Messina, 98100 Messina, Italy.
Unit of Thalassemia, Policlinico "G. Rodolico", Via S. Sofia 78, 95123 Catania, Italy.
Cells. 2025 May 15;14(10):724. doi: 10.3390/cells14100724.
Diabetes mellitus has been knowingly associated with increased risk of fractures, so much so that skeletal fragility is considered a complication of diabetes. Determinants of bone fragility in this chronic condition are several, and the diabetes treatment choice could influence bone metabolism. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have recently expanded the therapeutic armamentarium for type 2 diabetes mellitus (T2D); these antihyperglycemic drugs act by reducing renal glucose reabsorption in the proximal tubule and have a proven cardiorenal benefit. The role of SGLT2i towards phospho-calcium metabolism is still unclear, so we aimed to review the current evidence of the relationship between SGLT2i and calcium and phosphate homeostasis. The PubMed, Scopus, and Web of Knowledge databases were searched to identify original research articles, meta-analyses, and scientific reviews on effects on bone metabolism in T2D patients treated with SGLT2i. Emerging data indicate that SGLT2i may lead to a rise of bone turnover markers, promoting a lower skeletal bone density and an increased fracture risk on murine models, but in real-world studies, results are controversial. Therefore, more clinical trials are needed to further clarify this topic, and the effects of SGLT2i on calcium homeostasis remain to date poorly understood.
糖尿病与骨折风险增加之间的关联已为人所知，以至于骨骼脆弱被视为糖尿病的一种并发症。这种慢性病中骨脆弱的决定因素有多种，而糖尿病的治疗选择可能会影响骨代谢。钠-葡萄糖协同转运蛋白2抑制剂（SGLT2i）最近扩大了2型糖尿病（T2D）的治疗药物库；这些降糖药物通过减少近端小管的肾葡萄糖重吸收起作用，并且已证实具有心脏肾脏益处。SGLT2i对磷钙代谢的作用仍不清楚，因此我们旨在综述SGLT2i与钙和磷稳态之间关系的现有证据。检索了PubMed、Scopus和Web of Knowledge数据库，以识别关于SGLT2i治疗的T2D患者骨代谢影响的原始研究文章、荟萃分析和科学综述。新出现的数据表明，SGLT2i可能导致骨转换标志物升高，在小鼠模型中促进较低的骨骼骨密度和增加骨折风险，但在实际研究中，结果存在争议。因此，需要更多的临床试验来进一步阐明这个问题，并且迄今为止，SGLT2i对钙稳态的影响仍知之甚少。
