Update on the impact of type 2 diabetes mellitus on bone metabolism and material properties

Abstract

The prevalence of type 2 diabetes mellitus (T2DM) is increasing worldwide, especially as a result of our aging society, high caloric intake and sedentary lifestyle. Besides the well-known complications of T2DM on the cardiovascular system, the eyes, kidneys and nerves, bone strength is also impaired in diabetic patients. Patients with T2DM have a 40-70% increased risk for fractures, despite having a normal to increased bone mineral density, suggesting that other factors besides bone quantity must account for increased bone fragility. This review summarizes the current knowledge on the complex effects of T2DM on bone including effects on bone cells, bone material properties and other endocrine systems that subsequently affect bone, discusses the effects of T2DM medications on bone and concludes with a model identifying factors that may contribute to poor bone quality and increased bone fragility in T2DM.

Keywords: bone; diabetes.

Figure 1

Effects of T2DM on bone homeostasis. T2DM negatively affects trabecular bone mass, while cortical bone mass is increased. (1) The number and function of bone-forming osteoblast is reduced. In addition, vitamin D serum levels are decreased, which alters calcium and phosphate homeostasis. (2) Osteoblasts derive from MSC that favor differentiating into fat-storing adipocytes in T2DM leading to bone marrow adiposity and increased expression of cytokines and chemokines as well as to an elevated amount of free unsaturated fatty acids. (3) This results in increased inflammation leading to accumulation of pro-inflammatory M1 macrophages and reduced switch into anti-inflammatory M2 macrophages. (4) The network of osteocytes is reduced due to an increased apoptosis rate. They increase their expression of sclerostin, an inhibitor of osteoblast function, and RANKL, a promoter of osteoclastogensis. FGF-23, a phosphaturic hormone, is additionally increased. (5) Effects on osteoclasts are controversial in the literature, but T2DM is generally accepted to reduce bone turnover and thus also osteoclast function. (6) The amount of endothelial progenitor cells (EPC) is reduced in T2DM leading to vessel permeability. In addition, T2DM causes microhypoxia in bone niche, which in turn increases inflammation. (7) T2DM patients have an increased risk of falls and fractures due to reduced bone quality indicated by (8) an increased formation of advanced glycation end-products (AGEs) and (9) cortical porosity.