Impact of Diabetes Mellitus on Bone Health

Abstract

Long-term exposure to a diabetic environment leads to changes in bone metabolism and impaired bone micro-architecture through a variety of mechanisms on molecular and structural levels. These changes predispose the bone to an increased fracture risk and impaired osseus healing. In a clinical practice, adequate control of diabetes mellitus is essential for preventing detrimental effects on bone health. Alternative fracture risk assessment tools may be needed to accurately determine fracture risk in patients living with diabetes mellitus. Currently, there is no conclusive model explaining the mechanism of action of diabetes mellitus on bone health, particularly in view of progenitor cells. In this review, the best available literature on the impact of diabetes mellitus on bone health in vitro and in vivo is summarised with an emphasis on future translational research opportunities in this field.

Keywords: bone marrow dysfunction; bone remodeling; diabetes mellitus; fracture healing; mesenchymal stem cells; type 1 complications; type 2 complications.

Figure 1

The interaction between osteoblasts, adipocytes, MSCs, and the marrow environment is altered in diabetes mellitus. Hyperglycemia directly alters gene expression associated with osteoblast activity by the inhibition of MSC maturation and metabolism, and indirectly alters bone metabolism by tampering with the PTH and Vitamin D system. Insulinopenia and low levels of IGF-1 exert an additional inhibitory effect on osteoblasts at different stages of diabetes mellitus. Increased production of adipocytes feed the cycle of chronic inflammation by producing ROS and inflammatory cytokines, which induce osteoblast apoptosis. ROS upholds this process by facilitating MSC differentiation into adipocytes by mediating PPAR-γ and reducing WNT transcription. Additionally, increased production of AGEs leads to non-enzymatic cross-links between collagen fibers and increased inflammation by the activation of RAGE. The accumulation of these patho-mechanisms ultimately leads to decreased bone quality and bone turnover in diabetes mellitus.