Bone fragility in diabetes cannot be solely attributed to changes in bone mineral density (BMD) as BMD is on average higher in patients with type 2 diabetes mellitus (T2DM) than in healthy controls. High-resolution peripheral quantitative computed tomography (HR-pQCT) studies investigating bone microstructure in patients with diabetes indicate increased cortical porosity, and micro indentation studies of bone tissue from diabetic donors show decreased bone material strength resulting in overall weakened bone material properties [Thraikil et al, 2005; Shanbhogue et al, 2016]. These microstructural alterations relate to direct effects of diabetes on bone cells.
Generally, bone turnover, i.e. bone formation by osteoblasts and resorption by osteoclasts, is low in diabetic patients [Hygum et al, 2017]. Low osteoblast activity may be due to the progressive loss of β-cells, which are destroyed by the immune system; these cells produce osteoblast stimulating factors such as insulin, amylin and preptin, promoting bone formation [Thraikil et al, 2005]. Another possibility is that the glitazones, a class of drugs commonly used to treat T2DM, promote the differentiation of mesenchymal stem cells (MSCs) to adipocytes rather than osteoblasts thus reducing osteoblast number. Since bone cell response is driven by osteoblast-osteoclast coupling, a reduction in osteoblast activity or number ultimately reduces bone turnover, leading to microdamage accumulation [Shanbhogue et al, 2016]. Further, high glucose concentrations due to poor glycemic control can lead to advanced glycation endproducts (AGEs) in the bone collagen matrix, making the bone more brittle and susceptible to fracture. Importantly, sclerostin, a cytokine produced by osteocytes in response to changes in local mechanical strain has been shown to be elevated in patients with diabetes mellitus relative to controls, leading to lower levels of bone formation [Garcia-Martin et al, 2012].
