Diabetes and bone fracture: risk factors for old and young

Abstract

Diabetes mellitus may affect bone turnover in a number of ways, thus leading to impaired bone quality and a consequent increase in fracture risk. These factors are summarised in this commentary.Keywords Bone mineral density . Diabetes mellitus . Fracture . Osteocalcin . Type 1 diabetes . Type 2 diabetes Abbreviation BMD Bone mineral density Diabetes and the skeleton have been linked on a number of levels, including an increased risk of fractures. Diabetes may affect both the young and the elderly. The mechanisms behind the increased fracture risk may be related to:1. Low-grade inflammation mainly linked to obesity affecting turnover in the skeleton [1]. This would predominantly be expected to be a factor in type 2 diabetes. It would by nature lead to a low turnover state in the bones, which is what is seen in diabetes [2, 3]. 2. An altered relationship between the beta cells and bone [4], as osteocalcin is involved in bone turnover but may also affect the beta cells [5]. If bone turnover is low, osteocalcin levels will decrease, and this may in theory further impair insulin secretion from the beta cells.3. Decreased bone turnover resulting from decreased osteoclastic resorption in bone with glycated collagen [2,3]. Because of the coupling between osteoclasts and osteoblasts, bone turnover would decrease. 4. Altered glycation of collagen and thus impaired biomechanical competence [6]. An increase in fractures stemming from this mechanism would not necessarily be reflected in changes in areal bone mineral density (BMD) determined by dual-energy X-ray absorptiometry (DXA) or other scanning techniques relying on measurements of calcium content of the bones. 5. Lack of the anabolic effects of insulin, which would be present in type 1 diabetes, and less so in type 2 diabetes, where insulin levels may be increased. However, altered levels of IGF1 may also play a role [7]. 6. Negative calcium balance brought about by hyperglycaemia through increased urinary calcium excretion [8] and altered intestinal calcium absorption [9]. 7. Alterations in vitamin D metabolism [10]-in particular in patients with renal disease. 8. Functional hypoparathyroidism [11]. This may be a less significant factor, as, in theory, hypoparathyroidism should lead to increased [12] and not decreased BMD. 9. Drug-specific effects, such as negative effects of peroxisome proliferator-activated receptor γ agonists [13], but also potential effects of other drugs, such as insulin or the oral glucose-lowering drugs.Besides these mechanisms, which are linked to bone biomechanical competence, increased risk of falls (for example, from peripheral neuropathy, impaired vision, hypoglycaemia, ischaemic cerebral events) may also play a role. These effects would not be linked to BMD.To further study these factors it is necessary to determine whether differences exist with age (say, older individuals being more susceptible than younger) or whether sex

The Bone Marrow-Derived Stromal Cells: Commitment and Regulation of Adipogenesis

“…An increased BM adiposity has been reported in type 1 and type 2 diabetes (T1D and T2D). However, in T1D, there is a decrease in bone mass, whereas T2D is characterized by no change or higher bone mass and paradoxically increased risk for osteoporotic fractures ( 147 – 150 ). Studies are underway to examine the role of impaired glucose metabolism and its associated hyperglycemia and hyperinsulinemia on the biological functions of BMSC.…”

Liraglutide, the glucagon‐like peptide‐1 receptor agonist, has anabolic bone effects in diabetic Goto‐Kakizaki rats 利拉鲁肽，一种胰高血糖素样肽‐1受体激动剂，在糖尿病Goto‐Kakizaki大鼠中具有骨合成代谢作用

“…Evidence from rodents and human studies indicates defective bone quality and a higher risk of fractures in the diabetic state. 1,2 Thus, bone should be an additional target organ for diabetes treatment.…”

Insulin Signaling in Bone Marrow Adipocytes

“…Obesity and T2D are increasingly recognized as risk factor for bone fractures [77][78][79][80][81]. New therapeutic strategies are needed based on understanding the biological and molecular mechanisms of BMAT formation.…”