Diabetes and Bone Fragility

Abstract

Diabetes is a highly prevalent disease with complications that impact most bodily systems. However, the impact of diabetes on bone health is frequently ignored or underestimated. Both type 1 (T1D) and type 2 diabetes (T2D) are associated with a higher risk of fractures, albeit through different mechanisms. T1D is characterized by near total insulinopenia, which affects the anabolic tone of bone and results in reduced bone mineral density (BMD). Meanwhile, patients with T2D have normal or high BMD, but carry an increased risk of fractures due to alterations of bone microarchitecture and a local humoral environment that stimulates osteoclast activity. Chronic hyperglycemia induces non-enzymatic glycation of collagen in both types of diabetes. Epidemiological evidence confirms a largely increased fracture risk in T1D and T2D, but also that it can be substantially reduced by opportune monitoring of fracture risk and appropriate treatment of both diabetes itself and osteopenia or osteoporosis if they are present. In this review, we summarize the mechanistic, epidemiological, and clinical evidence that links diabetes and bone fragility, and describe the impact of available diabetes treatments on bone health.

Oxytocin and Bone: Review and Perspectives

“…The mechanisms involved in type 1 diabetes imply a reduced BMD as a consequence of insufficient anabolic tone from insulin, while in type 2 diabetes, BMD is normal or high, Regarding secondary types of osteoporosis, glucocorticoid treatment and diabetes are the most common causes. Glucocorticoid and diabetes induced osteoporosis share pathophysiological characteristics: a predominant decrease in bone formation rather than an increase in bone resorption and an increase in bone marrow adiposity [60][61][62]. In glucocorticoid-induced osteoporosis, after an early transient increase in bone resorption, there is a long-term suppression of bone formation related to an increased sclerostin secretion and up-regulation of peroxisome proliferator-activated receptor that favor the differentiation of pluripotent precursor cells to adipocytes rather than osteoblasts, contributing to bone marrow adipocyte expansion [63,64].…”

“…Fragility fractures are now recognized as an important complication of both diabetes mellitus type 1 and type 2, particularly in those with long-term disease, poor glycaemic control, β cells failure and insulin treatment [65]. The mechanisms involved in type 1 diabetes imply a reduced BMD as a consequence of insufficient anabolic tone from insulin, while in type 2 diabetes, BMD is normal or high, but there is an alteration of bone quality and microarchitecture [61]. Osteoporosis in diabetes is associated with a low bone turnover, an accumulation of advanced glycation end-products, inflammation, oxidative stress, adipokine alterations, WNT dysregulation and increased bone marrow fat [65].…”

Effects of Anti-Diabetic Drugs on Fracture Risk: A Systematic Review and Network Meta-Analysis

“…Currently, multiple anti-diabetic drugs are available, but previous research did not integrate all related data into one analysis and compare the available anti-diabetic drugs head-to-head. Therefore, associations between fracture events and anti-diabetic drug effects have not been clearly elucidated (12)(13)(14). To address this problem, we herein utilized Bayesian meta-analysis, a validated and mature statistical method, to compare the effects of all available anti-diabetic drugs on fracture risk (15).…”

Association Between Factors Involved in Bone Remodeling (Osteoactivin and OPG) With Plasma Levels of Irisin and Meteorin-Like Protein in People With T2D and Obesity

“…On the other hand, osteoporosis is a bone disorder that occurs when there is a decrease in bone density, increasing the risk of fracture. Diabetes has been strongly associated with an increased risk of osteoporosis-associated fractures (5). Similarly, obesity is closely interconnected with bone metabolism (6).…”