The impact of type 2 diabetes on bone metabolism

Abstract

Diabetes complications and osteoporotic fractures are two of the most important causes of morbidity and mortality in older patients and share many features including genetic susceptibility, molecular mechanisms, and environmental factors. Type 2 diabetes mellitus (T2DM) compromises bone microarchitecture by inducing abnormal bone cell function and matrix structure, with increased osteoblast apoptosis, diminished osteoblast differentiation, and enhanced osteoclast-mediated bone resorption. The linkage between these two chronic diseases creates a possibility that certain antidiabetic therapies may affect bone quality. Both glycemic and bone homeostasis are under control of common regulatory factors. These factors include insulin, accumulation of advanced glycation end products, peroxisome proliferator-activated receptor gamma, gastrointestinal hormones (such as the glucose-dependent insulinotropic peptide and the glucagon-like peptides 1 and 2), and bone-derived hormone osteocalcin. This background allows individual pharmacological targets for antidiabetic therapies to affect the bone quality due to their indirect effects on bone cell differentiation and bone remodeling process. Moreover, it’s important to consider the fragility fractures as another diabetes complication and discuss more deeply about the requirement for adequate screening and preventive measures. This review aims to briefly explore the impact of T2DM on bone metabolic and mechanical proprieties and fracture risk.

Metabolic and bone profile in postmenopausal women with and without type 2 diabetes: a cross-sectional study

“…The latest studies have established the active character of bone tissue, with important implications for the general homeostasis of the organism. It is now increasingly evident the role as endocrine organ exerted by the skeletal system, proving complex links with adipose tissue and glycaemic and energy metabolism [1,2]. Thus, osteocalcin secreted by osteoblast, in its undercarboxylated form, functions as a hormone with a role in regulating secretion and sensitivity to insulin, as well as energy consumption [1,[3][4][5][6].…”

“…On the other hand, insulin, insulin-like growth factor type 1 (IGF1) and incretin hormones have a role in regulating bone homeostasis [2]. The binding of insulin to specific receptors on osteoblast exerts anabolic effects, favoring survival, proliferation and differentiation of osteoblasts [3,8].…”

“…Current studies support the involvement of metabolic changes associated with T2DM in bone deterioration in terms of metabolism, structure and resistance. Chronic hyperglycemia affects both the bone cell component and the extracellular matrix by accumulating the final products of advanced glycation (AGEs) [1,2,[10][11][12]. This is responsible for collagen bone matrix stiffening, that would allow the formation and propagation of micro-cracks throughout bone matrix [11].…”

“…This is responsible for collagen bone matrix stiffening, that would allow the formation and propagation of micro-cracks throughout bone matrix [11]. Also, AGEs favors generation of reactive oxygen species within the bone, inducing an increase of inflammatory cytokines, that result in osteoblast dysfunction and osteoclast activation [2,13]. Diabetic bone disease is currently being considered a complication of diabetes mellitus, characterized by compromising osteoblasts function, but also by defects in microarchitecture and bone resistance, with a final effect of increasing the risk of fragility fracture [14].…”

“…Diabetic bone disease is currently being considered a complication of diabetes mellitus, characterized by compromising osteoblasts function, but also by defects in microarchitecture and bone resistance, with a final effect of increasing the risk of fragility fracture [14]. According to the ROTTERDAM study, patients with poorly controlled T2DM (HbA1c ≥ 7.5%) have a general risk of fracture by approximately 70% higher than nondiabetic subjects [1,2,16,17].…”