Pathophysiology and Management of Type 2 Diabetes Mellitus Bone Fragility

Abstract

Individuals with type 2 diabetes mellitus (T2DM) have an increased risk of bone fragility fractures compared to nondiabetic subjects. This increased fracture risk may occur despite normal or even increased values of bone mineral density (BMD), and poor bone quality is suggested to contribute to skeletal fragility in this population. These concepts explain why the only evaluation of BMD could not be considered an adequate tool for evaluating the risk of fracture in the individual T2DM patient. Unfortunately, nowadays, the bone quality could not be reliably evaluated in the routine clinical practice. On the other hand, getting further insight on the pathogenesis of T2DM-related bone fragility could consent to ameliorate both the detection of the patients at risk for fracture and their appropriate treatment. The pathophysiological mechanisms underlying the increased risk of fragility fractures in a T2DM population are complex. Indeed, in T2DM, bone health is negatively affected by several factors, such as inflammatory cytokines, muscle-derived hormones, incretins, hydrogen sulfide (H2S) production and cortisol secretion, peripheral activation, and sensitivity. All these factors may alter bone formation and resorption, collagen formation, and bone marrow adiposity, ultimately leading to reduced bone strength. Additional factors such as hypoglycemia and the consequent increased propensity for falls and the direct effects on bone and mineral metabolism of certain antidiabetic medications may contribute to the increased fracture risk in this population. The purpose of this review is to summarize the literature evidence that faces the pathophysiological mechanisms underlying bone fragility in T2DM patients.

Bone Mineral Density and Turnover After Sleeve Gastrectomy and Gastric Bypass: A Randomized Controlled Trial (Oseberg)

“…Second, there might also be a lack of statistical power due to the small sample size, with 6 studies having less than 50 participants ( 12 , 14 , 15 , 19 , 20 , 22 ). Third, type 2 diabetes is, despite having an increased risk of fragility fractures, associated with a higher BMD and lower bone turnover markers ( 36 , 37 ). Improved glycemic control postsurgery in our study population of patients solely with type 2 diabetes could therefore explain greater changes in aBMD and bone turnover markers than in some of the studies including few or no patients with diabetes ( 12 , 13 , 15–19 ).…”

Hypogonadism, Type-2 Diabetes Mellitus, and Bone Health: A Narrative Review

“…In particular, the prolonged use of thiazolidinediones (TZDs), such as pioglitazone and rosiglitazone, which activate peroxisome proliferator-activated receptor gamma (PPARγ), has been associated with negative effects on bone metabolism, despite a beneficial effect on glycemic control (reduced insulin resistance and improved insulin sensitivity). Specifically, by activating PPARγ, the use of TZDs leads to increased adipogenesis, decreased osteoblastogenesis while at the same time increasing osteoclastogenesis, and promotes osteocyte apoptosis, therefore resulting in decline in bone formation with enhancement of bone resorption ( 23 , 104 , 109 – 112 ), consequently poor bone biomechanical properties.…”

Vitamin D, Bone Metabolism, and Fracture Risk in Polycystic Ovary Syndrome

“…It has been observed that vitamin D supplementation in PCOS women may improve the steroidogenesis and enzymatic antioxidant activity in the human GC [ 94 ] and it may attenuate the actions of AGEs [ 95 , 96 ]. AGEs play a role in age-related bone loss [ 97 , 98 ]. AGEs provoke bone cell impairment and alter bone biomechanical properties.…”

“…AGEs provoke bone cell impairment and alter bone biomechanical properties. Pentosidine (PENT), a well-characterized AGE, is even considered a predictor of bone fracture [ 97 ]. It has been reported AGEs interfere with osteoblast maturation, leading to morphological cell modifications, function failure, and inhibition of the calcification process.…”