Review article: effects of type 2 diabetes therapies on bone metabolism

Abstract

Diabetes complications and osteoporotic fractures are two of the most important causes of morbidity and mortality in older patients, and they 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 function. The treatment of T2DM has been improved in the past two decades with the development of new therapeutic drugs. Each class has a pathophysiologic target related to the regulation of the energy metabolism and insulin secretion. However, both glycemic homeostasis and bone homeostasis are under the control of common regulatory factors. This background allows the individual pharmacological targets of antidiabetic therapies to affect bone quality due to their indirect effects on bone cell differentiation and the bone remodeling process. With a greater number of diabetic patients and antidiabetic agents being launched, it is critical to highlight the consequences of this disease and its pharmacological agents on bone health and fracture risk. Currently, there is little scientific knowledge approaching the impact of most anti-diabetic treatments on bone quality and fracture risk. Thus, this review aims to explore the pros and cons of the available pharmacologic treatments for T2DM on bone mineral density and risk fractures in humans.

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

“…Numerous studies indicate the presence of a low bone turnover in patients with T2DM [5,12,24,29]. This condition allows accumulation of micro-fractures in the bone, with altered bone quality and increased bone fragility, independent of BMD [5,29,30]. Multiple mechanisms are involved in the reduction of bone resorption and formation in type 2 diabetes, such as: hyperglycemia and insulin resistance, but also obesity and metabolic syndrome associated with diabetes, that tend to suppress bone turnover [24,[28][29][30].…”

“…This condition allows accumulation of micro-fractures in the bone, with altered bone quality and increased bone fragility, independent of BMD [5,29,30]. Multiple mechanisms are involved in the reduction of bone resorption and formation in type 2 diabetes, such as: hyperglycemia and insulin resistance, but also obesity and metabolic syndrome associated with diabetes, that tend to suppress bone turnover [24,[28][29][30]. The influence of these mechanisms explains the presence in our study of negative correlations between BMI and BMD on the one side and bone markers on the other side in diabetic patients.…”

Biological Impact of Metformin Versus Thiazolidinedione on Alveolar Bone of Induced Diabetic Rats (A Histological and Immuno-Histomorphometric Study).

“…The linkage between these two chronic diseases creates a possibility that certain anti-diabetic therapies may affect bone function. The treatment of Type 2 diabetes mellitus (T2DM) has been improved in the past two decades with the development of new therapeutic drugs (Vianna et al, 2017). The impact of diabetes and two of mostly used anti-diabetic medications on alveolar bone health was estimated in the present study.…”

Probiotics ameliorate pioglitazone-associated bone loss in diabetic rats

“…Previously, a lot of clinical and preclinical researches have revealed that pioglitazone decreases trabecular bone volume, BMD, and BMC (19,20). Therefore, it seems that this antidiabetic medicine (and the other insulin-sensitizing TZDs) can increase bone resorption and decrease bone formation by inhibiting osteoblast differentiation (21), speci cally in post-menopausal women (22,23).…”