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.

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.

Aims To evaluate whether there is a difference between the effects of dapagliflozin and gliclazide modified release (MR) on glycaemic variability (GV) and glycaemic control, as assessed by continuous glucose monitoring (CGM), in individuals with uncontrolled type 2 diabetes. Materials and methods This randomized, open‐label, active‐controlled study was conducted in individuals with uncontrolled type 2 diabetes who were drug‐naïve or on steady‐dose metformin monotherapy. Participants were treated once daily with 10 mg dapagliflozin or 120 mg gliclazide MR. CGM and GV index calculations were performed at baseline and after 12 weeks. Results In total, 97 participants (age 57.9 ± 8.7 years, 50.5% men, baseline glycated haemoglobin 63 ± 9.8 mmol/mol [7.9 ± 0.9%]) were randomized, and 94 completed the 12‐week protocol. Intention‐to‐treat (ITT) and per‐protocol (PP) analyses showed that the reduction in GV, as measured by the mean amplitude of glycaemic excursions, was superior in the dapagliflozin group versus the gliclazide MR group (−0.9 mmol/L [95% CI −1.5, −0.4] vs −0.2 mmol/L [95% CI −0.6, 0.3]; P = 0.030 [ITT]). The reductions in GV estimated by the coefficient of variation and SD were greater in the dapagliflozin group. Moreover, dapagliflozin increased the glucose time in range (TIR; 3.9–10 mmol/L) by 24.9% (95% CI 18.6, 31.2) vs. 17.4% (95% CI 11.6, 23.3) in the gliclazide MR group (P = 0.089 [ITT]; P = 0.041 [PP]). Conclusions Dapagliflozin improved GV and increased TIR more efficiently than gliclazide MR in individuals with type 2 diabetes over 12 weeks, as demonstrated by CGM.

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