The Impact of Diabetes and Diabetes Medications on Bone Health

Abstract

Patients with type 2 diabetes mellitus (T2DM) have an increased risk of fragility fractures despite increased body weight and normal or higher bone mineral density. The mechanisms by which T2DM increases skeletal fragility are unclear. It is likely that a combination of factors, including a greater risk of falling, regional osteopenia, and impaired bone quality, contributes to the increased fracture risk. Drugs for the treatment of T2DM may also impact on the risk for fractures. For example, thiazolidinediones accelerate bone loss and increase the risk of fractures, particularly in older women. In contrast, metformin and sulfonylureas do not appear to have a negative effect on bone health and may, in fact, protect against fragility fracture. Animal models indicate a potential role for incretin hormones in bone metabolism, but there are only limited data on the impact of dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 agonists on bone health in humans. Animal models also have demonstrated a role for amylin in bone metabolism, but clinical trials in patients with type 1 diabetes with an amylin analog (pramlintide) have not shown a significant impact on bone metabolism. The effects of insulin treatment on fracture risk are inconsistent with some studies showing an increased risk and others showing no effect. Finally, although there is limited information on the latest class of medications for the treatment of T2DM, the sodium-glucose co-transporter-2 inhibitors, these drugs do not seem to increase fracture risk. Because diabetes is an increasingly common chronic condition that can affect patients for many decades, further research into the effects of agents for the treatment of T2DM on bone metabolism is warranted. In this review, the physiological mechanisms and clinical impact of diabetes treatments on bone health and fracture risk in patients with T2DM are described.

Insulin use and Excess Fracture Risk in Patients with Type 2 Diabetes: A Propensity-Matched cohort analysis

“…Therefore, our findings suggest that insulin therapy may have played a role in this excess risk rather than, as has been suggested by previous authors, acting as a surrogate of longer disease duration or severity 31, 32 .…”

Fracture Risk in Type 2 Diabetes: Current Perspectives and Gender Differences

“…Because of their mechanism of action these drugs may influence calcium-phosphate homeostasis and potentially have an effect on bone metabolism and turnover. Several mechanisms may be involved: the raise of serum phosphate levels via increased tubular resorption of phosphate in the kidney; the increase of magnesium and PTH levels; the reduction of 25OH-vitamin D levels; and the increase of secretion of FGF23 by osteocytes; also weight loss frequently observed with SGLT2 may influence bone mass [100]. Serum phosphate, magnesium, and PTH levels are increased in subjects treated with dapagliflozin, as compared to those on placebo [101, 102]; however Ljunggren et al, in spite of a small increase in serum phosphate and magnesium levels, did not observe any changes from baseline in bone turnover markers or BMD after 50 weeks' treatment with dapagliflozin 10 mg/day versus placebo [101].…”

Bone fractures in patients with type 2 diabetes mellitus: prevalence and risk factors

“…Однако в одной из работ плохая компенсация СД была фактором риска переломов [19]. Дополнительным фактором риска переломов считается дефицит инсулина [20]. Так, при СД 1 типа при снижении уровня этого гормона развивается остеопения.…”

“…Средняя продолжительность СД в настоящем исследо-вании составила 7 лет, и зависимости возникновения пе-реломов от длительности заболевания найти не удалось. Кроме того, некоторые лекарственные препараты, пред-назначенные для терапии СД2 (например, тиазолидин-дионы), приводят к нарушению микроархитектоники кости и повышают риск развития переломов [20].…”