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What Are the Effects of Type 2 Diabetes Treatment on Bone Turnover Markers?


A recent study investigated whether different insulin regimens, such as metformin and rosiglitazone, influence bone metabolism in individuals with type 2 diabetes, who often have an increased risk of fractures.

Individuals with type 2 diabetes often face an increased risk of fractures. A recent study investigated whether different insulin regimens, such as metformin and rosiglitazone, influence bone metabolism, finding that the choice of insulin treatment does not influence bone turnover markers (BTM), metformin treatment may decrease BTMs, and the improvement of glycemic control may influence bone resorption activity.

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The study was a 2-year clinical trial designed to evaluate the effects of antidiabetic treatment. There were 371 patients with type 2 diabetes, who were randomized to short or long-acting human insulin and then randomized again to combinations of metformin and placebo, rosiglitazone and placebo, metformin and rosiglitazone, or 2 placebos.

“Several factors might influence fracture risk in T2D including higher prevalence of falls, renal disease, and anti-diabetic medication. Insulin resistance, hyperinsulinaemia and hyperglycaemia are dominant characteristics of T2D, but limited information is available regarding their effects on bone metabolism,” explained the authors. “Most clinical studies investigating biochemical markers of bone turnover (BTM) measured in peripheral blood or bone remodelling assessed in bone biopsies have reported lower bone turnover in T2D.”

The researchers measured BTM, representing bone resorption (CTX) and formation (PINP), including HbA1c, at baseline and after 3, 12, and 24 months. Additionally, trough steady-state plasma concentrations of metformin and rosiglitazone were measured after 3, 6, and 9 months of treatment. During the follow-up of the trial, the researchers analyzed the associations between treatments and BTMs.

The results revealed that BTMs increased from baseline to month 12; at month 24 they remained high with CTX increasing 28.5% and PINP increasing 23%. The allocation of insulin regimens was not associated with different levels of BTMs, according to the study. Furthermore, metformin and metformin + rosiglitazone, not rosiglitazone alone, were associated with lower bone formation (PINP). However, neither metformin nor rosiglitazone plasma concentrations were associated with BTMS, and HbA1c was inversely associated with CTX.

“In conclusion, short- or long-acting human insulin treatments are not causing different levels of BTMs, and metformin treatment did not increase bone formation, in patients with fairly well controlled T2D. Additionally, rosiglitazone was not associated with increased bone resorption, possibly explained by simultaneous insulin treatment,” concluded the authors. “Furthermore, our study shows that improved glycaemic control is associated with higher bone resorption, possibly portraying normalization rather than an abnormal increase in bone resorption.”

The study noted the need for further clinical trials investigating the effects of improved glycemic control on bone remodeling in addition to other biochemical markers of bone turnover in order to confirm if lowering glucose levels changes bone resorption and not formation.


Stage TB, Christensen MMH, Jorgensen NR, et al. [published online April 12, 2018]. Effects of metformin, rosiglitazone and insulin on bone metabolism in patients with type 2 diabetes. Bone. doi:10.1016/j.bone.2018.04.004.

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