Elsevier

Bone

Volume 112, July 2018, Pages 35-41
Bone

Full Length Article
Effects of metformin, rosiglitazone and insulin on bone metabolism in patients with type 2 diabetes

https://doi.org/10.1016/j.bone.2018.04.004Get rights and content
Under a Creative Commons license
open access

Highlights

  • The choice of short or long-acting insulin treatment had no impact on bone turnover markers.

  • Plasma levels of metformin and rosiglitazone were not associated with levels of bone turnover markers.

  • Improved glycaemic control associated with higher bone resorption, possibly reflecting normalization of bone turnover.

Abstract

Background

Fracture risk is increased in individuals with type 2 diabetes (T2D). The pathophysiological mechanisms accentuating fracture risk in T2D are convoluted, incorporating factors such as hyperglycaemia, insulinopenia, and antidiabetic drugs. The objectives of this study were to assess whether different insulin regimens, metformin and rosiglitazone influence bone metabolism. We explored if the concentration of metformin and rosiglitazone in blood or improved glycaemic control altered bone turnover.

Methods

Two-year clinical trial designed to investigate effects of antidiabetic treatment in 371 T2D patients. Participants were randomized to short or long-acting human insulin (non-blinded) and then further randomized to metformin + placebo, rosiglitazone + placebo, metformin + rosiglitazone or placebo + placebo (blinded). Fasting bone turnover markers (BTM) representing bone resorption (CTX) and formation (PINP) including HbA1c were measured at baseline and after 3, 12 and 24 months. Trough steady-state plasma concentrations of metformin and rosiglitazone were measured after 3, 6 and 9 months of treatment. Associations between treatments and BTMs during the follow-up of the trial were analysed in mixed-effects models that included adjustments for age, gender, BMI, renal function and repeated measures of HbA1c.

Results

BTMs increased from baseline to month 12 and remained higher at month 24, with CTX and PINP increasing 28.5% and 23.0% (all: p < 0.001), respectively. Allocation of insulin regimens was not associated with different levels of BTMs. Metformin and metformin + rosiglitazone but not rosiglitazone alone were associated with lower bone formation (PINP). Neither metformin nor rosiglitazone plasma concentrations was associated with BTMs. HbA1c was inversely associated with CTX but not P1NP.

Conclusions

The choice of insulin treatment is not influencing BTMs, metformin treatment may decrease BTMs, and improvement of glycaemic control may influence bone resorption activity.

Keywords

Type 2 diabetes
Bone turnover markers
Insulin
Metformin
Rosiglitazone

Cited by (0)