Effect of metformin treatment on circulating osteoprotegerin in patients with nonalcoholic fatty liver disease.

Purpose/introduction: Growing evidence suggests complex interplay between nonalcoholic fatty liver disease (NAFLD) and bone health. The present study's aim was to examine the impact of metformin treatment on circulating osteoprotegerin (OPG) in patients with NAFLD, a population in which this relationship has not yet been studied.

Methods: In a randomized, placebo-controlled study, 63 patients with NAFLD were assigned to one of two groups: Group 1 received daily metformin; Group 2 received a placebo. Metabolic parameters, insulin resistance markers and OPG levels were examined at baseline and at the end of the study.

Results: In the placebo group, liver function and OPG levels did not change during the study. Among metformin-treated patients, significant declines in OPG and alkaline phosphatase were observed. CRP and ALT decreased marginally during the 4-month treatment period. While at baseline circulating OPG levels did not differ significantly between the groups, by the end of the study OPG was significantly lower in patients treated with metformin than in the placebo group (p < 0.0001). Delta OPG was significantly greater in the metformin group than the placebo group (p = 0.001). In the general linear model, metformin treatment was the only significant independent predictor of endpoint and delta OPG.

Conclusions: Metformin treatment was associated with a significant decrease in OPG levels in patients with NAFLD. The effect on OPG was associated with exposure to metformin per se.

Clinical Trial Registration Number: NCT01084486.