Katrine Hygum Jensen - The effect of liraglutide on bone turnover, bone mass and bone cell function

Fractures are a serious complication to type 2 diabetes (T2D) and may give rise to pain, need of care, reduced quality of life, and increased mortality. Bone is remodelled throughout life through bone resorption by the osteoclasts and bone formation by the osteoblasts. The remodelling activity and the balance between resorption and subsequent formation are influenced by many factors including food consumption.

The gut hormone glucagone-like polypeptide 1 (GLP-1) is released in relation to food intake and reduces blood glucose in diabetes. Liraglutide is a GLP-1 analogue approved for the treatment of T2D and it has been speculated that liraglutide may have a positive effect on bone by favouring the amount of GLP-1.

The aim of the study is to conduct a clinical trial and an in vitro study to test the hypothesis that liraglutide increases the bone mineral density in T2D by decreasing bone resorption.

A randomised, double-blinded, placebo-controlled, prospective, clinical trial will be conducted by comparative treatment regimes with either subcutaneous liraglutide or placebo injections.

The primary endpoint is change in the bone resorption marker collagen I cross-linked C-terminal telopeptide.

Secondary endpoints are change in the bone formation markers, change in bone mineral density evaluated by Dual X-ray absorbtiometry, change in bone structure evaluated by quantitative CT and high resolution peripheral QCT, and change in HbA1c.

An in vitro study using osteoblast and osteoclast cultures will be performed to test the effect of GLP-1 on osteoblast proliferation, differentiation, and gene expression and osteoclast number and activity.