Short summary

How GIP affects bone remodeling remains elusive. Previous studies with short-term administration of GIP (minutes to hours) indicate an anti-resorptive effect, however continuous infusion of GIP in patients with type 1 diabetes had no effect on bone resorption after one day. Thus, the effect of long-acting receptor agonists on bone, is not known. This is particularly of interest after GLP-1/GIP receptor agonists (e.g. Tirzepatide) became available for the treatment of type 2 diabetes and obesity

Rationale

Fracture risk is increased in several conditions that affect a large proportion of the Danish population, such as type 2 diabetes and obesity. While fracture risk is particularly high in osteoporosis, these skeletal events are also prevalent in individuals with type 2 diabetes or visceral obesity. In contrast to osteoporosis, these conditions are characterized by low bone turnover that impairs bone strength with time. If GIP decreases bone resorption but not formation, it may be used to prevent bone loss. However, if GIP decreases bone turnover, long-standing treatment with GIP-based drugs could lead to hypermineralisation of bone, which increases fracture risk, as observed with enduring antiresorptive osteoporosis treatments. This project aims to determine if GIP uncouples bone resorption and bone formation in humans, by investigating if the effect of GIP on bone differs between intermittent and continuous administration.

Description of the cohort

Healthy volunteers (N=12). Inclusion criteria: Men and women aged 18-40 years. Exclusion criteria: Prediabetes or diabetes mellitus (HbA1c>42mmol/mol), body Mass Index > 28 kg/m2, fractures < 6 months, comorbidities/treatments that may influence bone metabolism or the procedures described in the project, pregnancy or inability to provide informed consent.

Data and biological material

Anthropomorphic data (gender, age, height, weight). Questionnaire data. Blod samples, bone marrow and bone tissue biopsies at fixed time points.

Collaborating researchers and departments

The Molecular Endocrinology Department (KMEB), OUH

• Professor, Phd, Morten Frost Nielsen
• Phd, physician, Morten Svarer Hansen

Department of Diabetes and Endocrinology University Hospital of Southern Denmark, Esbjerg, Denmark

• Professor, Phd, Claus Bogh Juhl