Short summary

This placebo-controlled blinded study aims to determine the clinical prospects of the emerging hypothesis that bone and glucose metabolism are linked. 64 male and female participants age 40-85 with low bone mass will be treated with either the anti-diabetic drug, semaglutide, a GLP-1 receptor agonist, or placebo for 1 year. Effects will be assessed by changes in bone turnover, strength, microarchitecture and bone mineral density.

Rationale

In vitro studies have shown that the gut hormone glucagon-like peptide 1, GLP-1, that aims to lower post prandial blood glucose through increased insulin secretion, changes activity of human bone resorbing cells, osteoclasts. Pre-clinical studies have shown beneficial effects of GLP-1 and GLP-1 receptor agnoists on bone in mostly murine models. In our study group we have shown that treatment of primary human osteoclasts with human GLP-1 increases the activity of bone resorbing cells in vitro. Results from in vivo studies are manly based on retrospective studies (primary meta-analysis or systematic reviews) and are conflicting regarding whether GLP-1 receptor agonist treatment protect against bone fracture. However, infusion of GLP-1 has been shown to acutely inhibit bone resorption measured by bio markers at least in hyperglycaemic patients. Putting this together there is a need for assessing the prolonged effects of GLP-1 receptor agonists on bone turnover, and if GLP-1 receptor agonists have potential to be repurposed as treatment of conditions with increased risk of bone fractures.

Description of the cohort

Men and women age 40-85 (women menopause for > 5 years). Low bone mass assessed by either DXA-scan (T-score between -1 and -2.5) or a low energy fracture within the last 3 years.

Data and biological material

We use biomarkers for bone formation and bone resorption measured in fasting blood samples. Furthermore, we assess bone strength by direct strength measurement using microindentation, and bone microsrchitecture and bone mass density using HR-pQCT resp. DXA-scans.

Collaborating researchers and departments

Medical Department, The Hospital of South West Jutland

• MD Stinus Hansen

Clinic for Molecular Endocrinology Treatment (KMEB), Odense University Hospital

• Professor Moustapha Kassem

Department of Clinical Biochemistry and Pharmacology, Odense University Hospital

• Tanja Bidstrup
• Anette Mikkelsen

Hospital Pharmacy Funen, Department of Clinical Biochemistry and Pharmacology, Odense University Hospital

• Lene Sehested

OPEN, Department of Clinical Research, University of Southern Denmark

• Nanna Rasmussen