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A Pilot Study Showing Acute Inhibitory Effect of GLP-1 on the Bone Resorption Marker CTX in Humans
Anne Nissen1,2, Simone Marstrand1,2, Kirsa Skov-Jeppesen1,2
1Department of Biomedical Sciences The Panum Institute, University of Copenhagen Copenhagen Denmark.
JBMR Plus
|November 6, 2019
Summary
Glucagon-like peptide-1 (GLP-1) receptor agonists, excluding GLP-1 (9-36)amide, were found to reduce bone resorption in healthy individuals. This suggests a role for GLP-1 in the gut-bone axis, impacting bone health.
Area of Science:
- Endocrinology
- Bone Biology
- Metabolic Research
Background:
- Glucagon-like peptide-1 (GLP-1) has been implicated in bone metabolism, but human studies yield conflicting results.
- The gut-bone axis, involving hormones like GLP-1, glucagon-like peptide-2, and glucose-dependent insulinotropic polypeptide, is an area of active investigation.
- Understanding the direct effects of GLP-1 receptor ligands on bone remodeling is crucial for elucidating their role in bone health.
Purpose of the Study:
- To investigate the acute effects of three GLP-1 receptor ligands—GLP-1 (7-36)amide, GLP-1 (9-36)amide, and exenatide—on markers of bone remodeling in humans.
- To explore the potential involvement of GLP-1 in the gut-bone axis by examining its impact on bone resorption markers.
Main Methods:
- A double-blinded, randomized clinical trial involving eight healthy participants.
- Administration of subcutaneous injections of GLP-1 (7-36)amide, GLP-1 (9-36)amide, exenatide, or saline (placebo).
- Analysis of plasma bone turnover markers, osteoprotegerin (OPG), PTH, and IGF-1 levels before and after injections.
- In vitro assessment of cAMP-inducing activity of the ligands on the human GLP-1 receptor.
Main Results:
- GLP-1 (7-36)amide significantly decreased C-terminal telopeptide (CTX) levels, a marker of bone resorption, compared to placebo.
- Exenatide also demonstrated a significant decrease in plasma CTX levels during the second hour post-injection, despite a delayed peak concentration.
- No significant effects were observed for GLP-1 (9-36)amide on CTX levels, nor were there changes in bone formation markers (P1NP, osteocalcin) or OPG, PTH, and IGF-1.
Conclusions:
- GLP-1 receptor agonists, specifically GLP-1 (7-36)amide and exenatide, can reduce bone resorption.
- The primary metabolite GLP-1 (9-36)amide does not appear to affect bone resorption.
- These findings support the hypothesis that GLP-1 plays a role in the gut-bone axis by modulating bone resorption.
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