Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

GLP-2 and GIP exert separate effects on bone turnover: A randomized, placebo-controlled, crossover study in healthy young men

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Possible link between FSH and RANKL release from adipocytes in men with impaired gonadal function including Klinefelter syndrome

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Bone mass development is sensitive to insulin resistance in adolescent boys

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Effects of metformin, rosiglitazone and insulin on bone metabolism in patients with type 2 diabetes

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. P2X7Rs are involved in cell death, growth and cellular signaling in primary human osteoblasts

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. The effect of chronic mild hyponatremia on bone mineral loss evaluated by retrospective national Danish patient data

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Assessment of Islet Alpha- and Beta-Cell Function

    Research output: Chapter in Book/Report/Conference proceedingBook chapterCommunication

  2. Intestinal sensing and handling of dietary lipids in gastric bypass-operated patients and matched controls

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Mechanisms involved in follistatin-induced hypertrophy and increased insulin action in skeletal muscle

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

BACKGROUND: Glucagon-like peptide-2 (GLP-2) and glucose-dependent insulinotropic polypeptide (GIP) both inhibit bone resorption in humans but the underlying mechanisms are poorly understood. In vitro, GLP-2 activates the GIP-receptor (GIPR).

OBJECTIVE: Based on in vitro studies, we hypothesized that the antiresorptive effect of GLP-2 was mediated through the GIPR. This was tested using the selective GIPR-antagonist GIP(3-30)NH2.

METHODS: The study was a randomized, single-blinded, placebo-controlled, crossover study conducted at Hvidovre University Hospital, Denmark. Eight healthy young men were included and studied on four study days: GIP (200 μg), GLP-2 (800 μg), GIP(3-30)NH2 (800 pmol/kg/min) + GLP-2 (800 μg), and placebo. The main outcomes were bone resorption measured as collagen type 1 C-terminal telopeptide (CTX) and bone formation measured as procollagen type 1 N-terminal propeptide (P1NP).

RESULTS: CTX (mean ± SEM) significantly decreased after both GIP (to 55.3 ± 6.3% of baseline at t = 90 min) and GLP-2 (to 60.5 ± 5.0% of baseline at t = 180 min). The maximal reduction in CTX after GIP(3-30)NH2 + GLP-2 (to 63.2 ± 3.1% of baseline) did not differ from GLP-2 alone (p = 0.95) nor did net AUC0-240 (-6801 ± 879%*min vs -6027 ± 648%*min, p = 0.56). At t = 30 min, GIP significantly (p < 0.0001) increased P1NP to 115.1 ± 2.2% of baseline compared with 103.1 ± 1.5% after placebo. Both GLP-2 and GIP(3-30)NH2 + GLP-2 significantly (p < 0.0001) decreased P1NP to 91.3 ± 1.1% and 88.1 ± 3.0% of baseline, respectively (at t = 45 min) compared with placebo.

CONCLUSIONS: GIPR antagonism did not inhibit the GLP-2-induced reduction in bone resorption (CTX) in healthy young men. In contrast to GLP-2, GIP increased P1NP despite decreasing CTX indicating an uncoupling of bone resorption from formation. Thus, GLP-2 and GIP seem to exert separate effects on bone turnover in humans.

CLINICAL TRIALS INFORMATION: ClinicalTrials.gov (NCT03159741).

Original languageEnglish
JournalBone
Volume125
Pages (from-to)178-185
Number of pages8
ISSN8756-3282
DOIs
Publication statusPublished - Aug 2019

Bibliographical note

Copyright © 2019 Elsevier Inc. All rights reserved.

    Research areas

  • Bone formation, Bone resorption, CTX, P1NP, PTH

ID: 57192398