The Antiresorptive Effect of GIP, But Not GLP-2, Is Preserved in Patients With Hypoparathyroidism—A Randomized Crossover Study

  • Kirsa Skov-Jeppesen
    Novo Nordisk Foundation Center for Basic Metabolic Research University of Copenhagen Copenhagen Denmark
  • Nicola Hepp
    Department of Endocrinology Hvidovre University Hospital Hvidovre Denmark
  • Jannika Oeke
    Department of Biomedical Sciences University of Copenhagen Copenhagen Denmark
  • Morten Steen Hansen
    Molecular Endocrinology Unit (KMEB), Department of Endocrinology Odense University Hospital Odense Denmark
  • Abbas Jafari
    Department of Cellular and Molecular Medicine, Novo Nordisk Foundation Center for Stem Cell Biology (Danstem) University of Copenhagen Copenhagen Denmark
  • Maria Saur Svane
    Department of Endocrinology Hvidovre University Hospital Hvidovre Denmark
  • Nariman Balenga
    Division of General and Oncologic Surgery, Department of Surgery, Marlene and Stewart Greenebaum Comprehensive Cancer Center University of Maryland School of Medicine Baltimore MD USA
  • John A Olson
    Division of General and Oncologic Surgery, Department of Surgery, Marlene and Stewart Greenebaum Comprehensive Cancer Center University of Maryland School of Medicine Baltimore MD USA
  • Morten Frost
    Molecular Endocrinology Unit (KMEB), Department of Endocrinology Odense University Hospital Odense Denmark
  • Moustapha Kassem
    Department of Cellular and Molecular Medicine, Novo Nordisk Foundation Center for Stem Cell Biology (Danstem) University of Copenhagen Copenhagen Denmark
  • Sten Madsbad
    Department of Endocrinology Hvidovre University Hospital Hvidovre Denmark
  • Jens-Erik Beck Jensen
    Department of Clinical Medicine University of Copenhagen Copenhagen Denmark
  • Jens Juul Holst
    Novo Nordisk Foundation Center for Basic Metabolic Research University of Copenhagen Copenhagen Denmark
  • Mette Marie Rosenkilde
    Department of Biomedical Sciences University of Copenhagen Copenhagen Denmark
  • Bolette Hartmann
    Novo Nordisk Foundation Center for Basic Metabolic Research University of Copenhagen Copenhagen Denmark

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<jats:title>ABSTRACT</jats:title> <jats:p>Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-2 (GLP-2) are gut hormones secreted postprandially. In healthy humans, both hormones decrease bone resorption accompanied by a rapid reduction in parathyroid hormone (PTH). The aim of this study was to investigate whether the changes in bone turnover after meal intake and after GIP- and GLP-2 injections, respectively, are mediated via a reduction in PTH secretion. This was tested in female patients with hypoparathyroidism given a standardized liquid mixed-meal test (n = 7) followed by a peptide injection test (n = 4) using a randomized crossover design. We observed that the meal- and GIP- but not the GLP-2-induced changes in bone turnover markers were preserved in the patients with hypoparathyroidism. To understand the underlying mechanisms, we examined the expression of the GIP receptor (GIPR) and the GLP-2 receptor (GLP-2R) in human osteoblasts and osteoclasts as well as in parathyroid tissue. The GIPR was expressed in both human osteoclasts and osteoblasts, whereas the GLP-2R was absent or only weakly expressed in osteoclasts. Furthermore, both GIPR and GLP-2R were expressed in parathyroid tissue. Our findings suggest that the GIP-induced effect on bone turnover may be mediated directly via GIPR expressed in osteoblasts and osteoclasts and that this may occur independent of PTH. In contrast, the effect of GLP-2 on bone turnover seems to depend on changes in PTH and may be mediated through GLP-2R in the parathyroid gland. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).</jats:p>

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