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

Kirsa Skov-Jeppesen, Nicola Hepp, Jannika Oeke, Morten Steen Hansen, Abbas Jafari, Maria Saur Svane, Nariman Balenga, John A. Olson, Morten Frost, Moustapha Kassem, Sten Madsbad, Jens Erik Beck Jensen, Jens Juul Holst, Mette Marie Rosenkilde, Bolette Hartmann*

*Corresponding author for this work

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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.

Original languageEnglish
JournalJournal of Bone and Mineral Research
Issue number8
Pages (from-to)1448-1458
Publication statusPublished - Aug 2021


  • GIP
  • GLP-2
  • Cross-Over Studies
  • Glucagon-Like Peptide 2
  • Humans
  • Female
  • Receptors, Gastrointestinal Hormone
  • Hypoparathyroidism/drug therapy


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