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The Gut-Bone Axis in Diabetes

  • Bone and Diabetes (A Schwartz and P Vestergaard, Section Editors)
  • Published:
Current Osteoporosis Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

To describe recent advances in the understanding of how gut-derived hormones regulate bone homeostasis in humans with emphasis on pathophysiological and therapeutic perspectives in diabetes.

Recent Findings

The gut-derived incretin hormone glucose-dependent insulinotropic polypeptide (GIP) is important for postprandial suppression of bone resorption. The other incretin hormone, glucagon-like peptide 1 (GLP-1), as well as the intestinotrophic glucagon-like peptide 2 (GLP-2) has been shown to suppress bone resorption in pharmacological concentrations, but the role of the endogenous hormones in bone homeostasis is uncertain. For ambiguous reasons, both patients with type 1 and type 2 diabetes have increased fracture risk. In diabetes, the suppressive effect of endogenous GIP on bone resorption seems preserved, while the effect of GLP-2 remains unexplored both pharmacologically and physiologically. GLP-1 receptor agonists, used for the treatment of type 2 diabetes and obesity, may reduce bone loss, but results are inconsistent.

Summary

GIP is an important physiological suppressor of postprandial bone resorption, while GLP-1 and GLP-2 may also exert bone-preserving effects when used pharmacologically. A better understanding of the actions of these gut hormones on bone homeostasis in patients with diabetes may lead to new strategies for the prevention and treatment of skeletal frailty related to diabetes.

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Authors and Affiliations

  1. Clinical Research, Copenhagen University Hospital–Steno Diabetes Center Copenhagen, Herlev, Denmark

    Henrik Maagensen, Tina Vilsbøll & Filip K. Knop

  2. Center for Clinical Metabolic Research, Copenhagen University Hospital–Herlev and Gentofte, Gentofte Hospitalsvej 7, 3rd floor, DK-2900, Hellerup, Denmark

    Henrik Maagensen, Mads M. Helsted, Lærke S. Gasbjerg, Tina Vilsbøll & Filip K. Knop

  3. Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Lærke S. Gasbjerg

  4. Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Tina Vilsbøll & Filip K. Knop

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H.M. and M.H. searched and analyzed the relevant literature and drafted the manuscript. LSG prepared the figure. All authors wrote, edited, and approved the present manuscript.

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Correspondence to Filip K. Knop.

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H.M. and M.M.H declare no conflict of interest. L.S.G. is minority shareholder of Antag Therapeutics. T.V. has served on scientific advisory panels, been part of speaker’s bureaus for, served as a consultant to and/or received research support from Abbot, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Gilead, GSK, MSD/Merck, Novo Nordisk, Sanofi, and Sun Pharmaceuticals. F.K.K. has served on scientific advisory panels, been part of speaker’s bureaus for, served as a consultant to and/or received research support from Amgen, AstraZeneca, Boehringer Ingelheim, Carmot Therapeutics, Eli Lilly, Gubra, MedImmune, MSD/Merck, Norgine, Novo Nordisk, Sanofi, ShouTi, SNIPR Biome, Zealand Pharma and Zucara; and is a minority shareholder of Antag Therapeutics.

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Maagensen, H., Helsted, M.M., Gasbjerg, L.S. et al. The Gut-Bone Axis in Diabetes. Curr Osteoporos Rep 21, 21–31 (2023). https://doi.org/10.1007/s11914-022-00767-2

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