How does the use of GLP-1 receptor agonists affect bone mineral density and fracture risk in obese individuals?
DOI:
https://doi.org/10.12775/JEHS.2026.87.68397Keywords
GLP-1RA, 'obesity, bone mineral density (BMD), Liraglutide, semiglutide, fracture riskAbstract
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are an important group of drugs widely used in the treatment of type 2 diabetes and obesity. Studies indicate their beneficial effect on glycemic control and weight reduction, as well as potential involvement in bone metabolism modulation. The aim of this review was to evaluate the current knowledge regarding the impact of GLP-1RAs on bone mineral density (BMD) and fracture risk.
A narrative literature review with elements of systematic searching was conducted, covering clinical and observational studies from 2015 to 2025. The available data indicate that GLP-1RAs do not cause a significant decrease in BMD compared to placebo or insulin glargine. Some studies observed a slight increase in bone resorption markers, which did not translate into clinically relevant decreases in BMD. Cohort studies data suggest a potential decreased risk of osteoporosis among GLP-1RA-treated population. Current literature confirms the overall safety of GLP-1RA therapy in the context of bone health, although further long-term studies are necessary to fully clarify their effects on bone microarchitecture and fracture risk.
References
1. Drucker DJ. The biology of incretin hormones. Cell Metab. 2006;3(3):153–165.
2. Nauck MA, Meier JJ. Incretin hormones: Their role in health and disease. Diabetes Obes Metab. 2018;20(S1):5–21.
3. Meier JJ. GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus. Nat Rev Endocrinol. 2012;8(12):728–742.
4. Wilding JPH, et al. Once-weekly semaglutide in adults with overweight or obesity (STEP 1). N Engl J Med. 2021;384:989–1002.
5. Mabilleau G, et al. Effect of glucagon-like peptide-1 on bone metabolism. J Endocrinol. 2017;233:R1–R11.
6. Seino Y, et al. Signaling pathways of GLP-1 receptor activation. J Diabetes Investig. 2017;8(5):515–526.
7. Holz GG, Chepurny OG. Glucagon-like peptide-1 signaling in insulin secretion. Diabetes. 2015;64:1571–1578.
8. Meier JJ, Nauck MA. Glucagon-like peptide 1 (GLP-1) and gastric emptying. Gastroenterology. 2011;140:1227–1237.
9. Nuche-Berenguer B, et al. GLP-1 promotes osteogenic differentiation of mesenchymal stem cells via PKA and β-catenin. Endocrinology. 2009;150(5):2029–2039.
10. Keller J, et al. GLP-1 receptor expression in human bone cells and its influence on osteoblast function. Bone. 2015;75:160–169.
11. Armstrong MJ, et al. Glucagon-like peptide-1 analogues in non-alcoholic fatty liver disease. Lancet Gastroenterol Hepatol. 2016;1(3):226–234.
12. Lee YS, Jun HS. Anti-inflammatory effects of GLP-1 receptor agonists and involvement of NF-κB. Diabetes Metab Res Rev. 2014;30(2):111–118.
13. Hölscher C. Dual GLP-1/GIP receptor agonists and neurodegenerative disease. Nat Rev Neurosci. 2020;21(12):707–719.
14. Jensen SBK, Sørensen V, Sandsdal RM, et al. Bone health after exercise alone, GLP-1 receptor agonist treatment, or combination treatment. JAMA Netw Open. 2024;7(6):e2416775.
15. Akyay OZ, et al. Effects of exenatide versus insulin glargine on bone metabolism in postmenopausal women with type 2 diabetes. Medicine (Baltimore). 2023;102:eXXXX.
16. Cai TT, et al. Effects of GLP-1 receptor agonists versus insulin glargine on bone mineral density in patients with type 2 diabetes. J Diabetes Res. 2021;2021:XXXXXX.
17. Iepsen EW, et al. Liraglutide prevents bone loss after very low-calorie diet–induced weight loss. J Clin Endocrinol Metab. 2015;100(8):2909–2917.
18 Li X, Zhang X, Wang Y, et al. Effects of Glucagon-Like Peptide-1 Receptor Agonists on Bone Mineral Density and Bone Turnover in Patients with Type 2 Diabetes Mellitus. International Journal of Endocrinology. 2024:1785321.
19. Chen M, et al. GLP-1 receptor agonist use and risk of osteoporosis in older adults with type 2 diabetes: A retrospective cohort study. Front Endocrinol. 2025;16:XXXXXX.
20. Thrailkill KM, Lumpkin CK, et al. Effects of GLP-1 receptor agonists on bone health in obesity. Calcif Tissue Int. 2023;113:27–42.
21. Anastasilakis AD, Polyzos SA, et al. Impact of GLP-1 receptor agonists on bone metabolism: Systematic review. Diabetes Metab Res Rev. 2022;38(6):e3556.
22. Hansen M, Pedersen R, et al. GLP-1 receptor agonists and fracture risk: Systematic review and meta-analysis. Bone. 2024;182:116–125.
23. Yu EW, Bouxsein ML. Bone metabolism changes associated with weight loss in obesity. J Clin Endocrinol Metab. 2024;109(1):1–12.
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Copyright (c) 2026 Jakub Zbigniew Zalewski, Alicja Cyrzan, Małgorzata Styczyńska , Martyna Iwanowska, Beata Flis, Adam Zysk, Mateusz Ząbek, Adrian Goss, Bartosz Fronczak, Maciej Wojewódzki

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