Effects of diabetes drugs on the skeleton - PubMed (original) (raw)
Review
Effects of diabetes drugs on the skeleton
Christian Meier et al. Bone. 2016 Jan.
Abstract
Type 2 diabetes is associated with increased fracture risk and the mechanisms underlying the detrimental effects of diabetes on skeletal health are only partially understood. Antidiabetic drugs are indispensable for glycemic control in most type 2 diabetics, however, they may, at least in part, modulate fracture risk in exposed patients. Preclinical and clinical data clearly demonstrate an unfavorable effect of thiazolidinediones on the skeleton with impaired osteoblast function and activated osteoclastogenesis. The negative effect of thiazolidinediones on osteoblastogenesis includes decreased activity of osteoblast-specific transcription factors (e.g. Runx2, Dlx5, osterix) and decreased activity of osteoblast-specific signaling pathways (e.g. Wnt, TGF-β/BMP, IGF-1). In contrast, metformin has a positive effect on osteoblast differentiation due to increased activity of Runx2 via the AMPK/USF-1/SHP regulatory cascade resulting in a neutral or potentially protective effect on bone. Recently marketed antidiabetic drugs include incretin-based therapies (GLP-1 receptor agonists, DPP-4 inhibitors) and sodium-glucose co-transporter 2 (SGLT2)-inhibitors. Preclinical studies indicate that incretins (GIP, GLP-1, and GLP-2) play an important role in the regulation of bone turnover. Clinical safety data are limited, however, meta-analyses of trials investigating the glycemic-lowering effect of both, GLP-1 receptor agonists and DPP4-inhibitors, suggest a neutral effect of incretin-based therapies on fracture risk. For SGLT2-inhibitors recent data indicate that due to their mode of action they may alter calcium and phosphate homeostasis (secondary hyperparathyroidism induced by increased phosphate reabsorption) and thereby potentially affect bone mass and fracture risk. Clinical studies are needed to elucidate the effect of SGLT2-inhibitors on bone metabolism. Meanwhile SGLT2-inhibitors should be used with caution in patients with high fracture risk, which is specifically true for the use of thiazolidinediones.
Keywords: DPP-4 inhibitors; Diabetes mellitus; Incretins; Metformin; SGLT2 inhibitors; TZDs.
Copyright © 2015 Elsevier Inc. All rights reserved.
Similar articles
- Effects of Incretin-Based Therapies and SGLT2 Inhibitors on Skeletal Health.
Egger A, Kraenzlin ME, Meier C. Egger A, et al. Curr Osteoporos Rep. 2016 Dec;14(6):345-350. doi: 10.1007/s11914-016-0337-9. Curr Osteoporos Rep. 2016. PMID: 27709509 Review. - Fracture risk associated with common medications used in treating type 2 diabetes mellitus.
Wolverton D, Blair MM. Wolverton D, et al. Am J Health Syst Pharm. 2017 Aug 1;74(15):1143-1151. doi: 10.2146/ajhp160319. Am J Health Syst Pharm. 2017. PMID: 28743778 Review. - Differential chemistry (structure), mechanism of action, and pharmacology of GLP-1 receptor agonists and DPP-4 inhibitors.
Neumiller JJ. Neumiller JJ. J Am Pharm Assoc (2003). 2009 Sep-Oct;49 Suppl 1:S16-29. doi: 10.1331/JAPhA.2009.09078. J Am Pharm Assoc (2003). 2009. PMID: 19801361 Review. - Antidiabetic therapy effects on bone metabolism and fracture risk.
Montagnani A, Gonnelli S. Montagnani A, et al. Diabetes Obes Metab. 2013 Sep;15(9):784-91. doi: 10.1111/dom.12077. Epub 2013 Feb 24. Diabetes Obes Metab. 2013. PMID: 23368527 Review. - Evaluating second-line treatment options for type 2 diabetes: focus on secondary effects of GLP-1 agonists and DPP-4 inhibitors.
Boland CL, Degeeter M, Nuzum DS, Tzefos M. Boland CL, et al. Ann Pharmacother. 2013 Apr;47(4):490-505. doi: 10.1345/aph.1R444. Epub 2013 Apr 2. Ann Pharmacother. 2013. PMID: 23548652 Review.
Cited by
- Antidiabetic Agents and Bone Quality: A Focus on Glycation End Products and Incretin Pathway Modulations.
Zaki MK, Abed MN, Alassaf FA. Zaki MK, et al. J Bone Metab. 2024 Aug;31(3):169-181. doi: 10.11005/jbm.2024.31.3.169. Epub 2024 Aug 31. J Bone Metab. 2024. PMID: 39307518 Free PMC article. - Effect of gut hormones on bone metabolism and their possible mechanisms in the treatment of osteoporosis.
Liu H, Xiao H, Lin S, Zhou H, Cheng Y, Xie B, Xu D. Liu H, et al. Front Pharmacol. 2024 Apr 25;15:1372399. doi: 10.3389/fphar.2024.1372399. eCollection 2024. Front Pharmacol. 2024. PMID: 38725663 Free PMC article. Review. - Effect of SGLT2 inhibitors on fractures, BMD, and bone metabolism markers in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.
Wang X, Zhang F, Zhang Y, Zhang J, Sheng Y, Wang W, Li Y. Wang X, et al. Osteoporos Int. 2023 Dec;34(12):2013-2025. doi: 10.1007/s00198-023-06908-2. Epub 2023 Sep 11. Osteoporos Int. 2023. PMID: 37695339 Review. - Treating the Side Effects of Exogenous Glucocorticoids; Can We Separate the Good From the Bad?
Pofi R, Caratti G, Ray DW, Tomlinson JW. Pofi R, et al. Endocr Rev. 2023 Nov 9;44(6):975-1011. doi: 10.1210/endrev/bnad016. Endocr Rev. 2023. PMID: 37253115 Free PMC article. Review. - Comparison of the Effects of Metformin and Thiazolidinediones on Bone Metabolism: A Systematic Review and Meta-Analysis.
Chen RD, Yang CW, Zhu QR, Li Y, Hu HF, Wang DC, Han SJ. Chen RD, et al. Medicina (Kaunas). 2023 May 8;59(5):904. doi: 10.3390/medicina59050904. Medicina (Kaunas). 2023. PMID: 37241136 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Miscellaneous