J Korean Diabetes.  2023 Dec;24(4):173-177. 10.4093/jkd.2023.24.4.173.

Anti-Diabetic Medications and Osteoporosis

• Kim K

• KMID: 2550156
• DOI: http://doi.org/10.4093/jkd.2023.24.4.173

Abstract

Osteoporosis and diabetes mellitus are chronic diseases that are rapidly increasing in our aging society. Several studies have reported that the incidence of osteoporosis and fractures is increased in diabetic patients. Although diabetes itself can affect bone density, anti-diabetic medications can also cause changes in bone mineral density, leading to osteoporosis. It is well known that thiazolidinedione increases the risk of fracture. In comparison, metformin, dipeptidyl peptidase-4 inhibitors, sodium glucose cotransporter 2 inhibitors, and glucagon-like peptide-1 receptor agonists have no significant effect on bone mineral density or fracture risk. Insulin and sulfonylureas should be used cautiously because of the risk of falls associated with hypoglycemia.

Keyword

Diabetes mellitus; Fractures, bone; Hypoglycemic agents; Osteoporosis

Reference

1.World Health Organization. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: report of a WHO study group. Geneva: World Health Organization;1994.

2.Choi YJ., Oh HJ., Kim DJ., Lee Y., Chung YS. The preva-lence of osteoporosis in Korean adults aged 50 years or older and the higher diagnosis rates in women who were beneficiaries of a national screening program: the Korea National Health and Nutrition Examination Survey 2008-2009. J Bone Miner Res. 2012. 27:1879–86.

3.Bae JH., Han KD., Ko SH., Yang YS., Choi JH., Choi KM, et al. Diabetes fact sheet in Korea 2021. Diabetes Metab J. 2022. 46:417–26.

4.Janghorbani M., Van Dam RM., Willett WC., Hu FB. Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture. Am J Epidemiol. 2007. 166:495–505.

5.Thrailkill KM., Lumpkin CK Jr., Bunn RC., Kemp SF., Fowl-kes JL. Is insulin an anabolic agent in bone? Dissecting the diabetic bone for clues. Am J Physiol Endocrinol Metab. 2005. 289:E735–45.

6.Krakauer JC., McKenna MJ., Buderer NF., Rao DS., White-house FW., Parfitt AM. Bone loss and bone turnover in diabetes. Diabetes. 1995. 44:775–82.

7.Liu Z., Aronson J., Wahl EC., Liu L., Perrien DS., Kern PA, et al. A novel rat model for the study of deficits in bone for-mation in type-2 diabetes. Acta Orthop. 2007. 78:46–55.

8.Compston J. Type 2 diabetes mellitus and bone. J Intern Med. 2018. 283:140–53.

9.Kurra S., Fink DA., Siris ES. Osteoporosis-associated fracture and diabetes. Endocrinol Metab Clin North Am. 2014. 43:233–43.

10.Eller-Vainicher C., Cairoli E., Grassi G., Grassi F., Catalano A., Merlotti D, et al. Pathophysiology and management of type 2 diabetes mellitus bone fragility. J Diabetes Res. 2020. 2020:7608964.

11.Zhu ZN., Jiang YF., Ding T. Risk of fracture with thiazolidinediones: an updated meta-analysis of randomized clinical trials. Bone. 2014. 68:115–23.

12.Zhang YS., Zheng YD., Yuan Y., Chen SC., Xie BC. Effects of anti-diabetic drugs on fracture risk: a systematic review and network meta-analysis. Front Endocrinol (Lausanne). 2021. 12:735824.

13.Sansome DJ., Xie C., Veedfald S., Horowitz M., Rayner CK., Wu T. Mechanism of glucose-lowering by metformin in type 2 diabetes: role of bile acids. Diabetes Obes Metab. 2020. 22:141–8.

14.Hidayat K., Du X., Wu MJ., Shi BM. The use of metformin, insulin, sulphonylureas, and thiazolidinediones and the risk of fracture: systematic review and meta-analysis of observational studies. Obes Rev. 2019. 20:1494–503.

15.Adil M., Khan RA., Kalam A., Venkata SK., Kandhare AD., Ghosh P, et al. Effect of anti-diabetic drugs on bone me-tabolism: evidence from preclinical and clinical studies. Pharmacol Rep. 2017. 69:1328–40.

16.Salari-Moghaddam A., Sadeghi O., Keshteli AH., Larijani B., Esmaillzadeh A. Metformin use and risk of fracture: a systematic review and meta-analysis of observational studies. Osteoporos Int. 2019. 30:1167–73.

17.Tao Y., E M., Shi J., Zhang Z. Sulfonylureas use and fractures risk in elderly patients with type 2 diabetes mellitus: a me-ta-analysis study. Aging Clin Exp Res. 2021. 33:2133–9.

18.Paschou SA., Dede AD., Anagnostis PG., Vryonidou A., Morganstein D., Goulis DG. Type 2 diabetes and osteoporosis: a guide to optimal management. J Clin Endocrinol Metab. 2017. 102:3621–34.

19.Vestergaard P., Rejnmark L., Mosekilde L. Relative fracture risk in patients with diabetes mellitus, and the impact of insulin and oral anti-diabetic medication on relative fracture risk. Diabetologia. 2005. 48:1292–9.

20.Khazai NB., Beck GR Jr., Umpierrez GE. Diabetes and fractures: an overshadowed association. Curr Opin Endocrinol Diabetes Obes. 2009. 16:435–45.

21.Ferrari S. Diabetes and bone. Calcif Tissue Int. 2017. 100:107–8.

22.Schwartz AV., Hillier TA., Sellmeyer DE., Resnick HE., Gregg E., Ensrud KE, et al. Older women with diabetes have a higher risk of falls: a prospective study. Diabetes Care. 2002. 25:1749–54.

23.Quandt SA., Stafford JM., Bell RA., Smith SL., Snively BM., Arcury TA. Predictors of falls in a multiethnic population of older rural adults with diabetes. J Gerontol A Biol Sci Med Sci. 2006. 61:394–8.

24.Clowes JA., Khosla S., Eastell R. Potential role of pancreatic and enteric hormones in regulating bone turnover. J Bone Miner Res. 2005. 20:1497–506.

25.Fu J., Zhu J., Hao Y., Guo C., Zhou Z. Dipeptidyl pepti-dase-4 inhibitors and fracture risk: an updated meta-anal-ysis of randomized clinical trials. Sci Rep. 2016. 6:29104.

26.Driessen JH., van den Bergh JP., van Onzenoort HA., Henry RM., Leufkens HG., de Vries F. Long-term use of dipeptidyl peptidase-4 inhibitors and risk of fracture: a retrospective population-based cohort study. Diabetes Obes Metab. 2017. 19:421–8.

27.Lee DH., Kim KY., Yoo MY., Moon H., Ku EJ., Oh TK, et al. Effect of dipeptidyl peptidase-4 inhibitors on bone health in patients with type 2 diabetes mellitus. J Clin Med. 2021. 10:4775.

28.Neal B., Perkovic V., Mahaffey KW., de Zeeuw D., Fulcher G., Erondu N, et al. Canagliflozin and cardiovascular and re-nal events in type 2 diabetes. N Engl J Med. 2017. 377:644–57.

29.Fralick M., Kim SC., Schneeweiss S., Kim D., Redelmeier DA., Patorno E. Fracture risk after initiation of use of cana-gliflozin: a cohort study. Ann Intern Med. 2019. 170:155–63.

30.Abrahami D., Douros A., Yin H., Yu OHY., Azoulay L. Sodi-um-glucose cotransporter 2 inhibitors and the risk of fractures among patients with type 2 diabetes. Diabetes Care. 2019. 42:e150–2.

31.van Dalem J., Werkman NCC., van den Bergh JP., Rossi B., Viggers R., Eastell R, et al. Use of sodium-glucose co-trans-porter 2 inhibitors, changes in body mass index and risk of fracture: a population-based cohort study. Diabetes Res Clin Pract. 2022. 190:109993.