Bone mineral changes in young adult females on short-term proton pump inhibitor: A retrospective cohort study

Bone mineral changes in courses of proton pump inhibitor treatment



proton pump inhibitor, bone mineral density, T-score, Z-score, osteopenia, osteoporosis


Background/Aim: Proton pump inhibitors (PPIs), despite being the most prescribed medications today, have generated controversy due to their potential impact on bone metabolism. Numerous studies have emphasized the potential of prolonged PPI use to reduce bone mineral density, thereby increasing the risk of bone fractures among elderly and young individuals. However, the precise impact of PPI usage for 1 year or less on bone mineral density in young adults remains incompletely understood.

Method: In this retrospective cohort study, we conducted a comprehensive review of all dual x-ray bone densitometric examinations conducted on females under 40 years old at our tertiary care center between 2010 and 2014. Among the initial 685 patients assessed, 117 samples met the predefined inclusion criteria and were consequently enrolled in the study. Subsequently, the enrolled cases were categorized into three distinct groups: Group 1 (n=46), which received PPI treatment for less than six months; Group 2 (n=31), which received PPIs for a duration ranging from 6 to 12 months; and Group 3 (n=40), comprising individuals with no history of PPI use, thus serving as the control group. Comprehensive baseline descriptive data, encompassing bone mineral density, t-scores, and z-scores, were meticulously compared among the three groups mentioned above.

Results: The overall mean age of the study population was 32.84 (5.27) years, with an age range spanning from 20 to 40 years. No statistically significant differences in age were discerned among the three groups. Similarly, the groups exhibited no significant body mass index (BMI) variations. Noteworthy findings emerged after examining the effects of PPI usage on bone mineral density, z-scores, and t-scores across the three groups. Specifically, the data suggested that PPIs might influence t-scores (Group 1: -0.48 (0.77); Group 2: -1.25 (0.86); Group 3: -0.33 (0.78)), yielding an F-value of 13.28 for (2.116), signifying statistical significance at P<0.001. Moreover, the observed mean square error (MSE) was 64, while the effect size (eta²) was 0.19. Subsequent post-hoc Tukey tests indicated a significant distinction in the T-score of Group 2 compared to the other two groups. Furthermore, the analysis of z-scores (Group 1: 0.46 (0.79); Group 2: -1.27 (0.76); Group 3: -0.35 (0.86)) revealed a similar trend, with an F-value of 13.21 for (2.116) and a P-value below 0.001. The corresponding MSE was 0.65, and the eta² stood at 0.19. Additional post-hoc Tukey tests indicated that the Z-score of Group 2 significantly diverged from the other groups. However, it is noteworthy that both t and z-scores for Group 1 and Group 3 did not exhibit statistically significant differences.

Conclusion: Prolonged use of PPIs for durations surpassing 6 months may potentially reduce bone mineral density among young adults. Nevertheless, this observed impact does not attain clinically significant levels of osteopenia. Conversely, using PPIs for periods under 6 months did not significantly affect bone mineral density.


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Cui G-L, Syversen U, Zhao C-M, Chen D, Waldum H. Long-term omeprazole treatment suppresses body weight gain and bone mineralization in young male rats. Scandinavian Journal of Gastroenterology. 2001;36(10):1011-5. DOI:

Jaynes M, Kumar AB. The risks of long-term use of proton pump inhibitors: a critical review. Therapeutic advances in drug safety. 2019;10:2042098618809927. DOI:

Recker RR. Calcium absorption and achlorhydria. New England Journal of Medicine. 1985;313(2):70-3. DOI:

Tuukkanen J, Väänänen H. Omeprazole, a specific inhibitor of H+− K+-ATPase, inhibits bone resorption in vitro. Calcif Tissue Int. 1986;38(2):123-5. DOI:

Costa‐Rodrigues J, Reis S, Teixeira S, Lopes S, Fernandes MH. Dose‐dependent inhibitory effects of proton pump inhibitors on human osteoclastic and osteoblastic cell activity. The FEBS journal. 2013;280(20):5052-64. DOI:

Kranioti EF, Bonicelli A, García-Donas JG. Bone-mineral density: clinical significance, methods of quantification and forensic applications. Research and Reports in Forensic Medical Science. 2019:9-21. DOI:

Golob AL, Laya MB. Osteoporosis: screening, prevention, and management. Med Clin North Am. 2015;99(3):587-606. doi: 10.1016/j.mcna.2015.01.010. PubMed PMID: 25841602. DOI:

Anam AK, Insogna K. Update on osteoporosis screening and management. Medical Clinics. 2021;105(6):1117-34. DOI:

Solomon DH, Diem SJ, Ruppert K, Lian YJ, Liu CC, Wohlfart A, et al. Bone mineral density changes among women initiating proton pump inhibitors or H2 receptor antagonists: a SWAN cohort study. J Bone Miner Res. 2015;30(2):232-9. doi: 10.1002/jbmr.2344. PubMed PMID: 25156141; PubMed Central PMCID: PMC4404624. DOI:

Ghebre YT. Proton pump inhibitors and osteoporosis: is collagen a direct target? Frontiers in Endocrinology. 2020;11:473. DOI:

Hussain MS, Mazumder T. Long-term use of proton pump inhibitors adversely affects minerals and vitamin metabolism, bone turnover, bone mass, and bone strength. Journal of Basic and Clinical Physiology and Pharmacology. 2022;33(5):567-79. DOI:

Poly T, Islam M, Yang H-C, Wu C, Li Y-C. Proton pump inhibitors and risk of hip fracture: a meta-analysis of observational studies. Osteoporosis International. 2019;30:103-14. DOI:

Targownik LE, Lix LM, Leung S, Leslie WD. Proton-pump inhibitor use is not associated with osteoporosis or accelerated bone mineral density loss. Gastroenterology. 2010;138(3):896-904. Epub 20091118. doi: 10.1053/j.gastro.2009.11.014. PubMed PMID: 19931262. DOI:

Vestergaard P, Rejnmark L, Mosekilde L. Proton pump inhibitors, histamine H2 receptor antagonists, and other antacid medications and the risk of fracture. Calcif Tissue Int. 2006;79(2):76-83. Epub 20060815. doi: 10.1007/s00223-006-0021-7. PubMed PMID: 16927047. DOI:

Watts NB. Fundamentals and pitfalls of bone densitometry using dual-energy X-ray absorptiometry (DXA). Osteoporosis International. 2004;15:847-54. DOI:

Silva ACV, Rosa MId, Fernandes B, Lumertz S, Diniz RM, Damiani MEFdR. Factors associated with osteopenia and osteoporosis in women undergoing bone mineral density test. Revista Brasileira de Reumatologia. 2015;55:223-8. DOI:

Karaguzel G, Holick MF. Diagnosis and treatment of osteopenia. Reviews in endocrine and metabolic disorders. 2010;11(4):237-51. DOI:

Richardson P, Hawkey CJ, Stack WA. Proton pump inhibitors: pharmacology and rationale for use in gastrointestinal disorders. Drugs. 1998;56:307-35. DOI:

Lundell L, Vieth M, Gibson F, Nagy P, Kahrilas P. Systematic review: the effects of long‐term proton pump inhibitor use on serum gastrin levels and gastric histology. Alimentary Pharmacology & Therapeutics. 2015;42(6):649-63. DOI:

Targownik LE, Lix LM, Metge CJ, Prior HJ, Leung S, Leslie WD. Use of proton pump inhibitors and risk of osteoporosis-related fractures. Cmaj. 2008;179(4):319-26. DOI:

Hussain S, Siddiqui AN, Habib A, Hussain MS, Najmi AK. Proton pump inhibitors’ use and risk of hip fracture: a systematic review and meta-analysis. Rheumatology International. 2018;38(11):1999-2014. DOI:

Aleraij S, Alhowti S, Ferwana M, Abdulmajeed I, Mutawwam IM. Effect of proton pump inhibitors on bone mineral density: A systematic review and meta-analysis of observational studies. Bone Reports. 2020;13:100732. DOI:

Cao JJ. Effects of obesity on bone metabolism. Journal of Orthopaedic Surgery and Research. 2011;6:1-7. DOI:

Leontiadis GI, Moayyedi P. Proton pump inhibitors and risk of bone fractures. Current Treatment Options in Gastroenterology. 2014;12:414-23. DOI:

Targownik LE, Leslie WD, Davison KS, Goltzman D, Jamal SA, Kreiger N, et al. The relationship between proton pump inhibitor use and longitudinal change in bone mineral density: a population-based from the Canadian Multicentre Osteoporosis Study (CaMos). The American Journal of Gastroenterology. 2012;107(9):1361. DOI:

Fournier MR, Targownik LE, Leslie WD. Proton pump inhibitors, osteoporosis, and osteoporosis-related fractures. Maturitas. 2009;64(1):9-13. DOI:

Mizunashi K, Furukawa Y, Katano K, Abe K. Effect of omeprazole, an inhibitor of H+, K+-ATPase, on bone resorption in humans. Calcif Tissue Int. 1993;53:21-5. DOI:

Shin YH, Gong HS, Baek GH. Lower trabecular bone score is associated with the use of proton pump inhibitors. Journal of Clinical Densitometry. 2019;22(2):236-42. DOI:

Ozdil K, Kahraman R, Sahin A, Calhan T, Gozden EH, Akyuz U, et al. Bone density in proton pump inhibitors users: a prospective study. Rheumatology international. 2013;33:2255-60. DOI:

Gray SL, LaCroix AZ, Larson J, Robbins J, Cauley JA, Manson JE, et al. Proton pump inhibitor use, hip fracture, and change in bone mineral density in postmenopausal women: results from the Women’s Health Initiative. Archives of Internal Medicine. 2010;170(9):765-71. DOI:

Bahtiri E, Islami H, Hoxha R, Qorraj-Bytyqi H, Rexhepi S, Hoti K, et al. Esomeprazole use is independently associated with significant reduction of BMD: 1-year prospective comparative safety study of four proton pump inhibitors. Journal of Bone and Mineral Metabolism. 2016;34:571-9. DOI:

Roux C, Goldstein J, Zhou X, Klemes A, Lindsay R. Vertebral fracture efficacy during risedronate therapy in patients using proton pump inhibitors. Osteoporosis International. 2012;23:277-84. DOI:






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Kucukdemirci O, Kapucu K, Mavis O. Bone mineral changes in young adult females on short-term proton pump inhibitor: A retrospective cohort study: Bone mineral changes in courses of proton pump inhibitor treatment. J Surg Med [Internet]. 2024 May 14 [cited 2024 Jun. 19];8(5):85-9. Available from: