Proton Pump Inhibitor Use and the Risk of Fractures Among an Older Adult Cohort

Overview

Journal Pharmacoepidemiol Drug Saf

Publisher Wiley

Specialties Pharmacology
Public Health

Date 2018 Mar 2

PMID 29493043

Citations 7

Authors

Barbara N Harding

Noel S Weiss

Rod L Walker

Eric B Larson

Sascha Dublin

Affiliations

Soon will be listed here.

Abstract

Purpose: The purpose of the study is to determine if the use of a proton pump inhibitor (PPI) is associated with an increased fracture risk, as some prior studies have suggested.

Methods: This retrospective cohort study included data on 4438 participants aged 65 and older who had no fracture in the year prior to baseline and had ≥5 years of enrollment history in Kaiser Permanente Washington, an integrated healthcare delivery system in Seattle, WA, during 1994 to 2014. Time-varying cumulative exposure to PPIs was determined from automated pharmacy data by summing standard daily doses (SDDs) across fills, and patients were categorized as no use (reference group, ≤30 SDD), light use (31-540 SDD), moderate use (541-1080 SDD), and heavy use (≥1081 SDD). Incident fractures were assessed using International Classification of Diseases, Ninth Revision codes from electronic medical records. Potential confounders, chosen a priori, were assessed at baseline and at each 2-year follow-up visit. Fracture risk was analyzed using a Cox proportional hazards model.

Results: Over a mean follow-up of 6.1 years, 802 (18.1%) participants experienced a fracture. No overall association was found between PPI use and fracture risk. Adjusted hazard ratios comparing users to the referent category were 1.08 (95% CI 0.83-1.40) for light users, 1.31 (95% CI 0.86-1.95) for moderate users, and 0.95 (95% CI 0.68-1.34) for heavy users. Among patients with SSD > 30, no appreciable increase in fracture risk was present in persons with recent versus distant use (adjusted hazard ratio of 1.14 [95% CI 0.91-1.42]).

Conclusions: No association was observed between PPI use and fracture risk among older adults.

Citing Articles

Effect of long-term proton pump inhibitors on phosphocalcium metabolism and bone mineral density.

Smaoui H, Chtourou L, Jallouli D, Jemaa S, Karaa I, Boudabbous M Future Sci OA. 2024; 10(1):FSO977.

PMID: 38841182 PMC: 11152587. DOI: 10.2144/fsoa-2023-0198.

Proton Pump Inhibitors and Bone Health: An Update Narrative Review.

Lespessailles E, Toumi H Int J Mol Sci. 2022; 23(18).

PMID: 36142643 PMC: 9504265. DOI: 10.3390/ijms231810733.

Establishing the Association Between Osteoporosis and Peptic Ulcer Disease: A Systematic Review.

Teresa Selvin S, Thomas S, Bikeyeva V, Abdullah A, Radivojevic A, Abu Jad A Cureus. 2022; 14(7):e27188.

PMID: 36039217 PMC: 9395758. DOI: 10.7759/cureus.27188.

New-user and prevalent-user designs and the definition of study time origin in pharmacoepidemiology: A review of reporting practices.

Luijken K, Spekreijse J, van Smeden M, Gardarsdottir H, Groenwold R Pharmacoepidemiol Drug Saf. 2021; 30(7):960-974.

PMID: 33899305 PMC: 8252086. DOI: 10.1002/pds.5258.

Proton Pump Inhibitors and Fractures in Adults: A Critical Appraisal and Review of the Literature.

Briganti S, Naciu A, Tabacco G, Cesareo R, Napoli N, Trimboli P Int J Endocrinol. 2021; 2021:8902367.

PMID: 33510787 PMC: 7822697. DOI: 10.1155/2021/8902367.

References

Buttery A, Busch M, Gaertner B, Scheidt-Nave C, Fuchs J . Prevalence and correlates of frailty among older adults: findings from the German health interview and examination survey. BMC Geriatr. 2015; 15:22. PMC: 4357063. DOI: 10.1186/s12877-015-0022-3. View

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. DOI: 10.1007/s00223-006-0021-7. View

Kaye J, Jick H . Proton pump inhibitor use and risk of hip fractures in patients without major risk factors. Pharmacotherapy. 2008; 28(8):951-9. DOI: 10.1592/phco.28.8.951. View

Khalili H, Huang E, Jacobson B, Camargo Jr C, Feskanich D, Chan A . Use of proton pump inhibitors and risk of hip fracture in relation to dietary and lifestyle factors: a prospective cohort study. BMJ. 2012; 344:e372. PMC: 3269660. DOI: 10.1136/bmj.e372. View

Parker M, Johansen A . Hip fracture. BMJ. 2006; 333(7557):27-30. PMC: 1488757. DOI: 10.1136/bmj.333.7557.27. View

Grigoryan M, Guermazi A, Roemer F, Delmas P, Genant H . Recognizing and reporting osteoporotic vertebral fractures. Eur Spine J. 2003; 12 Suppl 2:S104-12. PMC: 3591834. DOI: 10.1007/s00586-003-0613-0. View

Gray S, LaCroix A, Larson J, Robbins J, Cauley J, Manson J . Proton pump inhibitor use, hip fracture, and change in bone mineral density in postmenopausal women: results from the Women's Health Initiative. Arch Intern Med. 2010; 170(9):765-71. PMC: 4240017. DOI: 10.1001/archinternmed.2010.94. View

Hungin A, Hill C, Molloy-Bland M, Raghunath A . Systematic review: Patterns of proton pump inhibitor use and adherence in gastroesophageal reflux disease. Clin Gastroenterol Hepatol. 2011; 10(2):109-16. DOI: 10.1016/j.cgh.2011.07.008. View

Marks R . Hip fracture epidemiological trends, outcomes, and risk factors, 1970-2009. Int J Gen Med. 2010; 3:1-17. PMC: 2866546. View

10.

Andresen E, Malmgren J, Carter W, Patrick D . Screening for depression in well older adults: evaluation of a short form of the CES-D (Center for Epidemiologic Studies Depression Scale). Am J Prev Med. 1994; 10(2):77-84. View

11.

Targownik L, Lix L, Metge C, Prior H, Leung S, Leslie W . Use of proton pump inhibitors and risk of osteoporosis-related fractures. CMAJ. 2008; 179(4):319-26. PMC: 2492962. DOI: 10.1503/cmaj.071330. View

12.

Moberg L, Nilsson P, Samsioe G, Borgfeldt C . Use of proton pump inhibitors (PPI) and history of earlier fracture are independent risk factors for fracture in postmenopausal women. The WHILA study. Maturitas. 2014; 78(4):310-5. DOI: 10.1016/j.maturitas.2014.05.019. View

13.

Deyo R, Cherkin D, Ciol M . Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. J Clin Epidemiol. 1992; 45(6):613-9. DOI: 10.1016/0895-4356(92)90133-8. View

14.

Mackey D, Lui L, Cawthon P, Bauer D, Nevitt M, Cauley J . High-trauma fractures and low bone mineral density in older women and men. JAMA. 2007; 298(20):2381-8. DOI: 10.1001/jama.298.20.2381. View

15.

Colon-Emeric C, Saag K . Osteoporotic fractures in older adults. Best Pract Res Clin Rheumatol. 2006; 20(4):695-706. PMC: 1839833. DOI: 10.1016/j.berh.2006.04.004. View

16.

Teng E, Hasegawa K, Homma A, Imai Y, Larson E, Graves A . The Cognitive Abilities Screening Instrument (CASI): a practical test for cross-cultural epidemiological studies of dementia. Int Psychogeriatr. 1994; 6(1):45-58; discussion 62. DOI: 10.1017/s1041610294001602. View

17.

Hafferty J, Campbell A, Navrady L, Adams M, MacIntyre D, Lawrie S . Self-reported medication use validated through record linkage to national prescribing data. J Clin Epidemiol. 2017; 94:132-142. PMC: 5808931. DOI: 10.1016/j.jclinepi.2017.10.013. View

18.

Berg K, Kunins H, Jackson J, Nahvi S, Chaudhry A, Harris Jr K . Association between alcohol consumption and both osteoporotic fracture and bone density. Am J Med. 2008; 121(5):406-18. PMC: 2692368. DOI: 10.1016/j.amjmed.2007.12.012. View

19.

Corley D, Kubo A, Zhao W, Quesenberry C . Proton pump inhibitors and histamine-2 receptor antagonists are associated with hip fractures among at-risk patients. Gastroenterology. 2010; 139(1):93-101. PMC: 2902649. DOI: 10.1053/j.gastro.2010.03.055. View

20.

Chiu H, Huang Y, Chang C, Yang C . Use of proton pump inhibitors increased the risk of hip fracture: a population-based case-control study. Pharmacoepidemiol Drug Saf. 2010; 19(11):1131-6. DOI: 10.1002/pds.2026. View