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. 2021 Apr;80(4):423-431.
doi: 10.1136/annrheumdis-2020-218758. Epub 2020 Dec 11.

Concomitant use of oral glucocorticoids and proton pump inhibitors and risk of osteoporotic fractures among patients with rheumatoid arthritis: a population-based cohort study

Shahab Abtahi  1   2   3 , Johanna H M Driessen  1   2   3   4 , Andrea M Burden  1   5 , Patrick C Souverein  2 , Joop P van den Bergh  6   7   8 , Tjeerd P van Staa  2   9 , Annelies Boonen  6   10 , Frank de Vries  11   2   3   12
Affiliations

Concomitant use of oral glucocorticoids and proton pump inhibitors and risk of osteoporotic fractures among patients with rheumatoid arthritis: a population-based cohort study

Shahab Abtahi et al. Ann Rheum Dis. 2021 Apr.

Abstract

Background: Patients with rheumatoid arthritis (RA) commonly use oral glucocorticoids (GCs) and proton pump inhibitors (PPIs), both associated with osteoporotic fractures. We investigated the association between concomitant use of oral GCs and PPIs and the risk of osteoporotic fractures among patients with RA.

Methods: This was a cohort study including patients with RA aged 50+ years from the Clinical Practice Research Datalink between 1997 and 2017. Exposure to oral GCs and PPIs was stratified by the most recent prescription as current use (<6 months), recent use (7-12 months) and past use (>1 year); average daily and cumulative dose; and duration of use. The risk of incident osteoporotic fractures (including hip, vertebrae, humerus, forearm, pelvis and ribs) was estimated by time-dependent Cox proportional-hazards models, statistically adjusted for lifestyle parameters, comorbidities and comedications.

Results: Among 12 351 patients with RA (mean age of 68 years, 69% women), 1411 osteoporotic fractures occurred. Concomitant current use of oral GCs and PPIs was associated with a 1.6-fold increased risk of osteoporotic fractures compared with non-use (adjusted HR: 1.60, 95% CI: 1.35 to 1.89). This was statistically different from a 1.2-fold increased osteoporotic fracture risk associated with oral GC or PPI use alone. Most individual fracture sites were significantly associated with concomitant use of oral GCs and PPIs. Among concomitant users, fracture risk did not increase with higher daily dose or duration of PPI use.

Conclusions: There was an interaction in the risk of osteoporotic fractures with concomitant use of oral GCs and PPIs. Fracture risk assessment could be considered when a patient with RA is co-prescribed oral GCs and PPIs.

Keywords: epidemiology; glucocorticoids; osteoporosis; rheumatoid arthritis.

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Conflict of interest statement

Competing interests: JvB reports grants from Amgen, Eli Lilly and UCB, outside the submitted work. AB received research grants to her department from Celgene and AbbVie, and speakers’ fees or honoraria from Sandoz, UCB, Lilly, Novartis and Biogen, and Gilead also to her department, not related to this study. FV supervises three PhD students who are employed with F. Hoffmann La Roche (Basel, Switzerland/Welwyn Garden City, UK). He has not received any fees or reimbursements for this, and the topics of their PhD thesis are not related to the current study proposal. SA, JD, AMB, PCS and TPvS have no competing interests.

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