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

Abstract

BackgroundPatients 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.MethodsThis 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.ResultsAmong 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.ConclusionsThere 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.

Response to: ‘Correspondence on ‘Concomitant use of oral glucocorticoids and proton pump inhibitors and risk of osteoporotic fractures among patients with rheumatoid arthritis: a population-based cohort study’ by Gong and Zhang and Linet al

“…We read with much interest the two correspondences on our recently published paper by Lin et al and Gong and Zhang in the Annals of the Rheumatic Diseases. [1][2][3] We conducted a retrospective cohort study to evaluate the association between concomitant use of two commonly used medications in patients with rheumatoid arthritis (RA), that is, oral glucocorticoids (GCs) and proton pump inhibitors (PPIs), and risk of osteoporotic (OP) fractures. We used data from one of the largest primary care databases in the world, the Clinical Practice Research Datalink (CPRD).…”

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

“…If there is interaction between two factors, the effect of one factor on the outcome should be different across strata of the other factor, and vice versa. 2 In the study by Abtahi et al, 1 if there is interaction between oral use of GC and PPI, the combined effect of GC and PPI (ie, 1.60) should be larger than the sum of the individual effects of GC and PPI. The sum of the individual effects of GC and PPI are 1.45 ((1.23-1)+(1.22-1)+1) or 1.50 (1.23×1.22) on the basis of additive scale or multiplicative scale, respectively.…”

“…I read with great interest the article published by Abtahi et al recently. 1 The authors aimed to investigate the association between concomitant use of oral glucocorticoids (GCs) and proton pump inhibitors (PPIs) and the risk of osteoporotic fractures among patients with rheumatoid arthritis. 1 The study showed that concomitant current use of oral GCs and PPIs was associated with increased risk of osteoporotic fractures compared with non-use (adjusted HR: 1.60, 95% CI: 1.35 to 1.89).…”

“…1 The authors aimed to investigate the association between concomitant use of oral glucocorticoids (GCs) and proton pump inhibitors (PPIs) and the risk of osteoporotic fractures among patients with rheumatoid arthritis. 1 The study showed that concomitant current use of oral GCs and PPIs was associated with increased risk of osteoporotic fractures compared with non-use (adjusted HR: 1.60, 95% CI: 1.35 to 1.89). Both oral GC and PPI use alone were also associated with increased risk of osteoporotic fracture compared with non-use (adjusted HR: 1.23, 95% CI: 1.03 to 1.47 (oral GC use alone); adjusted HR: 1.22, 95% CI: 1.05 to 1.42 (PPI use alone)).…”

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

“…We read with deep interest the article by Abtahi et al 1 ; their study was aimed at investigating the concomitant use of oral glucocorticoids (GCs) and proton pump inhibitors (PPIs) and risk of osteoporotic fractures among patients with rheumatoid arthritis (RA). The authors concluded that there was an interaction between the risk of osteoporotic fractures and concomitant use of oral GCs and PPIs.…”