Increased Osteoporotic Fracture Risk With Concomitant GC, PPI Use in RA

Clasped hands of an elderly lady resting on a table alongside a variety of scattered medication tablets capsule and pills prescribed for her health and as diet.
Researchers assessed the association between concomitant use of oral glucocorticoids and proton pump inhibitors and osteoporotic fracture risk in rheumatoid arthritis.

Concomitant use of oral glucocorticoids (GCs) and proton pump inhibitors (PPIs) is associated with elevated risk for osteoporotic fractures in patients with rheumatoid arthritis (RA), according to study results presented at the American Society for Bone and Mineral Research (ASBMR) Annual Meeting, held virtually from September 11 to 15, 2020.

In a retrospective cohort study, researchers extracted data from the Clinical Practice Research Datalink from 1997 to 2017. The Clinical Practice Research Datalink includes deidentified medical records data from a network of general practitioner clinics across the United Kingdom. All patients with RA aged >50 years were eligible for cohort inclusion. Exposure to oral GCs and PPIs was determined by medical record review and stratified by recency of use, including current (<6 months); recent (7-12 months); or past (>1 year). The primary outcome was osteoporotic fracture, including fracture of the hip, vertebrae, humerus, forearm, pelvis, or ribs. Cox proportional hazards models were used to determine the risk for osteoporotic fractures in patients receiving GCs and PPIs compared with those who were not. Models were adjusted for age, sex, lifestyle factors, comorbid conditions, and other medications.

The study cohort included 12,351 patients with RA with a mean age of 68 years, among whom 69% were women. A total of 1411 osteoporotic fractures were observed during follow-up. Concomitant current use vs nonuse of oral GCs and PPIs was associated with significantly increased risk for osteoporotic fractures (hazard ratio [HR], 1.60; 95% CI, 1.35-1.89). Current use vs nonuse of GCs only (HR, 1.23) and PPIs only (HR, 1.22) also conferred increased risk for osteoporotic fractures, though not to the extent of concomitant use. Models assessing individual fracture sites revealed similar results. In patients with concomitant current use of GCs and PPIs, higher daily dose and longer duration of PPI use did not appear to further increase fracture risk. However, in age- and sex-adjusted hazard models, current PPI use was associated with a 1.3-fold increased risk for osteoporotic fracture compared to nonuse.

Overall, concomitant use of oral GCs and PPIs appeared to increase osteoporotic fracture risk beyond that observed with either medication alone.

Researchers concluded, “Considering the increasing life expectancies and high consumption of PPIs among elderly patients, these findings may be clinically relevant in patients [with] RA treated with oral GCs in combination with PPIs.”


Abtahi S, Driessen JHM, Burden AM, et al. Concomitant use of oral glucocorticoids and proton pump inhibitors and risk of osteoporotic fractures in patients with rheumatoid arthritis: a population-based cohort study. Presented at: ASBMR 2020 Virtual Annual Meeting; September 11-15, 2020. Poster #P-546.

This article originally appeared on Rheumatology Advisor