Glucocorticoid, proton pump inhibitor use linked to higher osteoporotic fracture risk in RA
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The simultaneous use of oral glucocorticoids and proton pump inhibitors is associated with a 1.6-fold increased risk for osteoporotic fractures in patients aged 50 years and older with rheumatoid arthritis, according to data.
“The contributors to increased fracture risk include the inflammatory process of RA and the pharmacological treatment of the disease, most importantly oral glucocorticoids (GCs),” Shahab Abtahi, MD, MSc, PhD, of Maastricht University Medical Center, in the Netherlands, and colleagues wrote in the Annals of the Rheumatic Diseases. “Patients with RA taking oral GCs have reduced bone mineral density (BMD) at the hip and vertebrae and up to a 35% increased 5-year fracture risk. Apart from GCs, patients with RA frequently use other medications that could also be associated with fragility fractures.”
“A population-based study reported a 2.4-fold increased risk of hip fracture among concomitant users of both [proton pump inhibitors (PPIs)] and high-dose oral GCs (15mg prednisolone equivalent dose [PED]),” they added. “But, to our knowledge, no studies have evaluated the effects of simultaneous use of both drugs on fracture risk in patients with RA, particularly in elderly patients who are regular users of PPIs.”
To examine the association between concomitant use of oral glucocorticoids and proton pump inhibitors and the risk for osteoporotic fractures in RA, Abtahi and colleagues a retrospective cohort study based on the Clinical Practice Research Datalink (CPRD) GOLD database. According to the researchers, CPRD is one of the largest databases of primary care information in the world and contains records of 674 practices in the United Kingdom from 2013, representing 4.4million active patients, or 6.9% of the total national population.
For their own study, Abtahi and colleagues analyzed data on 12,351 patients with RA aged 50 years or older between 1997 and 2017. Oral glucocorticoid and proton pump inhibitor exposure was classified based on the timing of the most recent prescription, with less than 6 months defined as “current use,” 7 to 12 months designated as “recent use,” and more than 1 year deemed “past use.” Exposure was additionally stratified by average daily and cumulative dose, as well as duration of use.
To estimate the risk for osteoporotic fractures — including hip, vertebrae, humerus, forearm, pelvis and ribs — the researchers used time-dependent Cox proportional-hazards models, statistically adjusted for lifestyle parameters, comorbidities and comedications.
According to the researchers, there were 1,411 total osteoporotic fractures among the included patients during the study period. Current concomitant use of oral glucocorticoids and proton pump inhibitors was associated with a 1.6-fold increased risk for osteoporotic fractures, compared with non-use (adjusted HR = 1.6; 95%CI, 1.35-1.89). This was statistically unique from the 1.2-fold increased risk for osteoporotic fracture linked to either oral glucocorticoid or proton pump inhibitor use alone, the researchers wrote.
In addition, most individual fracture sites were significantly associated with concomitant oral glucocorticoid and proton pump inhibitor use. Among concomitant users, the risk for fractures did not increase with higher daily dose or duration of proton pump inhibitors use.
“There was an interaction in the risk of [osteoporotic] fracture with concomitant use of oral GCs and PPIs,” Abtahi and colleagues wrote. “This increased risk seems to emerge from separate mechanisms of action of GCs and PPIs on bone or falling risk. Considering the increasing life expectancies and high consumption of PPIs among elderly patients, fracture risk assessment could be considered when a patient with RA is co-prescribed oral GCs and PPIs.”
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