Rheumatoid Arthritis (RA) is a chronic inflammatory disease with an increased risk of osteoporosis which is partly due to the disease itself and partly due to medication, in particular glucocorticoids (GC). About one quarter of RA patients are prescribed oral glucocorticoids which increases the fracture risk substantially. Proton pump inhibitors (PPI) are frequently co-prescribed in order to prevent gastrointestinal side effects of GC or Non-steroidal anti-inflammatory medications. PPI use has been associated to a possible increased fracture risk, however the magnitude and underlying mechanism of PPIs on fracture risk are not well understood.
A retrospective cohort study by Abtahi et al. included RA patients over 50 years of age who were included in the UK Clinical Practice database over a 20 years time frame. GC and PPI intake was stratified into current, recent or past use. Time-dependent Cox proportional-hazards models allowed to estimate the risk of an osteoporotic fracture in RA patients with concomitant current use of oral GCs and PPIs versus non-use.
Amongst the 12 351 RA patients, 1411 osteoporotic fractures occurred. Concomitant use of oral GC and PPI was associated with a 1.6 fold increased fracture risk compared with non-use of both drugs. Patients with either GC or PPI use alone were associated with a 1.2 fold higher fracture risk which was significantly lower than that of the combination treatment. PPI dose or duration did not seem to influence fracture risk. Interestingly, past use (> 6 months) of either GC or PPI was not associated with an increase in fracture risk confirming some aspects of reversibility in medication associated fracture risk. The authors conclude that the combination treatment of GC and PPI may significantly increase the fracture risk in RA patients and thus such patients should be considered for a fracture risk assessment.