Steroids + PPIs increase fracture risk

Combining glucocorticoids and PPIs increases risk of fragility fracture in rheumatoid arthritis patients, according to a large study.

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Taking glucocorticoids along with proton pump inhibitors is associated with an elevated risk of fragility fractures, according to an analysis of over 12,000 rheumatoid arthritis patients.

The retrospective analysis of patients aged 50 years and over “brings to the light an important issue focusing on multiple co-prescription of drugs potentially detrimental for skeletal health in patients with rheumatoid arthritis”, a trio of Italian researchers wrote in commentary on the study.

It also underscores the need to consider fracture risk in a common clinical scenario, where RA patients treated with oral glucocorticoids are co-prescribed proton pump inhibitors (PPIs) to manage side effects.

Newcastle rheumatologist Dr John Van Der Kallen said that while an increased risk of fractures with glucocorticoids is clear, data on the risk of fractures associated with PPI use has been varied, so the study provides some unique insights.

From a large primary care database of UK citizens, nearly 12,400 rheumatoid arthritis patients were identified and grouped as current, recent or past users of glucocorticoids and PPIs based on their most recent prescription. Current users were further stratified by dosage and duration of use, and their risk of osteoporotic fractures estimated.

Patients taking both glucocorticoids and PPIs had a 1.6-fold greater risk of osteoporotic fractures than patients using neither drug; fracture risk was 1.2-fold higher for patients taking either therapy alone vs non-use. Both findings were statistically significant.

Dr Van Der Kallen said that the increased risk associated with co-prescriptions would be significant enough to elevate someone who would be typically prescribed preventative strategies such as exercise, calcium and vitamin D, to the next level of care which might involve medications for osteoporosis.

“That’s quite a significant change in approach because now you’re trying to prevent complications of treatment,” he said. “It certainly changes the risk assessment for someone who has bone fragility.”

However, not all results from the study were as clear cut. Among concomitant users, fracture risk appeared higher in short-term PPIs users but no significant increase was observed among patients taking PPIs for more than a year.

Dr Van Der Kallen said this result was “hard to reconcile” but it comes back to the uncertainty around how PPI might be increasing bone fragility, which has in the past caused some controversy about PPI use and fracture risk.

The study also selected rheumatoid arthritis patients from primary care data, which did not include disease activity scores. However, patients with active disease may be prescribed higher doses of glucocorticoids which in itself creates a greater risk of fractures.

Similarly, no data was available on the effect of osteoporosis treatments or antidepressants, the latter being associated with a loss of bone density, Dr Van Der Kallen said.

However, that should not take away from the study findings which emphasise the need to try and minimise glucocorticoids doses and to think about alternative ways of treating patients’ gastrointestinal symptoms rather than with PPIs, he said.

“Look at patients’ use of these medications, and whether they can be minimised or ceased,” Dr Van Der Kallen said. “And if that’s not possible, then be vigilant with screening for osteoporosis and consider therapy, if indicated.”