Opioids, SSRIs Boost Fracture Risk in Rheumatoid Arthritis


The increased fracture risk may be the result of an increased risk of falls associated with these medications.

Both opioids and selective serotonin reuptake inhibitors (SSRIs) are associated with a higher risk of osteoporotic fractures in patients who have rheumatoid arthritis, according to new findings presented at the 2017 ACR/ARHP Annual Meeting, being held in San Diego.

Researchers at the University of Nebraska Medical Center in Omaha and the National Data Bank for Rheumatic Diseases in Wichita, Kansas, noted that chronic inflammation and pain predispose patients with rheumatoid arthritis to several comorbidities, including cardiovascular, mental, and GI disorders, that lead to frequent use of multiple medications and that some of the medications have been reported to influence fracture risk in the general population but the associations had not been studied in patients with rheumatoid arthritis.

They conducted a study to look at associations of various medications frequently used by patients with rheumatoid arthritis at risk for osteoporotic fracture.

“Even at younger ages, RA is associated with a twofold increased risk of osteoporosis and fractures due to chronic inflammation and glucocorticoid use,” said Gulsen Ozen, MD, Research Fellow at the University of Nebraska Medical Center in Omaha and a lead author. “More importantly, osteoporotic fractures significantly contribute to the disability, health-related costs and mortality with substantially higher complication in RA patients than the general population.”

He added, “Given the burden of osteoporotic fractures and the suboptimal osteoporosis care, it’s highly important to identify factors associated with fracture risk, particularly modifiable ones, in RA patients.”

In an observational cohort of patients with rheumatoid arthritis across the United States, the researchers studied associations between osteoporotic fracture risk and disease-modifying antirheumatic drugs (DMARDs), statins, antidepressants (including SSRIs), proton pump inhibitors, NSAIDs, anticonvulsants, and antipsychotics.

DMARDs were categorized as methotrexate monotherapy (comparator group), TNF-inhibitors, non-TNF biologics, and others, along with a separate glucocorticoid variable. All the other therapies were evaluated separately as current use versus nonuse and as short-term or long-term use.

The researchers evaluated 11,049 patients with rheumatoid arthritis. During a median follow-up time of 5.7 years, they found 863 osteoporotic fractures. Patients in whom fractures developed were significantly older and had higher disease activity, longer disease duration, higher rates of glucocorticoid use, higher fracture risk, and more comorbidity at baseline than patients who did not experience fractures.

The researchers also found significant increases in osteoporotic fracture risk when patients used SSRIs or opioids of any strength. Patients had an increase in their fracture risk starting after just 1 to 30 days of using opioids. Fracture risk associated with SSRI use started to rise after 3 months of taking them, and the risk was more prominent with long-term use, the study showed.

The increased fracture risk linked to the use of opioids or SSRIs may be the result of an increased risk of falls associated with these medications, the researchers concluded.

“Knowing the risks associated with the use of these medications can guide rheumatologists and other physicians in choosing the most appropriate management strategies in patients, particularly the ones who have a high fracture or fall risk,” said Dr Ozen.

“Some medications have important health impacts, and it’s impossible to avoid using them. In these situations, it is important that physicians are aware of the fracture risk to apply appropriate screening and preventive measures for osteoporotic fractures. Additionally, careful and regular reviewing of patient medications is an essential part of the RA patient care, as the use of medications that are not indicated anymore brings harm rather than a benefit.”

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