Patients with rheumatoid arthritis currently being treated with low doses of oral glucocorticoids (GCs) had a 59% increased risk of sustaining a vertebral fracture when compared with past users, results of a retrospective cohort study have shown.
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A patient undergoes a dual-energy x-ray absorptiometry scan.
Although the overall risk of an osteoporotic fracture was not increased when comparing current and past GC users, with a hazard ratio of 1.14 (95% confidence interval, 0.98-1.33), the HR for sustaining a spinal fracture was 1.59 (95% CI, 1.11-2.29).
“Clinicians should be aware that, even in RA patients who receive low daily glucocorticoid doses, the risk of clinical vertebral fracture is increased,” Shahab Abtahi, MD, of Maastricht (the Netherlands) University and coauthors reported in Rheumatology.
This is important considering around a quarter of RA patients are treated with GCs in the United Kingdom in accordance with European recommendations, they observed.
Conflicting randomized and observational findings on whether or not osteoporotic fractures might be linked to the use of low-dose GCs prompted Dr. Abtahi and associates to see if there were any signals in real-world data. To do so, they used data one of the world’s largest primary care databases – the Clinical Practice Research Datalink (CPRD), which consists of anonymized patient data from a network of primary care practices across the United Kingdom.
Altogether, the records of more than 15,000 patients with RA aged 50 years and older who were held in the CRPD between 1997 and 2017 were pulled for analysis, and just half (n = 7,039) were receiving or had received GC therapy. Low-dose GC therapy was defined as a prednisolone equivalent dose (PED) of 7.5 mg or less per day.
The use of low-dose GCs use during three key time periods was considered: within the past 6 months (current users), within the past 7-12 months (recent users), and within the past year (past users).
The analyses involved time-dependent Cox proportional-hazards models to look for associations between GC use and all types of osteoporotic fracture, including the risk for incident hip, vertebral, humeral, forearm, pelvis, and rib fractures. They were adjusted for various lifestyle parameters, comorbidities, and the use of other medications.
“Current GC use was further broken down into subcategories based on average daily and cumulative dose,” Dr. Abtahi observed. As might be expected, doses even lower than 7.5 mg or less PED did not increase the chance of any osteoporotic fracture but there was an increased risk for some types with higher average daily doses, notably at the hip and pelvis, as well as the spine.
“Low-dose oral GC therapy was associated with an increased risk of clinical vertebral fracture, while the risk of other individual OP fracture sites was not increased,” said the team, adding that the main results remained unchanged regardless of short- or long-term use.
“We know that vertebral fracture risk is markedly increased in RA, and it is well known that GC therapy in particular affects trabecular bone, which is abundantly present in lumbar vertebrae,” Dr. Abtahi wrote.
“Therefore, we can hypothesize that the beneficial effect of low-dose GC therapy on suppressing the background inflammation of RA could probably be enough to offset its negative effect on bone synthesis in most fracture sites but not in vertebrae,” they suggested.
One of the limitations of the study is that the researchers lacked data on the disease activity of the patients or if they were being treated with biologic therapy. This means that confounding by disease severity might be an issue with only those with higher disease activity being treated with GCs and thus were at higher risk for fractures.
“Another limitation was a potential misclassification of exposure with oral GCs, as we had only prescribing information from CPRD, which is roughly two steps behind actual drug use by patients,” the researchers conceded. The average duration of GC use was estimated at 3.7 years, which is an indication of actual use.
A detection bias may also be involved with regard to vertebral fractures, with complaints of back pain maybe being discussed more often when prescribing GCs, leading to more referrals for possible fracture assessment.
Dr. Abtahi and a fellow coauthor disclosed receiving research and other funding from several pharmaceutical companies unrelated to this study. All other coauthors had no conflicts of interest.