Disclosures: Abtahi reports grants from AbbVie and Celgene, as well as speaking fees or advisory board meetings from UCB, Eli Lilly & Co. and Galapagos, all paid to his department. Please see the study for all other authors’ relevant financial disclosures.
July 27, 2021
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Even low-dose glucocorticoids greatly increase vertebral fracture risk in RA

Disclosures: Abtahi reports grants from AbbVie and Celgene, as well as speaking fees or advisory board meetings from UCB, Eli Lilly & Co. and Galapagos, all paid to his department. Please see the study for all other authors’ relevant financial disclosures.
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Patients with rheumatoid arthritis who receive even low daily doses of glucocorticoids are at a 59% increased risk for clinical vertebral fracture, according to data published in Rheumatology.

The risk for non-vertebral fractures, however, was unaffected by low-dose glucocorticoids, the researchers added.

Patients with RA who receive even low daily doses of glucocorticoids are at a 59% increased risk for clinical vertebral fracture, according to data derived from Abtahi S, et al. Rheumatology. 2021;doi:10.1093/rheumatology/keab548.

“There has been, so far, little information on the association of low daily doses of oral glucocorticoids (GCs) and osteoporotic (OP) fracture risk in patients with rheumatoid arthritis,” Shahab Abtahi, MD, PhD, MSc, of Maastricht University Medical Center, in the Netherlands, told Healio Rheumatology. “In particular, the EULAR task force on the risk of harm — including OP fractures — in long-term GC therapy did not have firm conclusions for GC daily doses between 5 mg to 10 mg prednisone equivalent dose per day.”

To examine how low-dose glucocorticoids impacts the risk for osteoporotic fractures in patients with RA, Abtahi and colleagues conducted a retrospective cohort study of individuals from the Clinical Practice Research Datalink. According to the researchers, this database includes information from 4.4 million active patients from 674 practices in the United Kingdom. For their study, they included all 15,123 adults in the database aged 50 years or older who had been diagnosed with RA between Jan. 1, 1997, and Dec. 31, 2017. These included 7,039 glucocorticoid users.

Shahab Abtahi

Abtahi and colleagues stratified the included patients based on glucocorticoid exposure as of the most recent prescription. Stratification groups included “current,” or within less than 6 months; “recent,” defined as within the past 7 to 12 months; and “past,” or more than a year since their last prescription. Patients were also grouped based on average daily cumulative doses, with a “low dose” defined as 7.5 mg or less prednisolone equivalent per day. The mean follow-up time was 8.1 years for glucocorticoid users, and 6.2 years for nonusers.

The researchers estimated the risk for hip, vertebrae, humerus, forearm, pelvis and rib fracture using time-dependent — in 30-day periods — Cox proportional-hazards models, adjusting for life-style factors, comorbidities and comedications. Secondary analyses examined the risk for fracture with a combination of average daily and cumulative doses of oral glucocorticoids.

According to the researchers, a total of 1,640 osteoporotic fractures were reported among the total study population. Current low-dose oral glucocorticoid therapy was not associated with overall risk for osteoporotic fractures (adjusted HR = 1.14; 95% CI, 0.98-1.33), compared with past glucocorticoid use. However, current low-dose glucocorticoids were associated with an increased risk for clinical vertebral fracture (adjusted HR = 1.59; 95% CI, 1.11-2.29). These results remained unchanged regardless of a short-term or a long-term glucocorticoid use.

“When patients with RA are treated with low-dose oral GCs, there is an increased risk for vertebral fractures, but not that of non-vertebral osteoporotic fractures such as hip,” Abtahi said. “The increased risk of vertebral fractures could be translated into an additional two clinical vertebral fractures per 1,000 patients with RA in the United Kingdom who took low-dose oral GCs in one year.

“In addition, we know that only one-third of vertebral fractures would come into clinical attention, so another four vertebral fractures per 1,000 patients with RA in the United Kingdom have been caused by low-dose GC therapy in a year and would have been missed in practice,” he added. “The treating — and prescribing — physician should therefore be more vigilant of this increased risk of vertebral fractures with low-dose oral GCs.”