Longer, higher doses of glucocorticoids increase risk of vertebral fracture in RA patients

In patients with rheumatoid arthritis (RA), longer therapy with and higher doses of oral glucocorticoids (GCs) may increase their risk of sustaining vertebral fractures, but not hip or non-vertebral/non-hip fractures, according to research published in the Journal of Rheumatology.

Researchers led by Dam Kim, MD, PhD, Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea, and colleagues conducted this study to assess the effects of GCs on several different types of fractures in RA patients.

From the 2010 Korean National Healthcare Claims database, they identified 138,240 patients with RA (mean age: 54.2 years; 78.4% female), who were 19 years or older and who were followed for 3 years. In all, 48.6% were taking methotrexate and 2.6% took biologic agents. Notably, they excluded any patients with a history of osteoporosis.

During follow-up, 68.2% of patients had used oral GCs for more than 3 months, with a mean dose of 6.1 mg, and a highest daily dose of 16.2 mg.

In all, 11,599 fractures occurred in 9,964 patients. The incidence of fractures at any site was 232.0/10,000 patient years (PY); 144.7/10,000 PY in men, and 255.2/10,000 PY in women. The total incidence for vertebral fractures, hip fractures, and non-vertebral/non-hip fractures was 117.0/10,000 PY, 28.0/10,000 PY, and 89.0/10,000 PY, respectively.

Upon adjusted analysis, Dr. Kim and colleagues found an increased risk of vertebral fractures in patients who used GC for 6 months or more (OR: 1.76, P < 0.01), those who had a mean GC dose of 2.5 mg or greater (OR range: 1.37-1.71, P < 0.01), and those taking the highest daily dose of GCs of 10 mg or greater (OR range: 1.23-1.75, P < 0.03).

The risk of hip and non-vertebral/non-hip fractures, however, was not increased by the GC duration or dose.

Interestingly, the researchers also found that shorter use of GCs of 6 months or less decreased the risk of fracture, and that a daily mean dose of greater than 10 mg was protective against hip fractures.

“We presume that our conflicting results are caused by a difference in the anatomical characteristics and mechanisms of fractures at different sites,” they commented.

“In our study, GC use, accompanied by other demographic and clinical variables such as age, sex, comorbidities, and medications, was significantly associated with increased fracture risk. The longer the duration of GC use, the higher the mean dose; the greater the highest daily dose, the greater the risk of vertebral fracture. In contrast, neither the duration nor the dose of oral GC increased the risk of hip and non-vertebral/non-hip fractures in patients with RA,” concluded Dr. Kim and colleagues.