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Daily oral glucocorticoids can lead to spine fracture risk
Fracture risk increased by 1.62 for each increase of 10 mg/d of prednisone.
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UTRECHT, Netherlands — One year of daily dosing with oral glucocorticoids for chronic diseases is a strong predictor of spinal fracture. That risk, according to an analysis by a Dutch researcher at the 2002 Annual Meeting of the American College of Rheumatology in New Orleans, correlates with dose and is independent of bone mineral density.
“Up to one-half of patients on chronic glucocorticoid therapy may experience an osteoporotic fracture,” said Tjeer van Staa, MD, PhD, of the department of pharmacoepidemiology and pharmacotherapy, University of Utrecht. Van Staa said it has been known that oral corticosteroids can increase risk of fractures and low bone mass. What has been unclear is whether the risk is determined by dose size, duration of therapy, or BMD levels.
Van Staa’s study evaluated predictors for vertebral fracture and BMD thresholds in oral glucocorticoid users. The analysis included patients from two risedronate (Actonel, Procter & Gamble/Aventis) glucocorticoid-induced osteoporosis studies: a treatment study during which patients were assigned 7.5 mg/d prednisone for at least six months, and a prevention study of 7.5 mg/d with prednisone initiated within the prior three months.
In both trials, the combined total of 306 patients were assigned daily placebo or either 2.5 mg or 5.0 mg of risedronate. The patients in the prevention study were assigned 500 mg/d of calcium; patients in the treatment study were assigned 100 mg/d calcium and 400 IU/d vitamin D. Vertebral radiographs were collected a baseline and at month 12.
One-year fracture risk
For the BMD threshold analysis, the one-year fracture risk in postmenopausal placebo patients was compared to that of 2570 postmenopausal women not receiving corticosteroids from four other risedronate trials.
Mean patient age was 58 (about 68% female), and lumbar spine mean T-scores were –1.4 for the placebo group (n=111) and –1.2 for the risedronate group (n=195). Mean daily prednisone doses were 17.5 mg in the placebo group and 16.6 mg in the risedronate group.
Several factors were examined for their effect on fracture risk in the placebo group: number of prevalent fractures, daily glucocorticoid dose, cumulative glucocorticoid dose, smoking history, baseline lumbar spine BMD and body mass index. Only two of these, van Staa said, were significantly associated with increased fracture risk: daily glucocorticoid dose and baseline lumbar spine BMD.
Fracture risk increased by 1.62 for each increase of 10 mg/d of prednisone dose, and 1.85 for each decrease of one in T scores.
Van Staa said that fracture risk was comparable between the prevention and treatment studies (RR=1.16) despite differences in prior corticosteroid exposure (mean of 1.9 months in the prevention study vs. 59.4 months in the treatment study) and in baseline BMD.
Among patients assigned a placebo, vertebral fractures occurred in 34.8% with baseline BMD T scores <-2.5, and in 5.9% of those with T scores -2.5. In the risedronate groups, 15.0% and 2.2%, respectively, had vertebral fractures. Patients in the placebo group who received less than or more than 15 mg/day of glucocorticoids had 12.3% and 25.0% vertebral fracture rates, respectively. Among patients receiving risedronate, the rates were 5.4% and 7.8%, respectively.
Fractures occurred quickly
Van Staa said that analysis had shown that with daily oral glucocorticoid use, fractures occurred within one year to one in six patients (overall incidence of 16.5%) receiving placebo in both the prevention and treatment trials. This occurred despite the fact that glucocorticoid users were younger with higher baseline BMDs and fewer pre-existing fractures compared to non-users.
Daily corticosteroid dose, and not cumulative dose, was predictive of fracture risk. The effect of therapy with risedronate was to reduce fracture rate by 70%, to a rate of one in 18 patients (overall incidence of 6.2%).
Regarding the BMD inquiry, van Staa said that for patients at the same BMD, there was a sixfold increase in fracture risk, after adjustment for baseline factors, among those receiving chronic daily glucocorticoid therapy. That finding, he said in an interview, suggests steroid-induced changes in bone architecture, perhaps related to adverse steroid effects on osteocytes.
Van Staa said that the findings support the ACR guidelines, which recommend bisphosphonate therapy as first-line treatment for glucocorticoid-induced osteoporosis in men and postmenopausal women initiating chronic glucocorticoid therapy (>3 months duration), along with calcium, vitamin D and modification of lifestyle risk factors.
For your information:
- Van Staa TP. Predictors for vertebral fractures and fracture threshold in patients using oral glucocorticoids. Presented at the 2002 Annual Meeting of the American College of Rheumatology. Oct. 25-29, 2002. New Orleans.