The use of cytotoxic drugs and glucocorticoids are both risk factors for the occurrence of symptomatic osteonecrosis in patients with systemic lupus erythematosus, Dr. Graciela S. Alarcón of the University of Alabama, Birmingham, and her colleagues reported.
The study confirmed previous findings that glucocorticoid use in systemic lupus erythematous (SLE) patients is associated with osteonecrosis. “Our data suggest that exposure to high doses of glucocorticoids and probably the duration of use are the most important factors underlying this known association,” the researchers reported (Ann. Rheum. Dis. 2006;65:785-90).
However, the researchers noted in the study that they could not draw any definitive conclusions about the glucocorticoid association related to the route of administration, the mean dose, the cumulative dose, or the highest dose used.
The findings highlight the fact that glucocorticoids and cytotoxic drugs should be used only when “strictly indicated,” the researchers wrote.
The findings are based on a nested matched case-control design drawing on patients from a large, multiethnic, longitudinal lupus cohort—the LUMINA (Lupus in Minority Populations: Nature vs. Nurture) trial. The trial was made up of 571 SLE patients at the time the case-control study was conducted. The LUMINA study included participants from three ethnic groups—Hispanics from Texas and Puerto Rico, African Americans, and whites.
Within the LUMINA cohort, the researchers identified 33 cases of symptomatic osteonecrosis. One case was excluded because the diagnosis of osteonecrosis was made before the SLE diagnosis. Using the LUMINA database, researchers attempted to match two controls for each osteonecrosis case included in the study. Controls were matched by age, sex, ethnicity, disease duration, and study location. In five cases, only one control subject could be matched.
Researchers analyzed 91 patients (32 cases and 59 controls). Most patients (57%) were African American, 22% were Hispanics from Texas, 2% were Hispanics from Puerto Rico, and 19% were white. The mean total disease duration of patients included in the study was about 46 months.
Patients were evaluated at baseline and received follow-up care every 6 months for the first year and annually thereafter.
The results of multivariate analyses show that both cytotoxic drug use and glucocorticoid use were associated with symptomatic osteonecrosis, but the average daily dose of glucocorticoids had only “borderline significance,” according to the researchers. The odds ratio for the use of cytotoxic drugs was 3.89 when analyzed by the average daily dose of glucocorticoids and 3.04 when evaluated looking at the highest dose of glucocorticoids. The odds ratio was 1.03 for glucocorticoid use in the average dose model, as well as in the highest dose model.
There was also a “significant” negative association between osteonecrosis and serum triglycerides. In the model of average daily dose of glucocorticoids, the odds ratio was 0.99 and was statistically significant. Serum triglycerides also had an odds ratio of 0.99 in the highest dose of glucocorticoids but the significance was “borderline,” the researchers wrote.
Despite the findings related to serum triglycerides, the researchers concluded that they could not identify any protective factors for symptomatic osteonecrosis. The study also failed to show a link between other suspected risk factors for osteonecrosis, such as Raynaud's phenomenon, arthritis, and antiphospholipid antibodies.