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To identify associated factors for the development of osteonecrosis of a femoral head (ON) in patients with systemic lupus erythematosus (SLE).We conducted a retrospective nested case-control study from SLE patients who attended the Rheumatology Clinic at Phramongkutklao Hospital from 1992–2008. Cases were defined as SLE patients, who had clinically apparent ON (confirmed by plain radiographs or magnetic resonance imaging). For each case, a control was selected and matched to the case by age and disease duration. The main outcome measure was the odds ratio (OR) of ON among SLE patients. The clinical and laboratory variables thought to be risk factors of ON variables were compared between patients who did and did not develop ON. Significant and clinically relevant variables were then examined by a stepwise logistic regression model.Of 186 SLE patients, we identified 41 patients who developed ON during the course of follow-up. Twenty patients were available for data analysis. From the univariate analysis, incidence of renal involvement and the use of steroids (recorded as evidenced by maximum and mean daily prednisolone dose) were significantly higher in the ON group than in controls. The use of antimalarials was significantly lower in patients with ON than in controls. No difference in disease activity, lipid profiles or anticardiolipin antibody was found between groups. In the logistic regression, the presence of renal involvement remained as a positive associated factor for ON (OR = 7.80, CI = 1.249–48.748, P = 0.028) and the use of antimalarial drugs was a negative associated factor for ON (OR = 0.09, CI = 0.009–0.961, P = 0.046).The presence of renal involvement was associated with ON and the antimalarial use may have a protective effect for ON in Thai patients with SLE. The findings from this study further support the use of antimalarial drugs in SLE patients.