FRI0173 IDENTIFICATION OF RISK FACTORS FOR DEVELOPMENT OF OSTEONECROSIS IN SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: R. Kallas, J. LI, M. Petri
Journal: Annals of the Rheumatic Diseases (2020)

Background: Patient with Systemic Lupus Erythematosus (SLE), particularly those who received corticosteroids are at a high risk of osteonecrosis (ON). Objectives: In this analysis, we aimed at determining the predictors of ON in a longitudinal lupus cohort in which Caucasian and African-American ethnicities are well represented. Methods: The data were reviewed from the initiation of the cohort in 1987 until October 2019. 2428 patients were included in the analysis based on 224295 person-months of follow-up. ON was recorded using the Systemic Lupus Erythematosus International Collaborating Clinics/ American College of Rheumatology (SLICC/ACR) Damage Index. To calculate the rate of ON in each demographic and clinical subgroup, we calculated the number of ON events divided by the number of person-months at risk and converted this rate to rates per person-year. To assess the relationship between risk factors and rates of ON events, we used the pooled logistic regression. Rate ratios were adjusted for age. After identifying a set of variables related to ON incidence, we fit a final multivariable model to identify the most important risk factors for incident ON. Results: 287 ON cases were identified, giving a point prevalence of 11%. ON cases that occurred before cohort entry were excluded. 122 incident events of ON occurred after cohort entry and were included in the final analysis. In the multivariable analysis, African-Americans were at twice the risk for ON compared to Caucasians. Male gender and smokers had about 80% and 50% increased risk of ON compared to females and non-smokers respectively. For every 10 year increase in the age there was a 20% reduced risk for ON. Patients diagnosed after the 1990’s had a 50% reduced risk of ON compared to those diagnosed before 1990’s. A highest daily dose of prednisone of 40 mg or higher, even when administered for a month or less, increased significantly the risk of ON. Use of pulse steroid was not associated with an increased risk of ON. Conclusion: Ethnicity remains an important determinant in the risk of ON. African-American SLE patients are at double the risk of ON compared to Caucasians. APOL1 risk variants confer an increased risk of ON in this high-risk ethnic group. Oral prednisone more than 40 mg daily administered for a month or less, at any point in the disease course, remains the most important predictor of ON. Prednisone-free or prednisone-limited regimens should be reinforced in SLE trials. Table 1. Associations between ON rates and corticosteroids dose and duration based on a multivariable model Predictor RR (95% CI) p-value Max prednisone and duration 0- 40 mg/day for &lt;=1 month 1.00 (Ref) 0- 40 mg/day for &gt;1 month 1.49 (0.68, 3.26) 0.3162 40-60 mg/day for &lt;=1 month 2.76 (1.18, 6.39) 0.0182 40-60 mg/day for &gt;1 month 3.87 (1.73, 8.62) 0.0009 &gt;=60 mg/day for &lt;=1 month 6.6 (3.37, 12.93) &lt;0.0001 &gt;=60 mg/day for &gt;1 month 5.15 (2.55, 10.4) &lt;0.0001 Sex Male (vs. Female) 1.79 (1.04, 3.10) 0.0373 Ethnicity African American (vs. Caucasian) 1.94 (1.32, 2.83) 0.0007 Year of SLE diagnosis 1990 and after (vs. before 1990) 0.53 (0.36, 0.77) 0.0008 Age Per 10 year increase 0.77 (0.66, 0.89) 0.0006 Smoking Ever (vs. never) 1.51 (1.04, 2.19) 0.0293 Table 2. Associations between ON rates and pulse steroid stratified by max prednisone Subgroup No. of ONs Person years Rate per 1000 person years Age-adjusted RR (95% CI) Age-adjusted p-value Pulse among those with maximum prednisone dose of &lt;40 mg No 21 6752.1 3.11 1.00 (Ref) Yes 2 387.8 5.16 1.69 (0.40, 7.20) 0.4801 Pulse among those with maximum prednisone dose of &gt;=40 mg No 88 7202.3 12.2 1.00 (Ref) Yes 8 959.2 8.3 0.71 (0.35, 1.48) 0.3618 Pulse among those with maximum prednisone dose of &gt;=60 mg No 64 4329.9 3.11 1.00 (Ref) Yes 7 622.4 5.16 0.79 (0.36, 1.72) 0.5477 Acknowledgments: The Hopkins Lupus Cohort was funded by NIH Grant R01-AR069572 Disclosure of Interests: None declared