OSTEONECROSIS IS THE MOST COMMON ORGAN DAMAGE AND IS ASSOCIATED WITH CUMULATIVE STEROID DOSAGE AS WELL AS LUPUS NEPHRITIS ITSELF IN PATIENTS WITH SLE

Abstract

Background In patients with SLE, musculoskeletal system is common organ system involved cumulatively over time. Osteonecrosis (ON) is common in musculoskeletal damage accrual and often disabling. Steroid use has been a risk factor in the development of ON, but SLE itself has also been suggested to have a role. It is important to understand factors related to the development of ON.

Objectives We investigated the overall profile of organ damage accrual, particularly musculoskeletal damage and focused on factors associated with ON in a single Asian cohort.

Methods Patients with SLE who met American College of Rheumatology (ACR) criteria were enrolled and followed from 1998 to 2014 in the Hanyang BAE Lupus cohort. Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) was measured annually. ON was confirmed by X-ray, bone scan or MRI. Patients with ON was compared to controls without ON from the same cohort for clinical, laboratory, and therapeutic factors. Univariate logistic regression followed by multivariate logistic regression were used to determine risk factors for ON.

Results We recruited 1,219 SLE patients. The most common type of organ damage was musculoskeletal (205 patients, 16.8%). ON was the most common subtype (133 patients, 10.9%) of the musculoskeletal damage. The mean time from diagnosis of SLE to development of ON was 4.97±4.15 (0.17∼20.25) years.

One hundred twenty-six patients were eligible for identifying distribution of ON. Overall, 291 joints were affected by ON and mean number of ON joint per patients with ON was 2.3±1.23 (1∼9). The percentage of >2 joint involvement was 24.6%. The hip (femoral head) was the most frequently involved joint (65.6%), followed by the knee (distal femur, proximal tibia, proximal fibula, patella: 20.6%), shoulder (humeral head: 5.2%) and ankle (distal tibia, distal fibula, talus: 5.2%).

In univariate analysis, age at diagnosis, follow up duration, accumulative number of ACR criteria, serositis, renal disorder & neurologic disorder (based on ACR criteria), cyclophosphamide & mycophenolate use, and cumulative steroid dosage were significantly associated with ON. In multivariate analysis, renal disorder (p=0.0109), and cumulative steroid usage (p=0.0131) were significantly associated with ON.

To evaluate the effect of cumulative steroid usage on ON, age, sex and disease duration matched ON cases and controls (1:4, a total of 665 patients) were selected from the same cohort. Total cumulative steroid dosage was divided into 4 groups by grams (>0 & ≤5g, >5g & ≤10g, >10g & ≤20g, and >20g). More than 10g group of cumulative steroid use was significantly associated with ON. And then we stratified 530 patients according to biopsy proven lupus nephritis (class III to V) and cumulative steroid dose (10g cut-off), and tested by Chi-square test and logistic regression. ON was significantly higher in the group with lupus nephritis within >10g group of total cumulative steroid.

Conclusions ON was the most frequent damage in lupus patients. We confirmed again cumulative steroid dosage as a risk factor for the development of ON. In addition, lupus nephritis itself was suggested as an independent risk factor for ON.