Background/Purpose: In the general population, we and others have reported that higher osteoprotegerin (OPG), a protein involved in bone remodeling, is associated with higher levels of coronary artery calcification (CAC).  Higher levels of OPG have been reported in SLE associated bone fractures and nephritis. We have previously reported higher CAC in  women with systemic lupus erythematosus (SLE) vs. healthy controls (HC) in two SLE case-control studies, HEARTS and SOLVABLE but the association of OPG with CAC in SLE is unknown.  Therefore we hypothesized that in HEARTS and SOLVABLE, higher serum OPG would be associated with the higher levels of CAC seen in SLE.

Methods: Levels of OPG were assayed by ELISA in frozen samples of plasma (HEARTS) and serum (SOLVABLE).  CAC was measured by CT in both studies and ordinal logistic regression models were used to estimate adjusted ORs for being in a higher CAC category (0, 1-10, 11-100 and >100) vs. the next lower category. 

Results:

Combining HEARTS (n cases /controls=125/124, age and race-matched) and SOLVABLE (n cases/controls= 185/184, age and race-matched), mean age (for cases, controls) was 46, 48 years, % postmenopausal (45, 40%), % African-American (AA) (23, 22%), %current smoking (11, 10%) and %ever smoking (37, 44%).  The distribution of CAC among the 620 women was CAC=0: n=397 (218 HC and 179 SLE), CAC=1-10: n=109 (52 HC, 57 SLE), CAC 11-100: n=64 (29 HC, 35 SLE) and CAC>=100: n= 43(9 HC, 34 SLE.) In both studies, OPG was higher for SLE vs. HC, AA vs. white, and post- vs. premenopause (p<0.05).  Among the entire group, OPG was higher with higher CAC category, with OR (95%CI) = 1.35(1.14, 1.59) per SD OPG and 2.21(1.32, 3.71) for the 4^th vs. 1^stquartile of  OPG (Q4 vs. Q1).  Based on the racial differences noted in OPG levels, subgroup analyses were conducted by race and case-control status, showing a consistent positive association for white HC and SLE and AA HC. However, among AA SLE cases (n=67), there was no association of OPG with higher CAC (OR=1.0, p=0.9).  Therefore all subsequent analyses excluded AA SLE cases in models adjusted for study, race, LDL-C and smoking.  Higher OPG was significantly associated with higher CAC category for SLE cases, OR (95%CI) for Q4 vs. Q1= 2.80 (1.25-6.30) and for HC: 2.40 (1.03, 5.58), in separate models.   Among the entire group (HC+SLE), the OR for Q4 vs Q1 OPG in predicting higher CAC was 2.78 (1.57, 4.94), and with adjustment for SLE, was 2.72 (1.53, 4.84).  For SLE vs. HC, the OR for higher CAC was 2.20 (1.47, 3.29), and 2.14 (1.43, 3.22) when adjusted for OPG (quartiles).   Results were similar in sensitivity analyses restricted to HEARTS only, or white women only, or white post-menopausal women only.

Conclusion:

In 2 SLE case-control studies, higher OPG was associated both with SLE and with higher CAC among cases and controls, except for AA SLE cases. The association of SLE with higher CAC was only slightly attenuated by concurrent levels of OPG.  Longitudinal studies in larger samples are warranted to clarify the role of OPG in the increased CAC noted in SLE, and potential differences by race.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/osteoprotegerin-is-associated-with-lupus-and-with-coronary-artery-calcification/