Bone mineral density and carotid atherosclerosis in systemic lupus erythematosus: a controlled cross-sectional study

Abstract

Introduction: As osteoporosis is reported to be associated with atherosclerosis in the general population we examined the relationship between bone mass and carotid measurements in patients with systemic lupus erythematosus (SLE) and controls, and possible links between them in SLE.

Methods: In a cross-sectional study, 111 SLE-patient were compared with 111 age- and sex-matched controls, mean age 48.7(12.9) years, 89% were women, of which 51% postmenopausal. Carotid intima media thickness (cIMT), carotid plaque occurrence and echogenicity were determined by B-mode ultrasound and bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA).

Results: BMD and cIMT were inversely associated both in patients and controls. Patients, but not controls, with carotid plaque had higher cIMT at low BMD than at normal BMD, p = 0.010. Logistic regression indicated more than doubled odds ratio (OR) of carotid plaque in patients, particularly in post-menopausal women, than in controls in relation to all BMD measurements. For low BMD at hip, significant increased OR for echolucent plaque was shown for patients compared with controls. In patients, significant impact of age, body mass index, smoking, systolic blood pressure, blood lipids, diabetes mellitus, impaired renal function, low levels of complement C3 and C4, history of nephritis, SLE-damage index and ever use of antimalarial was found for association between BMD and higher cIMT and carotid plaque. In multivariate regression, low C4 was independent contributor to association between total BMD and upper cIMT tertile, accounted for OR (95% confidence interval) of 3.2 (1.03-10.01), and also for association with bilateral carotid plaque, OR of 4.8 (1.03-22.66). The contribution of low C4 for the association between BMD and carotid atherosclerosis was enhanced within the second and third tertiles of total BMD.

Conclusion: This study is the first to demonstrate inverse association between BMD and carotid measurements in both SLE-patients and controls. Our results suggest that SLE-patients may suffer higher burden of (sub)clinical atherosclerotic disease, especially presence of both echolucent and echogenic plaque, than controls with the same bone mineral status. Low complement C4 seems to play an important role in earlier development of carotid atherosclerosis already within (sub)normal ranges of total BMD in patients.

Figure 1

Scatter plot of the relationship between total body bone mineral density (BMD) (A) and T -score (B), lowest at any region, and carotid intima-media thickness (IMT) measurements in 111 patients with systemic lupus erythematosus (SLE) and 111 sex- and age-matched controls. (A) The Pearson correlation coefficient was −0.26, P = 0.006 for the patients, and −0.27, P = 0.005 for the controls. (B) The respective coefficients were −0.33, P = <0.001, and −0.24, P = 0.012.

Figure 2

Distribution of carotid plaque in relation to mean total body bone mineral density (BMD) by tertiles in patients with systemic lupus erythematosus (SLE) and sex- and age-matched controls. BMD tertiles: 1 <1.067, 3 >1.183 mg/cm².

Figure 3

Receiver operating characteristic (ROC) curves for association between total body bone mineral density (BMD) (A-B) the middle and upper tertiles of total body BMD, ≥1.067 mg/cm ² (C-D) and the upper mean (>0.659 mm) carotid intima-media thickness (cIMT) (A, C) and bilateral carotid plaque (B, D) in patients with systemic lupus erythematosus (SLE). The curves are based on multivariate models with traditional risk factors alone (dashed lines) or together with (solid lines) a low level of complement C4 (<0.13 g/l). For total body BMD in association with higher cIMT (A) areas under the ROC curves are 0.840 (95% CI 0.768, 0.912, P <0.001) and 0.858 (0.789, 0.927, p = <0.001) in corresponding models; and in association with bilateral carotid plaque (B) areas are 0.869 (0.797, 0.940, P <0.001) and 0.886 (0.813, 0.958, P <0.001), respectively. For association between the middle and upper tertiles of total body BMD and upper mean cIMT (C), areas under the ROC curves are 0.850 (0.777, 0.923, P <0.001) in analyses incorporating traditional risk factors, and 0.863 (0.786, 0.941, P <0.001) in models that also included low C4; respective areas for association with bilateral carotid plaque (D) are 0.869 (0.792, 0.946, P <0.001) and 0.911 (0.848, 0.974, P <0.001).