Effect of Combined Treatment With Bisphosphonate and Vitamin D on Atherosclerosis in Patients With Systemic Lupus Erythematosus

A Propensity Score-Based Analysis

Kazumasa Ohmura; Masaru Kato; Toshiyuki Watanabe; Kenji Oku; Toshiyuki Bohgaki; Tetsuya Horita; Shinsuke Yasuda; Yoichi M. Ito; Norihiro Sato; Tatsuya Atsumi


Arthritis Res Ther. 2018;20(72) 

In This Article



Of the 220 consecutive patients with SLE who received glucocorticoids (GC) at the Hokkaido University Hospital between January 2013 and August 2015, 117 underwent carotid ultrasonography to assess subclinical atherosclerosis. All 117 patients met the 1997 American College of Rheumatology (ACR) revised criteria for SLE.[6,7]

Study Design

This study was designed as a cross-sectional study in a single center to examine whether BP + VD was protective against atherosclerosis compared with other treatments for osteoporosis in patients with SLE. This study was approved by the local ethical committee of Hokkaido University (approve number 015–0459). Clinical data were retrospectively reviewed at the time of undergoing carotid ultrasonography. Traditional risk factors for atherosclerosis were defined as the presence of hypertension, diabetes mellitus, dyslipidemia, smoking, increased body mass index, or history of CVD. SLE-related risk factors for atherosclerosis included duration of disease, duration of GC use, disease activity assessed by SLE disease active index 2000 (SLEDAI-2 K), presence of antiphospholipid antibodies, and renal manifestations, as previously reported.[1]

Carotid Ultrasonography

Carotid plaque was defined as a localized lesion with maximum thickness of more than 1 mm, which had a point of inflection on the surface of the carotid intima-media complex. Measurement of mean carotid intima-media thickness (IMT) was performed on the bilateral common carotid arteries. The mean IMT was defined as the average of three points where plaque was absent.[8]

Bone Mineral Density Measurements

Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry at the lumbar spine (L2–4 anteroposterior view) and/or femoral neck in accordance with standard instrument procedures. All BMD measurements were expressed as absolute values in gram of bone mineral per square centimeter (g/cm2) and as the T-score, the number of standard deviations (SD) above or below the mean value for young adult women. According to World Health Organization criteria, low BMD (defined as including osteopenia and osteoporosis), osteopenia and osteoporosis were defined as a T-score below − 1.0, between − 1.0 and − 2.5, and below − 2.5, respectively, in at least one measured region.[9]

Statistical Analysis

Binary variables were compared using either the chi-square (χ 2) test or Fisher's exact test as appropriate. Continuous variables were compared using the Wilcoxon rank sum test. Correlation between BMD and mean IMT was evaluated using the Spearman test. The propensity score was calculated for each patient using the nine covariates including age, postmenopausal status, duration of disease, duration of GC use, current dose of GC, statin use, chronic kidney disease, BMD T-score and SLEDAI-2 K, which were considered appropriate for the calculation using the Kolmogorov-Smirnov test (Additional File 1: Table S1). Strata were compared using the Mantel-Haenszel test. All p values less than 0.05 were considered significant. All statistical analyses were performed with JMP Pro V.12.0.1 (SAS Institute Inc., Cary, NC, USA).