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


A total of 117 patients with SLE were included in this study. As previously reported,[10] BMD correlated negatively with mean IMT (Figure 1). Of the 117 patients, 42 (36%) were receiving BP + VD, 27 (23%) BP alone, 30 (26%) VD alone and 7 (6%) other agents, including denosumab, estrogen, teriparatide and calcium, to treat or prevent osteoporosis. Of the 72 patients receiving BP, 58 (81%) were on alendronate, 7 (10%) risedronate, 6 (8%) minodronate, and 1 (1%) ibandronate.

Figure 1.

Relationship between lumber spine bone mineral density (BMD) and mean intima-media thickness (IMT) measurements. The Spearman rank correlation coefficient was − 0.25, p < 0.01. BP, bisphosphonate; VD, vitamin D agent

We first compared the patients' demographics, BMD measurements, carotid measurements, and medications for SLE between the BP + VD and other treatment groups. Low BMD was more frequent, and carotid plaque was less prevalent in the BP + VD group compared with other treatment groups (Table 1). Among traditional and SLE-related risk factors for atherosclerosis, duration of disease and that of GC use were shorter in the BP + VD group compared with other treatment groups, possibly being associated with the less prevalent carotid plaque. The cumulative dose of GC was strongly correlated with duration of GC use (Spearman correlation coefficient = 0.93). Duration of anti-osteoporotic treatment was not different between the BP + VD and any of the other groups.

Next, we evaluated factors contributing to the development of carotid plaque by univariate (Table 2) and multivariate (Table 3) analyses. Among factors extracted by the univariate analysis including age, post menopause, duration of disease, history of lupus nephritis, estimated glomerular filtration rate, serum creatinine, history of cardiovascular disease, BMD (of both the lumbar spine and femoral neck), T-scores (of both the lumbar spine and femoral neck), mean IMT, cumulative dose of GC, duration of GC use, current dose of GC, concomitant use of immunosuppressants, antihypertensive agents and BP + VD treatment, only age (OR = 1.57) and BP + VD treatment (OR = 0.24) were shown by multivariate analysis to be promotive and protective factors, respectively. We excluded relevant confounding factors with age, including post menopause, estimated glomerular filtration rate, serum creatinine, mean IMT and antihypertensive agent, as variables in multivariate analysis.

To further confirm the protective role of BP + VD against carotid plaque development, we performed an unbiased analysis using propensity scoring. In 15 out of 117 patients, the propensity score could not be estimated due to the unavailability of T-scores. The remaining 102 patients were divided into 5 different strata using the propensity score calculated using age, postmenopausal status, duration of disease, duration of GC use, current dose of GC, statin use, chronic kidney disease, T-score and the SLEDAI-2 K (Additional File 1: Table S1) and ranged from 0.01 to 0.97. The borderlines of these five strata were 0.12, 0.28, 0.41 and 0.62. Stratum 1 included the patients with the lowest propensity score while stratum 5 included patients with the highest. Carotid plaque was less prevalent in the BP + VD group compared with other treatment groups in all 5 strata (Figure 2). The difference was considered significant using the Mantel-Haenszel test (p = 0.015).

Figure 2.

Comparison of the prevalence of carotid plaque in the bisphosphonate (BP) + vitamin D (VD) treatment group and other treatment groups according to propensity score quintile. Values are percent (number of patients with carotid plaque/total number of each group)