Background/Purpose: To determine the prevalence of subclinical atherosclerosis and impaired bone health in primary Sjogren’s syndrome (pSS) patients and to explore whether they associate with clinical and serological disease features, traditional risk factors for cardiovascular disease (CVD) and osteoporosis as well as with activation of the Receptor activator of nuclear factor kappa-B ligand (RANKL)-RANK system, previously implicated in the pathophysiology of both CVD and osteoporosis.

Methods: 64 consecutive pSS patients according to the American-European Classification Criteria (mean age ±SD 57.19±12.4) and 39 healthy controls οf similar age and sex distribution (mean age ±SD 53.6±7.04) were enrolled. Demographic data, clinical, laboratory and histopathological features were recorded and classical risk factors for atherosclerosis and osteoporosis were evaluated. Patients and controls underwent intimal-medial thickness score (IMT) and bone mineral density (BMD) levels measurements. The presence of carotid/femoral plaque and fractures was also determined by ultrasound and lateral spine radiographs respectively. Serum RANKL and osteoprotegerin levels were determined by ELISA. RANKL and osteoprotegerin mRNA levels were determined in cDNA derived from minor salivary gland (MSG) tissues from 19 pSS patients, 9 pSS patients complicated by lymphoma and 11 sicca controls by real time PCR. Determinants of IMT/BMD levels and the presence of plaque were assessed by univariate and multivariate models. Comparisons between groups were performed by Fisher’s exact two tailed test and Mann Whitney test.

Results: Increased prevalence of subclinical atherosclerosis (defined as IMT >0.90mm) and osteoporosis/osteopenia was detected in pSS patients compared to controls [58.7% vs 27.5%, p=0.0071 and 61.2% vs 20.5%, p=0.0001) with fracture rates not significantly differing between the two groups. Multivariate analysis in the pSS group revealed age, BMI and periepithelial disease (defined as peribronchial, interstitial nephritis, primary biliary cirrhosis) as independent predictors of IMT, age and lymphopenia as independent determinants of carotid and/or femoral artery plaque and increased urine PH, periepithelial disease and total steroid dose as independent predictors of osteoporosis and/or osteopenia. The latter was independently associated with the presence of plaque, when independent predictors for both variables were included in the multivariate model [(OR:4.75 (1.05-21.47, p=0.043)]. Compared to the control group, pSS patients displayed increased serum RANKL levels (p=0.0003) while at MSG tissue, mRNA RANKL/osteoprotegerin ratio was significantly increased in pSS patients complicated by lymphoma compared to sicca controls. 

Conclusion: pSS patients are characterized by higher levels of concomitantly occurring subclinical atherosclerosis and impaired bone health compared to their healthy counterparts, with traditional risk factors, disease related features and activation of RANKL system being potential contributors. The significance of RANKL activation in pathogenesis of SS related complications remains to be further explored.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/concomitant-atheosclerosis-and-impaired-bone-health-in-patients-with-primary-sjogrens-syndrome/