Circulating Osteoprotegerin and Soluble RANK Ligand in Systemic Sclerosis

Objective. Microvascular damage is an early pathogenetic event in systemic sclerosis (SSc). The receptor activator of nuclear factor-kappa B ligand (RANKL)/RANK/osteoprotegerin (OPG) system is involved in vascular biology. Our aim was to assess OPG and soluble RANKL (sRANKL) serum levels in patients with SSc and healthy controls. Methods. Sixty patients with SSc (median age 58, range 31-72 yrs) and 60 healthy subjects matched for age, sex, and menopausal status were recruited. Serum OPG, sRANKL, soluble vascular cell adhesion molecule (sVCAM; marker of endothelial activation/injury), and bone turnover markers were measured. Bone mineral density in patients was assessed and cardiovascular/coronary risk was estimated. Results. OPG was similar in the 2 groups, while sRANKL and sRANKL/OPG ratio was higher in patients (p = 0.01 for both). sVCAM was markedly higher in patients (p < 0.001). OPG levels correlated positively with age in both patients (Spearman R = 0.50, p < 0.001) and controls (R = 0.56, p < 0.001). In patients, OPG was lower in men and higher in those with active ulcers or calcinosis. sRANKL levels were higher in patients treated with platelet aggregation inhibitors, and correlated negatively with densitometric measures. 25-hydroxyvitamin D levels were significantly lower in patients (p < 0.001). In patients, OPG levels correlated positively with cardiovascular and coronary risk (R = 0.28, p = 0.05 and R = 0.34, p < 0.01, respectively) and were higher in patients with hypertension and left ventricular hypertrophy. sVCAM levels correlated positively with cardiovascular and coronary risk (R = 0.27, p = 0.06, and R = 0.38, p < 0.01, respectively). Conclusion. Higher sRANKL levels and sRANKL/OPG ratio in patients with SSc are likely to be a consequence of altered bone microenvironment. We show a dissociation between the well established marker of endothelial activation/injury, sVCAM, and the alleged marker of vascular damage, OPG, in patients with SSc. Further studies are needed to better ascertain the relationships of the RANKL/RANK/OPG system with the progression of macro- and microvascular damage. (First Release Oct 1 2008; J Rheumatol 2008;35:2206-13: doi: 10.3899/jrheum.080192)