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-kappaB 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).


CONCLUSIONS
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.
Clinica Medica Generale, Dipartimento di Scienze Cliniche e Biologiche, Università degli Studi di Torino, Regione Gonzole 10, Orbassano, Italy. andrea.dovio@unito.it
Andrea
A
Dovio
Valeria
V
Data
Renato
R
Carignola
Gilberto
G
Calzolari
Rosetta
R
Vitetta
Massimo
M
Ventura
Laura
L
Saba
Adriana
A
Severino
Alberto
A
Angeli
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D015519:Bone Density; D001842:Bone and Bones / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000453:epidemiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D053244:Osteoprotegerin / Q000097:blood*; D011237:Predictive Value of Tests; D053245:RANK Ligand / Q000097:blood*; D012307:Risk Factors; D012595:Scleroderma, Systemic / Q000097:blood* / Q000453:epidemiology; D012995:Solubility; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
D015415:Biomarkers; D053244:Osteoprotegerin; D053245:RANK Ligand; D019010:Vascular Cell Adhesion Molecule-1