Persistent increase of osteoprotegerin levels after cortisol normalization in patients with Cushing’s syndrome

Valentina Camozzi, Francesca Sanguin, Nora Albiger, Carla Scaroni, Franco Mantero, Martina Zaninotto, Annachiara Frigo, Michele Piccolo and Giovanni Luisetto

V Camozzi, Departement of Medical and Surgical Sciences, Padua University, Endocrinology Unit, Padova, Italy
F Sanguin, Departement of Medical and Surgical Sciences, Padua University, Endocrinology Unit, Padova, Italy
N Albiger, Padova, Italy
C Scaroni, Padova, Italy
F Mantero, Departement of Medical and Surgical Sciences, Padua University, Endocrinology Unit, Padova, Italy
M Zaninotto, Department of Laboratory Medicine,Padua University, Padova, Italy
A Frigo, Department of Environmental Medicine and Public Health, Padova, Italy
M Piccolo, Departement of Medical and Surgical Sciences, Padua University, Endocrinology Unit, Padova, Italy
G Luisetto, Departement of Medical and Surgical Sciences, Padua University, Endocrinology Unit, Padova, Italy

Valentina Camozzi, Email: camozzina@libero.it

Abstract

Objective: Osteoprotegerin (OPG) has been identified as a decoy receptor that inhibits osteoclast differentiation and recently as a paracrine regulator of vascular calcification. OPG is suppressed by glucocorticoids (GCs). Design: aim of this study was to evaluate OPG and bone metabolism in Cushing’s syndrome (CS) before and after cure.

Methods: 29 patients with CS (26 women and 3 men, mean age: 40.7-2.8 ys) and 27 age-, sex- and gonadal status- matched controls were studied for bone mineral density (BMD), bone metabolism, OPG, and receptor activator of nuclear factor-kB ligand (RANKL). Eighteen patients were studied from 6 to18 months after surgery, with normalization of cortisol levels in 12 of them.

Results: BMD was significantly lower in CS than in controls (lumbar spine:0.6±0.02 and 1.01±0.02, p<0.0001; femoral neck: 0.73±0.22 and 0.81±0.2, p=0,02). OPG was significantly higher and osteocalcin (OC) was significantly lower in CS than in controls (4.5±0.4 and 3.2±0.3 pmol/L, p= 0.02; 16.2+/-9.3 ng/ml and 21.2+/8.6ng/ml, p=0.03 respectively). Ca, P and PTH were similar. A significant positive correlation was found between serum cross laps (CLs) and OC levels (r2=0.43, p<0.01). After cure we found no difference in OPG levels but a significant increase of OC levels (16,4 ± 11 to 37,2 ±15; p=0,03 ng/ml, p=0.03).

Conclusion: In CS we found increased OPG that remained unchanged after recovery. High OPG was also observed in microvascular damage and was associated to an increased cardiovascular mortality. Therefore, high levels of OPG could reflects the persistent damage of the GCs on cardiovascular system.

From http://www.eje.org/cgi/content/abstract/EJE-09-0800v1