ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2008) 16 P48

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

Francesca Sanguin, Valentina Camozzi, Nora Albiger, Carla Scaroni, Franco Mantero & Giovanni Luisetto


Division of Endocrinology, Department of Medical and Surgical Sciences, Padova, Italy.


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 glucocorticoid administration. In this study, we evaluated OPG and bone metabolism in Cushing’s syndrome (CS) before and after surgical treatment. Twenty-nine patients with CS (26 women and 3 men, mean age: 40.7–2.8 years) and 27 age and sex-matched controls have been studied for bone mineral density, bone metabolism, OPG and receptor activator of nuclear factor-kB ligand (RANKL). Sixteen patients were studied for atleast 18 months after surgery, with normalization or reduction of cortisol levels. 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 levels were significantly increased in CS than in controls (4.5±0.4 and 3.2±0.3 pmol/l; P=0.02). Ca, P, osteocalcin (OC) and PTH did not differ between CS and controls. A significant positive correlation was found between serum cross laps and OC levels (r2=0.43, P<0.01) and between total alkaline phosphatase and RANKL (r2=0.42, P<0.005). After treatment we found no difference of OPG levels and a significant increase of OC levels (from 16.4±4.1 to 33.5±8.7 ng/ml, P=0.02). No other differences were observed between the two groups. Increased levels of OC after recovery confirm the inhibitory effect of GC on bone formation.

In CS we found increased levels of OPG maintained after remission of the disease. High serum OPG is also demonstrated in microvascular damage and was associated to an increased cardiovascular mortality. Therefore, high levels of OPG could reflects the persistent damage of the glucocorticoid on bone and cardiovascular system.

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