Increased serum osteoprotegerin in disorders characterized by persistent immune activation or glucocorticoid excess -: possible role in bone homeostasis

Objective: To investigate the possible role of osteoprotegerin (OPG) in bone metabolism in humans by measuring serum levels of OPG in five well-characterized patient populations with known or suspected pathology in bone homeostasis, but with differences in the pathogenesis of these disturbances. Design: The study comprised 34 patients with Cushing's syndrome (CS), 24 acromegalic patients. 16 patients with growth hormone deficiency (GHD), 29 HIV infected patients, 25 patients with common variable immunodeficiency (CVI) and 59 age- and sex-matched healthy controls (CTR). Methods: Serum levels of tumor necrosis factor (TNF)-alpha, OPG, C-terminal telopeptides of Type-I collagen (CTX-I) and osteocalcin were determined in all study subjects as well as cortisol (CS and CTR) and IGF-I (acromegaly, GHD and CTR). Results: OPG levels were significantly elevated in both CVI (median increase similar to 32%, P < 0.05) and HIV infected patients with especially high levels in the latter group (similar to 52%, P < 0.001), significantly correlated with increased TNF alpha levels (r = 0.47, P < 0.02). Also CS patients had elevated serum OPG (similar to 24%, P < 0.01), significantly correlated with increased serum cortisol (r = 0.35, P < 0.05). In contrast, OPG levels in acromegalic and GHD patients were not different from healthy controls. No relationships were found between OPG levels and CTX-I or osteocalcin. Conclusions: These findings suggest that enhanced OPG levels may be a compensatory response to enhanced osteoclast activity or negative bone remodeling balance in some conditions, but may also be a parameter of enhanced activity in the OPG system possibly correlated to enhanced activity of other members of the TNF family.