Serum osteoprotegerin and receptor activator of nuclear factors kB (RANKL) concentrations in normal children and in children with pubertal precocity, Turner's syndrome and rheumatoid arthritis

Abstract

Osteoprotegerin (OPG) is a secreted member of the TNF receptor superfamily. OPG is made by osteoblastic cells and is expressed in a wide variety of cell and tissue types. It acts as a decoy receptor by binding the receptor activator of nuclear factors kB (RANKL) and preventing RANKL-induced osteoclast formation and differentiation. Numerous cytokines and hormones (TGF-beta, PTH, vitamin D, glucocorticoids and oestrogens) exert their effects on osteoclastogenesis by regulating the production of OPG. In the present study we compared serum OPG and RANKL concentrations in a group of normal children (1-14 years old) with those of pair-aged children affected by different diseases [Turner's syndrome (TS), early/precocious puberty (PP) and rheumatoid arthritis (RA)]. OPG and RANKL concentrations were measured by an enzyme immunoassay method using a commercial kit. Mean (+/- SD) OPG level in normal children was 4.05 +/- 1.63 pmol/l with no difference between males and females. OPG values in children 1-4 years old (5.87 +/- 2.22 pmol/l) were significantly higher than in children 4-14 years old (3.55 +/- 0.97 pmol/l). OPG levels in children with RA were significantly higher than in controls (6.33 +/- 2.57 pmol/l vs. 4.05 +/- 1.63 pmol/l, P < 0.01); patients with TS or PP had OPG levels superimposable to those of controls (2.61 +/- 0.67 pmol/l and 3.99 +/- 0.85 pmol/l, respectively), but in TS OPG levels were significantly lower than in age-matched females. Mean RANKL concentration in normal subjects was 0.81 +/- 1.55 pmol/l; there was a slight decline in RANKL levels with age. RANKL concentrations in subjects with TS, PP, RA and controls did not differ significantly, and did not differ from those published in adult normal subjects. It appears from our data that OPG serum levels in healthy children aged > 4 years are similar to those present in young adult men, with higher levels in the first 4 years of life. Although the meaning of the alterations of OPG levels observed in pathological conditions is still obscure, they appear potentially interesting in view of a key role played by this protein in bone homeostasis.