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.


METHODS
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 approximately 32%, P < 0.05) and HIV-infected patients with especially high levels in the latter group ( approximately 52%, P < 0.001), significantly correlated with increased TNFalpha levels (r = 0.47, P < 0.02). Also CS patients had elevated serum OPG ( approximately 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.
Ueland
T
T
Section of Endocrinology, Medical Department, University of Oslo, Rikshospitalet, N-0027 Oslo, Norway. thor.ueland@klinmed.uio.no
Bollerslev
J
J
Godang
K
K
Müller
F
F
Frøland
S S
SS
Aukrust
P
P
D000172:Acromegaly / Q000097:blood; D000328:Adult; D000368:Aged; D016723:Bone Remodeling; D001842:Bone and Bones / Q000378:metabolism*; D017074:Common Variable Immunodeficiency / Q000097:blood; D003480:Cushing Syndrome / Q000097:blood; D005260:Female; D005938:Glucocorticoids / Q000378:metabolism*; D006023:Glycoproteins / Q000097:blood* / Q000502:physiology; D015658:HIV Infections / Q000097:blood; D006706:Homeostasis; D019382:Human Growth Hormone / Q000172:deficiency; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007153:Immunologic Deficiency Syndromes / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D010010:Osteoclasts / Q000502:physiology; D053244:Osteoprotegerin; D010446:Peptide Fragments / Q000097:blood; D011347:Procollagen / Q000097:blood; D018160:Receptors, Cytoplasmic and Nuclear / Q000097:blood* / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D005938:Glucocorticoids; D006023:Glycoproteins; D053244:Osteoprotegerin; D010446:Peptide Fragments; D011347:Procollagen; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506030:TNFRSF11B protein, human; D014409:Tumor Necrosis Factor-alpha; C042813:procollagen type I carboxy terminal peptide; D015675:Osteocalcin; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D006854:Hydrocortisone