Osteoprotegerin and RANKL in alcoholic liver cirrhosis.
OBJECTIVE
The mechanisms leading to osteoporosis in alcoholic liver disease remain poorly understood. Recently identified soluble circulating osteoprotegerin (OPG), is the osteoclastogenesis inhibitory factor. It acts as a decoy receptor for osteoclast activating factor, receptor activator of nuclear factor-kappaB ligand (RANKL), and impairs osteoclast function. The aim of our study was to investigate the OPG/RANKL system in alcoholic cirrhotic patients and their correlation with biochemical marker of bone turnover.


METHODS
Serum OPG, RANKL, osteocalcin (OC), C-terminal cross-linking telopeptide of type I collagen (CTX-I), bone alkaline phosphatase activity (bALP), and urinary hydroxyproline were measured in 30 patients with alcoholic cirrhosis, and in 20 age- and sex-matched healthy controls.


RESULTS
OPG levels were significantly increased in patients with alcoholic cirrhosis compared with healthy subjects (5.9 pmol/l, range 2.7-9.0 vs 4.1 pmol/l, range 1.2-6.6; P < 0.001). RANKL levels were significantly higher in patients with cirrhosis (0.48 pmol/l, range 0.01-1.34) than in healthy subjects (0.11 pmol/l, range 0.01-0.90). There was a positive correlation between serum OPG and RANKL (r = 0.37; P < 0.001), bALP (r = 0.66; P < 0.001) and urinary hydroxyproline (r = 0.51; P < 0.05) but not with OC and CTX-I.


CONCLUSIONS
OPG might partly represent a compensating mechanism to the negative balance of bone remodelling in patients with alcoholic cirrhosis.
Fábrega
Emilio
E
Gastroenterology and Hepatology Unit, Faculty of Medicine, University Hospital Marqués de Valdecilla, U.C. Santander, Avenida Valdecilla s/n, 39008 Santander, Cantabria, Spain. digfge@humv.es
Orive
Aitor
A
García-Suarez
Covadonga
C
García-Unzueta
Maite
M
Antonio Amado
Jose
J
Pons-Romero
Fernando
F
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001707:Biopsy, Needle; D002352:Carrier Proteins / Q000097:blood* / Q000378:metabolism; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D006023:Glycoproteins / Q000097:blood* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008104:Liver Cirrhosis, Alcoholic / Q000097:blood / Q000175:diagnosis*; D008111:Liver Function Tests; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood* / Q000378:metabolism; D008875:Middle Aged; D053244:Osteoprotegerin; D011336:Probability; D011379:Prognosis; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000097:blood* / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood* / Q000378:metabolism; D012016:Reference Values; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
D015415:Biomarkers; D002352:Carrier Proteins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human