Serum osteoprotegerin and RANKL levels in chronic alcoholic liver disease.
OBJECTIVE
Osteoprotegerin (OPG) is a decoy receptor that binds RANK-ligand (RANKL) and prevents osteoclast activation. Oestrogens, androgens, corticosteroids, parathyroid hormone (PTH), vitamin D, and several cytokines exert their effects on bone modulating the OPG/RANKL system. Since these substances become altered in chronic alcoholic liver disease, we investigated the OPG/RANKL system in alcoholic liver disease, its relation with bone mineral density (BMD) and with several hormones and cytokines.


METHODS
Serum OPG, RANKL, C-terminal cross-linking telopeptide of type 1 collagen, osteocalcin, insulin-like growth factor 1 (IGF-1), 1,25 dihydroxyvitamin D, IL-6, tumour necrosis factor (TNF)-alpha, PTH, estradiol, free testosterone and corticosterone were measured in 77 male alcoholic patients, 25 of them cirrhotics. All these patients underwent assessment of BMD at lumbar spine and left hip by a Hologic QDR-2000 (Waltham, MA) bone densitometer. Nineteen non-drinkers male sanitary workers of similar age served as controls.


RESULTS
Serum OPG levels were higher in patients (12.66 +/- 6.44 pmol/l) than in controls (6.59 +/- 1.58 pml/l, P < 0.005), especially in cirrhotics (15.97 +/- 7.03 pmol/l) vs non-cirrhotics (10.96 +/- 5.45 pmol/l, P < 0.001). Patients also showed higher telopeptide levels (0.60 +/- 0.36 vs 0.20 +/- 0.10 nmol/100 ml, P < 0.001), less IGF-1 [median = 192, interquartile range (IQR) = 46.7-175.99 ng/ml vs 150, IQR = 118.8-239.4 ng/ml, P < 0.001], vitamin D (25.5, IQR = 18.25-35 pg/ml vs 77.89, IQR = 57.48-98.53 pg/ml, P < 0.001) and osteocalcin (1.8, IQR = 1-3.6 ng/ml vs 6.04, IQR = 4.63-8.20 ng/ml, P < 0.001) than controls, but no differences in PTH and RANKL. Patients also showed lower Z-scores than controls at trochanter (-0.36 +/- 1.10 vs 0.26 +/- 0.87 in controls, P = 0.026), intertrochantereal area (-0.56 +/- 1.16 vs 0.46 +/- 1.01, P = 0.001), and total hip (-0.44 +/- 1.12 vs 0.42 +/- 1, P = 0.003). TNF-alpha levels were higher in patients (7.40, IQR = 4.30-17.80 pg/ml) than in controls (5.10, IQR = 4.40-8 pg/ml, P = 0.009), especially in cirrhotics (median = 13.90, IR = 6.10-21.10 pg/ml). OPG levels showed strong correlations with TNF-alpha (rho = 0.57, P < 0.001) and IL-6 (r = 0.62, P < 0.001), but not with BMD. Estradiol levels (31.83 +/- 13.11 pg/ml) were higher and free testosterone lower (13.62 +/- 11.96 pg/ml) in patients than in controls (20.36 +/- 3.08 and 18.19 +/- 4.68 pg/ml, respectively, P < 0.001 in both cases).


CONCLUSIONS
OPG is raised in alcoholics, especially in cirrhotics, showing no relationship with decreased BMD. Also, raised TNF and IL-6 were observed, and were strongly, directly related with OPG levels. Since TNF and IL-6 enhance bone resorption, their relation with OPG suggests a protective effect of raised OPG on bone loss.
Servicio de Medicina Interna, Hospital Universitario, Universidad de La Laguna, Tenerife, Canary Islands, Spain.
Elena
E
García-Valdecasas-Campelo
Emilio
E
González-Reimers
Francisco
F
Santolaria-Fernández
María José
MJ
De la Vega-Prieto
Antonio
A
Milena-Abril
María José
MJ
Sánchez-Pérez
Antonio
A
Martínez-Riera
María de Los Angeles
Mde L
Gómez-Rodríguez
D000328:Adult; D015519:Bone Density; D002352:Carrier Proteins / Q000097:blood*; D002908:Chronic Disease; D016207:Cytokines / Q000097:blood; D006023:Glycoproteins / Q000097:blood*; D006728:Hormones / Q000097:blood; D006801:Humans; D008104:Liver Cirrhosis, Alcoholic / Q000097:blood; D008108:Liver Diseases, Alcoholic / Q000097:blood*; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood*; D008875:Middle Aged; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000097:blood*; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood*
D002352:Carrier Proteins; D016207:Cytokines; D006023:Glycoproteins; D006728:Hormones; 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