Serum Osteoprotegerin and Rankl Levels in Chronic Alcoholic Liver Disease

Objectives: Osteoprotegerin (OPG) is a decoy receptor that binds RANK-ligand (RANKL) & prevents osteoclast activation. Oestrogens, androgens, corticosteroids, parathyroid hormone (PTH), vitamin D, & 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) & with several hormones & 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)- , PTH, estradiol, free testosterone & corticosterone were measured in 77 male alcoholic patients, 25 of them cirrhotics. All these patients underwent assessment of BMD at lumbar spine & 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) & 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 & 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), & total hip (-0.44 - 1.12 vs 0.42 - 1, P = 0.003). TNF- 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- (rho = 0.57, P < 0.001) & IL-6 (r = 0.62, P < 0.001), but not with BMD. Estradiol levels (31.83 - 13.11 pg/ml) were higher & free testosterone lower (13.62 - 11.96 pg/ml) in patients than in controls (20.36 - 3.08 & 18.19 - 4.68 pg/ml, respectively, P < 0.001 in both cases). Conclusion: OPG is raised in alcoholics, especially in cirrhotics, showing n