Alcohol and Alcoholism Advance Access originally published online on February 13, 2006
Alcohol and Alcoholism 2006 41(3):261-266; doi:10.1093/alcalc/agl004
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SERUM OSTEOPROTEGERIN AND RANKL LEVELS IN CHRONIC ALCOHOLIC LIVER DISEASE
1 Servicios de Medicina Interna, 2 Servicio de Laboratorio and 3 Servicio de Medicina Nuclear, Hospital Universitario, Universidad de La Laguna, Tenerife, Canary Islands, Spain
* Author to whom correspondence should be addressed at: Tel.: +34 922 678600; Fax.: +34 922 31 9279; E-mail: egonrey{at}ull.es
(Received 31 October 2005; first review notified 12 December 2005; accepted in revised form 12 January 2006)
Objectives: 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)-
, 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- 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) 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). Conclusion: 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.