Osteopenia in alcoholics: effect of alcohol abstinence.

AIMS: The aims of this study were to assess bone mineral density (BMD) and content (BMC), osteocalcin, serum telopeptide, PTH and vitamin D in alcoholics, and to determine if a 6-month period of abstinence leads to changes in these parameters. METHODS: Serum osteocalcin, insulin-like growth factor 1 (IGF-1), telopeptide (40 patients) and 1,25 dihydroxyvitamin D, were measured in 28 controls and 77 alcoholic patients, 48 of whom were evaluated again 6 months later. All patients underwent whole-body assessment of BMD by a Hologic QDR-2000 (Waltham, MA, USA) bone densitometer, at the beginning of the study and 6 months later. RESULTS: Patients showed higher serum telopeptide levels (0.59 +/- 0.40 versus 0.19 +/- 0.10 nmol/100 ml, P < 0.001), lower IGF-1 [median = 49, interquartile range (IQR) = 31-121 ng/ml versus 135, IQR = 116-237 ng/ml, P < 0.001], vitamin D [26.5, IQR = 17.0-37.8 pg/ml versus 82.4 (IQR = 60.9-107.4 pg/ml, P < 0.001] and osteocalcin (2.1, IQR = 1.1-3.6 ng/ml versus 6.65, IQR = 4.9-8.8 ng/ml, P < 0.001) than those in controls. Patients also showed lower BMD values, Z- and T-scores at many levels of the skeleton and reduced total BMC. After 6 months, those who continued drinking showed a loss of bone mass, whereas those who abstained showed either no change or increase, differences being especially marked at pelvis, right arm and total BMD and BMC. Simultaneously, abstainers showed a significant increase in osteocalcin (versus a decrease among those who continued drinking). Serum telopeptide increased in both groups. CONCLUSION: Ethanol consumption leads to osteopenia, and decreased serum osteocalcin, which improve with abstinence, whereas those who continue drinking show a worsening of both parameters.

Prognostic value of serum selenium levels in alcoholics.

In alcoholics, exposure of Kupffer cells to intestinal-borne Gram-negative bacteria increases free radical release, which may, in turn, enhance cytokine secretion, creating a positive feedback loop, which contributes to liver inflammation. Impaired antioxidant mechanisms further aggravates this scenario. Some trace elements, such as selenium, are main cofactors of antioxidant enzymes. Some authors have found low Se levels in alcoholics in relation either with undernutrition, liver dysfunction, or intensity of alcoholism, but in general, Se supplementation has no effect on survival. In this study we measured serum Se in 16 controls and 76 alcoholics, 34 of them cirrhotics, 68 of whom were followed up for a median period of 38 months; 17 died during this period. Se levels were lower in patients than in controls and were related to prothrombin activity and nutritional status, more closely to this last parameter (stepwise logistic regression analysis). Patients who died showed lower Se values than those who survived. Se values over the median were associated with better survival, assessed by Kaplan-Meier curves and log-rank test. However, in multivariate analysis (Cox regression model), prothrombin activity displaced serum Se as a prognostic factor. We conclude that serum Se levels are low in alcoholics; these low values depend more heavily on impaired nutrition but also on liver dysfunction; although low Se levels were associated with a higher mortality, prothrombin activity displaced serum Se when survival was assessed using Cox's regression model.

Brain atrophy in alcoholics: relationship with alcohol intake; liver disease; nutritional status, and inflammation.

OBJECTIVES: Brain atrophy is a common finding in alcoholics. Several mechanisms may be involved, including ethanol itself, malnutrition, liver failure, and, possibly, ethanol-induced hormone and cytokine changes. The aim of this study was to analyse the relation of brain atrophy-assessed by computerized tomography (CT) scan-and the aforementioned alterations. METHODS: Serum insulin-like growth factor 1 (IGF-1), interleukin (IL)-6, IL-8, IL-10, TNF alpha, PTH, estradiol, free testosterone, and corticosterone were measured in 36 alcoholics, ten of them cirrhotics, who also underwent brain CT, which recorded the presence of cortical atrophy or cerebellar atrophy, Evan's, Huckmann's, cella media, bicaudate, cortical atrophy, bifrontal, and ventricular indices, and diameter of the third ventricle; subjective nutritional assessment, midarm anthropometry, and evaluation of liver function. RESULTS: Patients showed marked alterations of all the CT indices compared with 12 controls, but poor relations between these indices and the other parameters analysed (IGF-1, handgrip strength and years of addiction with bifrontal index (P < 0.025 in all cases); PTH and Evan's index (r = 0.36, P = 0.032); mean corpuscular volume with cella index and cortical atrophy (P < 0.05). Cerebellar atrophy was associated with a greater daily ethanol consumption (t = 2.19, P = 0.034). CONCLUSION: Brain atrophy is frequently observed in alcoholics, but relationships with liver function, cytokines, nutritional status, and hormone levels are poor.

Pro-inflammatory cytokines in stable chronic alcoholics: relationship with fat and lean mass.

Cytokines are mediators of the inflammatory response, secreted by many tissues, including adipocytes. Chronic alcoholic liver disease and alcoholic hepatitis are associated with elevated serum cytokine levels which yield prognostic value in this situation. Most studies have been performed in patients with acute alcoholic hepatitis. However, cytokine alterations in stable alcoholics have been less studied, as is also the case for the relationship between cytokines and fat and lean mass in these patients. The aim of the present study was to analyse the relationships between some proinflammatory serum cytokine levels and lean mass, fat mass, nutritional status, and liver function parameters in stable alcoholic patients. We determined serum TNF-alpha, interleukin (IL)-6, IL-8 and TNF receptor 2 (TNFr2) in 77 male alcoholic patients in a stable phase (before hospital discharge). In all patients we performed a total-body composition analysis (Hologic DEXA), nutritional assessment including body mass index, triceps skinfold, brachial perimeter, and assessment of liver function. Forty-two healthy volunteer health workers served as controls. IL-8, TNF-alpha and TNFr2 were significantly higher in patients than in controls. No differences were observed between patients and controls regarding fat mass, but alcoholics showed significantly decreased lean mass than controls. Only IL-6 was significantly related with body fat in patients with elevated IL-6 levels. Poor relationships were observed between lean mass and cytokines; some nutritional parameters showed inverse relationships with serum TNF, whereas TNF and IL-8 were inversely related with albumin and prothrombin activity. Thus, cytokine levels were elevated in stable alcoholic patients, and IL-6 levels showed significant correlation with body fat mass, raising the possibility that adipose tissue contributes to the persistence of high levels of cytokines in stable alcoholics.

Rib fractures in chronic alcoholic men: Relationship with feeding habits, social problems, malnutrition, bone alterations, and liver dysfunction.

Rib fractures are common in alcoholics. This high prevalence might be due to ethanol-associated malnutrition, bone disease, liver dysfunction, or the peculiar lifestyle of the alcoholic with frequent trauma and altercations. In this study we try to discern the role of these factors on rib fracture (assessed on a plain thoracic X-ray film) in 81 consecutive alcoholic patients, 25 of them cirrhotics. Serum albumin, prothrombin aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), gamma-glutamyl transpeptidase, C-terminal cross-linking telopeptide of type 1 collagen, osteocalcin, insulin growth factor 1, 1,25-dihydroxyvitamin D, parathyroid hormone, estradiol, free testosterone, and corticosterone were measured, and the patients also underwent assessment of bone mineral density by a HOLOGIC QDR-2000 bone densitometer (Waltham, MA, USA). Body mass index, triceps skinfold, and brachial perimeter were also determined, and the patients and their families were asked about tobacco consumption, social and familial links, consumption of ethanol by other members of the family, kind of job, and feeding habits. Forty-two male nondrinker sanitary workers of similar age served as controls. Forty of the 81 patients showed rib fractures. There was a statistically significant association between rib fractures and disruption of social and familial links, irregular feeding habits (in bars or pubs, not at home), ethanol consumption by close relatives, and intensity of tobacco consumption, but not between rib fractures and liver function tests, nutritional parameters, or bone mineral density, besides a nearly significant trend (p = .053) with the presence of osteopenia at the femoral neck. Patients with major withdrawal symptoms at admission also presented more frequent rib fractures. We conclude that rib fractures in alcoholics are related to the peculiar lifestyle of these patients rather than to bone alterations, liver dysfunction, or nutritional status.

Prognosis of osteopenia in chronic alcoholics.

Osteoporosis is frequent among alcoholics all by a direct effect of ethanol, malnutrition, and liver failure. Therefore, it may be related to survival. The aim of this study was to assess bone mineral density (BMD), bone mineral content, hormonal status, and to determine prognostic value of these parameters in a total of 124 alcoholics followed up for a median period of 57 months. Several bone homeostasis-related hormones were measured in patients and age- and sex-matched controls. Whole-body densitometry was performed by a Hologic QDR-2000 (Waltham, MA) densitometer; nutritional status and liver function were assessed. Sixty patients underwent a second evaluation 6 months later. Patients showed lower serum insulin-like growth factor-1 (median=58, interquartile range [IQR]=33-135 vs. 135ng/mL, IQR=116-243ng/mL, P<.001), vitamin D (25.5, IQR=18.3-36.8 vs. 79.9pg/mL, IQR=59.2-107.8pg/mL, P<.001), and osteocalcin (2.1, IQR=1.1-4.5 vs. 6.5ng/mL, IQR=4.7-8.7ng/mL, P<.001) than controls, and lower BMD values, and lower Z- and T-scores at right and left legs and arms, thoracic and lumbar spine, pelvis, and right and left ribs. By multiple regression analysis, BMD mainly depends on nutritional parameters and liver function. Kaplan-Meier curves show that subtotal BMD and BMD at both arms and pelvis were significantly related with survival. Patients who had lost total hip BMD after 6 months showed a shorter survival than those who had not, but using Cox's regression, encephalopathy, ascites, and nutritional parameters displaced BMD as prognostic factor. Therefore, osteopenia ensues in chronic alcoholic patients. It mainly depends on poor nutrition and is related to survival, although surpassed in this sense by encephalopathy, ascites, and nutritional parameters.

Serum osteoprotegerin and RANKL levels in chronic alcoholic liver disease.

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)-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). 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.