Osteopenia in Alcoholics: Effect of Alcohol Abstinence
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.
Since the classic observations by Saville (1965) and Oppenheim (1977) on the bone fragility and high incidence of fractures observed in the so-called Battered alcoholic syndrome, and despite some studies with opposite results (Baron et al., 2001), several reports have stressed the importance of ethanol consumption in the pathogenesis of osteoporosis (Spencer et al., 1986; Peris et al., 1995a, 1995b). Indeed, osteoporosis is frequently observed in the alcoholic patient (Leslie et al., 2003). Ethanol decreases bone formation (Diamond et al., 1989) in a dose-dependent fashion (Turner, 2000), mainly through a direct toxic effect on osteoblast function, which may also account for an inhibition of bone growth in experimental animals (Wezeman et al., 2000) and, possibly, in humans (González-Reimers et al., 2007). It also alters, both directly and indirectly, bone mineral metabolism, including parathyroid hormone (PTH), vitamin D, testosterone, IGF-1 and cortisol levels. Recent research has also shown that several cytokines, which become altered in alcoholics, such as TNF alpha and IL-6, regulate the OPG/RANKL system (Lorenzo 2000; Yamada et al., 2002; Nagata et al., 2003) and may play a role in ethanol-induced bone loss (García-Valdecasas-Campelo et al., 2006). In this sense, ethanol seems to stimulate IL-6 production, causing via induction of RANKL, activation of osteoclastogenesis (Dai et al., 2000). Finally, other factors, such as irregular feeding and social margination, (Santolaria et al., 2000; González-Reimers et al., 2005), as well as protein deficiency (Molina-Pérez et al., 2000), also contribute to bone loss in alcoholics.
As in other ethanol-mediated systemic alterations, such as myocardiopathy (Nicolas et al., 2002) or brain atrophy (Pfefferbaum et al., 1995) in which reduction and/or withdrawal of ethanol intake partially reverses the lesion, alcohol abstinence may improve the alterations observed in bone. Some data point that age-matched abstaining women showed a higher bone mass than actually drinking women, although lower than that of non-alcohol-abusing women (Clark et al., 2003). Other authors have reported that abstainers show increased bone formation (osteoid, bone GLA protein) compared with active drinkers (Crilly et al., 1988; Diamond et al., 1989), so that abstainers for at least 2 years have biochemical markers of bone turnover similar to those of the controls (Lindholm et al., 1991). However, bone changes observed along several months in individuals who stop drinking or not is less well studied. This work was performed in order to analyse the effect of alcohol abstinence on bone changes observed in alcoholic individuals who stop drinking compared with those who did not in a second evaluation performed 6 months after a basal one.
Abstract and Introduction
Abstract
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.
Introduction
Since the classic observations by Saville (1965) and Oppenheim (1977) on the bone fragility and high incidence of fractures observed in the so-called Battered alcoholic syndrome, and despite some studies with opposite results (Baron et al., 2001), several reports have stressed the importance of ethanol consumption in the pathogenesis of osteoporosis (Spencer et al., 1986; Peris et al., 1995a, 1995b). Indeed, osteoporosis is frequently observed in the alcoholic patient (Leslie et al., 2003). Ethanol decreases bone formation (Diamond et al., 1989) in a dose-dependent fashion (Turner, 2000), mainly through a direct toxic effect on osteoblast function, which may also account for an inhibition of bone growth in experimental animals (Wezeman et al., 2000) and, possibly, in humans (González-Reimers et al., 2007). It also alters, both directly and indirectly, bone mineral metabolism, including parathyroid hormone (PTH), vitamin D, testosterone, IGF-1 and cortisol levels. Recent research has also shown that several cytokines, which become altered in alcoholics, such as TNF alpha and IL-6, regulate the OPG/RANKL system (Lorenzo 2000; Yamada et al., 2002; Nagata et al., 2003) and may play a role in ethanol-induced bone loss (García-Valdecasas-Campelo et al., 2006). In this sense, ethanol seems to stimulate IL-6 production, causing via induction of RANKL, activation of osteoclastogenesis (Dai et al., 2000). Finally, other factors, such as irregular feeding and social margination, (Santolaria et al., 2000; González-Reimers et al., 2005), as well as protein deficiency (Molina-Pérez et al., 2000), also contribute to bone loss in alcoholics.
As in other ethanol-mediated systemic alterations, such as myocardiopathy (Nicolas et al., 2002) or brain atrophy (Pfefferbaum et al., 1995) in which reduction and/or withdrawal of ethanol intake partially reverses the lesion, alcohol abstinence may improve the alterations observed in bone. Some data point that age-matched abstaining women showed a higher bone mass than actually drinking women, although lower than that of non-alcohol-abusing women (Clark et al., 2003). Other authors have reported that abstainers show increased bone formation (osteoid, bone GLA protein) compared with active drinkers (Crilly et al., 1988; Diamond et al., 1989), so that abstainers for at least 2 years have biochemical markers of bone turnover similar to those of the controls (Lindholm et al., 1991). However, bone changes observed along several months in individuals who stop drinking or not is less well studied. This work was performed in order to analyse the effect of alcohol abstinence on bone changes observed in alcoholic individuals who stop drinking compared with those who did not in a second evaluation performed 6 months after a basal one.