Binge alcohol treatment increases vertebral bone loss following ovariectomy: compensation by intermittent parathyroid hormone.

Despite decades of increased public awareness and medical intervention, osteoporosis remains a major health issue in the United States and abroad (Johnell and Kanis, 2004; Melton, 2003). While dietary factors and hormonal status are widely recognized for their importance to bone health, alcohol abuse is also an important risk factor for the development of osteoporosis (Olszynski et al., 2004). Alcoholism and alcohol abuse affect at least 14 million Americans (Grant et al., 2004). While previous investigators have reported on the increased prevalence of osteopenia and osteoporosis in male alcoholics (Bilke et al., 1985; Crilly et al., 1988; Diamond et al., 1989), little is known about the effects of alcohol abuse on bone health in women, although it has been demonstrated epidemiologically that women are more susceptible than men to alcohol-related organ injury and disease (Sato et al., 2001). The effects of moderate alcohol consumption on bone health in females may also be in question; whereas human epidemiological studies have shown some beneficial effects of moderate drinking on bone density (Angus et al., 1988; Felson et al., 1995; Laitinen et al., 1991), a recent study in rodents found that even moderate alcohol consumption caused decreased bone turnover, which could lead to detrimental effects on female skeletal health (Turner et al., 2001b). Animal models of both alcohol-induced bone loss and postmenopausal osteoporosis are important tools in the study of pathologic bone loss. Alcohol-induced bone loss in rats has been demonstrated in both long-term feeding models (Sampson, 1998; Turner et al., 1998; Wezeman et al., 2000) and binge exposure models (Callaci et al., 2004). The ovariectomized (OVX) rat has been extensively utilized as a model of postmenopausal osteoporosis. (Kalu, 1991). While alcohol abuse and menopause are recognized as important risk factors for the development of osteoporosis, previous investigations have examined only the effects of moderate alcohol intake on bone loss in OVX rats. These studies found that alcohol either did not accelerate bone loss (Kidder and Turner, 1998) or did not cause further decreases in bone mineral density (Sampson and Shipley, 1997) in OVX rats. Moderate alcohol exposure was actually shown to reduce bone resorption in another OVX model (Fanti et al., 1997). Although none of these studies reported additional alcohol-induced bone loss in OVX animals, bone loss in the OVX state is not maximal as demonstrated by the increased bone loss observed in studies of both whole-body skeletal unloading during spaceflight and hind limb immobilization studies performed in OVX animals (Cavolina et al., 1997; Westerlind et al., 1997). These unloading studies suggest that the post-OVX skeleton remains vulnerable to further bone loss. Furthermore, as previously noted, the alcohol studies in OVX animals that have been performed used moderate levels of alcohol exposure and did not examine the effects of higher blood alcohol concentrations (BACs) that can occur with alcoholic or binge drinking, suggesting that the OVX skeleton may be vulnerable to further alcohol-induced bone loss. Binge alcohol drinking is a pattern of alcohol consumption resulting in highly intoxicating BACs (Witt, 1994) coupled with repeated withdrawal phases (Lundqvist et al., 1995). There are over 13 million alcoholics and problem drinkers in the United States; between 2.7 and 4.5 million adult women fit this description (Blumenthal, 1998; Straussner and Attia, 2002). Binge drinking is common among alcoholics; alcoholic binge drinkers can achieve extremely high BACs (Penland et al., 2001). Although high BACs are common among binge drinking alcoholics, binge alcohol consumption is not limited to this population. Social binge drinking of high alcohol content beverages by nonalcoholics is a commonly observed phenomenon in many cultures (Kuntsche et al., 2004; Makela et al., 2001) and in college age and older adults in the United States (Dawson et al., 2004; Miller et al., 2004). A recent national survey found that approximately 25% of men and 20% of women ages 18 to 30 reported at least 1 binge drinking episode (6 or more drinks per occasion) in the 30 days preceding the study (Grossberg et al., 2004). Of these young adults reporting a history of binge drinking behavior, 12% of the men and 6% of the women reported that they actually engaged in binge drinking behavior 3 to 4 times in this same 30-day period, and 13% of men and 2.5% of women admitted engaging in binge drinking 5 or more times during the study period. Other estimates of adult female binge drinking show that 13.5% of US women aged 35 to 54 and 4.3% of women age 55 and over reported consuming alcohol in a binge pattern up to 7 times per year (Naimi et al., 2003). Despite the prevalence of binge drinking behavior, the effects of binge drinking and high BACs on bone health parameters had not been examined until recent studies in our laboratory (Callaci et al., 2004). Only one previous study attempted to examine the effects of binge drinking on bone in an actively growing rat model. This investigation administered alcohol at levels (43 to 106 mg/dL) that might be considered to be more representative of moderate drinking than true binge alcohol exposure and showed an unexpected beneficial effect on skeletal growth and BMD with a 2 d/wk alcohol binge (Sampson et al., 1999). The current study used intraperitoneal (IP) injection to administer alcohol to adult female OVX rats in a binge-like pattern, mimicking the high BACs seen in alcoholics and social binge drinkers. As our laboratory has previously shown that this binge alcohol treatment induces aggressive bone loss in male rats (Callaci et al., 2004) we hypothesized that binge-like alcohol treatment would also increase bone loss in OVX rats and that bone loss because of alcohol, OVX, or the combination of both treatments would be compensated by intermittent parathyroid hormone (PTH) treatment. Parathyroid hormone given as a daily injection has an anabolic effect on bone that is recognized as a viable alternative treatment for osteoporosis. Parathyroid hormone has been shown to increase bone mass in rats (Vahle et al., 2002; Wronski et al., 1993) and human osteoporotics (Lane, 2004) and may improve trabecular architecture by thickening existing trabeculae (Lane et al., 2003).