Skeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR, 97331, United States.
Biostatistics Program, School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR, 97331, United States.
Alcohol. 2021 Mar;91:53-59. doi: 10.1016/j.alcohol.2020.12.003. Epub 2021 Feb 3.
Chronic heavy alcohol use is often associated with reduced bone mineral density and altered bone turnover. However, the dose response effects of ethanol on bone turnover have not been established. This study examined the effects of graded increases of ethanol consumption on biochemical markers of bone turnover in young adult male cynomolgus macaques (Macaca fascicularis). For this study, 6.6-year-old (95% CI: 6.5, 6.7) male macaques were subjected to three 30-day sessions of increased ethanol intake over a 90-day interval. During the first 30 days, the monkeys drank a predetermined volume of ethanol corresponding to 0.5 g/kg/day, followed by 1.0 g/kg/day and 1.5 g/kg/day. Osteocalcin, a marker of bone formation, and carboxyterminal cross-linking telopeptide of type 1 collagen (CTX), a marker of resorption, were measured during each 30-day session. In addition, the ratio of osteocalcin to CTX was determined as a surrogate measure of global turnover balance. Mean osteocalcin decreased by 2.6 ng/mL (1.8, 3.5) for each one-half unit (0.5 g/kg/day) increase in dose (p < 0.001). Mean CTX decreased by 0.13 ng/mL (0.06, 0.20) for each one-half unit increase in dose (p < 0.001). Furthermore, there was an inverse relationship between dose and the ratio of osteocalcin to CTX, such that the mean ratio decreased by 0.9 (0.3, 1.5) for each one-half unit increase in dose (p = 0.01). In summary, male cynomolgus macaques had decreased blood osteocalcin and CTX, and osteocalcin to CTX ratio during the 90-day interval of graded increases in ethanol consumption, indicative of reduced bone turnover and negative turnover balance, respectively. These findings suggest that over the range ingested, ethanol resulted in a linear decrease in bone turnover. Furthermore, the negative bone turnover balance observed is consistent with reported effects of chronic alcohol intake on the skeleton.
慢性大量饮酒常与骨密度降低和骨转换改变有关。然而，乙醇对骨转换的剂量反应影响尚未确定。本研究检查了递增乙醇摄入对年轻成年雄性食蟹猴（Macaca fascicularis）骨转换生化标志物的影响。在这项研究中，6.6 岁（95%CI：6.5，6.7）的雄性猕猴接受了三次为期 30 天的递增乙醇摄入，时间间隔为 90 天。在最初的 30 天中，猴子饮用了与 0.5 g/kg/天相对应的预定体积的乙醇，然后是 1.0 g/kg/天和 1.5 g/kg/天。骨钙素，骨形成的标志物，和 I 型胶原羧基末端交联肽（CTX），骨吸收的标志物，在每个 30 天的过程中都被测量。此外，骨钙素与 CTX 的比值被确定为整体转换平衡的替代测量。对于剂量每增加半单位（0.5 g/kg/天），平均骨钙素下降 2.6ng/mL（1.8，3.5）（p < 0.001）。对于剂量每增加半单位，平均 CTX 下降 0.13ng/mL（0.06，0.20）（p < 0.001）。此外，剂量与骨钙素与 CTX 的比值呈负相关，因此，对于剂量每增加半单位，平均比值下降 0.9（0.3，1.5）（p = 0.01）。总之，雄性食蟹猴在递增乙醇摄入的 90 天期间，血液骨钙素和 CTX 以及骨钙素与 CTX 的比值下降，分别表明骨转换减少和负转换平衡。这些发现表明，在摄入范围内，乙醇导致骨转换呈线性下降。此外，观察到的负骨转换平衡与慢性饮酒对骨骼的影响一致。
