Comprehensive Alcohol Research Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana.
Department of Orthopedics, Louisiana State University Health Sciences Center, New Orleans, Louisiana.
Alcohol Clin Exp Res. 2019 Nov;43(11):2374-2383. doi: 10.1111/acer.14186. Epub 2019 Oct 1.
HIV infection is now largely a chronic condition as a result of the success of antiretroviral therapy. However, several comorbidities have emerged in people living with HIV (PLWH), including alcohol use disorders and musculoskeletal disorders. Alcohol use has been associated with lower bone mineral density, alterations to circulating bone turnover markers, and hypocalcemia. The pathophysiological basis of bone loss in the PLWH population is unclear but has been suggested to be linked to oxidative stress and inflammation. To test the hypothesis that PLWH consuming excessive alcohol have altered markers of bone turnover and/or calcium homeostasis in association with oxidative stress, we correlated measurements of alcohol consumption with markers of oxidative stress and inflammation, serum calcium concentrations, and measurements of bone turnover, including c-terminal telopeptide cross-links (CTX-1) and osteocalcin.
Data were drawn from cross-sectional baseline data from the ongoing New Orleans Alcohol Use in HIV (NOAH) study, comprised of 365 in care PLWH. Alcohol consumption measures (Alcohol Use Disorders Test, 30-day timeline follow-back calendar, and phosphatidylethanol [PEth]) were measured in a subcohort of 40 subjects selected based on highest and lowest PEth measurements. Multivariate linear regression was performed to test the relationships between alcohol consumption and systemic oxidative stress (4-hydroxynonenal; 4-HNE) and inflammation (c-reactive protein; CRP).
Serum calcium and CTX-1 did not differ significantly between the high and low-PEth groups. Individuals in the high-PEth group had significantly lower serum osteocalcin (median low-PEth group: 13.42 ng/ml, inter-quartile range [IQR] 9.26 to 14.99 ng/ml; median high-PEth group 7.39 ng/ml, IQR 5.02 to 11.25 ng/ml; p = 0.0005, Wilcoxon rank-sum test). Osteocalcin negatively correlated with PEth (Spearman r = -0.45, p = 0.05) and self-reported measures after adjusting for covariates. Alcohol consumption showed mild, but significant, positive associations with serum 4-HNE, but not with CRP. Osteocalcin did not correlate with either 4-HNE or CRP.
In this subcohort of PLWH, we detected significant associations between at-risk alcohol use and osteocalcin, and at-risk alcohol use and serum 4-HNE, suggesting suppression of bone formation independent of increased systemic oxidative stress with increasing alcohol consumption.
由于抗逆转录病毒疗法的成功，HIV 感染现在在很大程度上是一种慢性疾病。然而，HIV 感染者（PLWH）出现了多种合并症，包括酒精使用障碍和肌肉骨骼疾病。酒精使用与骨矿物质密度降低、循环骨转换标志物改变和低钙血症有关。PLWH 人群骨丢失的病理生理基础尚不清楚，但据推测与氧化应激和炎症有关。为了验证假设，即饮酒过量的 PLWH 与氧化应激相关，其骨转换标志物和/或钙稳态发生改变，我们将酒精摄入量的测量值与氧化应激和炎症标志物、血清钙浓度以及骨转换标志物（C 端肽交联[CTX-1]和骨钙素）进行了相关性分析。
数据来自正在进行的新奥尔良 HIV 中的酒精使用（NOAH）研究的横断面基线数据，该研究包括 365 名接受治疗的 PLWH。在根据最高和最低 PEth 测量值选择的 40 名受试者亚组中测量了酒精消耗量（酒精使用障碍测试、30 天时间线随访日历和磷脂酰乙醇 [PEth]）。进行了多元线性回归，以检验酒精消耗与全身氧化应激（4-羟基壬烯醛；4-HNE）和炎症（C 反应蛋白；CRP）之间的关系。
高和低 PEth 组之间血清钙和 CTX-1 无显著差异。高 PEth 组的血清骨钙素明显较低（低 PEth 组中位数：13.42ng/ml，IQR 9.26 至 14.99ng/ml；高 PEth 组中位数 7.39ng/ml，IQR 5.02 至 11.25ng/ml；p=0.0005，Wilcoxon 秩和检验）。骨钙素与 PEth 呈负相关（Spearman r=-0.45，p=0.05），且与调整协变量后的自我报告测量值相关。酒精消耗与血清 4-HNE 呈轻度但显著的正相关，但与 CRP 无关。骨钙素与 4-HNE 或 CRP 均不相关。
在该 PLWH 亚组中，我们检测到高危饮酒与骨钙素之间以及高危饮酒与血清 4-HNE 之间存在显著关联，提示随着饮酒量的增加，骨形成抑制独立于系统性氧化应激增加。
