Karl Landsteiner University of Health Sciences, Dr. Karl-Dorrek-Strasse 30, Krems, 3500, Austria.
Department of Internal Medicine 2, University Hospital Krems, Mitterweg 10, Krems, 3500, Austria.
BMC Cancer. 2021 Jun 28;21(1):744. doi: 10.1186/s12885-021-08518-9.
Increased bone turnover is frequently observed in advanced cancer and predominantly related to bone metastases or therapy. Cachexia represents an important cause of morbidity and mortality in cancer patients. Key features are weight loss, muscle wasting and chronic inflammation, which induce profound metabolic changes in several organs, including the bone. However, whether cachexia contributes to abnormal bone metabolism in cancer patients is unknown. Aim of the present study was to determine the potential correlation of bone turnover markers with body composition and laboratory parameters in treatment-naïve cancer patients.
In this cross-sectional study we measured the levels of carboxy terminal telopeptide of collagen (CTX), an indicator of bone resorption, as well as osteocalcin (Ocn) and procollagen type I N-terminal propeptide (PINP), indicators of bone formation, in 52 cancer patients and correlated with body composition and laboratory parameters. Univariate and multivariate logistic analysis were performed to identify determinants of negative bone remodeling balance, estimated by CTX/Ocn and CTX/PINP ratio.
Based on weight loss, body mass index and muscle mass, patients were divided into a cachectic (59.6%) and a control (40.4%) group. After correcting for the presence of bone metastases, our results showed a significant upregulation of CTX in cachectic patients compared to non-cachectic cancer patients (median 0.38 vs 0.27 ng/mL, p < 0.05), with no difference in Ocn and PINP levels (mean 14 vs. 16 ng/ml, p = 0.2 and median 32 vs. 26 μg/L, p = 0.5, respectively). In addition, the CTX/Ocn and the CTX/PINP ratio were indicative of bone resorption in 68% and 60% of cachexia patients, respectively (vs. 20% and 31% in the control group, p = 0.002 and p = 0.06). The main determinants of the unbalanced bone turnover were hypoalbuminemia for the CTX/Ocn ratio (OR 19.8, p < 0.01) and high CRP for the CTX/PINP ratio (OR 5.3, p < 0.01) in the multivariate regression analysis.
CTX is substantially higher in cachectic patients compared to non-cachectic oncological patients and hypoalbuminemia as well as elevated CRP concentrations are independent predictors of a negative bone remodeling balance in cancer patients. These results strongly indicate that cachexia correlates with exacerbated bone turnover in cancer.
晚期癌症患者常出现骨转换增加，主要与骨转移或治疗有关。恶病质是癌症患者发病率和死亡率的重要原因。其主要特征是体重减轻、肌肉减少和慢性炎症，这会导致包括骨骼在内的多个器官发生深刻的代谢变化。然而，恶病质是否会导致癌症患者的异常骨代谢尚不清楚。本研究旨在确定治疗初治癌症患者中骨转换标志物与身体成分和实验室参数的潜在相关性。
在这项横断面研究中，我们测量了 52 例癌症患者的羧基末端胶原肽（CTX）水平，CTX 是骨吸收的标志物，以及骨钙素（Ocn）和 I 型前胶原氨基端前肽（PINP），这两种标志物是骨形成的标志物，并与身体成分和实验室参数相关联。我们进行了单变量和多变量逻辑分析，以确定由 CTX/Ocn 和 CTX/PINP 比值估计的负性骨重塑平衡的决定因素。
根据体重减轻、体重指数和肌肉量，患者被分为恶病质组（59.6%）和对照组（40.4%）。在纠正骨转移的存在后，我们的结果显示，与非恶病质癌症患者相比，恶病质患者的 CTX 显著上调（中位数 0.38 与 0.27ng/ml，p<0.05），Ocn 和 PINP 水平无差异（均值 14 与 16ng/ml，p=0.2 和中位数 32 与 26μg/L，p=0.5）。此外，CTX/Ocn 和 CTX/PINP 比值分别在 68%和 60%的恶病质患者中提示骨吸收（对照组分别为 20%和 31%，p=0.002 和 p=0.06）。多变量回归分析的主要决定因素是低白蛋白血症与 CTX/Ocn 比值（OR 19.8，p<0.01）和高 CRP 与 CTX/PINP 比值（OR 5.3，p<0.01）。
与非恶病质肿瘤患者相比，CTX 在恶病质患者中明显升高，低白蛋白血症和 CRP 浓度升高是癌症患者负性骨重塑平衡的独立预测因子。这些结果强烈表明恶病质与癌症患者骨转换增加有关。
