Auzina D, Erts R, Lejniece S
Chemotherapy and Haematology Clinic, Riga East Clinical University Hospital, Riga LV 1079, Latvia.
Department of Physics, Riga Stradins University, Riga LV 1079, Latvia.
Exp Oncol. 2017 Mar;39(1):53-56.
Multiple myeloma (MM) is characterized by osteolytic bone disease resulting from increased osteoclast activity and reduced osteoblast function.
The aim of our research was to determine connection between bone turnover markers and presence of bone lesions, their degree of severity, to monitor MM bone disease and to assess effectiveness of anti-myeloma treatment.
Serum samples and clinical data from 123 patients with newly diagnosed MM were collected at Riga East Clinical University Hospital (Riga, Latvia) from June 2014 to June 2016. Bone lesions detected by radiography, CT scans, MRI, and PET/CT were divided into degrees from 0 to 3 (0 - no bone involvement, 1 - ≤ 3 bone lesions, 2 - ≥ 3 bone lesions, 3 - fracture). Staging was performed applying Durie/Salmon (DS) and International Staging System classifications. Progressive disease was defined as development of one or more new bone lesions. The levels of bone metabolic markers β-isomerized C-terminal telopeptide of collagen type I (β-CTX) and bone-specific alkaline phosphatase (bALP) were monitored regularly in the year.
Bone lesions were found in 86 (69%) patients. From these 6 (4%) patients had 1st degree, 11 (9%) had 2nd degree and 69 (56%) had 3rd degree bone lesions. Level of the bone resorption marker β-CTX in the control group was 0.41 ng/ml, which is lower than in MM patients (p < 0.001). Spearman correlation coefficient analysis found a positive and statistically significant correlation (rs = 0.51, p < 0.001) between bone lesions degree and β-CTX levels. Mean β-CTX for patients without bone lesions was 0.72 ng/ml (SD = 0.64), but for patients with 3rd degree bone lesions it was 1.34 ng/ml (SD = 0.65) difference being 38% (p < 0.001). In patients who responded to therapy after 6 months of treatment reduction of β-CTX was found compared to baseline values (M = -0.65). In contrast, in patients who did not respond to therapy, there was a statistically significant (p < 0.001) increase in β-CTX values after six months of treatment compared to baseline values (M = 0.42). Exact cutoff value of β-CTX is 0.79. When analyzing mean bALP, no significant difference between MM patients and control group was found. ANOVA statistical analysis showed no statistically significant differences in bALP levels at different degrees of bone lesions (p = 0.95) in MM patients. Analysis of bALP suitability as MM diagnostic marker using receiver operating characteristics curve showed that bALP is not applicable for clinical diagnosis of MM (AUC 0.5, p > 0.05). However, β-CTX was found to be an excellent diagnostic marker for MM (AUC 0.91; 95% confidence interval, 0.88-0.94; p < 0.001).
Patients with MM and bone lesions have increased value of bone resorption marker β-CTX. There is a correlation between bone resorption marker and degree of bone lesions. Changes in β-CTX levels may be used to monitor the effectiveness of myeloma treatment.
多发性骨髓瘤（MM）的特征是溶骨性骨病，这是由破骨细胞活性增加和成骨细胞功能降低所致。
我们研究的目的是确定骨转换标志物与骨病变的存在、严重程度之间的联系，监测MM骨病并评估抗骨髓瘤治疗的有效性。
2014年6月至2016年6月期间，在里加东临床大学医院（拉脱维亚里加）收集了123例新诊断MM患者的血清样本和临床数据。通过X线摄影、CT扫描、MRI和PET/CT检测到的骨病变分为0至3度（0 - 无骨受累，1 - ≤3处骨病变，2 - ≥3处骨病变，3 - 骨折）。采用Durie/Salmon（DS）和国际分期系统分类进行分期。疾病进展定义为出现一个或多个新的骨病变。在这一年中定期监测骨代谢标志物I型胶原β-异构化C末端肽（β-CTX）和骨特异性碱性磷酸酶（bALP）的水平。
86例（69%）患者发现有骨病变。其中6例（4%）为1度，11例（9%）为2度，69例（56%）为3度骨病变。对照组骨吸收标志物β-CTX水平为0.41 ng/ml，低于MM患者（p < 0.001）。Spearman相关系数分析发现骨病变程度与β-CTX水平之间存在正相关且具有统计学意义（rs = 0.51，p < 0.001）。无骨病变患者的平均β-CTX为0.72 ng/ml（标准差 = 0.64），而3度骨病变患者为1.34 ng/ml（标准差 = 0.65），差异为38%（p < 0.001）。治疗6个月后有反应的患者与基线值相比β-CTX降低（M = -0.65）。相反，治疗6个月后无反应的患者与基线值相比β-CTX值有统计学意义的增加（p < 0.001）（M = 0.42）。β-CTX的确切临界值为0.79。分析平均bALP时，未发现MM患者与对照组之间有显著差异。方差分析显示MM患者不同程度骨病变的bALP水平无统计学意义（p = 0.95）。使用受试者工作特征曲线分析bALP作为MM诊断标志物的适用性表明，bALP不适用于MM的临床诊断（曲线下面积0.5，p > 0.05）。然而，发现β-CTX是MM的优秀诊断标志物（曲线下面积0.91；95%置信区间，0.88 - 0.94；p < 0.001）。
伴有骨病变的MM患者骨吸收标志物β-CTX值升高。骨吸收标志物与骨病变程度之间存在相关性。β-CTX水平的变化可用于监测骨髓瘤治疗的有效性。
