Background: The receptor activator of the nuclear factor-kB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) pathway is a determining pathway in the balance between bone formation and resorption, and disruptions in this complex can affect bone metabolism. Methods: This study analyzes the changes in RANKL, OPG, and 25(OH)D levels; the RANKL/OPG ratio; and other bone turnover markers (BTMs) from diagnosis to complete remission in children with acute lymphoblastic leukemia (ALL). This is a prospective observational cohort study, carried out at the Instituto Mexicano del Seguro Social, Mexico City, including 33 patients (4–17 years) with newly diagnosed B-cell ALL. The patients were treated with the HP09 chemotherapy protocol. Children who had previously been treated with corticosteroids were excluded. A peripheral blood sample at diagnosis and remission was collected to determine the 25(OH)D and BTM concentrations. Results: Increased RANKL (p= 0.001) and osteocalcin (p< 0.001) levels and RANKL/OPG ratio (<0.001) and a decreased OPG level (p= 0.005) were observed at remission, predominantly in the high-risk (HR) relapse and vitamin D deficiency groups. A negative association between RANKL and OPG (r = −0.454,p= 0.008) was observed. Conclusions: we suggest that the RANKL/OPG ratio could serve as a bone remodeling marker in ALL patients.
背景：核因子κB受体激活因子（RANK）/RANK配体（RANKL）/骨保护素（OPG）通路是调控骨形成与骨吸收平衡的关键通路，该复合体的紊乱可影响骨代谢。方法：本研究旨在分析急性淋巴细胞白血病（ALL）患儿从确诊至完全缓解期间RANKL、OPG、25(OH)D水平、RANKL/OPG比值及其他骨转换标志物（BTMs）的动态变化。本研究为前瞻性观察队列研究，在墨西哥城墨西哥社会保障研究所开展，共纳入33例新诊断B细胞ALL患者（4-17岁）。所有患者均接受HP09化疗方案治疗，既往接受过糖皮质激素治疗的儿童被排除。分别在确诊时及缓解期采集外周血样本，测定25(OH)D及BTMs浓度。结果：缓解期观察到RANKL（p=0.001）和骨钙素（p<0.001）水平及RANKL/OPG比值（p<0.001）显著升高，OPG水平显著降低（p=0.005），这种变化在高危复发组及维生素D缺乏组尤为明显。RANKL与OPG呈负相关（r=-0.454，p=0.008）。结论：我们认为RANKL/OPG比值可作为ALL患者骨重塑的潜在标志物。
Changes in RANKL, OPG, and 25(OH)D Levels in Children with Leukemia from Diagnosis to Remission
肿瘤(癌症)患者之家