Department of Medicine, University of Otago, Christchurch 8140, New Zealand.
Peptides. 2012 Jul;36(1):54-9. doi: 10.1016/j.peptides.2012.04.017. Epub 2012 Apr 27.
Impaired bone growth and mineralization, and osteonecrosis are significant and common long-term sequelae of chemotherapy for childhood acute lymphoblastic leukemia (ALL). Here we have evaluated the relationship between linear bone growth during chemotherapy for ALL and bone derived C-type Natriuretic Peptide (CNP). CNP is known to be critical to normal endochondral bone growth in both rodents and humans, and plasma concentration of the amino terminal pro CNP (NTproCNP) is strongly correlated with concurrent height velocity in children. Plasma NTproCNP and CNP were measured by radio-immunoassay in 12 children aged 2-9 years during induction and maintenance chemotherapy for children with ALL. Height velocity was calculated from stadiometer readings at intervals of 3-12 months and related to plasma NTproCNP during each growth interval. Plasma NTproCNP was markedly suppressed in all subjects during induction chemotherapy. Brief periods of NTproCNP decline and rapid rebound during maintenance treatment coincided with the use of dexamethasone but not with other chemotherapeutics. Height velocity was markedly reduced during ALL induction but unaffected in maintenance phase, and these changes in growth were strongly correlated with plasma NTproCNP concentration. Plasma NTproCNP has potential use as a biomarker of glucocorticoid-induced bone toxicity.
成骨生长和矿化受损以及骨坏死是儿童急性淋巴细胞白血病（ALL）化疗的常见且严重的长期后遗症。在此，我们评估了 ALL 化疗过程中的线性骨生长与骨衍生 C 型利钠肽（CNP）之间的关系。已知 CNP 对啮齿动物和人类的正常软骨内骨生长至关重要，并且氨基末端前 CNP（NTproCNP）的血浆浓度与儿童同期身高增长速度密切相关。在 ALL 儿童诱导和维持化疗期间，通过放射免疫测定法测量了 12 名 2-9 岁儿童的血浆 NTproCNP 和 CNP。每隔 3-12 个月使用身高计读数计算身高增长速度，并在每个生长间隔期间与血浆 NTproCNP 相关。在诱导化疗期间，所有受试者的血浆 NTproCNP 均明显受到抑制。NTproCNP 的短暂下降和维持治疗期间的快速反弹与地塞米松的使用有关，但与其他化疗药物无关。ALL 诱导期间身高增长明显减慢，但维持阶段不受影响，这些生长变化与血浆 NTproCNP 浓度密切相关。血浆 NTproCNP 可能作为糖皮质激素诱导骨毒性的生物标志物。
