C-type Natriuretic Peptide: A novel biomarker of steroid induced bone toxicity in children with acute lymphoblastic leukemia (ALL)

• Published in: Peptides (New York, N.Y. : 1980) N.Y. : 1980), 2012-07, Vol.36 (1), p.54-59
• Main Authors: Prickett, Timothy C.R., Lyver, Amanda, Wilson, Rachel, Espiner, Eric A., Sullivan, Michael J.
• Format: Article
• Language: English
• Subjects: Alkaline Phosphatase - blood; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; biomarkers; Biomarkers - blood; Body Height - drug effects; Bone and Bones - drug effects; Bone and Bones - enzymology; Bone and Bones - metabolism; Bone Development - drug effects; Bones; Chemotherapy; Child; Child, Preschool; childhood; Children; Collagen - blood; complications (disease); Dexamethasone; Dexamethasone - pharmacology; Dexamethasone - therapeutic use; drug therapy; Glucocorticoids - pharmacology; Glucocorticoids - therapeutic use; Growth velocity; Humans; Induction Chemotherapy; Intervals; Leukemias; Linear growth; lymphocytic leukemia; Maintenance; Maintenance Chemotherapy; mineralization; Natriuretic Peptide, C-Type - blood; natriuretic peptides; NTproCNP; Peptide Fragments - blood; Peptides; Precursor Cell Lymphoblastic Leukemia-Lymphoma - blood; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Prednisolone - pharmacology; Prednisolone - therapeutic use; Prospective Studies; radioimmunoassays; rodents; Steroids; Toxicity
• ISSN: 0196-9781; 1873-5169
• DOI: 10.1016/j.peptides.2012.04.017

► Induction chemotherapy for ALL markedly supresses blood NTproCNP concentrations. ► Plasma NTproCNP rebounds rapidly after ceasing short courses of steroids. ► Plasma NTproCNP concentration was significantly correlated with height velocity. ► NTproCNP has potential as a biomarker of glucocorticoid-induced bone toxicity. 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.