title: C-type Natriuretic Peptide: a novel biomarker of steroid induced bone toxicity in children with acute lymphoblastic leukemia (ALL).
abstract: 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.
authors.affiliation: Department of Medicine, University of Otago, Christchurch 8140, New Zealand. tim.prickett@otago.ac.nz
authors.forename: Timothy C R
authors.initials: TC
authors.lastname: Prickett
authors.forename: Amanda
authors.initials: A
authors.lastname: Lyver
authors.forename: Rachel
authors.initials: R
authors.lastname: Wilson
authors.forename: Eric A
authors.initials: EA
authors.lastname: Espiner
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Sullivan
mesh_terms: D000469:Alkaline Phosphatase / Q000097:blood; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D001827:Body Height / Q000187:drug effects; D001846:Bone Development / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003094:Collagen / Q000097:blood; D003907:Dexamethasone / Q000494:pharmacology* / Q000627:therapeutic use; D005938:Glucocorticoids / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D060828:Induction Chemotherapy; D060046:Maintenance Chemotherapy; D020098:Natriuretic Peptide, C-Type / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000188:drug therapy; D011239:Prednisolone / Q000494:pharmacology* / Q000627:therapeutic use; D011446:Prospective Studies
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D005938:Glucocorticoids; D010446:Peptide Fragments; C110762:glutamyl-lysyl-alanyl-histidyl-aspartyl-glycyl-glycyl-arginine; D020098:Natriuretic Peptide, C-Type; D003907:Dexamethasone; D003094:Collagen; D011239:Prednisolone; D000469:Alkaline Phosphatase