title: Effects of a third intensification block of chemotherapy on bone and collagen turnover, insulin-like growth factor I, its binding proteins and short-term growth in children with acute lymphoblastic leukaemia.
abstract: Children with acute lymphoblastic leukaemia (ALL) have reduced bone turnover caused by the disease itself and early intensive chemotherapy, but the effects of later chemotherapy using different drug combinations are uncertain. We report here a longitudinal study on 9 children with ALL randomised to receive an additional third intensification block of chemotherapy, compared with 9 children receiving continuing chemotherapy over the same period. During third intensification, bone alkaline phosphatase, procollagen type I C-terminal propeptide, the carboxyterminal propeptide of type I collagen, procollagen type III N-terminal propeptide and lower leg length all decreased in response to dexamethasone, then returned to (but not beyond) baseline levels after dexamethasone was stopped and other drugs started. These changes were unrelated to circulating insulin-like growth factor (IGF)-I, IGF binding protein (IGFBP)-3 or IGFBP-2. In all children, bone alkaline phosphatase remained below the population mean throughout. We conclude that dexamethasone decreased bone and soft tissue turnover, probably through direct effects on target tissues. The postdexamethasone phase of third intensification and continuing chemotherapy had no major deleterious effect on collagen turnover, but there was evidence of continuing suboptimal bone mineralisation.
authors.affiliation: Department of Paediatric Biochemistry, Royal Hospital for Sick Children, Edinburgh, U.K.
authors.forename: P M
authors.initials: PM
authors.lastname: Crofton
authors.forename: S F
authors.initials: SF
authors.lastname: Ahmed
authors.forename: J C
authors.initials: JC
authors.lastname: Wade
authors.forename: M W
authors.initials: MW
authors.lastname: Elmlinger
authors.forename: M B
authors.initials: MB
authors.lastname: Ranke
authors.forename: C J
authors.initials: CJ
authors.lastname: Kelnar
authors.forename: W H
authors.initials: WH
authors.lastname: Wallace
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000378:metabolism / Q000627:therapeutic use*; D001862:Bone Resorption; D002648:Child; D002675:Child, Preschool; D003094:Collagen / Q000378:metabolism*; D005260:Female; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000378:metabolism; D016032:Randomized Controlled Trials as Topic
chemical_list: D018970:Insulin-Like Growth Factor Binding Protein 1; D009363:Neoplasm Proteins; D007334:Insulin-Like Growth Factor I; D003094:Collagen