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

Children with acute lymphoblastic leukaemia (ALL) have reduced bone turnove r caused by the disease itself and early intensive chemotherapy, but the ef fects 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. Du ring third intensification, bone alkaline phosphatase, procollagen type I C -terminal propeptide, the carboxyterminal propeptide of type I collagen, pr ocollagen type III N-terminal propeptide and lower leg length all decreased in response to dexamethasone, then returned to (but not beyond) baseline l evels after dexamethasone was stopped and other drugs started. These change s were unrelated to circulating insulin-like growth factor (IGF)I, IGF bind ing protein (IGFBP)-3 or IGFBP-2. In all children, bone alkaline phosphatas e remained below the population mean throughout. We conclude that dexametha sone decreased bone and soft tissue turnover, probably through direct effec ts on target tissues. The postdexamethasone phase of third intensification and continuing chemotherapy had no major deleterious effect on collagen tur nover, but there was evidence of continuing suboptimal bone mineralisation. (C) 1999 Elsevier Science Ltd. All rights reserved.