Bone turnover and growth during and after continuing chemotherapy in children with acute lymphoblastic leukemia

Children treated for acute lymphoblastic leukemia may develop reduced bone mineral density during treatment, but there is little information on the me chanisms involved. In a prospective, longitudinal study on 15 children with ALL, we undertook serial measurements of markers of bone and collagen turn over, insulinlike growth factor (IGE)-I and its binding proteins (IGFBPs)-3 and -2 during the second year of continuing chemotherapy. In eight patient s we also measured lower leg length by knemometry. Height SD scores, lower leg length velocity, IGF-I, and markers of bone collagen turnover did not d iffer significantly from healthy children. However, bone alkaline phosphata se, a marker of the differentiated osteoblast, was lower (mean SD score, -0 .64; p < 0.0001), whereas procollagen type III N-terminal propeptide (P3NP, a marker of soft tissue collagen turnover; mean SD score, +0.93, p < 0.05) , IGFBP-3 (mean SD score, +0.76; p < 0.01), and IGFBP-2 (mean SD score, +1. 24, p = 0.01) were all higher than in healthy children. IGFBP-3 decreased d uring episodes of afebrile neutropenia (p < 0.05). Within 3 mo after comple tion of treatment, bone ALP increased in all eight patients, but collagen m arkers showed little change. IGFBP-2 returned to normal posttreatment, but P3NP and IGFBP-3 remained significantly elevated compared with healthy chil dren (mean SD scores, +1.51 and +1.36, respectively; p < 0.01). We conclude that continuing chemotherapy was associated with normal growth and bone co llagen turnover but enhanced soft tissue collagen turnover. Bone bone alkal ine phosphatase was low throughout treatment, which suggests impaired osteo blast differentiation resulting from a direct effect of chemotherapy on bon e. Although the effect was reversible, the long-term implications for bone health in survivors remain uncertain.