Bone turnover and growth during and after chemotherapy in children with solid tumors

Children who are treated for malignancy have been shown to have decreased bone mineral density. We investigated the effect of serial courses of chemotherapy on growth and bone turnover in children with solid tumors. We measured height, weight, and lower leg length (LLL; n = 10) and markers of bone formation [bone alkaline phosphatase (BALP) and C-terminal propeptide of type I collagen (PICP)], bone resorption [C terminal telopeptide of type I collagen (ICTP)], soft tissue collagen turnover [N-terminal propeptide of type III procollagen (P3NP)], and the GH axis [IGF1 and its binding proteins (IGFBP3 and IGFBP2)] before and after each course (n = 25) and on completion of treatment (n = 12). Height SD score decreased during treatment (p < 0.01) and increased to pretreatment levels at 3 mo off treatment (p < 0.05). LLL growth increased off treatment (p < 0.01). At diagnosis, BALP, PICP, and IGFI SD score were low compared with age- and sex-matched reference groups (p < 0.001, p < 0.001, and p < 0.002, respectively) and IGFBP2 was elevated (p < 0.001). During treatment, PICP, ICTP, and P3NP showed a cyclical pattern decreasing after each course (p < 0.001) and increasing before the next course (p < 0.001). Precourse levels of BALP, PICP, ICTP, P3NP, IGFI, and IGFBP3 showed an upward trend during treatment. BALP remained suppressed throughout treatment (p < 0.001). Intense courses of treatment for solid tumors have a direct suppressive effect on bone turnover, with an imbalance between collagen synthesis and degradation.