Pm. Crofton et al., EFFECTS OF INTENSIVE CHEMOTHERAPY ON BONE AND COLLAGEN TURNOVER AND THE GROWTH-HORMONE AXIS IN CHILDREN WITH ACUTE LYMPHOBLASTIC-LEUKEMIA, The Journal of clinical endocrinology and metabolism, 83(9), 1998, pp. 3121-3129
To investigate the effects of disease and intensive chemotherapy on bo
ne turnover and growth in children with acute lymphoblastic leukemia (
ALL), a longitudinal prospective study was carried out in 22 children,
aged 1.2-13.5 yr, enrolled in the Medical Research Council-funded ran
domized trial of childhood ALL treatment in the UK. We measured lower
leg length and markers of bone formation [bone alkaline phosphatase (A
LP) and procollagen type I C-terminal propeptide (PICP)], bone resorpt
ion [pyridinoline, deoxypyridinoline, and carboxyl-terminal telopeptid
e of type I collagen (ICTP)], soft tissue turnover [procollagen type I
II N-terminal propeptide (P3NP)], and the GH axis [TGF-I, IGF-binding
protein-3 (IGFBP-3), IGFBP-2, and urinary GH] at 1- to 4-week interval
s from diagnosis to week 27 of treatment. In addition, GB-binding prot
ein was measured at diagnosis. At diagnosis, mean so scores were: bone
ALP, - 1.84; PICP -1.77; pyridinoline, -1.42; deoxypyridinoline, -1.6
6; ICTP, -0.42; P3NP, +1.45; GK, +24.4; IGF-I, -1.70; IGFBP-3, -0.88;
IGFBP-2, +2.42; and GH-binding protein, -0.69. Bone ALP, PICP, and IGF
BP-3 were all correlated (P less than or equal to 0.03). During induct
ion and intensification, there was shrinkage of the lower leg, with de
creases in PICP, pyridinoline, ICTP, and P3NP (P < 0.05), whereas IGF-
I and IGFBP-3 increased (P < 0.05). After prednisolone was discontinue
d, bone ALP and collagen markers increased markedly (P < 0.01), but th
ere was no significant change in IGF-I and IGFBP-3. In 12 children who
received high dose iv methotrexate, postglucocorticoid increases in b
one ALP and PICP were less, whereas those in ICTP and P3NP were greate
r, compared to levels in children who did not receive methotrexate (P
< 0.05). We conclude that ALL itself caused GH resistance and low bone
turnover. During early intensive chemotherapy, further suppression of
osteoblast proliferation and osteoclast activity occurred, not mediat
ed through the systemic GH axis, probably by the direct action of pred
nisolone on bone. The postglucocorticoid increase in bone turnover was
also independent of the GH axis and was modulated by high dose iv met
hotrexate, which depressed osteoblast recovery and enhanced osteoclast
activity.