Abstract
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 (P1CP)], bone resorption [C terminal telopeptide of type I collagen (1CTP)], 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 IGF1 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, P1CP, 1CTP, 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, P1CP, 1CTP, P3NP, IGF1, 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.
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Abbreviations
- BALP:
-
bone alkaline phosphatase
- BMI:
-
body mass index
- 1CTP:
-
C-terminal telopeptide of type I collagen
- IGFBP:
-
IGF-binding protein
- LLL:
-
lower leg length
- LLLV:
-
lower leg length velocity
- P1CP:
-
C-terminal propeptide of type I collagen
- P3NP:
-
N-terminal propeptide of type III procollagen
- SDS:
-
standard deviation score
References
Ahmed SF, Wallace WHB, Kelnar CKH 1997 An anthropometric study of children during intensive chemotherapy for acute lymphoblastic leukaemia. Horm Res 48: 178–183
Holm K, Nysom K, Hertz H, Muller J 1994 Normal final height after treatment for acute lymphoblastic leukaemia without irradiation. Acta Paediatr 83: 1287–1290
Hokken-Koelega ACS, Van Doorn JWD, Hählen K, Stijnen T, de Muinck Keizer-Schrama SM, Drop SL 1993 Long-term effects of treatment for acute lymphoblastic leukaemia with and without cranial irradiation on growth and puberty: a comparative study. Pediatr Res 33: 577–582
Crofton PM, Ahmed SF, Wade JC, Stephen R, Elminger MW, Ranke MB, Kelnar CJH, Wallace WHB 1998 Effects of intensive chemotherapy on bone and collagen turnover and the growth hormone axis in children with acute lymphoblastic leukaemia. J Clin Endocrinol Metab 83: 3121–3129
Ahmed SF, Wallace WHB, Kelnar CJH 1995 Knemometry in childhood: a study to compare the precision of two different techniques. Ann Hum Biol 22: 247–252
Crofton PM, Ahmed SF, Wade JC, Elmlinger MW, Ranke MB, Kelnar CJH, Wallace WHB 1999 Effects of a third intensification block of chemotherapy on bone and collagen turnover, insulin-like growth factor 1, its binding proteins and short term growth in children with acute lymphoblastic leukaemia. Eur J Cancer 35: 960–967
Crofton PM, Ahmed SF, Wade JC, Elmlinger MW, Ranke MB, Kelnar CJH, Wallace WHB 2000 Bone turnover and growth during and after continuing chemotherapy in children with acute lymphoblastic leukaemia. Pediatr Res 48: 490–496
Arikoski P, Komulainen J, Riikonen P, Voutilainen R, Knip M, Kroger H 1999 Alterations in bone turnover and impaired development of bone mineral density in newly diagnosed children with cancer: a 1-year prospective study. J Clin Endocrinol Metab 84: 3174–3181
Warner JT, Evans WD, Webb DK, Bell W, Gregory JW 1999 Relative osteopenia after treatment for acute lymphoblastic leukaemia. Pediatr Res 45: 544–551
Roman J, Villaizan CJ, Garcia-Foncillas J, Azcona C, Salvador J, Sierrasesumaga L 1995 Chemotherapy-induced growth hormone deficiency in children with cancer. 25: 90–95
Mellko J, Niemi S, Risteli L, Risteli J 1990 Radioimmunoassay of the carboxyterminal propeptide of human type I collagen. Clin Chem 36: 1328–1332
Ristelli J, Elooma I, Niemi S, Novamo A, Risteli L 1993 Radioimmunoassay for the pyrodinoline cross-linked carboxyterminal telopeptide of type I collagen: a new serum marker of bone collagen degradation. Clin Chem 39: 635–640
Ristelli J, Niemi S, Trivedi P, Maentausta O, Mowat AP, Risteli L 1988 Rapid equilibrium radioimmunoassay for the amino terminal propeptide of human type III procollagen. Clin Chem 34: 715–718
Peaston RT, Cooper J 1986 Affinity electrophoresis of alkaline phosphatase isoenzymes. Clin Chem 32: 235–236
Blum WF, Breier BH 1994 Radioimmunoassay for IGFs and IGFBPs. Growth Regul 4: 11–19
Blum WF, Ranke MB, Kietzmann K, Gauggel E, Zeisel JH, Bierich JR 1990 A specific radioimmunoassay for the growth hormone (GH)-dependent somatomedin-binding protein: its use for the diagnosis of growth hormone deficiency. J Clin Endocrinol Metab 70: 1292–1297
Elmlinger MW, Wimmer K, Biemer E, Blum WF, Ranke MB, Dannecker GE 1996 Insulin-like growth factor binding protein 2 (IGFBP-2) is differentially expressed in leukaemic T- and B-cell lines. Growth Regul 6: 152–157
Freeman JV, Cole TJ, Chinn S, Jones PRM, White EM, Preece MA 1990 Cross sectional stature and weight reference curves for the UK, 1990. Arch Dis Child 73: 17–24
Cole TJ, Freeman JV, Preece MA 1995 Body mass index reference curves for the UK, 1990. Arch Dis Child 73: 25–29
Crofton PM 1992 Wheat-germ lectin affinity electrophoresis for alkaline phosphatase isoforms in children: age-dependent reference ranges and changes in liver and bone disease. Clin Chem 38: 663–670
Blum WF 1996 Insulin-like growth factors and their binding proteins. In: Ranke MB (ed) Diagnostics of Endocrine Function in Children and Adolescents. JA Barth, Edition J&J, Heidelberg, pp 190–218.
Crofton PM, Wade JC, Taylor MRH, Holland CV 1997 Serum concentrations of the carboxyterminal propeptide of type I procollagen, the aminoterminal propeptide of type III procollagen, the cross-linked carboxyterminal telopeptide of type I collagen and their interrelationships in school children. Clin Chem 43: 1577–1581
Rosen CJ, Donahue LR, Hunter SJ 1994 Insulin-like growth factors and bone: the osteoporosis connection. Proc Soc Exp Biol Med 206: 83–102
Jackson Smith W, Jeong Nam T, Underwood LE, Busby WH, Celnicker A, Clemmons DR 1993 Use of insulin-like growth factor binding protein-2 (IGFBP-2), IGFBP-3, and IGF-1 for assessing growth hormone status in short children. J Clin Endocrinol Metab 77: 1294–1299
Ferry RJ, Cerri RW, Cohen P 1999 Insulin-like growth factor binding proteins: new proteins, new functions. Horm Res 51: 53–67
Kelley KM, Oh Y, Gargosky SE, Matsumoto T, Hwa V, Ng L, Simpson DM, Rosenfeld RG 1996 Insulin-like growth factor-binding proteins (IGFBPs) and their regulatory dynamics. Int J Biochem Cell Biol 28: 619–637
Crofton PM, Kelnar CJH 1998 Bone and collagen markers in paediatric practice. Int J Clin Pract 52: 557–565
Muller HL, Oh Y, Lehrnbecher T, Blum WF, Rosenfeld RG 1994 Insulin-like growth factor-binding protein-2 concentrations in cerebrospinal fluid and serum of children with malignant solid tumours or acute leukaemia. J Clin Endocrinol Metab 79: 428–434
Nesbit M, Krivit W, Heyn R, Sharp H 1976 Acute and chronic effects of methotrexate on hepatic, pulmonary, and skeletal systems. Cancer 37: 1048–1054
Tonshoff B, Jux C, Mehls O 1996 Glucocorticoids and growth. In: Kelnar CJH (ed) Bailliere's Clinical Paediatrics—Paediatric Endocrinology. Bailliere Tindall, London, pp 309–311.
Baron J, Huang Z, Oerter KE, Bacher JD, Cutler GB 1992 Dexamethasone acts locally to inhibit longitudinal bone growth in rabbits. Am J Physiol 263: E489–E492
Ahmed SF, Tucker P, Mushtaq T, Wallace AM, Williams DM, Hughes IA 2002 Short-term effects on linear growth and bone turnover in children randomised to receive prednisolone or dexamethasone. Clin Endocrinol 57: 185–191
The Italian Group for Antiemetic Research 2000 Dexamethasone alone or in combination with ondansetron for the prevention of delayed nausea and vomiting induced by chemotherapy. N Engl J Med 342: 1554–1559
Kim CH, Cheng SL, Kim GS 1999 Effects of dexamethasone on proliferation, activity, and cytokine secretion of normal human bone marrow stromal cells: possible mechanisms of glucocorticoid-induced bone loss. J Endocrinol 162: 371–379
Aisenberg J, Hsieh K, Kalaitzoglou G, Whittam E, Heller G, Schneider Sklar C 1998 Bone mineral density in young adult survivors of childhood cancer. J Pediatr Hematol Oncol 20: 241–245
Vassilopoulou-Sellin R, Brosnan P, Delpassand A, Zietz H, Klein MJ, Jaffe N 1999 Osteopenia in young adult survivors of childhood cancer. Med Pediatr Oncol 32: 272–278
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Supported by Serono Laboratories, the Child Growth Foundation and the Jennifer Fund.
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Bath, L., Crofton, P., Evans, A. et al. Bone Turnover and Growth during and after Chemotherapy in Children with Solid Tumors. Pediatr Res 55, 224–230 (2004). https://doi.org/10.1203/01.PDR.0000100903.83472.09
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DOI: https://doi.org/10.1203/01.PDR.0000100903.83472.09
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