Abstract
Summary
Acute leukemia is the most common malignancy in children. We showed that low bone mass is prevalent among children with leukemia, especially in femur. Serum calcium, exercise, chemotherapy protocol, and radiotherapy are the main contributing factors. We suggest that early diagnosis and treatment of this problem could improve bone health in them.
Introduction
Acute leukemia is the most common malignancy in children and has been reported to be associated with low bone mass. Due to lack of sufficient data about the bone mineral density of children with leukemia in the Middle East, and inconsistencies between possible associated factors contributing to decreasing bone density in these children, we aimed to conduct a case-control study in Iran.
Materials and methods
This case-control study was conducted on 60 children with acute leukemia and 60 age- and sex-matched healthy controls. Anthropometric data, sun exposure, puberty, physical activity, and mineral biochemical parameters were assessed. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DEXA). Data analysis was done by SPSS software v. 21.
Results
Serum calcium was higher in the control group (P = 0.012) while serum phosphorous, alkaline phosphatase, and serum 25(OH)D3 were higher in children with leukemia with P values of 0.04, 0.002, and 0.036, respectively. Sun exposure and physical activity were more in healthy controls (P values <0.001 and 0.003, respectively). Prevalence of vitamin D deficiency in case and control groups was 57.8 and 79.4 %, respectively. This prevalence was higher in healthy controls (P value = 0.007). Both lumbar and femoral neck bone mineral apparent density (BMAD) were higher in the control group (P value <0.001). Serum calcium, physical activity, and radiotherapy were the most relevant factors associated with lumbar BMAD. Femoral neck BMAD was associated with chemotherapy protocol.
Conclusion
Low bone mass for chronological age is prevalent among children with leukemia, especially in the femoral neck. Serum calcium, physical activity, chemotherapy protocol, and radiotherapy are the main contributing factors.
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References
Thomas IH, Donohue JE, Ness KK, Dengel DR, Baker KS, Gurney JG (2008 Dec 1) Bone mineral density in young adult survivors of acute lymphoblastic leukemia. Cancer 113(11):3248–3256
Kelly KM, Thornton JC, Hughes D, Osunkwo I, Weiner M, Wang J, Horlick M (2009 Jan) Total body bone measurements: a cross-sectional study in children with acute lymphoblastic leukemia during and following completion of therapy. Pediatr Blood Cancer 52(1):33–38
Tillmann V, Darlington AS, Eiser C, Bishop NJ, Davies HA (2002) Male sex and low physical activity are associated with reduced spine bone mineral density in survivors of childhood acute lymphoblastic leukemia. J Bone Miner Res 17(6):1073–1080
Burrows M, Baxter-Jones A, Mirwald R, Macdonald H, McKay H (2009) Bone mineral accrual across growth in a mixed-ethnic group of children: are Asian children disadvantaged from an early age? Calcif Tissue Int 84(5):366–378
Mostoufi-Moab S, Brodsky J, Isaacoff EJ, Tsampalieros A, Ginsberg JP, Zemel B, Shults J, Leonard MB (2012) Longitudinal assessment of bone density and structure in childhood survivors of acute lymphoblastic leukemia without cranial radiation. J Clin Endocrinol Metab 97(10):3584–3592
teWinkel ML, Pieters R, Hop WC, Roos JC, Bökkerink JP, Leeuw JA, Bruin MC, Kollen WJ, Veerman AJ, de Groot-Kruseman HA, van der Sluis IM, van den Heuvel-Eibrink MM (2014) Bone mineral density at diagnosis determines fracture rate in children with acute lymphoblastic leukemia treated according to the DCOG-ALL9 protocol. Bone 59:223–228
van der Sluis IM, van den Heuvel-Eibrink MM, Hählen K et al (2000) Bone mineral density, body composition and height in long term survivors of acute lymphoblastic leukemia in childhood. Med Pediatr Oncol 35:415–420
Halton JM, Atkinson SA, Fraher L et al (1995) Mineral homeostasis and bone mass at diagnosis in children with acute lymphoblastic leukemia. J Pediatr 126:557–564
Leonard MB, Propert KJ, Zemel BS et al (1999) Discrepancies in pediatric bone mineral density reference data: potential for misdiagnosis of osteopenia. J Pediatr 135:182–188
Boot AM, van den Heuvel-Eibrink MM, Hählen K et al (1999) Bone mineral density in children with acute lymphoblastic leukemia. Eur J Cancer 35:1693–1697
Heath JA, Ramzy JM, Donath SM (2010) Physical activity in survivors of childhood acute lymphoblastic leukaemia. J Paediatr Child Health 46:149–153
Hartman A, van den Bos C, Stijnen T, Pieters R (2008) Decrease in peripheral muscle strength and ankle dorsiflexion as long-term side effects of treatment for childhood cancer. Pediatr Blood Cancer 50:833–837
Spoudeas HA (2002) Growth and endocrine function after chemotherapy and radiotherapy in childhood. Eur J Cancer 38:1748–1759
Watsky MA, Carbone LD, An Q, Cheng C, Lovorn EA, Hudson MM, Pui CH, Kaste SC (2014) Bone turnover in long-term survivors of childhood acute lymphoblastic leukemia. Pediatr Blood Cancer 61(8):1451–1456
Gurney JG, Kaste SC, Liu W, Srivastava DK, Chemaitilly W, Ness KK, Lanctot JQ, Ojha RP, Nottage KA, Wilson CL, Li Z, Robison LL, Hudson MM (2014) Bone mineral density among long-term survivors of childhood acute lymphoblastic leukemia: results from the St. Jude Lifetime Cohort Study. Pediatr Blood Cancer 61(7):1270–1276
Choi YJ, Park SY, Cho WK, Lee JW, Cho KS, Park SH, Hahn SH, Jung MH, Chung NG, Cho B, Suh BK, Kim HK (2013) Factors related to decreased bone mineral density in childhood cancer survivors. J Korean Med Sci 28(11):1632–1638
Muszynska-Roslan K, Konstantynowicz J, Krawczuk-Rybak M, Protas P (2007) Body composition and bone mass in survivors of childhood cancer. Pediatr Blood Cancer 48(2):200–204
Vitanza NA, Hogan LE, Zhang G, Parker RI (2015) The progression of bone mineral density abnormalities after chemotherapy for childhood acute lymphoblastic leukemia. J Pediatr Hematol Oncol 37(5):356–361
Jeddi M, Roosta MJ, Dabbaghmanesh MH, Omrani GR, Ayatollahi SM, Bagheri Z, Showraki AR, Bakhshayeshkaram M (2013) Normative data and percentile curves of bone mineral density in healthy Iranian children aged 9–18 years. Arch Osteoporos 8:114
Bogunovic L, Doyle SM, Vogiatzi MG (2009) Measurement of bone density in the pediatric population. Curr Opin Pediatr 21:77–82
Cole JH, Scerpella TA, van der Meulen MC (2005) Fan-beam densitometry of the growing skeleton. J Clin Densitom 8:57–64
Fewtrell MS, on behalf of the British Paediatric & Adolescent Bone Group (2003) Bone densitometry in children assessed by dual X-ray absorptiometry: uses and pitfalls. Arch Dis Child 88:795–798
Gordon CM, Bachrach LK, Carpenter TO, Crabtree N, El-Hajj Fuleihan G, Kutilek S, Lorenc RS, Tosi LL, Ward KA, Ward LM, Kalkwarf HJ (2008) Dual energy X-ray absorptiometry interpretation and reporting in children and adolescents. The 2007 ISCD pediatric official positions. J Clin Densitom 11:43–58
Horlick M, Wang J, Pierson RN Jr, Thornton JC (2004) Prediction models for evaluation of total-body bone mass with dual energy X-ray absorptiometry among children and adolescents. Pediatrics 114:337–345
Yamashita N, Tanaka H, Moriwake T, Nishiuchi R, Oda M, Seino Y (2003) Analysis of linear growth in survivors of childhood acute lymphoblastic leukemia. J Bone Miner Metab 21(3):172–178
Kaushik A, Bansal D, Khandelwal N, Trehan A, Marwaha RK (2009) Changes in bone mineral density during therapy in childhood acute lymphoblastic leukemia. Indian Pediatr 46(3):245–248 Epub 2009 Jan 21
Atkinson SA, Halton JM, Bradley C, Wu B, Barr RD (1998) Bone and mineral abnormalities in childhood acute lymphoblastic leukemia: Influence of disease, drugs and nutrition. Int J Cancer 78(Supp1 1):35–39
Lee JM, Kim JE, Bae SH, Hah JO (2013) Efficacy of pamidronate in children with low bone mineral density during and after chemotherapy for acute lymphoblastic leukemia and non-Hodgkin lymphoma. Blood Res 48(2):99–106
Lethaby C, Wiernikowski J, Sala A, Naronha M, Webber C, Barr RD (2007) Bisphosphonate therapy for reduced bone mineral density during treatment of acute lymphoblastic leukemia in childhood and adolescence: a report of preliminary experience. J Pediatr Hematol Oncol 29(9):613–616
Karlsson KM, Karlsson C, Ahlborg HG et al (2003) Bone turnover responses to changed physical activity. Calcif Tissue Int 72(6):675–680
Whipple TJ, Le BH, Demers LM et al (2004) Acute effects of moderate intensity resistance exercise on bone cell activity. Int J Sports Med 25(7):496–501
Lester ME, Urso ML, Evans RK et al (2009) Influence of exercise mode and osteogenic index on bone biomarker responses during short-term physical training. Bone 45(4):768–776
Demark-Wahnefried W, Werner C, Clipp EC et al (2005) Survivors of childhood cancer and their guardians. Cancer 103(10):2171–2180
Ness KK, Leisenring WM, Huang S et al (2009) Predictors of inactive lifestyle among adult survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Cancer 115(9):1984–1994
Wilson CL, Ness KK (2013) Bone mineral density deficits and fractures in survivors of childhood cancer. Curr Osteoporos Rep 11(4):329–337
Strauss AJ, Su JT, Dalton VM et al (2001) Bony morbidity in children treated for acute lymphoblastic leukemia. J Clin Oncol 19(12):3066–3072
Xian CJ, Cool JC, Scherer MA et al (2007) Cellular mechanisms for methotrexate chemotherapy-induced bone growth defects. Bone 41(5):842–850
Marinovic D, Dorgeret S, Lescoeur B et al (2005) Improvement in bone mineral density and body composition in survivors of childhood acute lymphoblastic leukemia: a 1-year prospective study. Pediatrics 116:e102–e108
Van der Sluis IM, van den Heuvel-Eibrink MM (2008) Osteoporosis in children with cancer. Pediatr Blood Cancer 50:474–478
van Leeuwen BL, Kamps WA, Jansen HW et al (2000) The effect of chemotherapy on the growing skeleton. Cancer Treat Rev 26(5):363–376
Gleeson HK, Shalet SM (2001) Endocrine complications of neoplastic diseases in children and adolescents. Curr Opin Pediatr 13:346–351
Chemaitilly W, Sklar CA (2010) Endocrine complications in long-term survivors of childhood cancers. Endocr-Relat Cancer 17:R141–R159
Saki F, Dabbaghmanesh MH, Omrani GR, Bakhshayeshkaram M (2015 Jun) Vitamin D deficiency and its associated risk factors in children and adolescents in southern Iran. Public Health Nutr 8:1–6
Saki F, Omrani GR, Pouralborz Y, Dabbaghmanesh MH (2016) Vitamin D deficiency and the associated factors in children with type 1 diabetes mellitus in southern Iran. Int J Diabetes Dev Ctries. doi:10.1007/s13410-016-0499-0
O'Regan S, Carson S, Chesney RW, Drummond KN (1977) Electrolyte and acid-base disturbances in the management of leukemia. Blood 49(3):345–353
Sarno J (2013) Prevention and management of tumor lysis syndrome in adults with malignancy. J AdvPractOncol 4(2):101–106 Review
Arikoski P, Komulainen J, Riikonen P, Voutilainen R, Knip M, Kröger 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(9):3174–3181
Minaire P (1989) Immobilization osteoporosis: a review. Clin Rheumatol 8(Suppl 2):95–103 Review
Brunner R, Doderlein L (1996) Pathological fractures in patients with cerebral palsy. J Pediatr Orthop B 5(4):232–238
Seeman E (2002) Pathogenesis of bone fragility in women and men. Lancet 359(9320):1841–1850 Review
Gordon CM, Bachrach LK, Carpenter TO, Crabtree N, El-Hajj Fuleihan G, Kutilek S et al (2008) Dual energy X-ray absorptiometry interpretation and reporting in children and adolescents: the 2007 ISCD Pediatric Official Positions. J Clin Densitom 11(1):43–58
Acknowledgments
This study was supported by the Shiraz University of Medical Sciences with the grant number: 7165. We would like to thank Sheryl Nikpoor for English editing of the manuscript and Shirin Parand of Hematology Research Center, Shiraz University of Medical Sciences, for preparation of the manuscript.
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The Ethics Committee of the Shiraz University of Medical Sciences approved our study with the Grant number 93-01-32-7165.
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Bordbar, M.R., Haghpanah, S., Dabbaghmanesh, M.H. et al. Bone mineral density in children with acute leukemia and its associated factors in Iran: a case-control study. Arch Osteoporos 11, 36 (2016). https://doi.org/10.1007/s11657-016-0290-3
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DOI: https://doi.org/10.1007/s11657-016-0290-3