Mineral homeostasis and bone mass at diagnosis in children with acute lymphoblastic leukemia

doi:10.1016/S0022-3476(95)70349-7

The Journal of Pediatrics

Volume 126, Issue 4, April 1995, Pages 557-564

https://doi.org/10.1016/S0022-3476(95)70349-7 Get rights and content

Abstract

Objective: To determine whether the osteopenia and unusual fractures observed in children with acute lymphoblastic leukemia (ALL) were related to the disease rather than to its treatment. Design: Prospective analysis of the bone and mineral status in 40 consecutive children with ALL seen in a pediatric tertiary-care referral center. Methods: Biochemical indicators of mineral, endocrine, and vitamin D status were measured before initiation of therapy. Bone mass was determined radiographically and by dual-photon absorptiometry of the lumbar region of the spine (L2-L4). Correlations between clinical observations, leukemia variables, bone mass, and biochemical assessment were determined. Results: At the time of diagnosis musculoskeletal pain was present in 36% of patients and was more common in children with CD10-positive leukemia and leukocyte counts less than 20 × 10⁹ cells/L. Radiographic evidence of osteopenia and fractures was observed in 13% and 10% of children, respectively. The mean bone mineral content was normal. Bone mass measurement z scores correlated with plasma 1,25-dihydroxyvitamin D₃ concentrations (r = 0.43, p <0.05). Plasma calcium, magnesium, phosphorus, and 25-hydroxyvitamin D₃ levels were normal. Low plasma osteocalcin (mean ± SD, 1.6 ± 1.6 nmol/L) and 1,25-dihydroxyvitamin D₃ (33.4 ± 26.4 pmol/L) values were observed. Parathyroid hormone levels were low in 14% of children. Hypercalciuria was detected in 64% of children. Urinary deoxypyridinoline was lower (p <0.01) than in age-matched control subjects. Histomorphometric measurements of iliac bone showed abnormalities in mineralization in the biopsy specimens from three of nine children. Conclusion: Most children with ALL have alterations in bone metabolism and bone mass when first examined. These data suggest defective mineralization as the mechanism for decreased bone mass and implicate the leukemic process as causative. (J PEDIATR 1995;126:557-64)

Section snippets

Patients

Forty consecutive children (27 boys, 13 girls; aged, 0.3 to 17 years; median age, 3.9 years) with newly diagnosed ALL who were attending the hematology/oncology service in the Children's Hospital at Chedoke-McMaster, Hamilton, Ontario, were assigned a risk for relapse according to the Dana-Farber Cancer Institute criteria²: 18 were at standard risk, 16 at high risk, and 6 at very high risk. Children with B-cell leukemia (French-American-British classification L₃ morphologic features) were

Clinical assessment

At diagnosis all 40 children were within normal percentiles for height and weight for age (mean height, 111.3 cm; range, 67.5 to 174 cm; mean weight, 20.58 kg, range, 6.37 to 59 kg).¹¹ Of the 40 children, 14 had musculoskeletal pain. Lower extremity pain occurred in all children and was more frequent than pain in the upper extremity (three subjects) and spinal locations (one subject). Children with musculoskeletal symptoms had a longer duration from onset of illness to diagnosis (mean, 6.5

DISCUSSION

The present study establishes that the disease process contributes causally to the abnormalities observed in bone, vitamin D, and mineral metabolism in children with ALL. The observation that musculoskeletal pain was more common in the children with longer duration of symptoms, with low leukocyte counts and with CALLA-positive immunologic phenotype remains unexplained.

The metabolically active sites of bone in children are at the ends of bones close to the metaphysis, where radiographic changes

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^☆: From the Departments of Pediatrics, Radiology, and Nuclear Medicine, McMaster University, Hamilton, Ontario; Research Institute, St. Joseph's Hospital, University of Western Ontario, London; and Queen Elizabeth Hospital, University of Toronto, Toronto, Ontario, Canada

^☆☆: Supported by a grant from the Hospital for Sick Children Foundation, Toronto, Ontario, Canada. Dr. Halton held a Fellowship from the National Institute of Nutrition (Canada). Dr. Atkinson received a Career Scientist Award at McMaster University from the Ontario Ministry of Health. Dr. Fraher received a University Scholar's Award from the National Institute of Nutrition (Canada).

^★: †Deceased.

^★★: Reprint requests: Stephanie Atkinson, PhD, Department of Pediatrics, McMaster University, 1200 Main St. West, Room 3V42, Hamilton, Ontario, Canada L8N 3Z5.

^♢: 0022-3476/95/$3.00 + 0 9/20/62346

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Mineral homeostasis and bone mass at diagnosis in children with acute lymphoblastic leukemia☆,☆☆,★,★★,♢

Abstract

Section snippets

Patients

Clinical assessment

DISCUSSION

J PEDIATR

J Biol Chem

Anal Biochem

Am J Clin Nutr

J PEDIATR

Metab Bone Dis Relat Res

Bone Miner

Leukemia Res

Four agent induction and intensive asparaginase therapy for treatment of childhood acute lymphoblastic leukemia

N Engl J Med

Normative values for lumbar spine bone mass in children in relation to age, gender, dietary intake and physical activity [Abstract]

J Bone Miner Res