MINERAL HOMEOSTASIS AND BONE MASS AT DIAGNOSIS IN CHILDREN WITH ACUTELYMPHOBLASTIC-LEUKEMIA

Objective: To determine whether the osteopenia and unusual fractures o bserved in children with acute lymphoblastic leukemia (ALL) were relat ed to the disease rather than to its treatment. Design: Prospective an alysis of the bone and mineral status in 40 consecutive children with ALL seen in a pediatric tertiary-care referral center. Methods: Bioche mical indicators of mineral, endocrine, and vitamin D status were meas ured before initiation of therapy, Bone mass was determined radiograph ically and by dual-photon absorptiometry of the lumbar region of the s pine (L2-L4). Correlations between clinical observations, leukemia var iables, 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 a nd leukocyte counts less than 20 X 10(9) cells/L. Radiographic evidenc e of osteopenia and fractures was observed in 13% and 10% of children, respectively, The mean bone mineral content was normal. Bone mass mea surement z scores correlated with plasma 1,25-dihydroxyvitamin D-3 con centrations (r = 0.43, p <0.05). Plasma calcium, magnesium, phosphorus , and 25-hydroxyvitamin D-3 levels were normal. Low plasma osteocalcin (mean +/- SD, 1.6 +/- 1.6 nmol/L) and 1,25-dihydroxyvitamin D-3 (33.4 +/- 26.4 pmol/L) values were observed. Parathyroid hormone levels wer e low in 14% of children. Hypercalciuria was detected in 64% of childr en, 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.