Bone and mineral abnormalities in childhood acute lymphoblastic leukemia: Influence of disease, drugs and nutrition

In children with acute lymphoblastic leukemia (ALL), abnormalities in miner al homeostasis and bone mass were first reported by our group in the late 1 980s. Prospective longitudinal cohort studies in 40 consecutive patients re ceiving treatment according to the Dana-Farber Cancer Institute (DFCI) prot ocol 87-001 and 16 children receiving DFCI protocol 91-001 afforded us the opportunity to explore various etiologies of the observed abnormalities in mineral and bone metabolism, specifically the leukemic disease process and chemotherapeutic drugs such as steroids and amino glycoside antibiotics. At diagnosis of ALL, >70% of children had abnormally low plasma 1,25-dihydrox yvitamin D, 73% had low osteocalcin and 64% had hypercalciuria, indicating an effect of the leukemic process on vitamin D metabolism and bone turnover , During remission induction, treatment with high-dose steroid (prednisone or dexamethasone) resulted in further reduction in plasma osteocalcin and e levated parathyroid hormone levels. During 24 months of chemotherapy-mainta ined remission, reduction in bone mineral content (BMC), as measured by Z-s cores, occurred in 64% of children, most severely affecting those > 11 year s of age. A reduction in BMC during the first 6 months had a positive predi ctive value of 64% for subsequent fracture. By the end of 2 years of therap y. fractures occurred in 39% of children and radiographic evidence of osteo penia was found in 83% of the entire study group. Investigations of the bio chemical basis of the bone abnormalities revealed that by 6 months hypomagn esemia developed in 84% of children (of whom 52% were hypermagnesuric) and plasma 1,25-dihydroxyvitamin D remained abnormally low in 70%, Altered magn esium status was attributed to renal wastage of magnesium following cyclica l prednisone therapy and treatment with aminoglycoside antibiotics such as amikacin for fever accompanying neutropenia. Dietary intake and absorption of magnesium were normal. In 10 children treated for hypomagnesemia with su pplemental magnesium for up to 16-20 weeks, plasma magnesium normalized in only 50% of subjects. (C) 1998 Wiley-Liss, Inc.