Altered mineral metabolism and bone mass in children during treatment for acute lymphoblastic leukemia

Abstract

Children with acute lymphoblastic leukemia (ALL) often develop bone pain, abnormal gait, and unusual fractures while in remission and receiving continuing chemotherapy. A prospective longitudinal cohort study was undertaken of bone mass and biochemical mineral status in 40 consecutive children (27 male, 13 female, aged 0.3–17.0 years) receiving therapy on the Dana‐Farber Cancer Institute protocol 87–01. Radiography, lumbar spine dual‐photon absorptiometry, and biochemical measurements of mineral status were performed at diagnosis and at 6‐month intervals throughout 24 months of chemotherapy. Eleven patients were not completely evaluated (4 deaths and 7 off study). Radiographic evidence of osteopenia was observed in 10, 64, and 76% at diagnosis, 12 and 24 months, respectively. Fractures occurred in 39% of children during treatment. Reduction in bone mineral content (BMC), as measured by Z scores, occurred in 64% of patients and was most severe in those greater than 11 years of age at diagnosis. Reduction in BMC during the first 6 months of therapy had a positive predictive value of 64%, while an increase in BMC had a negative predictive value of 82% for subsequent fracture. By 6 months of therapy, 31/37 (84%) children were hypomagnesemic, of whom 16 (52%) were hypermagnesuric. Plasma osteocalcin was subnormal at diagnosis in 29/40 (73%) but increased to normal by 6 months of treatment. Vitamin D status was normal throughout, but plasma 1,25‐dihydroxyvitamin D remained subnormal in greater than 70% of children. Urinary cross‐link N‐telopeptide was normal at diagnosis and became elevated in 58% of children by the end of therapy. Suppressed bone mineralization is evident at diagnosis in a minority of children with ALL. Skeletal morbidity and a reduction in bone mineral mass become more prevalent during treatment, with increased bone resorption, perhaps mainly as a consequence of corticosteroid administration. (J Bone Miner Res 1996;11:1774–1783)