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Altered mineral metabolism and bone mass in children during treatment for acute lymphoblastic leukemia
J M Halton1, S A Atkinson, L Fraher
1Chedoke-McMaster Hospitals, Hamilton, Ontario, Canada.
Insights
Children undergoing chemotherapy for acute lymphoblastic leukemia (ALL) often experience bone loss and fractures. This study tracked bone health, revealing significant skeletal morbidity during treatment, particularly in older children.
Area of Science:
- Pediatric Oncology
- Bone Metabolism
- Chemotherapy Side Effects
Background:
- Children with acute lymphoblastic leukemia (ALL) frequently suffer bone pain, gait issues, and fractures during chemotherapy.
- Osteopenia and reduced bone mineral content are known complications, but their progression and biochemical correlates require further investigation.
Purpose of the Study:
- To prospectively evaluate bone mass and biochemical mineral status in children with ALL undergoing chemotherapy.
- To identify risk factors and predictors for skeletal morbidity during cancer treatment.
Main Methods:
- A longitudinal cohort study of 40 children (aged 0.3-17.0 years) receiving ALL treatment.
- Regular assessments included radiography, dual-photon absorptiometry for bone mineral content (BMC), and biochemical markers (minerals, osteocalcin, vitamin D metabolites, urinary N-telopeptide).
Main Results:
- Osteopenia prevalence increased from 10% at diagnosis to 76% by 24 months; 39% experienced fractures.
- 64% of patients showed reduced BMC (Z scores), most severely in those >11 years old.
- Hypomagnesemia affected 84% by 6 months; subnormal 1,25-dihydroxyvitamin D persisted in >70%.
Conclusions:
- Bone mineralization deficits are present at diagnosis and worsen during ALL chemotherapy.
- Skeletal morbidity, including reduced bone mass and increased resorption, is common and linked to treatment, potentially exacerbated by corticosteroids.
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.