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Prospective Study of Changes in Bone Mineral Density and Turnover in Children after Hematopoietic Cell Transplantation

Departments of Pediatrics (A.P., K.M.P., K.J.U., D.M.B., L.L.R., K.S.B.), Genetics, Cell Biology and Development (A.P.), Biostatistics (T.L.B.), Medicine (S.K.R.), and Laboratory Medicine and Pathology (D.M.B.), University of Minnesota, Minneapolis, Minnesota 55455

Address all correspondence and requests for reprints to: Anna Petryk, Department of Pediatrics, University of Minnesota, 13-124 PWB, MMC 404, 516 Delaware Street SE, Minneapolis, Minnesota 55455. E-mail: petry005{at}umn.edu.

Context: Osteoporosis is common in adults after hematopoietic cell transplantation (HCT). The data on bone mineral density (BMD) in children after HCT are limited.

Objective: The objective of the study was to determine the incidence, timing, magnitude, and possible predictors of bone loss in children after HCT.

Patients and Design: The study population included 49 patients (age 5–18 yr) who were eligible to receive HCT at the University of Minnesota. The patients were evaluated at baseline, 100 d, 6 months, and 1 yr after HCT. Lumbar BMD (LBMD) was assessed by dual-energy x-ray absorptiometry.

Results: The number of patients with osteopenia increased from 18% at baseline to 33% 1 yr after HCT, and with osteoporosis from 16–19%. Mean areal LBMD z-score decreased from –0.56 to –1.1 by 6 months (n = 27) and at 1 yr was –0.94 (n = 21), which was significant compared with standard normal distribution (P = 0.004 and P = 0.022, respectively). The absolute loss of bone mineral corresponded to a 5.3% reduction in areal LBMD and a 4.8% reduction in volumetric LBMD. The level of bone-specific alkaline phosphatase decreased by 30% by d 100 (P = 0.009), followed by recovery toward baseline by 6 months. The level of osteocalcin greater than 6.5 ng/ml at d 100 predicted recovery from the initial bone loss by 1 yr. A reduction in LBMD at 6 months correlated with a cumulative dose of glucocorticoids.

Conclusion: This study demonstrates that bone loss is common in children after HCT and is primarily due to suppression of bone formation. Further studies are necessary to validate osteocalcin as a predictive biomarker.