title: Bone density and structure in long-term survivors of pediatric allogeneic hematopoietic stem cell transplantation.
abstract: Children requiring allogeneic hematopoietic stem cell transplantation (alloHSCT) have multiple risk factors for impaired bone accrual. The impact of alloHSCT on volumetric bone mineral density (vBMD) and cortical structure has not been addressed. Tibia peripheral quantitative computed tomography (pQCT) scans were obtained in 55 alloHSCT recipients, ages 5 to 26 years, a median of 7 (range, 3-16) years after alloHSCT. pQCT outcomes were converted to sex- and race- specific Z-scores relative to age based on reference data in >700 concurrent healthy participants. Cortical section modulus (Zp; a summary measure of cortical bone structure and strength), and muscle and fat area Z-scores were further adjusted for tibia length for age Z-scores. AlloHSCT survivors had lower height Z-scores (-1.21 ± 1.25 versus 0.23 ± 0.92; p < 0.001), versus reference participants; BMI Z-scores did not differ. AlloHSCT survivors had lower trabecular vBMD (-1.05; 95% confidence interval [CI], -1.33 to -0.78; p < 0.001), cortical Zp (-0.63; 95% CI, -0.91 to -0.35; p < 0.001), and muscle (-1.01; 95% CI, -1.30 to -0.72; p < 0.001) Z-scores and greater fat (0.82; 95% CI, 0.54-1.11; p < 0.001) Z-scores, versus reference participants. Adjustment for muscle deficits eliminated Zp deficits in alloHSCT. Total body irradiation (TBI) was associated with lower trabecular vBMD (-1.30 ± 1.40 versus -0.49 ± 0.88; p = 0.01) and muscle (-1.34 ± 1.42 versus -0.34 ± 0.87; p < 0.01) Z-scores. Growth hormone deficiency (GHD) was associated with lower Zp Z-scores (-1.64 ± 2.47 versus -0.28 ± 1.24; p = 0.05); however, muscle differences were not significant (-1.69 ± 1.84 versus -0.78 ± 1.01; p = 0.09). History of graft versus host disease was not associated with pQCT outcomes. In summary, alloHSCT was associated with significant deficits in trabecular vBMD, cortical geometry, and muscle area years after transplantation. TBI and GHD were significant risk factors for musculoskeletal deficits. Future studies are needed to determine the metabolic and fracture implications of these deficits, and to identify therapies to improve bone accrual following alloHSCT during childhood.
authors.affiliation: Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA. moab@email.chop.edu
authors.forename: Sogol
authors.initials: S
authors.lastname: Mostoufi-Moab
authors.forename: Jill P
authors.initials: JP
authors.lastname: Ginsberg
authors.forename: Nancy
authors.initials: N
authors.lastname: Bunin
authors.forename: Babette
authors.initials: B
authors.lastname: Zemel
authors.forename: Justine
authors.initials: J
authors.lastname: Shults
authors.forename: Mary B
authors.initials: MB
authors.lastname: Leonard
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001827:Body Height / Q000502:physiology; D015519:Bone Density / Q000502:physiology*; D016723:Bone Remodeling / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D019587:Dietary Supplements; D005260:Female; D050723:Fractures, Bone / Q000473:pathology; D018380:Hematopoietic Stem Cell Transplantation; D019382:Human Growth Hormone / Q000172:deficiency; D006801:Humans; D008297:Male; D017741:Survivors; D013977:Tibia / Q000000981:diagnostic imaging / Q000502:physiology; D014057:Tomography, X-Ray Computed; D014184:Transplantation, Homologous; D014807:Vitamin D / Q000097:blood; D014916:Whole-Body Irradiation; D055815:Young Adult
chemical_list: D015415:Biomarkers; D019382:Human Growth Hormone; D014807:Vitamin D