Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
J Bone Miner Res. 2012 Apr;27(4):760-9. doi: 10.1002/jbmr.1499.
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.
儿童接受异基因造血干细胞移植（alloHSCT）后，有多种因素会导致骨骼积累受损。alloHSCT 对体积骨矿物质密度（vBMD）和皮质结构的影响尚未得到解决。对 55 名年龄在 5 至 26 岁的 alloHSCT 受者进行了胫骨外周定量计算机断层扫描（pQCT）检查，这些受者在 alloHSCT 后中位数为 7（范围为 3-16）年。pQCT 结果根据>700 名同时期健康参与者的参考数据，转换为与年龄相关的性别和种族特异性 Z 分数。皮质截面模数（Zp；皮质骨结构和强度的综合测量指标）以及肌肉和脂肪面积 Z 分数进一步根据胫骨长度调整为年龄 Z 分数。alloHSCT 幸存者的身高 Z 分数较低（-1.21±1.25 与 0.23±0.92；p<0.001），与参考参与者相比；BMI Z 分数没有差异。alloHSCT 幸存者的骨小梁 vBMD（-1.05；95%置信区间 [CI]，-1.33 至-0.78；p<0.001）、皮质 Zp（-0.63；95%CI，-0.91 至-0.35；p<0.001）和肌肉（-1.01；95%CI，-1.30 至-0.72；p<0.001）Z 分数降低，脂肪（0.82；95%CI，0.54-1.11；p<0.001）Z 分数升高，与参考参与者相比。调整肌肉缺陷后，alloHSCT 中的 Zp 缺陷得以消除。全身照射（TBI）与较低的骨小梁 vBMD（-1.30±1.40 与-0.49±0.88；p=0.01）和肌肉（-1.34±1.42 与-0.34±0.87；p<0.01）Z 分数相关。生长激素缺乏症（GHD）与较低的 Zp Z 分数有关（-1.64±2.47 与-0.28±1.24；p=0.05）；然而，肌肉差异不显著（-1.69±1.84 与-0.78±1.01；p=0.09）。移植物抗宿主病病史与 pQCT 结果无关。总之，alloHSCT 后多年，与骨小梁 vBMD、皮质几何形状和肌肉面积显著减少有关。TBI 和 GHD 是肌肉骨骼缺陷的重要危险因素。需要进一步研究以确定这些缺陷的代谢和骨折影响，并确定在儿童时期接受 alloHSCT 后改善骨骼积累的治疗方法。
