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Abstract：
Background: Autosomal recessive osteopetrosis (ARO) is a rare genetic disorder of bone metabolism, primarily affecting the remodelling function of osteoclasts. Haematopoietic stem cell transplantation (HSCT) is the first-line treatment for ARO. Traditional tools for the assessment of therapeutic response, such as measuring donor chimerism, do not provide information on bone remodelling. The use of bone turnover markers (BTMs) might be ideal. Here, we report a case of a paediatric ARO patient undergoing successful HSCT. Methods: For the evaluation of donor-derived osteoclast activity and skeletal remodelling throughout the transplantation, the bone resorption marker β-CTX (β-C-terminal telopeptide) was used. Results: The low baseline level of β-CTX markedly increased after transplantation and remained in the elevated range even after 3 months. Donor-derived osteoclast activity reached its new baseline level around the 50th percentile range after 5 months and proved to be stable during the 15-month follow-up time. The apparent increase of the baseline osteoclast activity after HSCT was in consonance with the radiographic improvement of the disease phenotype and the correction of bone metabolic parameters. Despite the successful donor-derived osteoclast recovery, craniosynostosis developed, and reconstructive surgery had to be performed. Conclusions: The use of β-CTX may be of aid in assessing osteoclast activity throughout the transplantation. Further studies could help to establish the extended BTM profile of ARO patients using the available osteoclast- and osteoblast-specific markers.
摘要：
背景:常染色体隐性遗传性骨硬化病(ARO)是一种罕见的骨代谢遗传病,主要影响破骨细胞的重塑功能。造血干细胞移植（HSCT）是ARO的一线治疗方法。评估治疗反应的传统工具，例如测量供体嵌合体，不要提供有关骨骼重塑的信息。使用骨转换标记（BTM）可能是理想的。这里,我们报告了一例儿科ARO患者成功接受HSCT的病例.方法：为了评估整个移植过程中供体来源的破骨细胞活性和骨骼重塑，使用骨吸收标志物β-CTX(β-C末端端肽)。结果：移植后β-CTX的低基线水平显着增加，甚至在3个月后仍保持在升高的范围内。供体来源的破骨细胞活性在5个月后达到其大约第50百分位数范围的新基线水平，并且在15个月的随访时间内被证明是稳定的。HSCT后基线破骨细胞活性的明显增加与疾病表型的影像学改善和骨代谢参数的校正相一致。尽管成功的供体来源的破骨细胞恢复，颅骨融合发展，必须进行重建手术。结论：使用β-CTX可能有助于评估整个移植过程中的破骨细胞活性。进一步的研究可能有助于使用可用的破骨细胞和成骨细胞特异性标志物建立ARO患者的扩展BTM谱。
