Rosenthal D I, Doppelt S H, Mankin H J, Dambrosia J M, Xavier R J, McKusick K A, Rosen B R, Baker J, Niklason L T, Hill S C
Department of Radiology, Massachusetts General Hospital, Boston 02114, USA.
Pediatrics. 1995 Oct;96(4 Pt 1):629-37.
Reversal of the hematologic and visceral abnormalities characteristic of Gaucher disease, the most common lipid storage disorder, with biweekly infusions of macrophage-targeted glucocerebrosidase (glucosylceramidase) is well documented. The extent to which the skeleton responds to enzyme replacement therapy has not been systematically investigated.
To assess the skeletal response to enzyme replacement therapy, we treated 12 patients with type 1 Gaucher disease, who had intact spleens, with macrophage-targeted glucocerebrosidase. The initial dose of enzyme was 60 U/kg body weight every 2 weeks for 24 months, followed by reduction in dosage to 30 and then 15 U/kg body weight every 2 weeks, each for 9 months.
The lipid composition of bone marrow, determined by direct chemical analysis, began to improve after 6 months of treatment at a time when noninvasive imaging studies showed no significant changes. By 42 months, improvement in marrow composition was demonstrable on all noninvasive, quantitative imaging modalities (magnetic resonance score, quantitative xenon scintigraphy, and quantitative chemical shift imaging) used in this study. Quantitative chemical shift imaging, the most sensitive technique, demonstrated a dramatic normalization of the marrow fat content in all patients. Net increases in either cortical or trabecular bone mass, as assessed by combined cortical thickness measurements and dual-energy quantitative computed tomography, respectively, occurred in 10 patients.
Prolonged treatment over 3 1/2 years with macrophage-targeted glucocerebrosidase produces objective reversal of disease in both the axial and appendicular skeleton in patients with Gaucher disease. Marked improvement occurs in marrow composition and bone mass in both children and adults.
每两周输注一次靶向巨噬细胞的葡萄糖脑苷脂酶（葡糖神经酰胺酶）可逆转戈谢病（最常见的脂质贮积病）的血液学和内脏异常，这已得到充分证实。骨骼对酶替代疗法的反应程度尚未得到系统研究。
为评估骨骼对酶替代疗法的反应，我们对12例1型戈谢病且脾脏完整的患者使用靶向巨噬细胞的葡萄糖脑苷脂酶进行治疗。酶的初始剂量为每2周60 U/kg体重，持续24个月，随后剂量减至每2周30 U/kg体重，再减至每2周15 U/kg体重，各持续9个月。
通过直接化学分析确定的骨髓脂质成分在治疗6个月后开始改善，此时非侵入性成像研究未显示出明显变化。到42个月时，本研究中使用的所有非侵入性定量成像方式（磁共振评分、定量氙闪烁扫描和定量化学位移成像）均显示骨髓成分有所改善。定量化学位移成像作为最敏感的技术，显示所有患者的骨髓脂肪含量显著恢复正常。分别通过皮质厚度测量和双能定量计算机断层扫描评估，10例患者的皮质骨或小梁骨量出现净增加。
对戈谢病患者使用靶向巨噬细胞的葡萄糖脑苷脂酶进行超过3年半的长期治疗，可使轴向和附属骨骼的疾病出现客观逆转。儿童和成人的骨髓成分和骨量均有显著改善。
