van Dussen L, Lips P, van Essen H W, Hollak C E M, Bravenboer N
Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, The Netherlands.
Endocrine Section, Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands.
Blood Cells Mol Dis. 2014 Sep;53(3):118-23. doi: 10.1016/j.bcmd.2014.05.005. Epub 2014 Jun 16.
Gaucher disease (GD) is a lysosomal storage disorder characterized by accumulation of glucosylceramide in macrophages, so-called Gaucher cells, as a result of a deficiency of the lysosomal enzyme glucocerebrosidase. Bone complications are an important cause of morbidity of GD and are thought to result from imbalance in bone remodeling. Bone manifestations among GD patients demonstrate a large variation including increased osteoclastic bone resorption, low bone formation and osteonecrosis. The purpose of the current case series is to describe the histological features observed in undecalcified bone samples, obtained from three GD patients, and evaluate the relationship with clinical features in these patients. Bone fragments were obtained from three adult type 1 GD patients with variable degrees of bone disease during orthopedic surgery. Specimens were embedded without prior decalcification in methylmethacrylate and prepared for histology according to standardized laboratory procedures. Histology revealed a heterogeneous pattern of bone involvement. High cellularity of bone marrow, abundant presence of Gaucher cells (GCs) and high turnover were observed in a patient with a history of multiple bone complications, while minimal bone turnover and few GCs were detected in the mildest affected patient in this series. An intermediate picture with relatively low bone turnover and a substantial amount of Gaucher cells was demonstrated in the third, moderately affected patient. No gross abnormalities in three biochemical markers of bone turnover (osteocalcin, N-terminal propeptide of type 1 procollagen and type 1 collagen C-terminal telopeptide) were noted. Plastic embedding and subsequent Goldner and TRAP staining offered a unique possibility to study bone histological findings in GD. Our data show that bone manifestations in GD may vary both clinically as well as histologically and bone disease in GD will likely require a personalized approach.
戈谢病（GD）是一种溶酶体贮积症，其特征是由于溶酶体酶葡萄糖脑苷脂酶缺乏，导致葡糖神经酰胺在巨噬细胞（即所谓的戈谢细胞）中蓄积。骨骼并发症是GD发病的重要原因，被认为是由骨重塑失衡所致。GD患者的骨骼表现差异很大，包括破骨细胞性骨吸收增加、骨形成减少和骨坏死。本病例系列的目的是描述从三名GD患者获取的未脱钙骨样本中观察到的组织学特征，并评估这些患者的组织学特征与临床特征之间的关系。在骨科手术期间，从三名患有不同程度骨病的成年1型GD患者获取了骨碎片。标本在不预先脱钙的情况下包埋于甲基丙烯酸甲酯中，并根据标准化实验室程序进行组织学制备。组织学显示骨受累情况呈异质性模式。在一名有多次骨并发症病史的患者中，观察到骨髓细胞增多、大量戈谢细胞（GCs）存在和高周转率，而在本系列中受影响最轻的患者中检测到最小的骨周转率和少量GCs。在第三名中度受影响的患者中，显示出骨周转率相对较低和大量戈谢细胞的中间情况。未发现骨转换的三种生化标志物（骨钙素、I型前胶原N端前肽和I型胶原C端肽）有明显异常。塑料包埋及随后的戈德纳染色和抗酒石酸酸性磷酸酶（TRAP）染色为研究GD的骨组织学发现提供了独特的可能性。我们的数据表明，GD的骨骼表现在临床和组织学上都可能有所不同，GD的骨病可能需要个性化的治疗方法。
