Section on Skeletal Disorders and Mineral Homeostasis, National Institutes of Dental and Craniofacial Research (NIDCR), National Institutes of Health (NIH), Bethesda, MD, USA.
Endocrinology Department, School of Medicine, Pontificia Universidad Catolica de Chile, Santiago, Chile.
J Bone Miner Res. 2018 Oct;33(10):1870-1880. doi: 10.1002/jbmr.3522. Epub 2018 Jul 20.
Nephropathic cystinosis is a rare lysosomal storage disorder. Patients present in the first year of life with renal Fanconi syndrome that evolves to progressive chronic kidney disease (CKD). Despite the multiple risk factors for bone disease, the frequency and severity of skeletal disorders in nephropathic cystinosis have not been described. We performed systematic bone and mineral evaluations of subjects with cystinosis seen at the NIH (n = 30), including history and physical examination, serum and urine biochemistries, DXA, vertebral fracture assessment, skeletal radiographs, and renal ultrasound. Additionally, histomorphometric analyses are reported on six subjects seen at the UCLA Bone and Mineral Metabolism Clinic. In NIH subjects, mean age was 20 years (range, 5 to 44 years), 60% were CKD stages G1 to G4, and 40% had a renal transplant. Mean bone mineral density (BMD) Z-scores were decreased in the femoral neck, total hip, and 1/3 radius (p < 0.05). Low bone mass at one or more sites was present in 46% of subjects. Twenty-seven percent of subjects reported one or more long bone fractures. Thirty-two percent of subjects had incidental vertebral fractures, which were unrelated to transplant status. Long-bone deformity/bowing was present in 64%; 50% had scoliosis. Diffuse osteosclerosis was present in 21% of evaluated subjects. Risk factors included CKD, phosphate wasting, hypercalciuria, secondary hyperparathyroidism, hypovitaminosis D, male hypogonadism, metabolic acidosis, and glucocorticoid/immunosuppressive therapy. Sixty-one percent of the non-transplanted subjects had ultrasonographic evidence of nephrocalcinosis or nephrolithiasis. Histomorphometric analyses showed impaired mineralization in four of six studied subjects. We conclude that skeletal deformities, decreased bone mass, and vertebral fractures are common and relevant complications of nephropathic cystinosis, even before renal transplantation. Efforts to minimize risk factors for skeletal disease include optimizing mineral metabolism and hormonal status, combined with monitoring for nephrocalcinosis/nephrolithiasis. © 2018 This article is a U.S. Government work and is in the public domain in the USA.
遗传性胱氨酸病是一种罕见的溶酶体贮积症。患者在生命的第一年即出现肾范可尼综合征，随后进展为进行性慢性肾脏病（CKD）。尽管存在多种骨骼疾病的危险因素，但遗传性胱氨酸病患者的骨骼疾病的频率和严重程度尚未得到描述。我们对 NIH 就诊的胱氨酸病患者（n=30）进行了系统的骨骼和矿物质评估，包括病史和体格检查、血清和尿液生化检查、双能 X 线吸收法（DXA）、椎体骨折评估、骨骼 X 线摄影和肾脏超声检查。此外，还报告了在 UCLA 骨骼和矿物质代谢诊所就诊的 6 名患者的组织形态计量学分析。在 NIH 患者中，平均年龄为 20 岁（范围为 5 至 44 岁），60%为 CKD 1 至 4 期，40%接受了肾脏移植。股骨颈、全髋关节和 1/3 桡骨的骨矿物质密度（BMD）Z 评分降低（p<0.05）。46%的患者存在一处或多处骨量减少。27%的患者报告有一处或多处长骨骨折。32%的患者存在偶然的椎体骨折，与移植状态无关。64%的患者存在长骨畸形/弯曲，50%的患者存在脊柱侧凸。21%接受评估的患者存在弥漫性骨质硬化。危险因素包括 CKD、磷酸盐丢失、高钙尿症、继发性甲状旁腺功能亢进、维生素 D 缺乏、男性性腺功能减退、代谢性酸中毒和糖皮质激素/免疫抑制剂治疗。61%未接受移植的患者有超声检查证实的肾钙质沉着症或肾结石。组织形态计量学分析显示，在 6 名研究对象中有 4 名存在矿化受损。我们的结论是，骨骼畸形、骨量减少和椎体骨折是遗传性胱氨酸病的常见且重要的并发症，甚至在进行肾脏移植之前就已经存在。为减少骨骼疾病的危险因素，应努力优化矿物质代谢和激素状态，并结合对肾钙质沉着症/肾结石的监测。
