EVALUATION OF A ROLE FOR 1,25-DIHYDROXYVITAMIN-D3 IN THE PATHOGENESIS AND TREATMENT OF X-LINKED HYPOPHOSPHATEMIC RICKETS AND OSTEOMALACIA
EVALUATION OF A ROLE FOR 1,25-DIHYDROXYVITAMIN-D3 IN THE PATHOGENESIS AND TREATMENT OF X-LINKED HYPOPHOSPHATEMIC RICKETS AND OSTEOMALACIA
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DOI：
10.1172/jci109930
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发表时间：
1980-01-01
影响因子：
15.9
通讯作者：
HARRELSON, JM
中科院分区：
文献类型：
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作者：
DREZNER, MK;LYLES, KW;HARRELSON, JM
虽然磷酸盐肾转运缺陷似乎是X连锁低磷血症性佝偻病和骨软化症发病机制的主要异常，但一些观察结果表明，肾性磷酸盐消耗和低磷血症不能单独解释这种疾病的异常特征。研究了维生素D代谢异常在这种疾病发病机制中的潜在作用以及1，25-二羟维生素D3治疗对这种疾病和骨软化症的生化异常特征的影响。4名未接受治疗的患者，年龄14-30岁，有正常钙血症（9.22 ± 0.01）。0.06 mg/dl）;低磷酸盐血症（2.25 . ±. 0.11每升肾小球滤液中磷酸盐重吸收的肾小管最大值降低（2.12 ± 0.001 mg/dl）。0.09 mg/dl）;正常血清免疫反应性甲状旁腺激素浓度;负磷酸盐平衡;和骨软化症的骨活检证据。血清25-羟基维生素D3浓度为33.9 ± 0.001。7.2 ng/ml，尽管有低磷酸盐血症，但1，25-二羟维生素D3的血清水平没有增加，而是正常的30.3 ±。2.8 pg/ml。维生素D代谢的异常稳态可能是X连锁低磷血症性佝偻病/骨软化症表型表达的第二个核心缺陷。这一假设得到了3例受试者对药理学量的1，25-二羟维生素D3治疗的长期反应评价的支持。治疗方案导致血清1，25-二羟维生素D水平升高至超生理范围内的值。血清磷酸盐和肾小管最大磷酸盐重吸收每升肾小球滤液增加接近正常，而磷酸盐平衡变得显着积极。重复骨活检显示，治疗对疾病的骨软化成分产生了积极影响，导致矿化前沿活动正常化。这种活性维生素D代谢的血清水平与矿化前沿活性之间的线性关系表明，1，25-二羟基维生素D3在骨软化骨矿化中起着重要作用。1，25-二羟维生素D3的相对缺乏是X连锁低磷血症性佝偻病和骨软化症发病机制中的一个因素，并可能调节这种疾病的表型表达。
Although a defect in renal transport of phosphate seems well established as the primary abnormality underlying the pathogenesis of X-linked hypophosphatemic rickets and osteomalacia, several observations indicate that renal phosphate wasting and hypophosphatemia cannot solely account for the spectrum of abnormalities characteristic of this disease. The potential role of abnormal vitamin D metabolism in the pathogenesis of this disorder and the effect of 1,25-dihydroxyvitamin D3 therapy on the biochemical abnormalities characteristic of this disease and osteomalacia were investigated. Four untreated patients, ages 14-30 yr, had normocalcemia (9.22 .+-. 0.06 mg/dl); hypophosphatemia (2.25 .+-. 0.11 mg/dl); a decreased renal tubular maximum for the reabsorption of phosphate per liter of glomerular filtrate (2.12 .+-. 0.09 mg/dl); normal serum immunoreactive parathyroid hormone concentration; negative phosphate balance; and bone biopsy evidence of osteomalacia. The serum 25-hydroxyvitamin D3 concentration was 33.9 .+-. 7.2 ng/ml and, despite hypophosphatemia, the serum level of 1,25-dihydroxyvitamin D3 was not increased, but was normal at 30.3 .+-. 2.8 pg/ml. Abnormal homeostasis of vitamin D metabolism might be a 2nd defect central to the phenotypic expression of X-linked hypophosphatemic rickets/osteomalacia. This hypothesis was supported by evaluation of the long-term response to pharmacological amounts of 1,25-dihydroxyvitamin D3 therapy in 3 subjects. The treatment regimen resulted in elevation of the serum 1,25-dihydroxyvitamin D levels to values in the supraphysiological range. The serum phosphate and renal tubular maximum for the reabsorption of phosphate per liter of glomerular filtrate increased towards normal whereas the phosphate balance became markedly positive. Repeat bone biopsies revealed that therapy had positively affected the osteomalacic component of disease, resulting in normalization of the mineralization front activity. A central role for 1,25-dihydroxy-vitamin D3 in the mineralization of the osteomalacia bone is suggested by the linear relationship between the serum level of this active vitamin D metabolism and the mineralization front activity. A relative deficiency of 1,25-dihydroxyvitamin D3 is a factor in the pathogenesis of X-linked hypophosphatemic rickets and osteomalacia and may modulate the phenotypic expression of this disease.