Extraskeletal钙化在Hutchinson-Gilford早衰症综合征。
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克利夫兰RH戈登•厘米Baltrusaitis K,马萨罗J, RB达Sr,梁MG,斯奈德B,沃尔特斯M,李X,布拉多克DT, Kleinman我,基兰MW,戈登磅
Extraskeletal钙化在Hutchinson-Gilford早衰症综合征。
骨头。2019年8月,125:103 - 111。doi: 10.1016 / j.bone.2019.05.008。2019年5月8日Epub。
- PubMed ID
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31077852 (在PubMed]
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目的:Hutchinson-Gilford儿童早衰症综合征(hgp),一种罕见的过早衰老疾病,展览extraskeletal钙化检测到射线分析和物理考试。本研究的目的是描述的自然历史和病理生理学异常钙化在计画,并确定是否药物和/或补品在临床试验中测试改变他们的发展。方法:孩子们连续两个临床试验管理1)lonafarnib (n = 26)和2)lonafarnib +普伐他汀+ zoledronic酸(n = 37)在基线(治疗前)进行了研究,在治疗一年,在end-of-therapy基线(3.3 - -4.3年后访问)。钙补充(口服碳酸钙)是在第一年的第二次审判管理,随后被停止。钙化信息来自于身体检查,射线照片,血清和尿生化措施。两个皮肤取出钙化的矿物含量是由x射线衍射。结果:Extraskeletal钙化检测放射学在12/39(31%)的患者在基线。展示钙化的几率随着年龄的增加(p = 0.045)。lonafarnib的几率被收到影响,普伐他汀,zoledronate疗法。然而,补充政府的碳酸钙,与所有三个治疗药物,患钙化的几率明显增加(p = 0.009),与补充的停药后的停滞不前的状态。 Composition analysis of calcinosis cutis showed hydroxyapatite similar to bone. Although serum calcium, phosphorus, and parathyroid hormone (PTH) were within normal limits at baseline and on-therapy, PTH increased significantly after lonafarnib initiation (p<0.001). Both the urinary calcium/creatinine ratio and tubular reabsorption of phosphate (TRP) were elevated at baseline in 22/39 (56%) and 31/37 (84%) evaluable patients, respectively, with no significant changes while on-therapy. The mean calciumxphosphorus product (CaxPi) was within normal limits, but plasma magnesium decreased over both clinical trials. Fibroblast growth factor 23 (FGF23) was lower compared to age-matched controls (p=0.03). CONCLUSIONS: Extraskeletal calcifications increased with age in children with HGPS and were composed of hydroxyapatite. The urinary calcium/creatinine ratio and TRP were elevated for age while FGF23 was decreased. Magnesium decreased and PTH increased after lonafarnib therapy which may alter the ability to mobilize calcium. These findings demonstrate that children with HGPS with normal renal function and an unremarkable CaxPi develop extraskeletal calcifications by an unidentified mechanism that may involve decreased plasma magnesium and FGF23. Calcium carbonate accelerated their development and is, therefore, not recommended for routine supplementation in these children.
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