PXE Health and Research Center, University Hospital of Angers, Angers, France; MitoVasc, UMR CNRS 6015 - Inserm 1083, School of Medicine, UBL University, Angers, France.
Department of Rheumatology, University Hospital of Angers, Angers, France.
Bone. 2017 Oct;103:88-92. doi: 10.1016/j.bone.2017.06.017. Epub 2017 Jun 27.
Pseudoxanthoma elasticum (PXE; OMIM 264800, prevalence 1/25,000 to 1/50,000) is an autosomal recessive multisystem disease due to deficiency in ABCC6, an ATP-binding cassette, sub-family C transporter. The PXE phenotype is mainly characterized by progressive ectopic calcification of connective tissues (namely skin, retinal Bruch's membrane and peripheral arteries) but the impact of PXE on bone structure is currently unknown. The present study sought to investigate bone mineralization and its potential link with vascular calcification in a large cohort of PXE patients with inherited mutations of the ABCC6 gene.
96 patients (61 women) matching the PXE criteria participated in this study. Their clinical history and status and bone biological markers were collected. Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry and expressed as T- and Z-scores. Osteoporotic fractures were identified by X-ray, and coronary (CAC) and lower limb arterial calcification (LLAC) scores were determined by CT scan.
44% of the women were menopausal. Osteopenia was disclosed in 46% (17 women) while 23% (9 women) exhibited osteoporosis, 3 with severe osteoporosis. Fractures of an osteoporotic nature were authenticated in 3 patients (1 woman). Markers of bone remodelling processes (CTX, BSAP and osteocalcin) were within the normal range for our laboratory standards. Severe vitamin D deficiency (<25nmol/L) was found in 15%, while 51% exhibited no vitamin D deficiency (vitamin D≥50nmol/L). LLAC and CAC scores were significantly higher in the patients with a low T- and/or Z-score, although this difference disappeared in multivariate analysis with age as a confounding factor. There was no significant difference in LLAC and CAC between PXE patients with and without osteoporotic fractures. There was no statistically significant association between BMD, LLAC and CAC and any of the bone remodelling factors.
This is the first report on the bone mineralization process in PXE patients. Our data shows that PXE patients are not markedly prone to exaggerated bone demineralization and fracture risk, and prevalence of osteoporosis remains within the normal range for the general population. Furthermore, the relationships between LLAC, but not CAC, and BMD with age are similar to those observed in the general population. Therefore, despite its pivotal role in ectopic calcification, ABCC6 deficiency does not interfere with the bone-vascular axis. The lack of PXE-related disturbances between BMD and arterial calcification also supports vitamin D supplementation in PXE patients with vitamin D deficiency. ClinicalTrials.gov Identifier: NCT01446393.
弹性假黄瘤（PXE；OMIM 264800，患病率为 1/25000 至 1/50000）是一种常染色体隐性多系统疾病，由 ABCC6 缺乏引起，ABCC6 是一种 ATP 结合盒，亚家族 C 转运蛋白。PXE 表型主要表现为结缔组织（即皮肤、视网膜布鲁赫膜和外周动脉）的进行性异位钙化，但 PXE 对骨结构的影响目前尚不清楚。本研究旨在调查遗传性 ABCC6 基因突变的 PXE 患者中骨矿化及其与血管钙化的潜在联系。
96 名符合 PXE 标准的患者（61 名女性）参与了本研究。收集了他们的临床病史和状态以及骨生物标志物。通过双能 X 射线吸收法测量骨矿物质密度（BMD），并表示为 T-和 Z-评分。通过 X 射线确定骨质疏松性骨折，通过 CT 扫描确定冠状动脉（CAC）和下肢动脉钙化（LLAC）评分。
44%的女性处于绝经期。46%（17 名女性）显示骨量减少，23%（9 名女性）显示骨质疏松症，3 名严重骨质疏松症。3 名患者（1 名女性）确诊为骨质疏松性骨折。我们实验室标准的骨重塑过程标志物（CTX、BSAP 和骨钙素）在正常范围内。15%存在严重维生素 D 缺乏症（<25nmol/L），而 51%无维生素 D 缺乏症（维生素 D≥50nmol/L）。尽管在考虑年龄作为混杂因素的多变量分析中，这种差异消失，但低 T-和/或 Z-评分的患者的 LLAC 和 CAC 评分明显更高。在有和没有骨质疏松性骨折的 PXE 患者之间，LLAC 和 CAC 没有统计学差异。BMD、LLAC 和 CAC 与任何骨重塑因素之间均无统计学显著关联。
这是首次报道 PXE 患者的骨矿化过程。我们的数据表明，PXE 患者并非明显容易发生过度去矿化和骨折风险，骨质疏松症的患病率仍在普通人群的正常范围内。此外，LLAC 与年龄的关系，而非 CAC，与 BMD 与年龄的关系与普通人群相似。因此，尽管 ABCC6 在异位钙化中起关键作用，但 ABCC6 缺乏不会干扰骨-血管轴。BMD 和动脉钙化之间缺乏 PXE 相关的干扰也支持维生素 D 缺乏的 PXE 患者补充维生素 D。临床试验注册号：NCT01446393。
