X-linked hypophosphatemia (XLH) is characterized by rickets and osteomalacia, caused by inactivating mutations in the Phosphate-regulating endopeptidase homolog X-linked (PHEX) gene. With aging, adult patients develop paradoxical heterotopic calcifications of tendons and ligaments at their insertion sites (enthesophytes), and joint alterations. Understanding the progression of this structural damage that severely affects patients’ quality of life will help to improve the management of XLH. Here, we characterized the occurrence of enthesophytes and joint alterations through a 12 month in vivo micro-CT follow-up in the Hyp mouse, a murine model of XLH (n = 5 mice per group). Similar to adult patients with XLH, Hyp mice developed calcaneal enthesophytes, hip joint alterations, erosions of the sacroiliac joints and periarticular calcifications. These lesions were already present at month 3 and gradually worsened over time. In sharp contrast, no abnormalities were observed in control mice at early time points. Histological analyses confirmed the presence of bone erosions, calcifications and expansion of mineralizing enthesis fibrocartilage in Hyp mice and their absence in controls and suggested that new bone formation is driven by altered mechanical strain. Interestingly, despite a strong deformation of the curvature, none of the Hyp mice displayed enthesophyte at the spine. Peripheral enthesophytes and joint alterations develop at the early stages of the disease and gradually worsen overtime. Overall, our findings highlight the relevance of this preclinical model to test new therapies aiming to prevent bone and joint complications in XLH.

X连锁性低磷血症（XLH）的特征在于ets症和骨软化症，是由于磷酸盐调节内肽酶同源X连锁（PHEX）基因的失活引起的。随着年龄的增长，成年患者在其插入部位（食道植物）会出现腱和韧带的反常异位钙化，以及关节改变。了解这种严重影响患者生活质量的结构性损伤的进展将有助于改善XLH的管理。在这里，我们描述了在12个月内内生植物和关节改变的发生体内 微型CT随访 炒作 小鼠，XLH（ñ=每组5只小鼠）。与成人XLH患者相似，炒作小鼠发展了跟骨内生植物，髋关节改变，the关节侵蚀和关节周围钙化。这些病变已在第3个月出现，并随着时间逐渐恶化。与之形成鲜明对比的是，在早期时间点的对照小鼠中未观察到异常。组织学分析证实存在骨侵蚀，钙化和矿化性纤维软骨扩张。炒作小鼠及其在对照组中的缺失，表明新的骨骼形成是由改变的机械应变驱动的。有趣的是，尽管曲率发生了很大的变形，但没有一个炒作小鼠在脊柱处显示出附生植物。在疾病的早期阶段发展周围的共生植物和关节改变，并随着时间的推移逐渐恶化。总体而言，我们的研究结果突显了该临床前模型与测试旨在预防XLH骨骼和关节并发症的新疗法的相关性。