X连锁低磷血症(XLH)是一种遗传性疾病,主要与PHEX基因突变相关,可增加FGF23血清水平。导致成人低磷酸盐血症和骨软化症,虽然受影响的儿童,此外,发展为病。大多数患有XLH的成年人由于与肢体畸形相关的慢性骨和关节痛而遭受生活质量下降和身体残疾。早期骨关节炎,功能不全骨折延迟愈合,和病。牙齿感染,肌肉功能障碍,耳聋也很常见。目前的治疗包括每天口服2-5次磷酸盐联合活性维生素D,通常耐受性差,立即消化副作用,负责不良的合规性。从长远来看,它可能导致肾钙化和甲状旁腺功能亢进。Burosumab,抗FGF23阻断抗体,在许多国家被批准用于治疗XLH儿童。一项为期24周的随机安慰剂对照试验,随后对134例接受1mg/kgburosumab/4周治疗的XLH成人进行了相同持续时间的开放标签期.在burosumab治疗期间,94%的患者使血清磷酸盐值正常化,而安慰剂组为7%。与安慰剂治疗的患者相比,骨折愈合增加了16.7倍。所有疼痛和残疾测试均以时间依赖性方式显着改善。在分析成对骨活检的单臂纵向研究中,Burosumab48周改善了骨软化症的组织学病变。另一个单臂,开放标签研究调查了20例随访3.2年的成年患者服用burosumab的长期安全性和有效性.Burosumab对疼痛和残疾评分以及骨重塑标志物有益。没有重大副作用,特别是没有高磷酸盐血症的报道。总的来说,在患有XLH临床和/或生物学并发症的成年患者中,burosumab的获益/风险比为阳性。Burosumab纠正低磷酸盐血症,促进骨折愈合,并对XLH诱导的主观疼痛和残疾症状产生适度但显著的影响。
■常规治疗和burosumab对X连锁低磷酸盐血症成人的影响。X连锁低磷酸盐血症(XLH)是一种遗传起源的疾病,会影响矿化组织(骨骼和牙齿)并损害肌肉功能。它诱导血液磷酸盐水平的降低。这导致骨骼矿化和愈合缓慢的不足骨折,与以自发性牙脓肿为特征的不良牙齿健康相关。患有XLH的成年人患有慢性疼痛和肢体畸形,这改变了他们的生活质量。目前,他们每天服用维生素D和几种每日剂量的磷酸盐。这种治疗可能会导致甲状旁腺功能障碍和肾脏中的矿物质沉积。如果没有严密监控,这些副作用可能导致三级甲状旁腺功能亢进和需要甲状旁腺手术,或可能发展为慢性肾脏疾病的肾钙质沉着症。Burosumab是一种阻断FGF23作用的抗体,FGF23是在血液中循环过量的因子,并负责XLH中的磷酸盐肾渗漏。三项研究表明burosumab,每4周注射一次,是有效和安全的治疗成人XLH。
X-linked hypophosphatemia (XLH) is a genetic disease mostly related to PHEX gene mutations which increases FGF23 serum levels, leading to hypophosphatemia and osteomalacia in adults, while affected children, in addition, develop rickets. Most of adults with XLH suffer from reduced quality of life and physical disability due to chronic bone and joint pain related to limb deformities, early osteoarthritis, delayed-healing of insufficiency fractures, and enthesopathies. Dental infections, muscle dysfunction, and deafness are also frequent. The current treatment consists of 2-5 times daily oral administration of phosphate combined to active vitamin D, often badly tolerated with immediate digestive side effects, responsible for poor compliance. In the long term, it may induce nephrocalcinosis and hyperparathyroidism.
Burosumab, an anti-FGF23 blocking antibody, was approved for treating children with XLH in many countries. A randomized 24-week-long placebo-controlled trial, followed by an open-label period of equal duration was conducted in 134 XLH adults treated with 1 mg/kg burosumab/4 weeks. During burosumab treatment, 94% of the patients normalized serum phosphate values versus 7% in the placebo group. Fracture healing was increased 16.7 times compared with placebo-treated patients. All pain and disability tests improved significantly in a time-dependent manner.
Burosumab for 48 weeks improved histological lesions of osteomalacia in a single-arm longitudinal study analyzing paired bone biopsies. Another single-arm, open-label study investigated the long-term safety and efficacy of
burosumab in 20 adult patients followed for 3.2 years.
Burosumab was beneficial on pain and disability scores and on bone remodeling markers. No major side effects especially no hyperphosphatemic episodes were reported. Overall, the benefit/risk ratio of burosumab is positive in adult patients with clinical and/or biological complications of XLH.
Burosumab corrects hypophosphatemia, promotes fracture healing, and induces a modest but significant effect on XLH-induced subjective pain and disability symptoms.
UNASSIGNED: Effects of conventional treatment and burosumab in adults with X-linked hypophosphatemia.X-linked hypophosphatemia (XLH) is a disease of genetic origin that affects mineralized tissues (skeleton and teeth) and impairs muscle function. It induces a decrease in blood phosphate levels. This leads to under mineralization of bones and insufficiency fractures that heal slowly, associated with poor dental health characterized by spontaneous dental abscesses. Adults with XLH suffer from chronic pain and limb deformities that alter their quality of life. They are currently treated with daily administration of vitamin D and several daily doses of phosphate. This treatment may induce parathyroid gland dysfunction and mineral deposits in the kidney. If not tightly monitored, these side effects may lead to tertiary hyperparathyroidism and the need for parathyroid gland surgery, or to nephrocalcinosis which may proceed to chronic kidney disease. Burosumab is an antibody that blocks the action of FGF23 the factor that circulates in excess in blood and is responsible for phosphate renal leak in XLH. Three studies demonstrated that burosumab, injected every 4 weeks, is efficient and safe for treating adults with XLH.