Wang Songqi, Sun Lei, Hu Jing, Zhang Qian, Wang Ou, Jiang Yan, Xia Weibo, Xing Xiaoping, Li Mei
Department of Endocrinology, National Health Commission Key Laboratory of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
Orphanet J Rare Dis. 2025 Apr 6;20(1):162. doi: 10.1186/s13023-025-03663-x.
Hypophosphatasia (HPP) is a rare inherited disorder caused by ALPL gene mutations, with fracture nonunion being a serious complication. This study investigated the effects of teriparatide and asfotase alfa (AA) on femoral fracture healing of an adult patient with HPP, accompanied with a literature review.
A 37-year-old woman wheelchair-bound was diagnosed with HPP due to an extremely low serum alkaline phosphatase (ALP) level (4-10 U/L), who suffered from bilateral femur pain and non-union of femoral shaft fractures on both sides. Compound heterozygous missense mutations (c.382G > A and c.461C > T) were identified in exon5 of ALPL gene. The patient received teriparatide sequential AA therapy. Serum levels of ALP, β-isomerized carboxy-telopeptide of type I collagen (β-CTX) and procollagen type 1 amino-terminal peptide (P1NP), bone mineral density (BMD) and skeletal X-ray were measured during the treatment. Literature was searched by keywords of "Hypophosphatasia", "HPP", "ALPL", "TNSALP", "ALP" combined with "Asfotase alfa", "AA", "enzyme replacement therapy", and "ERT".
After unsuccessful 6-month teriparatide treatment for femoral fracture, AA treatment was initiated, at a dose of 2 mg/kg, 3 times a week. After the first month of AA treatment, serum ALP level increased from 4 to 9206 U/L, and serum calcium and phosphate levels decreased, with increase in PTH, β-CTX, and P1NP levels. After 4 months of AA treatment, her bone pain significantly alleviated, accompanied by significant shortening of the fracture line. After 10 months of AA therapy, the fracture demonstrated complete healing and the patient could walk independently. BMD at lumbar spine and hips was significantly increased. Among 295 adult patients with HPP reported in the literature, 213 (72.2%) exhibited skeletal-related symptoms and 91 (30.8%) presented with bone fractures. In addition to skeletal manifestations, the patients presented with early tooth loss, muscle weakness and ectopic calcification. AA treatment, spanning 9 weeks to 3 years, has been shown to increase ALP levels, promote fracture healing, improve mobility, and alleviate bone pain.
Adult HPP patients mainly present with recurrent or poorly healing fractures, bone pain, and early loss of teeth. AA replacement therapy can effectively promote fracture healing, relieve bone pain, and enhance mobility.
低磷性佝偻病（HPP）是一种由ALPL基因突变引起的罕见遗传性疾病，骨折不愈合是其严重并发症。本研究调查了特立帕肽和阿法骨化醇（AA）对一名成年HPP患者股骨骨折愈合的影响，并进行了文献综述。
一名37岁轮椅依赖女性因血清碱性磷酸酶（ALP）水平极低（4 - 10 U/L）被诊断为HPP，双侧股骨疼痛且双侧股骨干骨折不愈合。在ALPL基因外显子5中鉴定出复合杂合错义突变（c.382G＞A和c.461C＞T）。患者接受了特立帕肽序贯AA治疗。治疗期间测量血清ALP、I型胶原β-异构化羧基端肽（β-CTX）和I型前胶原氨基端肽（P1NP）水平、骨密度（BMD）及骨骼X线。通过“低磷性佝偻病”“HPP”“ALPL”“TNSALP”“ALP”与“阿法骨化醇”“AA”“酶替代疗法”“ERT”等关键词检索文献。
特立帕肽治疗股骨骨折6个月未成功后，开始AA治疗，剂量为2mg/kg，每周3次。AA治疗第1个月后，血清ALP水平从4 U/L升至9206 U/L，血清钙和磷水平下降，PTH、β-CTX和P1NP水平升高。AA治疗4个月后，她的骨痛明显缓解，骨折线明显缩短。AA治疗10个月后，骨折完全愈合，患者可独立行走。腰椎和髋部的骨密度显著增加。文献报道的295例成年HPP患者中，213例（72.2%）有骨骼相关症状，91例（30.8%）出现骨折。除骨骼表现外，患者还出现早期牙齿脱落、肌肉无力和异位钙化。AA治疗9周至3年，已显示可提高ALP水平、促进骨折愈合、改善活动能力并缓解骨痛。
成年HPP患者主要表现为反复骨折或骨折愈合不良、骨痛和早期牙齿脱落。AA替代疗法可有效促进骨折愈合、缓解骨痛并增强活动能力。
