Laroche Michel, Couture Guillaume, Faruch Marie, Ruyssen-Witrand Adeline, Porquet-Bordes Valérie, Salles Jean Pierre, Degboe Yannick
Centre de Rhumatologie du Centre Hospitalo-Universitaire de Toulouse [Rheumatology Center of Toulouse University Hospital] Toulouse France.
Service de Radiologie du Centre Hospitalo-Universitaire de Toulouse [Department of Radiology of Toulouse University Hospital] Toulouse France.
JBMR Plus. 2021 Mar 5;5(4):e10449. doi: 10.1002/jbm4.10449. eCollection 2021 Apr.
Treatment with asfotase alfa has transformed the prognosis of hypophosphatasia in children and improves the bone and muscle signs in adults. The doses used in adults are the same as in children, whereas bone remodeling is different between them. We report on the cases of two patients treated with 1 mg/kg/day of asfotase alfa who developed spinal cord compression from spinal ossifications during treatment. The first patient, 50 years old, presented after 2 years of treatment with quadraparesis secondary to an increase in ossifications of the cervical vertebral ligaments. The neurological damage was resolved after laminectomy, and the patient was then treated for 18 months with doses of 80 mg per week, without recurrence of the bone and muscle signs. The second patient, 26 years old, 78 kg, developed pain and cervical stiffness with pyramidal tract irritation secondary to ossifications of the vertebral ligaments. This improved with a reduction of doses to 80 mg/week, which then, after 6 months of follow-up, enabled maintained improvement of the bone and muscle pain that was initially obtained. To our knowledge, these are the first reported cases of increased spinal ligamentous ossifications with neurological complications. Biological monitoring in adults does not seem to enable asfotase alfa doses to be adjusted. The levels of serum alkaline phosphatase (ALP) while on the recommended treatment of 1 mg/kg/day are significantly supraphysiological (5000 to 20,000 IU) and the assays of pyrophosphate and pyridoxal phosphate are not correlated with clinical efficacy. In both of our patients, the treatment with 80 mg of asfotase alfa per week, which was proposed after the occurrence of spinal complications, seemed as effective, after a follow-up of 18 months and 6 months, as the initial treatment for improving the bone and muscle signs, and could be provided as "attack" doses after healing of the pseudoarthroses. © 2021 American Society for Bone and Mineral Research © 2020 The Authors. published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.
阿法骨化醇酶治疗改变了儿童低磷性骨软化症的预后，并改善了成人的骨骼和肌肉症状。成人使用的剂量与儿童相同，然而两者之间的骨重塑情况有所不同。我们报告了两名接受每日1mg/kg阿法骨化醇酶治疗的患者病例，他们在治疗期间因脊柱骨化而出现脊髓受压。第一名患者为50岁，在接受2年治疗后出现四肢瘫，继发于颈椎韧带骨化增加。椎板切除术后神经损伤得到缓解，随后患者接受每周80mg剂量治疗18个月，骨骼和肌肉症状未复发。第二名患者为26岁，体重78kg，因椎体韧带骨化继发疼痛和颈部僵硬以及锥体束激惹。剂量减至每周80mg后病情改善，在随访6个月后，最初出现的骨骼和肌肉疼痛得以持续改善。据我们所知，这些是首次报道的脊柱韧带骨化增加伴神经并发症的病例。成人的生物学监测似乎无法用于调整阿法骨化醇酶的剂量。在推荐的每日1mg/kg治疗剂量下，血清碱性磷酸酶（ALP）水平显著高于生理水平（5000至20000IU），焦磷酸盐和磷酸吡哆醛的检测与临床疗效无关。在我们的两名患者中，脊柱并发症发生后采用每周80mg阿法骨化醇酶治疗，在随访18个月和6个月后，似乎与初始治疗改善骨骼和肌肉症状的效果相同，并且在假关节愈合后可作为“冲击”剂量使用。©2021美国骨与矿物质研究学会 ©2020作者。由Wiley Periodicals LLC代表美国骨与矿物质研究学会出版。
