Dahir Kathryn McCrystal, Dunbar Nancy S
Program for Metabolic Bone Disorders at Vanderbilt, Endocrinology and Diabetes, Division of Endocrinology, Vanderbilt University Medical Center, 8210 Medical Center East, 1215 21St Avenue South, Nashville, TN, 37232-8148, USA.
Pediatric Metabolic Bone Program, Division of Pediatric Endocrinology, Connecticut Children's Medical Center, Farmington, CT, 06117, USA.
Curr Osteoporos Rep. 2025 Mar 18;23(1):14. doi: 10.1007/s11914-025-00906-5.
Hypophosphatasia (HPP) is a rare, dento-osseous disorder caused by impaired activity of tissue non-specific alkaline phosphatase (TNSALP), a key enzyme in tissue mineralization. This review provides a clinical perspective on the current medical treatment of both children and adults with HPP.
Dental problems, rickets in children, and osteomalacia in adults are common in HPP. However, disease manifestations in individual patients are exceptionally variable. Recent studies broadened our understanding of HPP symptoms. For example, data showed behavioral health challenges in HPP children, and a large, real-world data set from the Global HPP Registry demonstrated that HPP adults regardless of the time of disease onset exhibit significant disease burden and are broadly affected by non-skeletal impairments, such as pain and chronic fatigue. Treatment for HPP relies on the enzyme replacement asfotase alfa. Small, mostly pediatric trials initially established dosing, safety and efficacy of asfotase alfa, and latest data corroborated the long-term safety and efficacy in both children and pediatric-onset adults. Data from several recent observational studies, including the Global HPP Registry, underscored that asfotase alfa improves physical functions, non-skeletal symptoms such as pain, and quality-of-life (QoL) in adults irrespective of age-of-onset. Clinical use of asfotase alfa is based on prescribing information and evidence-based consensus guidelines. However, recommendations for initiation of therapy are just emerging. Alternatives to asfotase alfa remain limited, but a derivative, efzimfotase alfa, currently undergoes clinical testing. Studies in larger HPP patient populations suggest efficacy of enzyme replacement therapy independent of patient age and time of disease onset.
低磷性佝偻病（HPP）是一种罕见的牙骨疾病，由组织非特异性碱性磷酸酶（TNSALP，组织矿化中的关键酶）活性受损引起。本综述从临床角度阐述了目前对儿童和成人HPP的医学治疗。
牙齿问题、儿童佝偻病和成人骨软化症在HPP中很常见。然而，个体患者的疾病表现差异极大。最近的研究拓宽了我们对HPP症状的认识。例如，数据显示HPP儿童存在行为健康挑战，全球HPP注册中心的一个大型真实世界数据集表明，无论疾病发病时间如何，HPP成人都表现出显著的疾病负担，并广泛受到非骨骼损伤（如疼痛和慢性疲劳）的影响。HPP的治疗依赖于酶替代药物阿法骨化醇。小型试验（大多为儿科试验）最初确定了阿法骨化醇的给药剂量、安全性和疗效，最新数据证实了其在儿童和儿童期发病成人中的长期安全性和疗效。包括全球HPP注册中心在内的几项近期观察性研究的数据强调，无论发病年龄如何，阿法骨化醇均可改善成人的身体功能、疼痛等非骨骼症状以及生活质量（QoL）。阿法骨化醇的临床应用基于处方信息和循证共识指南。然而，关于开始治疗的建议刚刚出现。阿法骨化醇的替代药物仍然有限，但一种衍生物阿法依西美坦目前正在进行临床试验。在更大的HPP患者群体中进行的研究表明，酶替代疗法的疗效与患者年龄和疾病发病时间无关。
