Tsiantouli Eleni, Biver Emmanuel, Chevalley Thierry, Petrovic Robert, Hannouche Didier, Ferrari Serge
Division of Bone Diseases, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Institute of Medical Biology, Genetics and Clinical Genetics, University Hospital Bratislava, Bratislava, Slovakia.
Calcif Tissue Int. 2022 Jun;110(6):703-711. doi: 10.1007/s00223-022-00949-1. Epub 2022 Feb 28.
Hypophosphatasia (HPP) is a rare genetic disorder characterized by low serum alkaline phosphatase (ALP), its manifestations may include atypical femoral fractures (AFF). However, the prevalence of low serum ALP and HPP in patients with AFF remains unknown. We retrospectively analyzed ALP levels and clinical manifestations compatible with HPP in 72 adult patients with confirmed AFF by chart review. ALP values were compared with those of a control group of patients with prior proximal femoral fracture during antiresorptive treatment (n = 20). Among the AFF patients, 18 (25%) had at least one serum ALP value ≤ 40 IU/L, although in all but one case, at least one ALP value > 40 IU/L was also detected at another time point. Most low ALP values were associated with antiresorptive treatment (P = 0.049) and lowest levels of ALP did not differ between the AFF and the control groups (P = 0.129). However, low ALP values among AFF patients were associated with a higher rate of bilateral AFF (50% vs 22%, P = 0.025), metatarsal fracture (33% vs 7%, P = 0.006), and with trends for more frequent use of glucocorticoid (22% vs 8%, P = 0.089) and proton pump inhibitor (61% vs 44%, P = 0.220). In one AFF patient with low ALP and clinical suspicion of HPP, a rare pathogenic heterozygous variant of the ALPL gene was identified. In conclusion, low ALP values are common among subjects with AFF and mainly related to concomitant antiresorptive medication. Hence, low serum ALP has low specificity for HPP among AFF patients.
低磷性骨软化症（HPP）是一种罕见的遗传性疾病，其特征为血清碱性磷酸酶（ALP）水平降低，其表现可能包括非典型股骨骨折（AFF）。然而，AFF患者中血清ALP降低和HPP的患病率仍不清楚。我们通过病历回顾对72例确诊为AFF的成年患者中与HPP相符的ALP水平和临床表现进行了回顾性分析。将ALP值与抗吸收治疗期间既往股骨近端骨折患者的对照组（n = 20）进行比较。在AFF患者中，18例（25%）至少有一次血清ALP值≤40 IU/L，尽管除1例病例外，在其他时间点也检测到至少一次ALP值>40 IU/L。大多数低ALP值与抗吸收治疗相关（P = 0.049），AFF组和对照组的最低ALP水平无差异（P = 0.129）。然而，AFF患者中的低ALP值与双侧AFF发生率较高（50%对22%，P = 0.025）、跖骨骨折（33%对7%，P = 0.006）相关，并且糖皮质激素（22%对8%，P = 0.089）和质子泵抑制剂（61%对44%，P = 0.220）的使用频率有更高的趋势。在1例ALP低且临床怀疑为HPP的AFF患者中，鉴定出ALPL基因的一种罕见致病杂合变异。总之，低ALP值在AFF患者中很常见，主要与同时使用抗吸收药物有关。因此，血清ALP降低在AFF患者中对HPP的特异性较低。
