Clinical Trial Unit, Orthopedic Department, University of Wuerzburg, Brettreichstrasse 11, 97074, Wuerzburg, Germany.
Osteoporos Int. 2021 Feb;32(2):377-385. doi: 10.1007/s00198-020-05612-9. Epub 2020 Sep 2.
In adult hypophosphatasia (HPP) patients, elevated lumbar spine dual X-ray absorptiometry (DXA) values are associated with markers of disease severity and disease-specific fracture risk while femoral bone mineral density (BMD), being largely unaffected by the disease severity, may still be useful to monitor other causes of increased fracture risk due to low BMD.
Hypophosphatasia (HPP) is a rare inherited metabolic disorder due to deficient activity of the tissue-nonspecific alkaline phosphatase (TNAP). Clinical manifestation in adult HPP patients is manifold including an increased risk for fractures, but data regarding clinical significance of DXA measurement and associations with fracture risk and disease severity is scarce.
Retrospective single-center analysis of DXA scans in patients with confirmed HPP (documented mutation, clinical symptoms, low alkaline phosphatase activity). Further data evaluation included disease-related fractures, laboratory results (alkaline phosphatase, pyridoxalphosphate, phosphoethanolamine), and medical history.
Analysis included 110 patients (84 female, mean age of 46.2 years) of whom 37.3% (n = 41) were harboring two mutations. Average T-Score level at the lumbar spine was - 0.1 (SD 1.9), and mean total hip T-Score was - 1.07 (SD 0.15). Both lower ALP activity and higher substrate levels (pyridoxalphosphate and phosphoethanolamine) were significantly correlated with increased lumbar spine T-Score levels (p < 0.001) while BMD at the hip was not affected by indicators of disease severity. Increased lumbar spine BMD was significantly associated with an increased risk for HPP-related fractures, prevalent in 22 (20%) patients (p < 0.001) with 21 of them having biallelic mutations.
BMD in adult HPP patients is not systematically reduced. Conversely, increased lumbar spine BMD appears to be associated with severely compromised mineralization and increased risk for HPP-related fractures while BMD at the hip appears unaffected by indicators of disease severity, suggesting suitability of this anatomic location for assessing and discerning disorders with increased fracture risk owing to reduced BMD like osteoporosis.
German register for clinical studies (DRKS00014022) DATE OF REGISTRATION: 02/10/2018 - retrospectively registered.
在成人低磷酸酶血症（HPP）患者中，升高的腰椎双能 X 线吸收法（DXA）值与疾病严重程度和特定疾病骨折风险的标志物相关，而股骨骨密度（BMD）在很大程度上不受疾病严重程度的影响，仍可用于监测因低 BMD 导致的其他骨折风险增加的原因。
低磷酸酶血症（HPP）是一种罕见的遗传性代谢疾病，由于组织非特异性碱性磷酸酶（TNAP）活性缺乏所致。成人 HPP 患者的临床表现多种多样，包括骨折风险增加，但关于 DXA 测量的临床意义以及与骨折风险和疾病严重程度的相关性的数据却很少。
回顾性分析了在确诊的 HPP 患者（有记录的突变、临床症状、低碱性磷酸酶活性）中进行的 DXA 扫描的单中心分析。进一步的数据评估包括与疾病相关的骨折、实验室结果（碱性磷酸酶、吡哆醛磷酸盐、磷酸乙醇胺）和病史。
分析纳入了 110 名患者（84 名女性，平均年龄 46.2 岁），其中 37.3%（n=41）携带两种突变。腰椎的平均 T 评分水平为-0.1（标准差 1.9），总髋部 T 评分平均为-1.07（标准差 0.15）。较低的 ALP 活性和较高的底物水平（吡哆醛磷酸盐和磷酸乙醇胺）与腰椎 T 评分的升高显著相关（p<0.001），而髋部的 BMD 不受疾病严重程度的指标影响。腰椎 BMD 的增加与 HPP 相关骨折的风险增加显著相关，22 名（20%）患者发生了 HPP 相关骨折（p<0.001），其中 21 名患者有双等位基因突变。
成人 HPP 患者的 BMD 并非系统性降低。相反，腰椎 BMD 的增加似乎与严重的矿化受损和 HPP 相关骨折的风险增加相关，而髋部的 BMD 不受疾病严重程度指标的影响，提示该解剖部位适合评估和辨别因 BMD 降低导致骨折风险增加的疾病，如骨质疏松症。
德国临床研究注册处（DRKS00014022）注册日期：2018 年 10 月 2 日-回顾性注册。
