Hull Royal Infirmary, Hull, UK.
Academic Unit of Bone Metabolism, University of Sheffield, Sheffield, UK.
Bone. 2021 Mar;144:115795. doi: 10.1016/j.bone.2020.115795. Epub 2020 Dec 7.
This study sought to identify the clinical and biochemical characteristics that would help distinguish hypophosphatasia (HPP) from other metabolic bone diseases in adult patients attending a metabolic bone clinic by comparing patients who have genetically confirmed HPP with a group of patients with low bone mineral density (BMD) in the osteoporotic or osteopenic range.
Data were collected from February 2016 to October 2018 for 41 patients (n = 20 in the HPP group, n = 21 in the low-BMD group) attending the metabolic bone clinic at Sheffield, United Kingdom (UK) or who were recruited via the Rare UK Diseases Study (RUDY) platform during the same period. A study questionnaire was administered to all patients, and assessments were conducted for laboratory values, physical functions, BMD, and spine imaging.
Patients with HPP were characterized as being younger, more likely to have metatarsal or femoral shaft fractures, and less likely to have vertebral fractures compared with patients in the low-BMD group. The HPP group had lower total and bone-specific alkaline phosphatase, higher pyridoxal 5'-phosphate (PLP), and lower, albeit sufficient, 25-hydroxyvitamin D. Low-BMD group had lower C-terminal telopeptide and tartrate-resistant acid phosphatase 5b (61.9% were on bisphosphonates at enrollment). Dual X-ray absorptiometry (DXA) analysis found that the HPP group had higher total hip and lumbar BMD T- and Z-scores compared with the low-BMD group. There were no differences found between the two groups with physical functional assessments. Results of receiver operating characteristic analysis indicated strong diagnostic accuracy of these biomarkers for HPP. Thresholds of total alkaline phosphatase (ALP) activity of 43 IU/L or less and PLP level of 120 nmol/L or more were determined to be potentially clinically useful for distinguishing HPP from other metabolic bone diseases.
This study supported the use of ALP and PLP measurements as predictive of HPP diagnosis along with certain demographic and clinical characteristics (younger age, metatarsal or femoral fractures without low mean BMD T- and Z-scores on a DXA scan) that can aid in recognizing adults who should be further evaluated for HPP. The critical values identified need to be applied to an independent sample to be tested for diagnostic accuracy.
本研究旨在通过比较基因确诊为低磷酸酯酶症（HPP）的患者和骨密度（BMD）处于骨质疏松或骨量减少范围内的低 BMD 患者，确定有助于区分代谢性骨病的临床和生化特征。方法：2016 年 2 月至 2018 年 10 月期间，英国谢菲尔德代谢骨科诊所的 41 名患者（HPP 组 20 名，低 BMD 组 21 名）或同期通过 Rare UK Diseases Study（RUDY）平台招募的患者，收集了他们的数据。对所有患者进行研究问卷调查，并进行实验室值、身体功能、BMD 和脊柱影像学评估。结果：与低 BMD 组相比，HPP 组患者的特点是年龄较小、更有可能发生跖骨或股骨干骨折，而较少发生椎体骨折。HPP 组的总碱性磷酸酶和骨特异性碱性磷酸酶较低，吡哆醛 5'-磷酸（PLP）较高，25-羟维生素 D 水平较低（尽管充足）。低 BMD 组的 C 端肽和抗酒石酸酸性磷酸酶 5b 较低（61.9%在入组时接受双膦酸盐治疗）。双能 X 线吸收法（DXA）分析发现，HPP 组的总髋部和腰椎 BMD T-和 Z-评分高于低 BMD 组。两组的身体功能评估结果无差异。受试者工作特征分析结果表明，这些生物标志物对 HPP 的诊断具有很强的准确性。总碱性磷酸酶（ALP）活性低于 43IU/L 或 PLP 水平高于 120nmol/L 被确定为区分 HPP 与其他代谢性骨病的潜在临床有用的阈值。结论：本研究支持使用 ALP 和 PLP 测量作为 HPP 诊断的预测指标，同时还支持某些人口统计学和临床特征（年龄较小、跖骨或股骨干骨折，DXA 扫描的平均 BMD T-和 Z-评分不低），这些特征有助于识别应进一步评估 HPP 的成年人。需要将确定的临界值应用于独立样本，以测试其诊断准确性。
