Purpose

The study aimed to define the clinical, biochemical and genetic features of adult patients with osteopenia/osteoporosis and/or bone fragility and low serum alkaline phosphatase (sALP).

Methods

Twenty-two patients with at least two sALP values below the reference range were retrospectively enrolled after exclusion of secondary causes. Data about clinical features, mineral and bone markers, serum pyridoxal-5’-phosphate (PLP), urine phosphoethanolamine (PEA), lumbar and femur bone densitometry, and column X-ray were collected. Peripheral blood DNA of each participant was analyzed to detect ALPL gene anomalies.

Results

Pathogenic ALPL variants (pALPL) occurred in 23% and benign variants in 36% of patients (bALPL), while nine patients harbored wild-type alleles (wtALPL). Fragility fractures and dental anomalies were more frequent in patients harboring pALPL and bALPL than in wtALPL patients. Of note, wtALPL patients comprised women treated with tamoxifen for hormone-sensitive breast cancer. Mineral and bone markers were similar in the three groups. Mean urine PEA levels were significantly higher in patients harboring pALPL than those detected in patients harboring bALPL and wtALPL; by contrast, serum PLP levels were similar in the three groups. A 6-points score, considering clinical and biochemical features, was predictive of pALPL detection [P = 0.060, OR 1.92 (95% CI 0.972, 3.794)], and more significantly of pALPL or bALPL [P = 0.025, OR 14.33 (95% CI 1.401, 14.605)].

Conclusion

In osteopenic/osteoporotic patients, single clinical or biochemical factors did not distinguish hypophosphatasemic patients harboring pALPL or bALPL from those harboring wtALPL. Occurrence of multiple clinical and biochemical features is predictive of ALPL anomalies, and, therefore, they should be carefully identified. Tamoxifen emerged as a hypophosphatasemic drug.

中文翻译：

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成人慢性低磷血症患者的临床、生化和遗传学发现

目的

该研究旨在确定患有骨质减少/骨质疏松症和/或骨脆性和低血清碱性磷酸酶 (sALP) 的成年患者的临床、生化和遗传特征。

方法

在排除次要原因后，回顾性招募了 22 名至少有两个 sALP 值低于参考范围的患者。收集有关临床特征、矿物质和骨标志物、血清 5'-磷酸吡哆醛 (PLP)、尿磷酸乙醇胺 (PEA)、腰椎和股骨骨密度测定以及柱 X 射线的数据。分析每个参与者的外周血 DNA 以检测ALPL基因异常。

结果

致病性ALPL变异（p ALPL）发生在 23% 的患者中，良性变异发生在 36% 的患者中（b ALPL），而 9 名患者携带野生型等位基因（wt ALPL）。携带 p ALPL和 b ALPL的患者比 wt ALPL患者更易发生脆性骨折和牙齿异常。值得注意的是，wt ALPL患者包括用他莫昔芬治疗激素敏感性乳腺癌的女性。三组中的矿物质和骨标志物相似。携带 p ALPL的患者的平均尿 PEA 水平显着高于携带 b ALPL和 wt ALPL的患者中检测到的水平; 相比之下，三组的血清 PLP 水平相似。考虑到临床和生化特征，6 分评分可预测 p ALPL检测 [ P  = 0.060, OR 1.92 (95% CI 0.972, 3.794)]，更显着的是 p ALPL或 b ALPL [ P  = 0.025, OR 14.33 (95% CI 1.401, 14.605)]。

结论

在骨质减少/骨质疏松症患者中，单一的临床或生化因素无法区分携带 p ALPL或 b ALPL的低磷血症患者与携带 wt ALPL的患者。多种临床和生化特征的出现预示着ALPL异常，因此，应仔细识别它们。他莫昔芬作为一种低磷血症药物出现。