Evidence map›Paper›PMID 42113233›Full record

ArticleOsteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA2026

Identification of hypophosphatasia in adults with persistent hypophosphatasemia: clinical-genetic characterization and a validated diagnostic tool.

Yazhao Mei, Ziyuan Wang, Na Ren, Li Shen, Xiang Li, Hua Yue, Hao Zhang, Jiemei Gu, Weiwei Hu, Jie Wang and 12 more

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Article in Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors.

Yazhao Mei *Shanghai Clinical Research Center of Bone Disease, Department of Osteoporosis and Bone Diseases, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Ziyuan Wang *Shanghai Clinical Research Center of Bone Disease, Department of Osteoporosis and Bone Diseases, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Na RenShanghai Clinical Research Center of Bone Disease, Department of Osteoporosis and Bone Diseases, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Li ShenClinical Research Center, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Xiang LiShanghai Clinical Research Center of Bone Disease, Department of Osteoporosis and Bone Diseases, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Hua YueShanghai Clinical Research Center of Bone Disease, Department of Osteoporosis and Bone Diseases, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Hao ZhangShanghai Clinical Research Center of Bone Disease, Department of Osteoporosis and Bone Diseases, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Jiemei GuShanghai Clinical Research Center of Bone Disease, Department of Osteoporosis and Bone Diseases, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Weiwei HuShanghai Clinical Research Center of Bone Disease, Department of Osteoporosis and Bone Diseases, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Jie WangMedical Examination Center, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shanshan LiShanghai Clinical Research Center of Bone Disease, Department of Osteoporosis and Bone Diseases, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Chao GaoShanghai Clinical Research Center of Bone Disease, Department of Osteoporosis and Bone Diseases, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Zhe WeiShanghai Clinical Research Center of Bone Disease, Department of Osteoporosis and Bone Diseases, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yang XuShanghai Clinical Research Center of Bone Disease, Department of Osteoporosis and Bone Diseases, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shuqin XuShanghai Clinical Research Center of Bone Disease, Department of Osteoporosis and Bone Diseases, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Wei HongDepartment of Osteoporosis, Huadong Hospital Affiliated to Fudan University, Shanghai, China.
Qiongyao ShiDepartment of Endocrinology, Ningbo Fourth Hospital, Ningbo, Zhejiang, China.
Ya WangShanghai Clinical Research Center of Bone Disease, Department of Osteoporosis and Bone Diseases, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Jing XuDepartment of Stomatology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Gao GaoMedical Examination Center, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. gaogao520@sjtu.edu.cn.ORCID http://orcid.org/0000-0001-7722-115X
Zhenlin ZhangShanghai Clinical Research Center of Bone Disease, Department of Osteoporosis and Bone Diseases, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. zzl2002@medmail.com.cn.ORCID http://orcid.org/0000-0002-4339-1617
Chun WangShanghai Clinical Research Center of Bone Disease, Department of Osteoporosis and Bone Diseases, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. wangchun66@sjtu.edu.cn.ORCID http://orcid.org/0000-0003-4124-1575

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

This study systematically analyzed 72 adults with genetically confirmed hypophosphatasia and compared them with 36 individuals with persistent hypophosphatasemia but negative ALPL variants. Using four routinely available indicators, a simplified diagnostic tool was developed and externally validated to facilitate the early identification of adult hypophosphatasia in clinical practice. PURPOSE: Hypophosphatasia (HPP), an underdiagnosed inborn error of disorder caused by ALPL mutations, poses diagnostic challenges in adults due to phenotypic heterogeneity. This study aimed to establish a large adult HPP cohort in China and develop a practical diagnostic tool using routine clinical parameters.

methodsClinical and genetic characteristics were systematically analyzed in 72 genetically confirmed adult HPP patients and 36 individuals with persistent hypophosphatasemia and negative ALPL genetic testing. Two models were developed to predict HPP: Model 0 (alkaline phosphatase (ALP)+pyridoxal-5'-phosphate (PLP)) and Model 1 (ALP+height Z-score+family history+chronic musculoskeletal pain). Model performance was evaluated by tenfold cross-validation, decision curve analysis (DCA) and external validation (n = 40, including 28 HPP).

resultsHPP patients exhibited lower ALP (27.0 (21.8, 33.3) U/L vs. 36.00 (32.0, 38.0) U/L; P < 0.001), elevated PLP (214.3 (121.3, 457.7) nmol/L vs. 42.6 (31.9, 63.5) nmol/L; P < 0.001), growth impairment, and higher prevalence of chronic musculoskeletal pain and family history. Optimal ALP and PLP cutoffs were 28.2 U/L and 114.9 nmol/L, respectively. Compound heterozygotes and crown domain variants in ALPL gene showed lower ALP and higher PLP levels. Model 1 performed comparably to Model 0 (AUC 0.918 vs. 0.896; P = 0.513), remained robust in the age-stratified sensitivity analysis (<50 years), and achieved an AUC of 0.833 in external validation. A nomogram based on Model 1 was constructed.

conclusionThis study provides the largest clinical-genetic characterization of adult HPP in China and proposes a simple four-variable nomogram that enables accurate recognition of HPP without PLP testing, facilitating earlier diagnosis in routine practice.

Indexed as

Alkaline phosphataseALPL geneExternal validationHypophosphatasiaNomogramPyridoxal 5′ phosphate

Identifiers

PMID42113233

What Socratic holds

Textmetadata
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.