Evidence map›Paper›PMID 42844428›Full record

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

Prevalence of hypophosphatasia in general and selected patient populations: a systematic review.

Valentin S Schäfer, Jessica Hinman, Katie Moss, Julia F Charles, Jonathan D Adachi, Andrea J Singer, Vrinda Saraff, Asma Deeb, Fatih Süheyl Ezgü, Fumio Otsuka and 3 more

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In one paragraph

Review 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

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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

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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

Corrections and comments

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5 · Who and what money

Authors and funding

13 authors.

Valentin S SchäferMedical Clinic III for Oncology, Hematology, Immune-Oncology and Rheumatology, University Hospital Bonn, Bonn, Germany.
Jessica HinmanEpiExcellence, LLC, Philadelphia, PA, USA.
Katie MossSt. George's University Hospitals, London, UK.
Julia F CharlesBrigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Jonathan D AdachiMcMaster University, Hamilton, ON, Canada.
Andrea J SingerMedStar Georgetown University Hospital and Georgetown University Medical Center, Washington, DC, USA.
Vrinda SaraffBirmingham Women's and Children's Hospital, Birmingham, UK.
Asma DeebSheikh Shakhbout Medical City, Faculty of Health and Science, Abu Dhabi and Gulf Medical School, Khalifa University, Ajman, UAE.
Fatih Süheyl EzgüDepartments of Pediatrics and Inborn Metabolic Diseases, Faculty of Medicine, Gazı University, Ankara, Turkey.
Fumio OtsukaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Liliana-Georgiana WegmannAlexion, AstraZeneca Rare Disease, Baar, Switzerland.
Shona FangEpidemiology and Real World Science, Alexion, AstraZeneca Rare Disease, Boston, MA, USA.
Carolina TorneroRheumatology Unit, La Paz University Hospital, Madrid, Spain. carolina.tornero@salud.madrid.org.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hypophosphatasia (HPP) has diverse manifestations overlapping other skeletal and rheumatic disorders. This systematic review assessed frequency of HPP in select and general clinical populations with persistently low alkaline phosphatase (ALP) activity. Undiagnosed HPP was frequently identified. Clinicians should consider HPP for patients with persistently low ALP and hallmark manifestations.

backgroundDiagnosis of hypophosphatasia (HPP) can be missed owing to its rare disease status and heterogeneous manifestations that can overlap with other skeletal or rheumatic disorders. The objective of this systematic review was to assess the frequency of HPP among patients with persistently low alkaline phosphatase (ALP) activity and determine overall HPP prevalence in the general population.

methodsEnglish language articles published from January 1, 2015, to September 29, 2025, were identified in PubMed and Embase and through manual searching. Observational studies conducted in patients of any age from general and select clinical populations (e.g., rheumatology, endocrinology) were included if the frequency of HPP or potential HPP was reported or could be enumerated from results. Risk of bias was assessed based on 4 predefined criteria. HPP prevalence was determined from general clinical population studies with the lowest risk of bias.

resultsA total of 710 articles were retrieved; 27 met the inclusion criteria. The frequency of genetically confirmed HPP among patients with persistently low ALP activity in studies with low risk of bias (≥3 predefined criteria) was 10.4-26.2% in general clinical populations, 46.4-56.5% in rheumatology populations, and 57.1-87.5% in osteoporosis populations. The total prevalence of HPP in the general population may be 17.6-36.0 per 100,000 population based on 3 studies meeting all 4 criteria.

conclusionUndiagnosed patients with HPP were frequently identified in studies of ALP screening, highlighting the importance of screening. Clinicians should consider a diagnosis of HPP for patients with persistently low ALP and hallmark manifestations.

Indexed as

alkaline phosphataseALPL variantsdiagnosishypophosphatasiaprevalenceSystematic review

Identifiers

PMID42844428

What OpenQuestion holds

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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 OpenQuestion graph.