Prevalence of hypophosphatasia in rheumatology and osteoporosis care clinics: a systematic literature review

Schfer Valentin S.; Katie Moss; Carolina Tornero; Charles Julia F.; Adachi Jonathan D.; Singer Andrea J.; Jessica Hinman; Liliana-Georgiana Wegmann; Shona Fang

doi:10.1530/obabs.08.P55

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Bone Abstracts (2026) 8 P55 | DOI: 10.1530/obabs.08.P55

OP2026 Poster Presentations Original Research (32 abstracts)

Prevalence of hypophosphatasia in rheumatology and osteoporosis care clinics: a systematic literature review

Valentin S. Schfer ¹ , Katie Moss ² , Carolina Tornero ³ , Julia F. Charles ⁴ , Jonathan D. Adachi ⁵ , Andrea J. Singer ⁶ , Jessica Hinman ⁷ , Liliana-Georgiana Wegmann ⁸ & Shona Fang ⁹

Author affiliations

¹Department of Rheumatology and Clinical Immunology, Clinic of Internal Medicine III, University Hospital Bonn, Bonn, Germany;²St. Georges Hospital, London, United Kingdom;³Hospital Universitario La Paz, Madrid, Spain;⁴Brigham and Womens Hospital and Harvard Medical School, Boston, USA;⁵McMaster University, Hamilton, Canada;⁶MedStar Georgetown University Hospital, Washington, DC, USA;⁷Epi Excellence, LLC, Philadelphia, USA;⁸Alexion, AstraZeneca Rare Disease, Baar, Switzerland;⁹Alexion, AstraZeneca Rare Disease, Boston, USA

Background: Hypophosphatasia (HPP) is a rare, inherited metabolic disease caused by deficient tissue-nonspecific alkaline phosphatase (ALP) activity stemming from ALPL variants. Because of its heterogeneous clinical presentation, HPP can be misdiagnosed as osteoporosis or fibromyalgia, among other disorders. We systematically reviewed the prevalence of HPP in rheumatology and osteoporosis settings.

Methods: We conducted a systematic review of full-length, English language studies indexed in PubMed and published 2015 to 2024 using search terms related to HPP, prevalence, ALP, rheumatology, and osteoporosis. Data were extracted on study characteristics, number and percentage of individuals with persistently low ALP activity, and number of patients with HPP. HPP prevalence overall and among individuals with persistently low ALP activity is reported.

Results: Of 331 publications identified, 28 were analyzed for data extraction. Of these, 3 reported studies in patients treated in rheumatology settings and 2 in patients in osteoporosis settings. One additional study reported with full text in German and abstract in English was included because of its relevance. The percentage of outpatients with persistently low ALP activity ranged from 0.4% (7/1839) to 1.2% (28/2289). In 2 studies in rheumatology outpatients, the prevalence of genetically confirmed HPP among those with persistently low ALP was 46.4% (13/28) and 56.5% (13/23). One study in patients with fibromyalgia and ALP activity below the lower limit of normal reported that 9.3% (57/611) had persistently low ALP, but this did not exclude secondary causes of low ALP and HPP was not confirmed. Among rheumatology and internal medicine inpatients with persistently low ALP activity, 6.0% (11/182) had genetically confirmed HPP. Among patients at an osteoporosis clinic with persistently low ALP, prevalence of genetically confirmed HPP was 57.1% (4/7). In another study in patients at an osteoporosis clinic, 87.5% (14/16) of those with persistently low ALP had potentially pathogenic ALPL variants, although specific manifestations of HPP were not stated.

Conclusion: Among adults with persistently low ALP in rheumatology and osteoporosis clinic settings, 46.4% to 57.1% had genetically confirmed HPP. Practitioners in these clinics are advised to test for ALP activity in patients with manifestations of HPP.