Diagnosis guide for clinicians

Hypophosphatasia (HPP): when to suspect it and what to test

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Hypophosphatasia is a rare inherited disease of bones and teeth caused by loss of function variants in ALPL, the alkaline phosphatase gene.Source HPP IWG diagnostic criteria

The HPP International Working Group says diagnosis is often missed or delayed, particularly in adults, and cites a median registry delay of 5.7 years.

Source HPP IWG diagnostic criteria

Low ALP on routine panels is easy to pass over; in a German multicenter study, most adults with low ALP had no further evaluation.

Source Hoff 2025 German multicenter study

5.7 yearsMedian time from first signs to diagnosis in the Global HPP Registry (194 patients)HPP IWG diagnostic criteria

47%Adults with persistently low ALP, other causes excluded, who carried an ALPL variant in a Madrid screening studyTornero 2020 Madrid low ALP study

Before age 5Early nontraumatic loss of primary teeth, a major criterion for children in the 2024 HPP IWG criteriaHPP IWG pediatric criteria

E83.39ICD-10-CM code, other disorders of phosphorus metabolism, used for HPPNLM ICD-10-CM lookup

Orphanet recordORPHA:436 ↗

Inheritance

Autosomal dominant, Autosomal recessive

Age of onset

All ages

Prevalence

Under 1 per 1,000,000 point prevalence, China

Also called

HPP, Phosphoethanolaminuria, Rathbun disease

Live from Orphanet (INSERM) via Orphadata, licensed CC BY 4.0, data version 2026-06-23.

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Patterns to test Red flags Often mistaken for What to test Family screening ICD-10 codes Once confirmed For the patient

Patterns that should prompt a test for Hypophosphatasia (HPP)

Each sign below is common on its own, which is why Hypophosphatasia (HPP) is missed. Published studies describe these combinations as the picture to act on. Rows are ordered from the highest published figure to the lowest, within each kind of measure.

Where testing finds it

Share of each screened or biopsied group found to have Hypophosphatasia (HPP), from the cited studies. A bar spans the lowest to the highest published figure.

1
ALP repeatedly at or below 35IU/L, none above 45IU/L+No secondary cause of low ALP+Musculoskeletal pain or metatarsal stress fractures
85 adults with persistently low ALP found by screening the laboratory records of 386,353 people in Madrid
Of the 85, 40 (47%) carried an ALPL variant, and pain and ALP under 25IU/L were linked to carrying a variant (Tornero 2020).Tornero 2020 Madrid low ALP study
47%
2
ALP below the 2.5th percentile for age and sex, more than once+Dental abnormalities+Impaired linear growth
339 children with persistently low ALP found by daily laboratory surveillance of 178,778 children at a Suzhou hospital
HPP was confirmed in 32 of 339 (9.4%), with 25 more suspected and 57 asymptomatic carriers (Zhang 2026).Zhang 2026 Suzhou pediatric screening study
9.4%
3
Referred for osteoporosis+ALP below the reference range at least once
168 osteoporosis clinic patients with at least 1 low ALP, among 1839 attendees in Melbourne
HPP was found in 3% of clinic patients with at least 1 low ALP, and 4 of the 5 had persistently low ALP (Ng 2023).Ng 2023 Melbourne osteoporosis clinic study
3%

How often diagnosed patients show it

Share of patients already diagnosed who had the finding, in the group named on each row. Groups differ by age and type, so read each row with its group.

1
Primary teeth lost early without trauma+Shed teeth with the root still intact+Low ALP for age and sex
Children with HPP pooled across published studies with more than 10 patients, in the HPP International Working Group review
Early nontraumatic loss of primary teeth had a pooled prevalence of 57% in pediatric HPP (Rush 2024).HPP IWG pediatric criteria
57%
2
Fractures, including subtrochanteric femoral fractures+Chondrocalcinosis or pyrophosphate arthropathy+Musculoskeletal pain with low ALP
22 adults diagnosed with HPP at Mayo Clinic from 1976 to 2008
A fracture history was found in 54%, and radiographic chondrocalcinosis in 27%, seen only in women (Berkseth 2013).Berkseth 2013 Mayo Clinic adult series
54%
3
Persistently low ALP+Knee chondrocalcinosis on ultrasound
42 adults with persistently low ALP and a positive ALPL test in Madrid, compared with 36 who tested negative
Chondrocalcinosis was found in 9 of 42 (21.4%) ALPL positive adults against 2 of 36 (5.6%) ALPL negative adults (Tornero 2024).Tornero 2024 chondrocalcinosis study
21.4%

These figures describe published study groups. They are not the chance that any one patient has Hypophosphatasia (HPP), and bars whose ranges overlap are not in a settled order.

Red flags for Hypophosphatasia (HPP)

What the cited sources describe, grouped by life stage and organ. Each line links to its source.

Routine labs

Persistently low ALP for age and sex with no other identifiable cause, the finding the 2024 HPP IWG criteria start from.HPP IWG diagnostic criteria
The IWG pediatric paper asks for ALP below the age and sex reference limit on 2 or more measurements separated by time.HPP IWG pediatric criteria
At a large rural clinic, persistent ALP of 30IU/L or less was found in 1 of 1544 adults, who had more chondrocalcinosis and crystalline arthritis.McKiernan 2014 Marshfield clinic study
Of about 6.9 million adult ALP results at a single German laboratory, 8.46% were under 30U/L, and only 0.59% of those had PLP measured.Schmidt 2021 German laboratory study

Teeth

Primary teeth lost early, by age 4 per the IWG, that exfoliate with the root intact and may have an abnormal shape, color or structure.HPP IWG diagnostic criteria
Early nontraumatic loss of primary teeth had a pooled prevalence of 57% across published pediatric HPP studies with more than 10 patients.HPP IWG pediatric criteria
Early atraumatic tooth loss, an adult minor criterion, and periodontal disease; the IWG says the mildest form shows only tooth findings.HPP IWG diagnostic criteria

Bones, joints and muscles in adults

Atypical femoral fractures, also called pseudofractures, and recurrent metatarsal fractures, both major criteria for adults in the 2024 IWG criteria.HPP IWG diagnostic criteria
Poorly healing fractures, chronic musculoskeletal pain, chondrocalcinosis and nephrocalcinosis, listed as minor criteria for adults.HPP IWG diagnostic criteria
Among 22 Mayo Clinic adults with HPP, 54% had a fracture history and 27% had radiographic chondrocalcinosis, seen only in women.Berkseth 2013 Mayo Clinic adult series
In a Madrid study of persistent low ALP, an ALPL variant was linked to musculoskeletal pain, and metatarsal stress fractures occurred only in carriers.Tornero 2020 Madrid low ALP study
The IWG notes that adult neuropsychiatric features may be subtle, such as fatigue, headache, depression and anxiety.HPP IWG diagnostic criteria

Children

Rickets on radiographs is a major criterion for children, and short stature, delayed motor milestones and craniosynostosis are minor criteria.HPP IWG diagnostic criteria
Nephrocalcinosis and vitamin B6 responsive seizures are also minor criteria for children in the 2024 IWG criteria.HPP IWG diagnostic criteria
The IWG pediatric paper notes that rickets with low ALP would not be expected in nutritional or hypophosphatemic rickets, where ALP is commonly high.HPP IWG pediatric criteria
In Chinese children found through low ALP screening, dental abnormalities and impaired linear growth were the leading features.Zhang 2026 Suzhou pediatric screening study

Family history

An affected first-degree relative had a pooled prevalence of 35% in pediatric HPP, and the IWG stresses a 3-generation pedigree.HPP IWG pediatric criteria
Inheritance may be autosomal dominant or recessive, according to the HPP International Working Group.HPP IWG diagnostic criteria

Hypophosphatasia (HPP) is often mistaken for

Diagnoses patients commonly carry first, and why the sources say they are confused.

First diagnosis	Why it is confused
Osteoporosis	HPP may be misdiagnosed as osteoporosis; in a Melbourne osteoporosis clinic, 3% of patients with at least 1 low ALP had HPP.Ng 2023 Melbourne osteoporosis clinic study
Fibromyalgia, rheumatic disease or osteopenia	In a German multicenter study, 35 adults with low ALP and 4 or more typical HPP signs had those signs attributed to these diagnoses.Hoff 2025 German multicenter study
Nutritional rickets	The IWG advises checking serum 25-hydroxyvitamin D to exclude vitamin D inadequacy, which can also coexist with HPP.HPP IWG diagnostic criteria
X-linked hypophosphatemia	The IWG describes high FGF23, renal phosphate wasting and low TmP/GFR in XLH, with ALP raised rather than low.HPP IWG diagnostic criteria
Osteogenesis imperfecta	Both cause fractures, but the IWG notes serum ALP is usually normal in OI, or high in type VI or after recent fractures.HPP IWG diagnostic criteria
Periodontal disease alone	The IWG says patients at the mildest end of the spectrum present with only tooth loss or periodontal disease.HPP IWG diagnostic criteria
Calcium pyrophosphate deposition disease	Knee chondrocalcinosis was seen in 21.4% of ALPL positive adults against 5.6% of ALPL negative adults with low ALP.Tornero 2024 chondrocalcinosis study

Codes patients often carry before this diagnosis

For spotting the pattern in a problem list or registry. Descriptions are checked daily against NLM's ICD-10-CM service; this is not coding advice.

Abnormal levels of other serum enzymes R74.8

A persistently low ALP for age and sex is the finding the 2024 IWG criteria start from.HPP IWG diagnostic criteria

Age-related or other osteoporosis without current pathological fracture M81.0, M81.8

HPP may be misdiagnosed as osteoporosis and treated with antiresorptives, according to Ng and colleagues.Ng 2023 Melbourne osteoporosis clinic study

Stress fracture of the right, left or unspecified foot, initial encounter M84.374A, M84.375A, M84.376A

Recurrent metatarsal fractures are a major criterion for adult HPP in the 2024 IWG criteria.HPP IWG diagnostic criteria

Other chondrocalcinosis, unspecified or multiple sites M11.20, M11.29

Chondrocalcinosis was more common in ALPL positive than ALPL negative adults with persistently low ALP.Tornero 2024 chondrocalcinosis study

Fibromyalgia M79.7

Typical HPP signs in adults with low ALP were attributed to fibromyalgia and rheumatic disease in a German multicenter study.Hoff 2025 German multicenter study

Exfoliation of teeth due to systemic causes K08.0

Primary teeth in HPP exfoliate early with the root intact, according to the IWG.HPP IWG diagnostic criteria

Rickets, active, or short stature in a child E55.0, R62.52

Rickets on radiographs is a major criterion and short stature a minor criterion for childhood HPP.HPP IWG diagnostic criteria

Testing for Hypophosphatasia (HPP), step by step

The testing order the cited guidance describes, by who it applies to. It summarizes published guidance and is not a plan for any one patient.

Anyone with a low ALP result

Repeat ALP against the right reference range
The IWG pediatric paper makes ALP below the age and sex limit an obligate criterion, shown on 2 or more measurements separated by time.HPP IWG pediatric criteria
Use pediatric reference values
The IWG says ALP in children and adolescents must be benchmarked to age, or bone age if delayed, and sex.HPP IWG diagnostic criteria
Collect the sample correctly
The IWG advises lithium heparin tubes, because EDTA and oxalate bind magnesium and lower measured ALP activity. It also lists citrate tubes and hemolysis as laboratory causes of low ALP.HPP IWG diagnostic criteria
Exclude other causes of low ALP
The IWG lists antiresorptives, chemotherapy, excess vitamin D, hypothyroidism, hypoparathyroidism, hypercortisolism, myeloma, Wilson disease, celiac disease and magnesium or zinc deficiency.HPP IWG diagnostic criteria

Persistently low ALP with no other cause

Natural substrates
The IWG pediatric paper says plasma pyridoxal 5'-phosphate (PLP) and urine phosphoethanolamine (PEA) are the substrates most commonly measured.HPP IWG pediatric criteria
Time the PLP test
The IWG criteria say measuring plasma vitamin B6 requires stopping pyridoxine supplements 1 week before the test.HPP IWG diagnostic criteria
ALPL gene testing
The IWG says ALPL analysis helps confirm the diagnosis and covers about 95% of documented variants; confirm whether deletion/duplication testing is included.HPP IWG diagnostic criteria
A negative gene test
The IWG states that a pathogenic ALPL variant is not seen in all patients with HPP and is not required for the diagnosis.HPP IWG diagnostic criteria
Apply the 2024 criteria
The IWG diagnoses HPP with 2 major criteria, or 1 major and 2 minor criteria, using separate adult and child lists.HPP IWG diagnostic criteria
Variant plus substrates is not enough alone
The IWG pediatric paper warns these 2 major criteria alone could misdiagnose asymptomatic heterozygous carriers with only biochemical findings.HPP IWG pediatric criteria

Children

Skeletal survey
The IWG says a skeletal survey helps identify rickets or craniosynostosis in children being evaluated for HPP.HPP IWG diagnostic criteria

Adults

Imaging for fractures and calcification
The IWG lists radiographs for pseudofractures, metatarsal fractures and chondrocalcinosis, bone scan, MRI or CT for pseudofractures, and renal ultrasound for nephrocalcinosis.HPP IWG diagnostic criteria

Where testing goes wrong

Most low ALP has another cause; in a Rio de Janeiro review, 398 of 410 adults with repeatedly low ALP had a secondary cause.Vieira 2021 Rio de Janeiro study
Low ALP can be temporary in severe illness such as sepsis or trauma, a Leipzig study notes, which is why persistence matters.Hennings 2024 Leipzig study
Only 40.9% of 22 Austrian laboratories used proper pediatric ALP ranges, and 36.4% called an abnormal sample from a 4-year-old normal for ALP.Steininger 2025 Austrian laboratory study
The IWG pediatric paper notes ALP can transiently normalize in HPP during pregnancy or after a recent long bone fracture.HPP IWG pediatric criteria
The IWG says most people with suppressed ALP while taking bisphosphonates do not have HPP, because the drug suppresses ALP.HPP IWG diagnostic criteria
For harm avoidance, the IWG warns that bisphosphonates may further impair mineralization in HPP and raise the risk of atypical femoral fractures.HPP IWG diagnostic criteria
Sutton and colleagues reported atypical subtrochanteric femoral fractures in a woman with undiagnosed adult HPP after 4 years of bisphosphonates.Sutton 2012 case report
McKiernan and colleagues advise caution in prescribing bisphosphonates to adults with persistently low ALP, many of whom carry ALPL variants.McKiernan 2017 ALPL variant study
Ng and colleagues describe antiresorptive therapy as relatively contraindicated in HPP, which may be mistaken for osteoporosis.Ng 2023 Melbourne osteoporosis clinic study
In a Göttingen series, every adult with ALP of 25IU/L or less had a disease-causing variant, but higher values did not exclude HPP.Hummel 2026 Göttingen study
The same study found DXA T-scores did not separate variant carriers from noncarriers, and it highlights the limits of DXA and FRAX in HPP.Hummel 2026 Göttingen study
Carrying a variant is not the disease; among 70 Vanderbilt carriers with records, 65.7% had low ALP and 12.9% met the IWG criteria.Dahir 2026 Vanderbilt biobank study
Asymptomatic carriers can show low ALP with raised PLP or PEA, which Montero-Lopez and colleagues say risks overdiagnosis and unnecessary treatment.Montero-Lopez 2026 carrier study
The PAN Foundation lists ICD-10 code E83.39 on its hypophosphatasia fund page.PAN Foundation HPP fund page
Orphanet records HPP as ORPHA:436 and maps it to WHO ICD-10 category E83.3 as an inclusion term without its own code.Orphanet cross-references

Where to test

NIH Genetic Testing Registry: hypophosphatasia: Lists ALPL sequencing and deletion/duplication tests, bone fragility and mineralization panels, and urine phosphoethanolamine tests submitted by laboratories. NIH does not independently verify submissions or endorse any laboratory.NIH GTR
Plasma PLP and urine PEA: Sutton and colleagues note that assays for the 2 natural substrates and ALPL mutation analysis are available in commercial laboratories.Sutton 2012 case report

Family screening and referral

Who else in the family

The IWG says transmission may be autosomal dominant or recessive, and genetic counseling helps identify affected relatives and supports reproductive counseling.HPP IWG diagnostic criteria
An Italian expert panel calls molecular analysis mandatory to confirm the diagnosis in children and for genetic counseling.Italian pediatric expert opinion
Sutton and colleagues describe a variant that causes severe infantile HPP with a second defective allele but mild dental HPP when heterozygous.Sutton 2012 case report
Pathogenic or likely pathogenic ALPL variants appeared in 1 in 341 unselected genomes, yet only 12.9% of carriers with records met the criteria.Dahir 2026 Vanderbilt biobank study
The IWG pediatric paper did not make family history a criterion, to avoid diagnoses based on biochemical or molecular findings alone.HPP IWG pediatric criteria

Who to refer to

An Italian expert panel on pediatric HPP brought together pediatric endocrinologists, a pediatric neurologist, a pediatric odontologist, a clinical geneticist and a molecular biologist.Italian pediatric expert opinion
The same panel says neurological and dental features of HPP should be thoroughly investigated in children.Italian pediatric expert opinion
The IWG adult review says HPP often remains underdiagnosed or misdiagnosed, particularly by clinicians unfamiliar with this rare disorder.HPP IWG adult review
The 2024 IWG criteria came from a multidisciplinary team of HPP experts in Europe and North America, supported by GRADE methodologists.HPP IWG diagnostic criteria
The IWG pediatric paper cautions that meeting the diagnostic criteria does not by itself make a patient a candidate for enzyme replacement therapy.HPP IWG pediatric criteria

Find a specialist by state

From the CMS NPI Registry, a public directory of US clinicians by registered specialty. A listing is not an endorsement and says nothing about experience with Hypophosphatasia (HPP); patient organizations and academic centers can often name experienced clinicians.

ICD-10-CM codes for Hypophosphatasia (HPP)

For orders, referrals and prior authorization. Each code is checked daily against NLM's ICD-10-CM service.

E83.39Other disorders of phosphorus metabolismCurrent in NLM's ICD-10-CM listNLM ICD-10-CM lookup

Once the diagnosis is confirmed

Hypophosphatasia (HPP) drugs for prescribersA prescribing guide: Strensiq.Open trials: 8Screen a de-identified patient against every recruiting Hypophosphatasia (HPP) study on ClinicalTrials.gov.Patient and family pageThe plain-language Hypophosphatasia (HPP) page, with trials, treatments and help paying.

For the patient: why your doctor ordered this test

Plain language a patient can read or take home.

Your doctor ordered these tests because a low alkaline phosphatase result can be a sign of hypophosphatasia, often called HPP.

HPP is an inherited condition that keeps bones and teeth from hardening the way they normally should.

In children it can make baby teeth fall out early, often with the whole root still attached.

In adults it can cause slow-healing foot fractures, thigh bone fractures, joint pain or early tooth loss.

The tests may include repeat alkaline phosphatase checks, a vitamin B6 blood level, a urine test and a gene test.

Please tell your doctor about any vitamin B6 supplement, because it can change 1 of these test results.

Many other things can lower alkaline phosphatase, and your doctor will look for those causes as well.

If HPP is found, parents, brothers, sisters or children may be offered testing, because it can run in families.

Questions clinicians ask about Hypophosphatasia (HPP) testing

Which combinations of findings should prompt testing for hypophosphatasia (HPP)?

In published screening and biopsy studies, the highest yields came from ALP repeatedly at or below 35IU/L, none above 45IU/L (47% of 85 adults with persistently low ALP found by screening the laboratory records of 386,353 people in Madrid), and from ALP below the 2.5th percentile for age and sex, more than once plus dental abnormalities (9.4% of 339 children with persistently low ALP found by daily laboratory surveillance of 178,778 children at a Suzhou hospital). Among patients already diagnosed, the most common combination began with primary teeth lost early without trauma, seen in 57% of children with HPP pooled across published studies with more than 10 patients, in the HPP International Working Group review. These figures describe study groups, not any one patient's chance of having hypophosphatasia (HPP).

What does a persistently low alkaline phosphatase mean?

It can signal hypophosphatasia, but the HPP International Working Group says other conditions and drugs must be excluded first. In a Rio de Janeiro review, 398 of 410 adults with repeatedly low ALP had a secondary cause. In a Madrid study, 47% of adults with persistently low ALP and no secondary cause carried an ALPL variant.

What are the diagnostic criteria for hypophosphatasia?

The 2024 HPP IWG criteria start from persistently low ALP for age and sex, then require 2 major or 1 major and 2 minor criteria. Adult major criteria are a pathogenic or likely pathogenic ALPL variant, raised natural substrates, atypical femoral fractures and recurrent metatarsal fractures. For children, early nontraumatic loss of primary teeth and rickets replace the fracture criteria.

Which labs confirm hypophosphatasia?

Plasma PLP and urine PEA are the substrates most commonly measured, according to the IWG pediatric paper, alongside ALPL gene testing. The IWG criteria note that plasma vitamin B6 measurement requires stopping pyridoxine supplements 1 week before. A pathogenic ALPL variant supports the diagnosis, but the IWG says it is not required.

Are bisphosphonates a concern when alkaline phosphatase is low?

Published guidance urges caution, because the IWG says bisphosphonates may further impair mineralization in HPP and raise atypical femoral fracture risk. McKiernan and colleagues advise caution in prescribing them to adults with persistently low ALP. The IWG also notes that most people with low ALP while on bisphosphonates do not have HPP.

Why does losing baby teeth with the root attached suggest HPP?

In HPP, poor cementum mineralization loosens primary teeth, which the IWG says exfoliate with the root intact, by age 4. The IWG pediatric criteria make early nontraumatic loss of primary teeth, before age 5, a major criterion. It had a pooled prevalence of 57% across published pediatric studies.

What is the ICD-10 code for hypophosphatasia?

Hypophosphatasia is commonly coded E83.39, other disorders of phosphorus metabolism, which is current in NLM's ICD-10-CM lookup checked November 10, 2026. The PAN Foundation lists E83.39 on the page for its hypophosphatasia fund. Orphanet maps HPP to the WHO ICD-10 category E83.3 as an inclusion term.

Sources

Hypophosphatasia diagnosis: current state of the art and proposed diagnostic criteria for children and adults. Osteoporosis International 2024;35(3):431-438 (Khan AA, Brandi ML, Rush ET, Ali DS et al for the HPP International Working Group; unrestricted Alexion funding via the IOF, and many authors report Alexion or AstraZeneca ties), via PubMed Central, 2023-11-20.
Proposed diagnostic criteria for the diagnosis of hypophosphatasia in children and adolescents: results from the HPP International Working Group. Osteoporosis International 2024;35(1):1-10 (Rush E, Brandi ML, Khan A et al), via PubMed Central, 2023-11-20.
The challenge of hypophosphatasia diagnosis in adults: results from the HPP International Working Group Literature Surveillance. Osteoporosis International 2024;35(3):439-449 (Brandi ML, Khan AA, Rush ET et al), via PubMed abstract, 2023-11-20.
The diagnosis of hypophosphatasia in children as a multidisciplinary effort: an expert opinion. Journal of Endocrinological Investigation 2024;47(3):739-747 (Baroncelli GI, Mora S et al; no competing interests declared), via PubMed abstract, 2023-09-26.
Can we identify individuals with an ALPL variant in adults with persistent hypophosphatasaemia?. Orphanet Journal of Rare Diseases 2020;15:51 (Tornero C, Aguado P et al; one author reports Alexion advisory fees), via PubMed abstract, 2020-02-17.
Prevalence of chondrocalcinosis and calcium pyrophosphate deposition disease in a cohort of adult patients with low alkaline phosphatase levels and a positive versus negative genetic ALPL study. JBMR Plus 2024;8(11):ziae124 (Tornero C, Aguado P et al; 2 authors report Alexion fees and grants), via PubMed abstract, 2024-09-26.
Clinical and radiographic findings in adults with persistent hypophosphatasemia. Journal of Bone and Mineral Research 2014;29(7):1651-1660 (McKiernan FE, Berg RL, Fuehrer J), via PubMed abstract; funding and disclosures not seen, 2014-07.
Mutational and biochemical findings in adults with persistent hypophosphatasemia. Osteoporosis International 2017;28(8):2343-2348 (McKiernan FE et al), via PubMed abstract; funding and disclosures not seen, 2017-04-12.
Prevalence of low alkaline phosphatase activity in laboratory assessment: Is hypophosphatasia an underdiagnosed disease?. Orphanet Journal of Rare Diseases 2021;16:452 (Schmidt T, Barvencik F et al; one author reports Alexion fees and grants), via PubMed abstract, 2021-10-28.
Active search of adult patients with persistently low serum alkaline phosphatase levels for the diagnosis of hypophosphatasia. Archives of Endocrinology and Metabolism 2021;65(3):289-294 (Vieira LHR et al; no conflicts declared), via PubMed abstract, 2021-04-12.
Clinical presentation of adults with persistently low alkaline phosphatase activity: a retrospective multicentre, cross-sectional study in Germany. BMJ Open 2025;15(7):e097235 (Hoff P et al; sponsored by Alexion, with an Alexion employee as author), via PubMed abstract, 2025-07-01.
A low serum alkaline phosphatase may signal hypophosphatasia in osteoporosis clinic patients. Osteoporosis International 2023;34(2):327-337 (Ng E, Sztal-Mazer S et al), via PubMed abstract; funding and disclosures not seen, 2022-11-24.
Low alkaline phosphatase in adults: implications for the diagnosis of hypophosphatasia during evaluation for osteoporosis. Osteoporosis International, online ahead of print (Hummel LS, Siggelkow H et al; no conflicts declared), via PubMed abstract, 2026-08-05.
Screening for Hypophosphatasia in Adult Patients at a Maximum Care Provider: Retrospective Analyses over Fifteen Years. Journal of Clinical Medicine 2024;13(23):7313 (Hennings R, Roth A et al; no conflicts declared), via PubMed abstract, 2024-12-02.
Diagnostic Yield of Laboratory-Based Screening for Hypophosphatasia Among Chinese Children With Low Alkaline Phosphatase. Journal of Clinical Endocrinology and Metabolism, online ahead of print, dgag400 (Zhang D, Chen T et al), via PubMed abstract; funding and disclosures not seen, 2026-09-30.
Clinical spectrum of hypophosphatasia diagnosed in adults. Bone 2013;54(1):21-27 (Berkseth KE, Wermers RA et al), via PubMed abstract; funding and disclosures not seen, 2013-01-22.
"Atypical femoral fractures" during bisphosphonate exposure in adult hypophosphatasia. Journal of Bone and Mineral Research 2012;27(5):987-994 (Sutton RA, Whyte MP et al), via PubMed abstract; funding and disclosures not seen, 2012-05.
Hypophosphatasia: low penetrance of pathogenic and likely-pathogenic ALPL variants identified through an unselected biorepository. Journal of Bone and Mineral Research 2026;41(3):270-281 (Dahir KM, Bastarache L et al; no conflicts declared), via PubMed abstract, 2026-03-02.
Biochemical phenotype of hypophosphatasia in asymptomatic individuals carrying ALPL variants. Journal of Bone and Mineral Research 2026;41(3):259-269 (Montero-Lopez R, Högler W et al; many authors report Alexion or AstraZeneca ties), via PubMed abstract, 2026-03-02.
Inadequate pediatric reference ranges impede the diagnosis of X-linked hypophosphatemia and hypophosphatasia in Austria. Wiener klinische Wochenschrift 2025;137:764-767 (Steininger J, Raimann A et al; supported by Kyowa Kirin and Alexion grants), via PubMed abstract, 2025-05-19.
Hypophosphatasia: About the Disease and Diagnosis Codes. PAN Foundation, 2026-11-10.
Hypophosphatasia, ORPHA:436, rare disease cross-referencing (Orphadata API). Orphanet, INSERM, via Orphadata, CC BY 4.0, 2026-06-23.
NIH Genetic Testing Registry tests for hypophosphatasia, concept C0020630 (54 clinical tests listed in NCBI E-utilities on November 10, 2026). National Center for Biotechnology Information, NIH, 2026-11-10.
ICD-10-CM search results for "E83.39" (Clinical Table Search Service). National Library of Medicine, 2026-11-10.

A reference for licensed professionals, checked against its sources on November 10, 2026. It summarizes what the cited guidance says and does not tell anyone how to diagnose or treat a specific patient. Guidelines change; the current guideline and the treating clinician's judgment govern. Trial Friend is an independent information service, not a medical provider.