Evidence map›Paper›PMID 26590809›Full record

ReviewCalcified tissue international2016

Alkaline Phosphatase and Hypophosphatasia.

José Luis Millán, Michael P Whyte

Open access · hybridAbstract readReview
In one paragraph

Review in Calcified tissue international, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 188 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
188citing papers in PubMed, 2 pooled it
18.6field-weighted citation impact, top 1% of its field
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

188 citing papers in PubMed, 2 syntheses or guidelines pooled it, 380 citations in OpenAlex.

  1. Pooled it
  2. Hypophosphatasia: Canadian update on diagnosis and management.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2019
    Guideline
  3. Trial
  4. Trial
  5. Article
  6. Article
  7. Low alkaline phosphatase in adults: implications for the diagnosis of hypophosphatasia during evaluation for osteoporosis.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2026
    Article
  8. Review
  9. Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology · 2026
    Article
  10. [Metabolic bone disorders: what the internist must not overlook].Innere Medizin (Heidelberg, Germany) · 2026
    Review
  11. Article
  12. Article
  13. Article
  14. Successful treatment using asfotase alfa for delayed healing of a metatarsal stress fracture in an adolescent girl with hypophosphatasia.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2026
    Article
  15. Article
  16. External validation of the proposed diagnostic criteria for hypophosphatasia in adults of a Spanish cohort.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2026
    Article
  17. Article
  18. ENPP1 inhibition as a therapeutic approach for later-onset hypophosphatasia.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2026
    Article
  19. Hypophosphatasia-pathophysiological understanding, preclinical data looking beyond the skeleton, and upcoming treatments.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2026
    Review
  20. Article

128 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

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

2 authors at 2 institutions in 1 country.

José Luis MillánSanford Children's Health Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 92037, USA. millan@burnham.org.
Michael P WhyteCenter for Metabolic Bone Disease and Molecular Research, Shriners Hospital for Children, St. Louis, MO, 63110, USA.
Barnes-Jewish Hospital · USSanford Burnham Prebys Medical Discovery Institute · US

Funding

MOLECULAR PATHOGENESIS/TREATMENT OF HYPOPHOSPHATASIAR01DE012889 · NIDCR · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI MILLAN, JOSE LUIS · 1999 to 2020
$9.2M
NIDCR NIH HHS DE12889NIDCR NIH HHS R01 DE012889
6 · The paper itself

Abstract

Hypophosphatasia (HPP) results from ALPL mutations leading to deficient activity of the tissue-non-specific alkaline phosphatase isozyme (TNAP) and thereby extracellular accumulation of inorganic pyrophosphate (PPi), a natural substrate of TNAP and potent inhibitor of mineralization. Thus, HPP features rickets or osteomalacia and hypomineralization of teeth. Enzyme replacement using mineral-targeted TNAP from birth prevented severe HPP in TNAP-knockout mice and was then shown to rescue and substantially treat infants and young children with life-threatening HPP. Clinical trials are revealing aspects of HPP pathophysiology not yet fully understood, such as craniosynostosis and muscle weakness when HPP is severe. New treatment approaches are under development to improve patient care.

Indexed as

HypophosphatasiaAlkaline PhosphataseAnimalsHumansMiceAlkaline PhosphataseALPL protein, humanCalcificationEnzyme replacementOsteomalaciaRicketsSeizures

Identifiers

PMID26590809
PMCPMC4824800
OpenAlexW2172461241

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.