February 2026 Research Update

At a glance

Adult diagnosis: tests matter

Adult hypophosphatasia criteria matched people better when ALPL genetic testing and key add-on lab markers were included, while symptoms alone did not separate groups well.

Low enzyme in stool (early study)

In a small comparison, alkaline phosphatase activity was low in stool as well as blood in people with HPP, but this is early research and not a routine test.

What this month adds

Overall, the findings mainly affect how adult HPP evaluations are interpreted when genetic or specialized lab results are missing, and they need confirmation in larger settings.

Overview

Adult hypophosphatasia identification looked more reliable this month when low alkaline phosphatase was combined with genetic results and certain add-on lab markers, while symptom-only approaches looked less dependable. The strongest practical message across the findings was that the same label of "low alkaline phosphatase" can lead to very different certainty depending on which supporting tests are actually available.

In adults with persistently low alkaline phosphatase who had ALPL genetic testing, proposed diagnostic criteria did a strong job matching people who had ALPL gene changes when both genetics and biochemical substrate information were included. When those pieces were removed, the criteria captured fewer genetically positive individuals. Relying on clinical features alone did not separate genetically positive from genetically negative adults very well, which helps explain why real-world evaluations can look inconsistent across clinics.

A separate, smaller line of work pushed beyond bones and suggested that low alkaline phosphatase activity in hypophosphatasia may also involve the gut. People with hypophosphatasia had lower enzyme activity in both blood and stool than healthy controls, and the intestinal form did not appear to rise to compensate. The bone-related and intestinal enzyme activities tended to rise and fall together, but this early study cannot show whether these enzyme changes cause digestive symptoms.

Taken together, the month strengthened diagnostic clarity when testing is complete, while leaving open how these findings translate across broader settings and larger groups.

Research topics this month

Limitations

• Diagnostic-criteria performance was evaluated in adults with persistently low alkaline phosphatase who had genetic testing, which may not reflect settings where testing access differs.
• When genetic or specialized substrate lab results were removed, the criteria became less sensitive, leaving uncertainty for real-world evaluations with incomplete data.
• The gut-related alkaline phosphatase findings came from a small comparison with healthy controls and cannot show whether enzyme changes cause symptoms.
• Whether these results hold in larger groups and different clinical settings remains uncertain.

Important information

• This document summarizes recent research from PubMed-indexed publications using automated methods.
• It is intended for educational purposes and does not replace medical advice.
• Links to the original studies are provided via PubMed, where readers can explore abstracts and, when available, access full-text articles.
• Some studies may include additional details that were not accessible for this summary.
• Readers seeking more complete detail or context may find it helpful to review the original studies directly.

1. 1.Tornero C, Navarro-Compán V, Heath KE, Modamio-Høybjør S, Buño A, García-Carazo S, Monjo I, Aguado P. External validation of the proposed diagnostic criteria for hypophosphatasia in adults of a Spanish cohort. Osteoporos Int (2026). Open in new tab
2. 2.Martínez-Heredia L, González-Cejudo T, Andreo-López MC, Contreras-Bolívar V, García-Fontana C, García-Fontana B, Muñoz-Torres M. Tissue nonspecific and intestinal alkaline phosphatase crosstalk: a missing link in hypophosphatasia pathophysiology?. J Transl Med (2026). Open in new tab