Hypophosphatasia, or HPP, is a rare inherited disease that can weaken bones and teeth throughout a person’s life.
A new European study shows that many people living with the condition experience persistent pain, fractures and other serious health problems, yet very few receive the only approved treatment designed specifically for the disease.
The research examined patients from five countries in Central and Eastern Europe. The findings were published in 2026 in the journal Frontiers in Endocrinology.
HPP is caused by harmful changes in a gene called ALPL. This gene normally helps the body make an enzyme called alkaline phosphatase, which plays an important role in putting minerals into bones and teeth so they become hard and strong.
When this enzyme does not work properly, bones may not harden as they should. The effects can range from relatively mild dental problems in some people to severe bone disease and life-threatening complications in others.
More than 450 disease-causing changes in the ALPL gene have been identified. This wide genetic variation is one reason HPP can look very different from one patient to another and can begin at almost any age.
In babies and children, severe HPP can interfere with normal growth and bone development. Some children develop bent or misshapen bones, lose baby teeth unusually early, suffer repeated fractures or, in the most serious cases, experience breathing problems or seizures.
Adults can also develop significant symptoms. Persistent pain in bones, muscles and joints may make walking, working, sleeping and completing ordinary daily activities much more difficult.
To understand the disease in Central and Eastern Europe, researchers reviewed existing medical records from Slovakia, Austria, Slovenia, Latvia and Hungary. Because this was a retrospective study, the scientists analyzed information that had already been collected during patients’ medical care.
The researchers initially considered 49 people suspected of having HPP who had a confirmed change in the ALPL gene and enough medical information for evaluation. After excluding people with missing information or other diagnoses, the final study included 34 patients, consisting of 14 males and 20 females.
The team examined symptoms including chronic pain, fractures, abnormal bone development and dental problems. They also reviewed blood tests, X-rays, bone density measurements and information about pain medicines and disease-specific treatment.
Pain emerged as one of the clearest problems. More than 70% of patients experienced ongoing bone and muscle pain, and many needed several types of pain medicine to manage their symptoms.
Fractures were also common. About 44% of the patients had experienced fractures, while 26% had lost teeth earlier than expected and 18% had developed bone deformities.
The pattern of illness differed depending on when HPP began. People whose symptoms started during childhood were more likely to experience fractures, abnormal bone development and early tooth loss.
People whose symptoms appeared in adulthood were more likely to report long-lasting pain and joint problems. This difference shows why HPP can be difficult to recognize when doctors expect every patient to have the same symptoms.
The disease also affected more than bones and teeth. Nearly 30% of patients had breathing-related problems, including repeated pneumonia, while more than 10% developed kidney stones or calcium deposits in the kidneys.
One of the most important clues was found in routine blood tests. About 97% of the patients had low levels of alkaline phosphatase, or ALP, which is a key laboratory sign of HPP.
Low ALP can sometimes receive less attention than unusually high ALP levels in everyday medical care. The researchers argue that recognizing persistently low levels could help doctors identify people who need further testing for HPP.
Perhaps the most striking result involved treatment. Only one of the 34 patients was receiving asfotase alfa, an enzyme replacement treatment that replaces the activity missing in HPP and is the only approved therapy that directly targets the disease.
This does not necessarily mean that every participant should have received the drug, because treatment decisions depend on disease severity, age, approval rules and access in each country. Still, the extremely low use of targeted therapy highlights possible gaps in diagnosis, specialist care and access to treatment.
The study has important limitations. Only 34 patients were included, and information came from medical records rather than from a study designed to follow everyone in exactly the same way, so some symptoms or medical details may have been missed.
Even so, studying a rare disease across several countries provides useful information that can be difficult to obtain. The findings show that HPP can affect many parts of life and that chronic pain is especially common among diagnosed patients in this region.
The results also underline a practical message for healthcare professionals: persistently low ALP should not automatically be ignored. When it appears alongside unexplained fractures, early tooth loss, bone pain or other suggestive symptoms, HPP may be worth considering and further testing could help patients receive appropriate care sooner.
If you care about health, please read studies about vitamin K deficiency linked to hip fractures in old people, and these vitamins could help reduce bone fracture risk.
For more health information, please see recent studies that Krill oil could improve muscle health in older people, and eating yogurt linked to lower frailty in older people.
Source: Frontiers in Endocrinology study authors and participating Central and Eastern European research centers.
