A rare inherited disorder can cause intense bone pain, frequent fractures, and premature tooth loss, often going undiagnosed for years.
Recent research from Central and Eastern Europe indicates that a simple clue from routine blood tests might enable healthcare providers to better detect this condition.
This disorder is known as hypophosphatasia, often abbreviated as HPP. A study involving patients from five European nations, published in 2026 in Frontiers in Endocrinology, highlights the significant impact of pain and other health issues associated with HPP.
Healthy bones aren’t just solid calcium deposits; they are constantly being built, repaired, and reshaped, a process that relies on enzymes and minerals functioning properly.
In HPP, a genetic mutation disrupts one of those critical processes. The disease affects the ALPL gene, which encodes an enzyme essential for proper mineralization and strengthening of bones and teeth.
When enzyme activity falls below normal, bones may stay soft and fragile, and teeth can suffer because their mineralization and attachment to the jaw depend on this enzyme as well.
HPP’s severity varies widely. A severe form that begins in infancy can be life-threatening, while milder cases often go unnoticed until adulthood.
This variability complicates diagnosis. For instance, an adult with unexplained joint or bone pain might not be immediately linked to HPP, unlike a child with noticeable bone deformities and premature tooth loss.
To better understand HPP in Central and Eastern Europe—where detailed regional data has been scarce—researchers examined medical records from Slovakia, Austria, Slovenia, Latvia, and Hungary.
This retrospective study reviewed previously collected medical data rather than enrolling new participants. Out of an initial 49 potential patients, 34 met the criteria for the study.
Among these, 14 were men, and 20 women—all exhibiting clinical signs of HPP confirmed by genetic testing.
Researchers documented issues such as chronic bone and muscle pain, fractures, bone deformities, and dental health problems. They also analyzed lab tests, imaging scans, bone density measurements, and medications prescribed.
Over 70% of patients experienced persistent pain in their bones and muscles, often requiring multiple types of pain relief, indicating the condition’s profound effect on daily life.
Fractures affected nearly half of the group at 44%, with about a quarter suffering from early tooth loss, and 18% showing bone deformities.
Symptoms’ onset age seemed to influence the pattern of health issues. Childhood-onset cases more frequently involved fractures, deformities, and early loss of teeth, whereas adult-onset HPP was more associated with ongoing pain and joint problems. This overlap with other more common conditions can make diagnosis tricky.
The disease’s effects extended beyond the skeleton; nearly 30% had respiratory issues like recurrent pneumonia, and over 10% faced kidney stones or calcium deposits in the kidneys.
A striking finding was that about 97% of the patients had low blood levels of alkaline phosphatase (ALP).
ALP is routinely measured in many blood panels. Elevated levels often raise concerns of liver or bone disease, but persistently low levels may be overlooked.
In HPP, low ALP is a key indicator since the disorder directly impacts this enzyme. When low ALP occurs repeatedly alongside bone pain or dental problems, it should prompt consideration of HPP.
Another concerning discovery was the gap in targeted treatment. Only one patient out of 34 was receiving asfotase alfa, the approved enzyme replacement therapy addressing the enzyme deficiency underlying HPP.
This limited treatment access could be due to criteria for therapy eligibility, costs, availability, age, or symptom severity, and doesn’t necessarily mean the others were denied treatment—just that various barriers may exist across healthcare systems.
Limitations of the study include its small sample size and reliance on existing medical records, which may not capture all symptoms uniformly. It also isn’t enough to estimate how common HPP is in the broader population.
Nevertheless, gathering data across five countries provides valuable insights into this complex disease, which can affect bones, teeth, muscles, lungs, and kidneys while causing significant long-term pain.
The takeaway may be surprisingly straightforward: a consistently low ALP result in someone with unexplained bone or dental issues should not be dismissed, as this small Lab clue could lead to an earlier and more accurate diagnosis.
If you’re interested in health topics, explore recent research linking vitamin K deficiency to increased risk of hip fractures in seniors, as vitamin K supplementation might help reduce such fractures.
Additional findings include studies suggesting that krill oil could enhance muscle health in older adults, and regular consumption of yogurt might lower the risk of frailty among seniors.
Source: Study authors and participating research centers from Central and Eastern Europe, published in Frontiers in Endocrinology.