Research shows that low alkaline phosphatase in an adult with repeated fractures and slow bone healing should prompt testing for hypophosphatasia, a rare inherited bone disease, before osteoporosis is assumed. According to research reviewed by Gram, one 47-year-old man’s diagnosis was delayed for years until a pyridoxal 5’-phosphate level of 494 mcg/L pointed to the condition.
A new case report in Cureus describes a 47-year-old man who was treated for osteoporosis for years despite repeated broken thigh bones that healed very slowly. According to research reviewed by Gram, his doctors eventually found that his blood levels of two key markers, alkaline phosphatase and pyridoxal 5’-phosphate, did not match osteoporosis. Instead, they pointed to adult hypophosphatasia, a rare inherited condition that affects how bones mineralize. Genetic testing later confirmed a likely cause. After starting treatment with a drug called asfotase alfa, the man regained the ability to walk without a cane. The authors say that when an adult has low alkaline phosphatase along with repeated fractures, doctors should check for this condition before assuming osteoporosis. Because the report describes only one patient, it cannot prove how common the condition is, but it offers a useful reminder that a diagnosis does not have to wait for genetic results.
Key Statistics
A 2026 case report in Cureus described a 47-year-old man whose pyridoxal 5’-phosphate level reached 494 mcg/L, far above the 5 to 50 mcg/L reference range, which helped lead to a diagnosis of adult hypophosphatasia.
In this 2026 case report, treatment with asfotase alfa was associated with the patient regaining the ability to walk without a cane after years of recurrent femoral fractures beginning at age 30.
The 2026 Cureus case report noted that the patient’s tooth loss began at age four, and that his adult diagnosis of hypophosphatasia was made clinically in 2017, before genetic testing confirmed a likely cause.
The Quick Take
- What they studied: The researchers asked whether a rare inherited bone disease called hypophosphatasia could be missed in adults who are assumed to have osteoporosis, especially when they have repeated fractures and slow healing.
- Who participated: One man, age 47, who had been treated for osteoporosis. He had thigh bone fractures at ages 30 and 39, chronic bone and muscle pain, early childhood tooth loss, and kidney calcium deposits. Several of his relatives also had related symptoms.
- Key finding: The man’s blood levels of alkaline phosphatase stayed low, and his pyridoxal 5’-phosphate level was 494 mcg/L, far above the normal range of 5 to 50 mcg/L. After treatment with asfotase alfa, he regained the ability to walk without a cane. Because this is a single case, these results show what happened in one patient rather than proving a general rule.
- What it means for you: If you have had repeated fractures or bones that heal unusually slowly, along with ongoing bone pain, it is worth asking your doctor whether a test for hypophosphatasia makes sense, especially if osteoporosis has been the only explanation. This report alone does not mean you have the condition. Only a doctor who examines you and reviews your test results can make that call.
The Research Details
This is a case report, a detailed written description of one patient’s medical history, symptoms, test results, and treatment. Case reports are often used to share unusual or easily missed conditions with other doctors. They help medical teams notice patterns they might otherwise overlook.
In this report, the authors reviewed the man’s history from childhood through adulthood. They included his fractures, his pain, his dental problems, his kidney findings, and the results of many blood and hormone tests. Doctors checked his thyroid, parathyroid, cortisol, pituitary, kidney, liver, and vitamin D levels, and all of these were normal. This step helped rule out other common causes of bone problems.
The team also described how the diagnosis was made. Doctors first made a clinical diagnosis in 2017 based on his symptoms and lab results. Genetic testing came later and found a likely disease-causing change in the ALPL gene, which controls an enzyme important for bone health.
A case report cannot measure how often a disease occurs or prove that a treatment works for everyone. However, it is well suited to showing how a rare condition can look in real life and how it was missed for years. This kind of detailed story can help other doctors recognize the same pattern in their own patients.
Because the authors described the full timeline, readers can see how a long delay in diagnosis affected this man’s life. They also show that a diagnosis was made before genetic confirmation, which is a useful lesson for clinicians who might otherwise wait for expensive or hard-to-get tests.
Case reports are considered an early and limited type of evidence. Their main strength is detail, and their main weakness is that they involve only one person. Results from one patient may not apply to others, and the report cannot show that asfotase alfa caused every improvement, since other factors can also influence recovery.
The report was published in Cureus, a peer-reviewed journal, which means outside experts reviewed it before publication. Still, its findings should be treated as a useful clue for doctors and researchers rather than a final answer about how to diagnose or treat the condition.
What the Results Show
The most important finding was that the man’s alkaline phosphatase level stayed low over time. Alkaline phosphatase is an enzyme that helps bones grow and harden. When it stays low in an adult, it can suggest a problem with how bone forms, even if the person has been told they have osteoporosis.
Another key result was his very high pyridoxal 5’-phosphate level of 494 mcg/L. The normal range is 5 to 50 mcg/L. This marker is closely linked to hypophosphatasia, so its level helped support the diagnosis and pointed doctors away from osteoporosis as the main explanation.
After diagnosis, the man started treatment with asfotase alfa, a medicine designed to replace the missing enzyme activity. The report states that this treatment was associated with marked improvement. Most notably, he was able to walk again without a cane. The authors describe this improvement as a clear change in his daily life, though they note it comes from a single case.
The authors also emphasize that the diagnosis was made clinically in 2017, before genetic testing confirmed a likely cause. This suggests that doctors do not always need a gene test to start looking into hypophosphatasia when symptoms and blood results fit the pattern.
The man had atraumatic tooth loss in early childhood, meaning his teeth fell out without a clear injury. Tooth loss at a young age is one of the clues linked to hypophosphatasia, and it was noticed long before his bone problems were fully addressed.
His bone scan showed multiple fractures in the small bones of the feet, and imaging found nephrocalcinosis, which means calcium deposits in the kidneys. Both findings are consistent with the condition and add to the overall picture.
Several of his relatives had related symptoms. This family history suggests that the condition may be inherited, which fits with the gene change found in testing.
Hypophosphatasia is known to be rare, and it is often recognized first in infants and children because its effects on bone growth and tooth development can be severe. Adult cases are less widely recognized, and they are often mistaken for osteoporosis or other common bone problems. This report fits with the growing view that adults with unexplained fractures and slow healing should be screened more carefully.
The finding that clinical diagnosis can come before genetic testing also matches the approach many specialists take with rare conditions, where a combination of symptoms and lab results can guide early decisions. Still, this single case cannot establish new standards on its own, and larger studies would be needed to confirm how common adult cases are.
The biggest limitation is that the report describes only one patient. Because of this, it cannot show how often adult hypophosphatasia occurs, how well asfotase alfa works across different people, or whether the improvement seen here would happen for others.
The report also does not include long-term follow-up data, so it is unclear how durable the benefits were over many years. Additionally, the man’s genetic result is described as apparently homozygous and likely pathogenic, which means the testing experts were confident but not entirely certain about its meaning.
Finally, because the report is a narrative of one person’s care, it can reflect the choices and context of one medical team. Other clinics may approach diagnosis and treatment differently.
The Bottom Line
Doctors may want to consider hypophosphatasia when an adult has repeated fractures, slow bone healing, chronic bone pain, and persistently low alkaline phosphatase, especially before settling on osteoporosis as the cause. This recommendation is based on a single case, so the confidence level is low to moderate. Testing and specialist referral decisions should be made by a clinician who can evaluate the full medical picture.
People who have been treated for osteoporosis without much improvement may benefit from asking their doctor whether other causes have been ruled out. This is a reasonable question to raise, though it should not be treated as a reason to change medicines on your own.
Adults who have had several fractures, slow bone healing, or unexplained bone or muscle pain may find this report relevant, especially if they also have a family history of bone problems or early tooth loss. Doctors who treat bone disease, including endocrinologists, orthopedic surgeons, and primary care physicians, may also find it useful.
People with healthy bones and no unusual symptoms do not need to apply these findings. Children with bone or tooth concerns should be evaluated by a pediatric specialist, since hypophosphatasia is often first noticed in early life.
Diagnosis can take a long time when a condition is rare and symptoms look like something more common. In this case, years passed between the first fractures and the diagnosis. If testing and treatment are started, people may notice changes in pain or mobility over months, but the timeline varies widely and should be discussed with a specialist. Bone healing and strength generally change slowly, so patience and regular follow-up are important.
Frequently Asked Questions
Can low alkaline phosphatase mean an adult has a bone disease other than osteoporosis?
Persistently low alkaline phosphatase in an adult with recurrent fractures and slow healing may point to hypophosphatasia, a rare inherited condition. A 2026 Cureus case report found this pattern led to a diagnosis in a 47-year-old man who had been treated for osteoporosis.
What are the signs of adult hypophosphatasia?
Adult hypophosphatasia often shows up as repeated broken bones, slow fracture healing, chronic bone and muscle pain, and early tooth loss. In a 2026 case report, tooth loss began at age four, and kidney calcium deposits were also found. Symptoms are nonspecific, so they are easily mistaken for other conditions.
Does a genetic test have to confirm hypophosphatasia before treatment can start?
Diagnosis does not have to wait for genetic confirmation. In a 2026 Cureus case report, doctors diagnosed adult hypophosphatasia clinically in 2017, and genetic testing came later. Treatment with asfotase alfa was associated with marked improvement in the patient’s ability to walk.
Want to Apply This Research?
- Track each bone-related event, such as a fracture, pain flare, or unusually slow healing, with the date, body area, and a pain rating from 0 to 10. Also log any tooth problems or unexplained dental issues. Sharing this log with your doctor can help them see patterns over time.
- Use the app to set reminders for scheduled lab tests and appointments, and to record questions for your doctor, such as whether a test for alkaline phosphatase or hypophosphatasia makes sense for you. Bring a written summary of your fracture history and symptoms to each visit.
- Over the long term, record monthly symptom scores for pain, mobility, and any new fractures, along with any medicines you take and their start dates. Note walking distance or the need for a cane or other support as a simple mobility measure. Review the trends every three to six months with your healthcare team so that changes can be assessed early.
This article summarizes a single case report and is for general information only. It is not medical advice and cannot diagnose or treat any condition. The findings describe one patient and may not apply to you. If you have repeated fractures, slow bone healing, or ongoing bone pain, talk with a qualified healthcare provider before making any decisions about testing, medicines, or treatment.
This research translation is published by Gram Research, the science division of Gram, an AI-powered nutrition tracking app.