Researchers studied 713 patients diagnosed with fibromyalgia to see if some might actually have a different condition called hypophosphatasia, a rare bone disease. They found that about 3% of fibromyalgia patients had low levels of an enzyme called alkaline phosphatase, which could indicate hypophosphatasia instead. This matters because the two conditions need different treatments, and missing a hypophosphatasia diagnosis could lead to bone fractures. The study suggests doctors should test fibromyalgia patients for this enzyme to make sure they’re getting the right diagnosis and treatment.

The Quick Take

  • What they studied: Whether some patients diagnosed with fibromyalgia might actually have a rare bone disease called hypophosphatasia that was missed
  • Who participated: 713 patients (mostly women, average age 50) who had been diagnosed with fibromyalgia and had enzyme level measurements on file from 2014-2021
  • Key finding: About 3 out of every 100 fibromyalgia patients (16 patients total) had persistently low alkaline phosphatase enzyme levels, and one-third of those showed signs suggesting they might have hypophosphatasia instead
  • What it means for you: If you’ve been diagnosed with fibromyalgia, a simple blood test checking your alkaline phosphatase enzyme level might reveal you actually have a different condition that needs different treatment. This is important because treating the wrong disease could lead to bone problems.

The Research Details

This was a retrospective study, meaning researchers looked back at medical records from 2014 to 2021 for 713 patients who had been diagnosed with fibromyalgia. They reviewed each patient’s blood test results, specifically looking at alkaline phosphatase enzyme levels. If a patient had low enzyme levels on at least two separate tests, the researchers did additional testing including checking other bone-related chemicals in the blood and genetic testing to look for mutations in the gene that controls this enzyme.

The researchers were trying to answer an important question: could some patients who think they have fibromyalgia actually have a rare bone disease called hypophosphatasia that was never diagnosed? This matters because the two conditions cause similar symptoms but need different treatments.

This research approach is important because it looks at a real-world problem in actual patient records rather than just testing a theory in a lab. By checking existing medical data, researchers could see how often this misdiagnosis might happen in everyday medical practice. The additional testing they did on suspicious cases helped them figure out which patients truly might have the bone disease versus just having low enzyme levels for other reasons.

This study has some strengths: it included a large number of patients (713), used actual medical records, and did thorough follow-up testing on suspicious cases. However, it also has limitations: it only looked at one hospital’s fibromyalgia clinic, so results might be different elsewhere; it was done in the past (2014-2021) so practices may have changed; and the researchers couldn’t do genetic testing on all 713 patients, only the ones with low enzyme levels. The fact that none of the patients with suspected hypophosphatasia had the genetic mutation suggests the diagnosis is more complicated than expected.

What the Results Show

Out of 713 fibromyalgia patients studied, 16 patients (3.2%) had persistently low alkaline phosphatase enzyme levels. All 16 of these patients were women with an average age of 50 years. This finding is important because low alkaline phosphatase is a red flag for hypophosphatasia, a rare bone disease that can cause fractures and other bone problems.

When researchers did additional testing on these 16 patients, they found something interesting: 5 of them (about one-third) had elevated levels of a chemical called PLP (pyridoxal-5’-phosphate), which is a substance that builds up when alkaline phosphatase isn’t working properly. This pattern is typical of hypophosphatasia. However, when genetic testing was done, none of the 16 patients had mutations in the gene that causes hypophosphatasia, which was unexpected and suggests the diagnosis might be more complicated than doctors thought.

The researchers also noticed that some of the patients with low alkaline phosphatase had other health conditions, including subclinical hypothyroidism (a thyroid condition that doesn’t cause obvious symptoms) and were taking dietary supplements or multivitamins. These findings suggest that low alkaline phosphatase might sometimes be caused by other factors besides hypophosphatasia, making diagnosis even trickier. The study also noted that none of these patients had experienced fractures at the time of the study, even though hypophosphatasia typically increases fracture risk.

Previous research had suggested that mild forms of hypophosphatasia might be hiding in fibromyalgia patient populations and going undiagnosed. This study confirms that suspicion—about 3% of fibromyalgia patients do have low alkaline phosphatase levels. However, the fact that genetic testing didn’t find the expected mutations suggests that either the diagnosis is more complex than previously thought, or that low alkaline phosphatase in fibromyalgia patients might sometimes come from different causes. This adds an important piece to the puzzle that future research will need to solve.

This study has several important limitations to keep in mind. First, it only looked at patients from one hospital’s fibromyalgia clinic, so the results might be different in other places or populations. Second, the researchers couldn’t do genetic testing on all 713 patients—only on the 16 with low enzyme levels—so they might have missed cases in the rest of the group. Third, the study is from 2014-2021, so medical practices and knowledge have evolved since then. Fourth, the unexpected finding that none of the patients had the genetic mutation suggests researchers may not fully understand what’s causing the low enzyme levels in these fibromyalgia patients. Finally, this was a one-time look at medical records, not a study that followed patients over time to see what actually happened to them.

The Bottom Line

Based on this research, doctors should consider testing alkaline phosphatase enzyme levels in patients diagnosed with fibromyalgia, especially women around age 50. This is a simple blood test that could catch a serious but treatable condition. However, a single low result shouldn’t automatically mean someone has hypophosphatasia—the test should be repeated to confirm the pattern, and additional testing may be needed. If you have fibromyalgia and haven’t had this enzyme tested, it’s reasonable to ask your doctor about it. Confidence level: Moderate—the research suggests this is worth doing, but more studies are needed to confirm how helpful it really is.

This research is most relevant to people diagnosed with fibromyalgia, particularly women around age 50 who have symptoms like bone pain or a history of fractures. It’s also important for doctors who treat fibromyalgia patients. People with other diagnoses shouldn’t assume they need this test without talking to their doctor. If you have fibromyalgia and have experienced unexplained fractures or bone problems, this research is especially relevant to you.

If you do have hypophosphatasia instead of fibromyalgia, getting the right diagnosis could help prevent future bone fractures and other complications. However, this isn’t a condition where you’ll see dramatic changes overnight. The benefit comes from getting proper treatment and monitoring over months and years to prevent bone problems before they happen. If you get tested and results are normal, you can feel reassured that this particular issue isn’t contributing to your symptoms.

Want to Apply This Research?

  • Track your alkaline phosphatase enzyme levels over time if your doctor orders this test. Record the date, the result, and the normal range for your lab. Also note any bone pain, fractures, or falls during the same period to see if there’s a pattern.
  • If you have fibromyalgia, use the app to set a reminder to ask your doctor about alkaline phosphatase testing at your next appointment. Keep a record of any bone-related symptoms (fractures, bone pain, falls) to share with your healthcare provider, which can help them decide if this testing is right for you.
  • If your doctor finds low alkaline phosphatase levels, use the app to track follow-up test results, any bone health symptoms, and your treatment plan. Monitor for new fractures or bone pain, and track any supplements or medications you’re taking that might affect enzyme levels. This information helps your doctor manage your condition effectively over time.

This research suggests that some fibromyalgia patients may have a different bone condition, but it does not provide a diagnosis or treatment plan for any individual. If you have been diagnosed with fibromyalgia or have concerns about your bone health, please discuss these findings with your doctor or rheumatologist. Do not change your treatment or stop taking medications based on this information. This study was conducted at one medical center and may not apply to all populations. Genetic testing and additional medical evaluation are needed to confirm any diagnosis of hypophosphatasia. Always consult with qualified healthcare professionals before making any medical decisions.