If you have followed my work for any length of time, you know that I am a strong believer in looking beyond the bone density test. A DEXA scan shows bone mineral density, but bone turnover markers such as CTX and P1NP show something a DEXA cannot: how fast bone is being broken down and rebuilt right now. A newly reported international survey adds an important caution—your bone marker result may not mean exactly the same thing from one laboratory to another.
I have long used biochemical testing as another window into the dynamic process of bone breakdown and bone formation, and I still do.
That doesn’t mean we should stop using bone markers. Far from it. It means we need to understand how to use them intelligently.
Key takeaways
- A 2026 IOF-IFCC survey of 231 laboratories in 41 countries found wide variation in how bone and mineral metabolism tests are measured, reported and interpreted.
- Reference ranges for CTX, P1NP, PTH and vitamin D varied considerably between laboratories, even among those using the same manufacturer’s instrument.
- To track bone turnover markers over time, use the same laboratory, test at the same time of day, and for CTX use a morning fasting sample.
- For vitamin D status, the right test is generally 25-hydroxyvitamin D [25(OH)D], not 1,25-dihydroxyvitamin D.
- Look at patterns and trends alongside the whole clinical picture, not at one isolated number.
How much do bone marker tests vary between laboratories?
On September 22, 2026, the International Osteoporosis Foundation (IOF) announced the findings of an international survey examining how laboratories around the world measure and report what researchers call Bone Status Indices. The underlying study, conducted by the Joint IOF-IFCC Committee on Bone Metabolism and published online August 7, 2026 in Clinical Chemistry and Laboratory Medicine, collected 231 laboratory responses from 41 countries across six continents.
Researchers looked at laboratory practices for tests related to bone and mineral metabolism, including:
- Total alkaline phosphatase (ALP)
- Parathyroid hormone (PTH)
- CTX (β-CTX-I), a marker of bone resorption, or breakdown
- P1NP (PINP), a marker of bone formation
- Bone-specific alkaline phosphatase
- TRAP5b
- 25-hydroxyvitamin D [25(OH)D]
- 1,25-dihydroxyvitamin D [1,25(OH)2D]
What they discovered was substantial variation in the way these tests are measured, reported and interpreted.
Can the same lab result be interpreted differently?
Yes. One of the findings I find particularly important is that reference ranges varied considerably among laboratories—even when laboratories were using the same manufacturer’s instrument. You might have a CTX, P1NP, PTH or vitamin D result interpreted according to one laboratory’s reference range and then have the same test performed somewhere else using a different reference interval. A number that looked comfortably within one laboratory’s range might look quite different on another report.
The researchers also found differences in the instruments being used, specimen types, reporting units and participation in external quality assessment programs. For CTX and P1NP in particular, participation in external quality assessment programs was lower than it was for commonly measured markers such as alkaline phosphatase and PTH.
None of this means these tests have no value. It means context matters.
Are bone turnover markers still useful?
Yes—but they are not standalone answers. There is no single test that tells us the entire story of our bones. Not a DEXA. Not a CTX. Not a P1NP. Not even a vitamin D test. Each is one piece of a much larger puzzle.
CTX helps us understand the rate at which bone is being broken down, while P1NP gives us information about bone formation. When appropriately collected and interpreted, these markers can be useful for assessing bone turnover and monitoring changes over time. But I am much more interested in the pattern than in becoming frightened—or overly reassured—by one isolated number. For more on how the different tests fit together, see bone testing: assessing bone breakdown and bone loss, Am I losing bone right now? The NTx test, and What’s the cause of your osteoporosis? Diagnostic tests and what they mean.
How can I get comparable bone marker results over time?
Here is one of the most practical lessons I take from this research: whenever possible, use the same laboratory for repeat testing. If you are trying to determine whether your CTX or P1NP has meaningfully changed over several months, switching laboratories can introduce another variable into the comparison. And the laboratory isn’t the only variable.
This is particularly important with CTX. CTX follows a daily rhythm and is affected by food intake. International recommendations advise collecting CTX in the morning, generally between about 7:30 and 10:00 AM, after an overnight fast, to reduce this variability. So if your first CTX test was at 8:00 AM while fasting and your next was in the afternoon after lunch, you have introduced a variable that makes the two numbers more difficult to compare.
For anyone monitoring changes over time, I suggest aiming for consistency:
- Use the same laboratory when possible.
- Test at approximately the same time of day.
- For CTX, use a morning fasting sample.
- Keep the testing conditions as similar as reasonably possible.
- Look at trends rather than becoming overly focused on one result.
P1NP is less affected by food intake and time of day than CTX, but consistency is still helpful when you are following your own results over time.
Which vitamin D test should I ask for: 25(OH)D or 1,25(OH)2D?
The survey also uncovered substantial variation in how vitamin D testing is handled. In particular, researchers reported frequent ordering of 1,25-dihydroxyvitamin D when 25-hydroxyvitamin D [25(OH)D] is generally the appropriate test for assessing vitamin D status. This distinction causes a great deal of confusion.
The vitamin D test most people need is 25-hydroxyvitamin D, or 25(OH)D. This is the primary circulating form used to assess vitamin D status.
The active hormone, 1,25-dihydroxyvitamin D, is tightly regulated by factors including parathyroid hormone, calcium and phosphorus. It can sometimes remain normal—or even be elevated—despite low vitamin D stores, so it generally isn’t the test we use to determine whether someone has adequate vitamin D status. There are specific medical situations in which measuring 1,25(OH)2D is appropriate, but for routine assessment of vitamin D status, I look to 25(OH)D.
What does this study show—and what doesn’t it show?
It is important not to overinterpret these findings. This was a survey of laboratory practices. It did not determine that thousands of people have been incorrectly diagnosed or treated because of laboratory variation. Nor does it prove that one laboratory’s reference range is right and another’s is wrong.
Instead, the study documents something researchers and clinicians need to take seriously: laboratory practices for bone and mineral metabolism markers are not yet fully harmonized around the world. The researchers concluded that greater standardization is needed in areas including reporting units, reference intervals, interpretation, quality assessment and clinician education. I agree. But while the laboratory community works toward that, there are things we can do right now to make these tests more useful.
Dr. Brown’s take: don’t chase numbers—look for patterns
For decades, my approach to osteoporosis has been to ask a broader question: Why is this person’s bone being lost? A low bone density measurement tells us that bone has been lost. It doesn’t necessarily tell us why. That is why I encourage people with significant bone loss to undertake a thoughtful medical workup looking for the underlying causes of excessive bone breakdown or inadequate bone formation. Bone turnover markers can be one very useful part of that investigation.
But I would never want someone to look at a single CTX result and think, “This number tells me everything I need to know about my bones.” It doesn’t. I look at bone turnover markers alongside the larger picture: bone density, fracture history, nutrient status, parathyroid function, thyroid function, digestive health, inflammation, medications, lifestyle, exercise and other factors that influence bone. (Testing is also becoming part of how we protect bone before surgery—see osteoporosis and joint replacement: new IOF statement urges bone testing before surgery.)
Then we watch what happens over time. If you improve your nutrition, correct nutrient insufficiencies, address an underlying medical issue, strengthen your body and reduce the factors contributing to excessive bone breakdown, does the pattern begin to change? That is where testing becomes empowering.
The lesson from this new research is not that bone marker testing is useless. Quite the opposite. The lesson is that good testing requires good context. Know which test you are getting. Pay attention to how and when it is collected. Try to use the same laboratory for follow-up testing. And most importantly, don’t allow one laboratory number—whether it is a T-score, CTX, P1NP or vitamin D level—to define the health of your entire skeleton.
Your bones are living tissue. And understanding how that living tissue is changing over time gives us information we can use to build stronger bones.
Frequently asked questions
What are bone turnover markers?
Bone turnover markers are blood tests that reflect how fast bone is being broken down and rebuilt. CTX (β-CTX-I) is a marker of bone resorption, or breakdown, and P1NP is a marker of bone formation.
Why do CTX and P1NP results differ between laboratories?
A 2026 IOF-IFCC survey found that laboratories differ in instruments, specimen types, reporting units and reference intervals, and that reference ranges varied even among labs using the same manufacturer’s instrument. Participation in external quality assessment programs was also lower for CTX and P1NP than for ALP and PTH.
When should I have my CTX test drawn?
International recommendations advise collecting CTX in the morning, generally between about 7:30 and 10:00 AM, after an overnight fast, because CTX follows a daily rhythm and is affected by food intake.
Should I use the same laboratory for repeat bone marker tests?
Whenever possible, yes. Switching laboratories adds another variable when you are trying to tell whether a CTX or P1NP value has truly changed over time.
Which vitamin D test measures my vitamin D status?
25-hydroxyvitamin D [25(OH)D] is generally the appropriate test for assessing vitamin D status. 1,25-dihydroxyvitamin D is tightly regulated and can be normal or elevated despite low vitamin D stores, so it is used only in specific medical situations.
Does this study mean my bone marker results are wrong?
No. It was a survey of laboratory practices and did not find that people were misdiagnosed. It shows that results are best interpreted in context and tracked consistently over time.
References
- Cavalier E, Kapoula G, Bhattoa HP, et al. IOF-IFCC international survey of global laboratory practices for bone status indices. Clinical Chemistry and Laboratory Medicine. Published online August 7, 2026. DOI: 10.1515/cclm-2026-0941.
- International Osteoporosis Foundation. Global Survey Reveals Major Variation in the Measurement of Bone and Mineral Metabolism Biomarkers. September 22, 2026.
- Szulc P, Naylor K, Hoyle NR, Eastell R, Leary ET. Use of CTX-I and PINP as bone turnover markers: National Bone Health Alliance recommendations to standardize sample handling and patient preparation to reduce pre-analytical variability. Osteoporosis International. 2017;28:2541–2556.
This article is for educational purposes and is not a substitute for individual medical advice. Talk with your healthcare provider about which tests are right for you.
