Uncovering Active Bone Loss - Bone Turnover Markers

Welcome to episode #4 of the Bone Coach Podcast. Kevin Ellis here. Today I’m going to be giving you an introduction to bone turnover markers...an important set of tools for anyone with low bone density and osteoporosis.

In this episode, I'm going to share:

• How not to be surprised at your next DEXA scan?

• How you can identify if you're actively losing bone?

• What do bone turnover markers actually measure?

• Markers for bone resorption

• Markers for bone formation

• What the results can tell you?

• Why bone turnover markers are important?

Resources Mentioned:

--->Claim your FREE 7-Day Osteoporosis Kickstart here!

Dr. Keith McCormick’s Book “The Whole Body Approach To Osteoporosis”

Lab Tests you can order on your own if your physician won't order them and if your budget allows:

Bone-Specific Alkaline Phosphatase

C-Telopeptide

N-Telopeptide

Osteocalcin

Deoxypyridinoline (DPD) Cross Link Test Urine Test

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Full Transcript below:

Welcome to episode #4 of the Bone Coach Podcast. Kevin Ellis here. Today I’m going to be giving you an introduction or a primer on bone turnover markers. This is a fairly short episode. We’re not going to go into too much detail, and I’m going to try and make sure this is really easy to understand and not too technical.

All of the information shared in this episode, the show notes, the resources, and the lab testing I’m going to mention throughout can be found at bonecoach.com/bone-turnover-markers

In the prior episode, episode 3, I mentioned that if you’ve recently and even unexpectedly been diagnosed with low bone density or osteoporosis, the biggest question you need to answer right now is: are you actively losing bone?

If you’ve been diagnosed with osteopenia or osteoporosis, and you had a DEXA scan of the hip and spine, then you have at least one piece of the puzzle--a baseline bone mineral density reading from what’s currently considered the gold standard test for the diagnosis of osteoporosis...that’s the DEXA scan.

But what that single DEXA scan reading can’t tell you and won’t tell you is if you’re actively losing bone.

You would need another bone density scan conducted 1-2 years later, on the exact same machine, with proper positioning and interpretation by the technician, in order for you to determine whether you are losing or gaining bone.

1-2 years is a long time…

And bone is dynamic tissue...

During that 1-2 year period, your bones are remodeling. Bone is being formed. Bone is being broken down.

So how can you tell what’s taking place in your bones in the meantime? That’s what bone turnover markers can help with.

Bone turnover markers are tests that can give you insight into the activity level of the cells that are breaking down or building up your bones...it’s the activity level of osteoclasts and osteoblasts.

These can be rapid, reliable, and cost-effective tools used for assessing bone remodeling, bone resorption, and bone formation.

Think of bone turnover markers as your leading indicators of bone health. If your bone health were a car, and your next DEXA scan is the destination 1-2 years ahead of you, bone turnover markers would be like signs on the side of the road giving you an idea of what you might expect when you arrive at your destination.

There are two different types of bone turnover markers we’re going to talk about…

The first are bone resorption markers.

These markers tell us the level of osteoclast activity. This is the activity level of the cells that are breaking down or chewing up that bone.

Personally, I’m a visual learner. I realize this is an audio podcast, so since you’re listening to this, I’m going to help you visualize what these tests are actually measuring.

I’m summarizing here Keith McCormick’s description from his book on osteoporosis because it really helps bring this image of bone resorption to life...Just like how carpenter ants chew and tunnel through wood leaving piles of sawdust behind, osteoclasts chew up and tunnel through bone...but instead of leaving behind sawdust, they leave behind collagen bone proteins. And the amount of collagen detected during testing is directly correlated to how much bone is being chewed up by the osteoclasts.

So we’re using these test to look at how much sawdust, or in our case, collagen bone protein, is being released from the bone. This can give us insight into the amount of bone being broken down.

Here's an overview of your bone resorption markers.¹

Bone Resorption Markers

CTX or C-terminal telopeptide.

Serum or blood test and it measures bone resorption via a specific part of type I collagen found in bone. Preferred and most accurate bone resorption marker to date. CTX can also be done through a urine sample, but that’s not as accurate as through a blood sample.

So, serum CTX, in most cases, will be your best bone resorption marker. You’ll want to get this first thing in the morning while you’re still fasting, so no eating or drinking other than water.

When you get your results, the reference range for CTX is typically higher the younger you are and decreases with age.

The reference range for men and women is also different.

For example, men aged 30-50 have a reference range around 70-780pg/ml while males above 50 have a reference range of around 80-350 pg/ml.

Women aged 30-50, on the other hand, can have a range anywhere from 50-650 and women over the age of 50 could have a wider reference range than that.

Those are pretty wide ranges.

Many physicians prefer to see people toward the lower ends of these ranges.

NTX or N-terminal telopeptide:

Either a urine (preferred) or blood test. Measures bone break down via a small fragment of the collagen protein matrix. If you get the urine NTX test, which is the preferred form by many physicians, you’ll want it to be the second urine of the day, or the second time you’ve peed that day for the collection. When you get your results, the reference range is somewhere in between 9-60. Many physicians consider being closer to mid range, around 30 to 40, as ideal.

Those are the two most important ones to start with: CTX (blood) and NTX (urine).

There are other markers of bone resorption, but CTX and NTX should be the ones you focus on.

You don’t need to remember or request the others I’m about to list, but in case you’re curious to know what they are, or you just want to familiarize yourself with some of these different terms, I’m going to share them here. So, the other bone resorption markers are:

• Hydroxyproline and Pyridinium crosslinks which measures collagen breakdown.

• Bone sialoprotein.

• Osteoclast enzymes like Tartrate-resistant acid phosphatase (TRAP) and Cathepsin K.

• Osteocyte activity markers: Receptor activator of nuclear factor kappa-B ligand (RANKL), Osteoprotegerin (OPG), and Sclerostin²

Again, you do not need to remember those ones I just listed. I just want you to be familiar with the terms in case you hear your doctor or someone else mention them at some point...you have a better understanding of what they’re related to.

Now let’s talk about bone formation markers³…

Each of these has the potential to give you greater insight into osteoblast bone building activity taking place.

Bone Formation Markers

P1NP or Procollagen type 1 N-terminal propeptide:

This is a blood test that reflects the rate of collagen and bone formation. P1NP is the most sensitive marker of bone formation and directly reflects the activity of osteoblasts.

Osteocalcin:

This is another blood test. Osteocalcin is a protein produced by osteoblasts and is important for activating bone mineralization. It does this by taking calcium from our blood and binding it to the bone matrix.⁴

Bone-Specific Alkaline Phosphatase:

This is also a blood test. Now, if you’ve ever had basic lab work run, like a Comprehensive Metabolic Panel (CMP), you’ve probably seen the words Alkaline Phosphatase. Alkaline phosphatase is an enzyme found in the liver, the GI tract, and the bone.

If your levels of ALP are elevated, it could be coming from one of these areas including the bone.

That’s where Bone-Specific Alkaline Phosphatase comes in...when you ask for this test, they are looking at just the portion of the Alkaline Phosphatase that’s coming from the bone.

Bone-Specific Alkaline Phosphatase is another marker of bone formation that detects early signs of osteoblast activity....so, it is a bone formation marker.

At the same time, and this is not to scare you, it’s just to be something to be aware of, it can also be an indicator of certain bone disorders, or even possibly be an indicator of a condition like multiple myeloma if serum calcium is also elevated.

Those are your bone formation markers…

A few important notes about these bone turnover markers:

• You want to have these bone formation tests ordered at the same time, during the same lab draw, as the bone resorption markers like the CTX and NTX.

• It’s also good to know that there are factors that can cause variation in the test results including the time of day, the season, food intake, physical activity and others. So, when you have these tests done, go get them done first thing in the morning, while you’re fasted.

What can the results tell me?

A high level of one or more bone markers could mean an increase in bone breakdown or an increase in bone formation.

What bone markers won’t tell you is the cause…because they’re not diagnostic.

Conditions that can cause elevated levels of these markers, especially for bone resorption, include:

• Hyperparathyroidism

• Hyperthyroidism

• Paget disease

• Cancer that has spread to the bone (metastatic bone disease)

• Osteomalacia in adults and rickets in children—lack of bone mineralization, often due to vitamin D or calcium deficiency

• Chronic kidney disease (renal osteodystrophy)

• Excess use or high doses of glucocorticoids or Cushing syndrome

• Fracture. These markers can stay elevated 4-12 months after sustaining a fracture.⁵

A low or normal level would suggests no excessive bone turnover.

So, if you’ve been diagnosed with osteoporosis via DEXA scan, you get these tests run and your levels are low or normal, it could be an indicator that you’re not actively losing bone, and you just never achieved peak bone mass.

If you come to find you have high or really low levels of certain markers, you’ll want to work with your doctor to figure out what could be contributing to the results. I’d also consider monitoring at least twice a year, or even more frequently, depending on the circumstances.

If you’re working with an endocrinologist or a rheumatologist, or another type of bone health specialist, there is a good chance they will already be familiar with these bone turnover marker tests and may already order some of these tests in their patient work up.

If you’re working with your primary care doctor, they may not be as familiar and may be reluctant to order...So, first, try finding a doctor who understands bone health. If not, or if you can’t, don’t be afraid to express to your physician your desire to order these tests.

There is one more test that I want to talk about that I think is important for everyone who has osteoporosis to have done and that’s the 24 Hour Urine Calcium Test.

24 Hour Urine Calcium Test

Now this 24 Hour Urine Calcium test is different from bone turnover markers in that it’s not looking at the collagen based by-product or the secretion of one of the bone cells.

It’s looking at calcium. If you’re excreting high amounts of calcium, it could be an indicator of bone loss. All you’re doing for this test is collecting your urine for 24-hours with some sort of collection cup and a jug to pour it in and then you bring it back to the lab for analysis.

This 24 Hour Urine Calcium test essentially helps identify if you’re peeing out too much calcium. This is called hypercalciuria, which I talked about in episode 3 on causes of osteoporosis.

So, how do you know if you’re peeing out too much calcium? What’s a high amount?

The standard reference range that’s considered normal is 100 - 300 mg/24 hrs. If you’re taking in 1,200mg calcium a day, most would agree that your urine calcium levels should be less than 300mg.

Ideally, you want to be on the lower to middle end of this range. 100, 150 even 200...And that’s considered about average for most adults even without osteoporosis.

If your levels are greater than 300 in 24 hours (>300 mg/24 hr) it could be an indicator that you’re either taking in too much calcium, too much salt, or it could also be a sign of a parathyroid issue, or one of the other causes of hypercalciuria I outlined in the episode 3.

So, if your 24 Hour Urine Calcium comes back elevated, work with your doctor to identify the cause, because it may only be something that requires some nutritional adjustments.

When it comes to testing in general, the part I see most people struggle with is having the conversation with their doctor about why they would like the testing to be done.

Some of the reasons as to why I personally consider these tests important:

• You’re trying to understand if you’re actively losing bone...because if you are actively losing bone...and there is a secondary cause of your low bone density...the cause needs to be addressed before your bones can get better. If you haven’t listened to Episode 3 where I talk about secondary causes of osteoporosis, I’d highly recommend that you check that out.

• You’re trying to establish a baseline from which to monitor future bone formation and resorption

• They can be helpful in identifying how changes you’ve made regarding diet, lifestyle, and supplementation are impacting your bone health.

At the very least, have a conversation with your doctor about monitoring at least one of each of these: one of each of the bone turnover markers (Let’s say it’s CTX and Osteocalcin) and then that 24 Hour Urine Calcium test. If you can get more than one of each, even better.

If for some reason your doctor won’t order these tests, or they make it really hard for you, and you can afford it, don’t worry, you can still pay-out-pocket and order some these tests (Like the C-telopeptide, N-telopeptide, Osteocalcin, Bone-Specific Alkaline Phosphatase, and others) online. You would just order the tests and find a lab to conduct the blood draw. If you choose to order them on your own, I’ll link to those lab tests in the show notes which you can find at bonecoach.com/bone-turnover-markers.

Last thing I want to mention with regards to bone turnover markers, and I think this is a great transition to the next podcast episode, is that they are frequently used to help monitor treatment with osteoporosis medications (like Bisphosphonates and some of the others).

If you’re newly diagnosed with low bone density or osteoporosis, you may have heard your doctor mention these medications...and you may be wondering, like I did, if those osteoporosis drugs should have a part in improving your bone health.

For me, as part of my own personal bone health journey, after taking my circumstances into account, learning about the osteoporosis drugs on the market along with their side effects, I made the decision not to use any osteoporosis medications and instead opted to focus on optimizing diet, lifestyle, supplements, exercise, and other areas of my life as the means for improving my bone health.

And that’s why a major focus of this podcast, especially in future episodes, is focused on the diet and lifestyle aspects of bone health.

Now, we’re all different...our circumstances are different…yours are different than mine...mine are different than the next persons…but I think there’s some helpful, general information to have about osteoporosis medications as you’re making the decision for yourself. That’s what that next episode is all about.

In the next episode, I’m going to talk about osteoporosis medications, how I reached my decision to forgo them, and why diet, lifestyle, proper supplementation, and exercise are all going to be key for improving your bone health, regardless of the choice you make.

Remember, when you use these bone turnover markers, they can help you answer the single most important question you need to know at this point…

Am I actively losing the bone.

And it can also help prevent any surprises in between now and your next bone density scan which may be 1-2 years away.

If you know someone who could benefit from understanding what’s taking place with their bone health, maybe it’s a coworker, a friend, an aunt, a mother, or even a group of people, you can share this information with them by clicking the 3 little dots in the bottom right hand corner and sharing via text, email, or even on social media.

Thanks again for listening to the show.

I think that’s it for this one, I’m your Bone Coach Kevin Ellis...see you in the next episode.

[blogSourcesStart]

1 - https://labtestsonline.org/tests/bone-markers

2 - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5105571/

3 - https://labtestsonline.org/tests/bone-markers

4 - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4566462/

5 - https://www.ncbi.nlm.nih.gov/pubmed/17488197

[blogSourcesEnd]