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Osteoporosis bone markers are valuable tools that help your doctor assess and monitor your bone health. Your access to bone turnover marker testing may vary depending on several factors: where you live, what type of insurance you have, and whether your physician is familiar with and comfortable using these tests.
To help you understand bone markers better, I spoke with Dr. Stuart Silverman, an expert in bone health. Dr. Silverman runs a private rheumatology practice and serves as a clinical professor of medicine at both Cedar-Sinai in Los Angeles and UCLA. His passion for understanding and treating osteoporosis spans decades – he even helped develop and launch nasal spray calcitonin in its early stages.
Osteoporosis Bone Markers
As an experienced practitioner, Dr. Silverman regularly uses osteoporosis bone markers in his practice and considers them invaluable diagnostic tools. His expertise extends beyond clinical practice – he has contributed to important bone turnover marker research with the International Osteoporosis Foundation (IOF). The IOF has worked to standardize these markers and make them more practical for both patients and their doctors.
But before we dive into what bone turnover markers are, let’s understand something fundamental: how your bones constantly rebuild themselves through a process called bone turnover.
Bone Loss and Formation: How Bone Turnover Works
Your bones are alive and constantly renewing themselves through two key bone remodeling processes: resorption and formation. Think of it as your body’s natural renovation project.
During bone resorption, special cells called osteoclasts act like tiny demolition crews. They create small pits in your bone by breaking down old or damaged bone tissue.
Next comes bone formation, where builder cells called osteoblasts get to work. These cells fill those pits with fresh bone material called osteoid, which then hardens with calcium. It’s like pouring and setting new concrete to repair a damaged sidewalk.
This continuous cycle of breakdown and rebuilding serves two important purposes:
- It repairs tiny cracks in your bones
- It helps your bones adapt to physical stress
A complete renovation of any bone area takes about three months. In healthy bones, this process stays balanced – your body removes and rebuilds the same amount of bone tissue. However, in conditions like osteoporosis, this balance tips: your body breaks down more bone than it rebuilds, leading to weaker bones over time.
What Are Bone Turnover Markers?
Doctors can measure how quickly your bones are remodeling by checking specific substances in your blood called bone turnover markers. These markers show up during bone breakdown and bone formation, giving your doctor valuable clues about your bone health.
Think of these markers as leaving footprints in your blood – they reveal how active your bone remodeling process is. Your doctor can track these markers through various blood tests, also called assays.
Let’s explore the different types of osteoporosis bone markers and what they can tell us about your bone health.
Which Serum Level Indicates the Rate of Bone Turnover?
Leading medical organizations have joined forces to recommend specific tools for measuring bone turnover. The International Osteoporosis Foundation (IOF), European Calcified Tissue Society (ECTS), and International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) all agree on using two key serum level (blood) tests:
- P1NP (N-terminal propeptide of type one collagen) for measuring bone formation
- CTx for measuring bone breakdown
Let’s examine this further :
- When your bone-building cells (osteoblasts) are at work, they release P1NP into your bloodstream
- When your bone-breakdown cells (osteoclasts) are active, they release CTx
By measuring these markers in your blood, your doctor can tell whether your bones are building up or breaking down too quickly.
How Do Postmenopausal Osteoporosis Bone Markers Measure Bone Formation and Resorption?
How do doctors measure bone formation and breakdown using osteoporosis bone markers? The secret lies in tracking specific proteins in your blood that appear during bone remodeling.
Think of it this way:
- When new bone forms, it leaves behind fragments of collagen in your blood
- When bone breaks down, pieces of amino acids get released into your bloodstream
Doctors focus on two key markers to monitor these processes:
- P1NP (N-terminal propeptide of type one collagen)
- This appears when new bone is being built
- It’s like finding sawdust that shows where construction is happening
- CTx (C-terminal telopeptide)
- This shows up when bone is being broken down
- It’s similar to finding debris from a demolition site
Exercise and Osteoporosis
Dr. Silverman told me that a well constructed exercise program therapeutic exercise needs to be part of your osteoporosis treatment program.
But what exercises should you do and which ones should you avoid? What exercises build bone and which ones reduce your chance of a fracture? Is Yoga good for your bones? Who should you trust when it comes to exercises for osteoporosis?
A great resource on exercise and osteoporosis is my free, seven day email course called Exercise Recommendations for Osteoporosis. After you provide your email address, you will receive seven consecutive online educational videos on bone health — one lesson each day. You can look at the videos at anytime and as often as you like.
I cover important topics related to osteoporosis exercise including:
- Can exercise reverse osteoporosis?
- Stop the stoop — how to avoid kyphosis and rounded shoulders.
- Key components of an osteoporosis exercise program.
- Key principles of bone building.
- Exercises you should avoid if you have osteoporosis.
- Yoga and osteoporosis — should you practice yoga if you have osteoporosis?
- Core strength and osteoporosis — why is core strength important if you have osteoporosis?
Enter your email address and I will start you on this free course. I do not SPAM or share your email address (or any information) with third parties. You can unsubscribe from my mail list at any time.
Osteoporosis Bone Marker P1NP: Bone Formation Marker
Let’s explore how your bone-building cells (osteoblasts) create bone markers we can measure. When these cells are working, they produce two types of substances:
- Special enzymes and proteins that show osteoblast activity
- Type 1 collagen, which we track through P1NP (marker of bone formation)
The collagen story is particularly fascinating. Think of building bone like crafting a rope:
- First, your body creates strands of collagen (called procollagen)
- Before these strands can be twisted together into their final form (the triple helix), they need trimming
- The trimmed pieces don’t go to waste – doctors can measure these fragments to understand how much new bone you’re building [1]
Osteoporosis Bone Marker CTx: Bone Resorption Marker
Just as we can track bone building, we can also measure bone breakdown by watching what osteoclasts (your bone breakdown cells) leave behind. The key marker doctors look for is CTx.
Think of your bones’ collagen structure like a tightly woven fabric. When osteoclasts break down bone:
- The collagen fibers begin to unravel
- Small pieces break free
- These fragments (called CTx) float into your bloodstream
When your doctor tests your blood for CTx levels, a marker of bone resorption, they’re essentially measuring how quickly your bones are being broken down. It’s like finding threads from a unraveling sweater – the more threads you find, the more the sweater is coming apart.
Clinical Use of Bone Markers in Osteoporosis Treatment
While bone turnover markers help doctors understand how osteoporosis medications work [2], using them to guide individual treatment can be tricky. Why? The test results can vary between laboratories, and doctors are still learning the best ways to interpret these results.
Dr. Silverman has developed a practical approach to overcome this challenge. He uses a three-point diagnostic triangle that combines:
- Bone markers (showing dynamic bone activity)
- DEXA scans (measuring bone density)
- Trabecular Bone Score (TBS) (assessing bone quality)
Before considering any medications, Dr. Silverman starts with the basics:
- A tailored osteoporosis exercise program
- Proper nutrition guidance
Think of the diagnostic triangle like a three-legged stool:
- Two legs (bone density and quality) give you a snapshot of your current bone health
- The third leg (bone markers) shows how quickly your bone tissue is changing
Let’s explore each of these measurements in detail and understand how they work together to create a complete picture of your bone health.
Source: Dr. Stuart Silverman
Static Measures of Bone Health
The health history of your bones can be told through two key snapshots:
- Bone Quantity: The DEXA Score
- Think of this like measuring bone mass or how much bone material you have
- It’s similar to weighing your bones
- Bone Quality: The Trabecular Bone Score (TBS)
- This reveals your bone’s internal architecture
- Imagine it as examining your bones’ internal scaffolding
Together, these static measurements form the foundation of Dr. Silverman’s diagnostic pyramid. They’re like reading the history book of your bones – telling the story of how your bones have changed over time.
Dynamic Measures of Bone Health
At the top of Dr. Silverman’s diagnostic pyramid sits the most dynamic measure: bone turnover markers. While DEXA and TBS tell us about your bone’s past, these markers give us a glimpse into its future.
Think of it this way:
- DEXA and TBS are like looking at a photograph of your bones
- Bone markers are more like watching a live video of what’s happening right now
These markers help Dr. Silverman answer crucial questions about your current bone health:
- Are you actively losing bone tissue?
- Is your medication working to stop bone loss?
- Is your treatment successfully building new bone?
It’s like having a real-time monitor of your bone activity s, helping guide treatment decisions when they matter most.
Blood or Urine Test for Bone Turnover Markers?
Dr. Silverman explained several options for testing biochemical markers of bone turnover. While you can measure N-telopeptide (NTx) through a urine test, he recommends following the International Osteoporosis Federation’s (IOF) preferred method of blood or serum tests.
These tests, which measure serum CTx and P1NP, provide more reliable results than urine tests like NTx, which can show significant variability. Though some healthcare providers still use the NTx urine test, Dr. Silverman follows the IOF guidelines and uses the CTx serum test for more consistent results.
How Dr. Silverman Uses Bone Markers for the Treatment of Osteoporosis
To assess a patient’s complete bone health, Dr. Silverman combines three key measurements:
- Bone density (DEXA)
- Bone quality (TBS)
- Bone markers
This comprehensive approach helps him identify patients who need treatment, even when some test results appear normal. For instance, a patient might show:
- Moderate bone loss (osteopenia) on their DEXA scan
- Normal bone quality on their TBS test
- BUT their bone markers reveal rapid bone loss
In these cases, Dr. Silverman may recommend starting medication to prevent future fractures, rather than waiting until more serious bone loss occurs. By tracking all three measurements, he can catch and treat bone loss early, helping patients maintain their bone health.
Exercise Recommendations for Osteoporosis
Dr. Silverman told me that a well constructed exercise program therapeutic exercise needs to be part of your osteoporosis treatment program.
But what exercises should you do and which ones should you avoid? What exercises build bone and which ones reduce your chance of a fracture? Is Yoga good for your bones? Who should you trust when it comes to exercises for osteoporosis?
A great resource on exercise and osteoporosis is my free, seven day email course called Exercise Recommendations for Osteoporosis. After you provide your email address, you will receive seven consecutive online educational videos on bone health — one lesson each day. You can look at the videos at anytime and as often as you like.
I cover important topics related to osteoporosis exercise including:
- Can exercise reverse osteoporosis?
- Stop the stoop — how to avoid kyphosis and rounded shoulders.
- Key components of an osteoporosis exercise program.
- Key principles of bone building.
- Exercises you should avoid if you have osteoporosis.
- Yoga and osteoporosis — should you practice yoga if you have osteoporosis?
- Core strength and osteoporosis — why is core strength important if you have osteoporosis?
Enter your email address and I will start you on this free course. I do not SPAM or share your email address (or any information) with third parties. You can unsubscribe from my mail list at any time.
Clinical Applications of Bone Markers
Dr. Silverman uses bone turnover markers in five important ways to monitor and improve patient care:
- Tracking Response to Bone-Building Medications. When patients take bone-forming medications like teriparatide or abaloparatide, Dr. Silverman monitors their P1NP levels. A rise in this bone formation marker indicates the treatment is working effectively.
- Confirming Treatment Adherence. The CTx bone marker helps Dr. Silverman verify that patients are taking their prescribed medications. Following IOF guidelines, he looks for a drop in CTx levels when patients start medications like oral bisphosphonates – a clear sign they’re following their treatment plan.
- Managing Drug Holidays. For patients taking oral bisphosphonates, Dr. Silverman uses bone markers to:
- Monitor treatment effectiveness during the typical 3-5 year treatment period
- Determine when medication effectiveness begins to decline
- Guide decisions about continuing or pausing treatment
- Adjusting Treatment Frequency. When managing treatments like IV zoledronic acid (an infusion form of bishophonate), bone markers help Dr. Silverman:
- Monitor effectiveness of preventive doses given every two years
- Detect declining effectiveness
- Decide whether to adjust treatment intervals to one or two years
- Enhancing Fracture Risk Assessment. Dr. Silverman combines bone marker results with DEXA scans to create a more complete picture of bone health. This dual approach helps him:
- Identify patients who need treatment even when their DEXA scores fall just below treatment thresholds
- Better assess fracture risk in patients with high bone turnover
- Make more informed treatment decisions
Important Note: While bone markers provide valuable insights, Dr. Silverman emphasizes that they should not be used alone to make treatment decisions. The management of osteoporosis and metabolic bone disease is more complex than that. Instead, they work best when combined with bone density and quality measurements and other clinical factors to guide patient care.
Understanding Bone Marker Test Variability
Bone marker tests have become more reliable as clinicians better understand how to control various factors that affect test results. Dr. Silverman contributed to this advancement through his work with the 2012 National Bone Health Alliance project [3], which helped standardize sample collection procedures and establish reference ranges for P1NP and CTx tests.
Factors You Can Control Before Testing:
- Fast for 8-10 hours before the blood draw
- Avoid exercise before the the blood draw
- Schedule blood draws at the same time of day to account for circadian rhythm
- Stop taking supplements as directed before the blood draw
Factors Beyond Control:
- Age
- Sex
- Ethnicity
- Recent fractures (which increase bone turnover and marker levels)
- Kidney or liver function
Laboratory Considerations:
Your test results will be most reliable when you:
- Use the same accredited laboratory for all tests
- Ensure the lab follows proper reference standards
Insurance Coverage for Bone Marker Tests:
Before scheduling regular bone marker tests:
- Check with your health insurance provider about coverage
- Ask how frequently they will cover these tests
- Confirm which specific tests are included in your plan
This careful attention to testing conditions helps provide more accurate results that your healthcare provider can use to guide your treatment decisions. While past variability issues limited the use of bone marker tests, today’s standardized procedures make them a valuable tool for monitoring bone health.
How to Measure Changes in Bone Markers
Clinicians use a concept called “least significant change” to determine meaningful differences between test results, be it positve or negative. Here’s what they look for:
- Urine NTX test: A 50% decline between readings to indicate changes in fracture risk
- Serum CTx and P1NP tests: A 30% decline between scores
Understanding What Bone Markers Tell Us
Bone markers serve as valuable predictors of:
- Rate of bone loss
- Future fracture risk
However, it’s important to note that bone markers alone cannot diagnose osteoporosis. Research supports their predictive value – for example, the 2005 OFELY study [4] that Dr. Silverman often references identified three independent factors that increase fracture risk:
- Low bone mineral density (BMD)
- Elevated bone markers
- History of prior fractures
This research helps explain why doctors, like Dr. Silverman, use bone markers alongside other measurements and patient health history to assess a patient’s overall bone health and fracture risk.
Current Use of Bone Turnover Markers
Dr. Silverman explains that the use of bone marker tests varies significantly among medical providers. While he regularly uses them in his Los Angeles clinic, adoption depends largely on a specialist’s training and experience.
Who typically uses bone marker tests:
- Endocrinologists
- Rheumatologists
- Specialized bone health clinics
Who rarely uses bone marker tests:
- Primary care physicians
- General practitioners
This limited adoption highlights that bone marker testing remains a specialized tool, primarily used by doctors who focus on bone health and metabolic disorders. As understanding of these tests grows and standardization improves, their use may become more widespread in general medical practice.
Bone Markers and After Discontinuing Prolia/Xgeva (Denosumab)
When patients stop taking Prolia, they face a unique challenge: rapid bone loss that can lead to spinal fractures in as little as seven months after their last injection, from my clinical observation. While all osteoporosis medications show some bone loss after Prolia discontinuation, Prolia’s effects are particularly swift and severe compared to other treatments like Fosamax, which may take five years to show significant decline.
Current Treatment Protocol
For patients completing five years of Prolia treatment, doctors typically prescribe an antiresorptive medication, usually IV Reclast (zoledronic acid) as a follow-on agent. The recommendations regarding the usage of bone markers to monitor bone loss, however, vary from region to region.
The European Calcified Society (ECTC) [5] recommends the following:
- Use zolendronic acid as a follow-on agent
- Three to six months after the IV injection, monitor changes in bone activity with bone markers
Using Bone Markers to Prevent Fractures
Dr Silverman states that bone markers, particularly CTx, can play a vital role in monitoring patients after Prolia discontinuation. He recommends:
- Check bone markers six months after last the last Prolia injection to assess treatment response
- Test again at six months later to confirm continued effectiveness
- Consider a second IV zolendronic acid injection if CTx levels indicate ongoing bone loss
Why This Matters
This monitoring strategy helps doctors:
- Identify patients who aren’t responding well to IV zolendronic acid
- Catch dangerous bone loss before fractures occur
- Adjust treatment plans promptly when needed
This new approach using bone markers represents an important advance in protecting patients during the critical transition period after stopping Prolia.
Getting Bone Marker Tests in the United States
Major commercial laboratories offering bone marker tests include:
- Quest Diagnostics
- LabCorp
Cost and Ordering Process
- The CTx test typically costs around $200
- Doctors can order the test on standard laboratory requisition forms
- No special laboratory arrangements needed – your doctor can use their regular lab service provider
Making Testing Easier
This straightforward testing process means your doctor can:
- Order bone marker tests alongside other routine blood work
- Use their existing relationship with commercial labs
- Monitor your bone health through established testing networks
Remember to check with your insurance provider about coverage for these tests, as policies vary regarding bone marker testing frequency and reimbursement.
Conclusion and Summary
Osteoporosis bone markers provide a dynamic view of bone health, complementing static measures like DEXA and TBS. While variability has historically limited their use, advancements in standardization and interpretation are expanding their role in osteoporosis care.
By integrating bone markers into a broader diagnostic framework, Dr. Silverman exemplifies how these tools can guide personalized treatment decisions, improve medication adherence, and reduce fracture risk. For patients, understanding the factors that influence test results and staying informed about treatment options are crucial steps toward maintaining bone health.
Margaret Martin
Further Readings
References
- Lumachi F, Ermani M, Camozzi V, Tombolan V, Luisetto G. Changes of bone formation markers osteocalcin and bone-specific alkaline phosphatase in postmenopausal women with osteoporosis. Ann N Y Acad Sci. 2009 Sep;1173 Suppl 1:E60-3. doi: 10.1111/j.1749-6632.2009.04953.x. PMID: 19751416.
- Naylor KE, Jacques RM, Paggiosi M, et al. Response of bone turnover markers to three oral bisphosphonate therapies in postmenopausal osteoporosis: the TRIO study. Osteoporos Int 2016;27, 21–31.
- Bauer D, Krege J, Lane N, Leary E, Libanati C, Miller P, Myers G, Silverman S, Vesper HW, Lee D, Payette M, Randall S. National Bone Health Alliance Bone Turnover Marker Project: current practices and the need for US harmonization, standardization, and common reference ranges. Osteoporos Int. 2012 Oct;23(10):2425-33. doi: 10.1007/s00198-012-2049-z. Epub 2012 Jul 14. PMID: 22797491; PMCID: PMC4011662.
- Sornay-Rendu E, Munoz F, Garnero P, Duboeuf F, Delmas PD. Identification of osteopenic women at high risk of fracture: the OFELY study. J Bone Miner Res. 2005 Oct;20(10):1813-9. doi: 10.1359/JBMR.050609. Epub 2005 Jun 20. PMID: 16160738.
- Tsourdi E, Zillikens MC, Meier C, Body JJ, Gonzalez Rodriguez E, Anastasilakis AD, Abrahamsen B, McCloskey E, Hofbauer LC, Guañabens N, Obermayer-Pietsch B, Ralston SH, Eastell R, Pepe J, Palermo A, Langdahl B. Fracture risk and management of discontinuation of denosumab therapy: a systematic review and position statement by ECTS. J Clin Endocrinol Metab. 2020 Oct 26:dgaa756. doi: 10.1210/clinem/dgaa756.
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