Your skeleton is a never-ending home repair project. Throughout your lifetime, you experience the breakdown and removal of bone tissue (resorption) and the creation of new bone (formation). This is an expected, healthy process known as bone turnover.
If your body breaks down more bone that it forms, your bones start to lose density and become weak and brittle. Eventually, you may be diagnosed with osteoporosis using an enhanced form of X-ray technology called a dual-energy X-ray absorptiometry (DXA) scan. This scan uses a tiny amount of radiation to measure bone density, or how many grams of calcium and other bone minerals are packed into a unit of bone segment. DXA scans can also be used to monitor treatment for osteoporosis.
To complement the information obtained from a DXA scan, some clinicians may add certain specialized labs tests called bone turnover markers (BTMs).
Bone turnover markers are simple lab tests that measure how fast your bone is being formed and broken down. These markers represent tiny materials, such as bits of collagen, that are released into your blood and urine when bone is built up or broken down. BTMs can be measured on samples of your urine or blood.
There are two types of BTMs: Those that monitor resorption and those that monitor bone formation.
- Bone resorption markers. Bone resorption markers such as cross-linked C-telopeptide of type 1 collagen (CTX) can be measured in blood. Others such as N-terminal telopeptide (NTX) can be measured in blood or, more popularly, in urine.
- Bone formation markers. A popular bone formation marker is bone-specific alkaline phosphatase (BSAP). It is measured in blood.
In osteoporosis, both types of bone turnover markers may be high.
Krupa B. Doshi, M.D., a Mayo Clinic endocrinologist, routinely uses BTMs in her practice. She answers our questions about how they work best.
Who is a good candidate for getting bone markers checked?
First, not everyone who has osteoporosis needs to have bone turnover markers measured. However, if a clinician needs to measure the rate of change of bone turnover, then monitoring them over time can be pretty helpful.
I find checking these markers most helpful when starting an oral medication for osteoporosis such as a bisphosphonate. Oral bisphosphonates — such as alendronate (Binosto, Fosamax), ibandronate (Boniva) and risedronate (Actonel, Atelvia) — can make the bone stronger and denser, through reducing bone resorption. BTMs can be an important measurement option with oral bisphosphonates because oral bisphosphonates are poorly absorbed. In fact, only 1% to 5% of the medicine is actually absorbed in the gut. So one way to find out quickly if someone is absorbing the medicine is to measure BTMs before starting the medication and then again after it’s been taken for a few months. If the BTMs drop significantly, we know that the individual is taking the medicine as prescribed and the medicine is being absorbed in a sufficient quantity to be effective.
Why wouldn’t you just use a bone density test?
Bone density is far slower to change. So, an optimal interval for repeating a DXA scan is at least one year or longer because a rapid change in a bone density test in a short time is not expected. Thus, bone markers save time since they can be done much sooner — in several months rather than a year or more.
Medications that are currently used to treat osteoporosis greatly reduce fracture risk. Unfortunately, overall adherence to current therapies is quite low. Therefore, optimal fracture reduction is frequently not achieved in clinical practice. Thus, besides bone density tests (which are slow to change), a critical need was felt for newer and faster ways to show people that these medications are effective. Showing them that their marker has changed when they take their medications is an excellent way for people to feel confident that their treatment is working.
If you take the example of managing hypertension with a new blood pressure medication, you can actually see that blood pressure is better a few weeks after starting to take the medication. Similarly, having your cholesterol panel compared before and several weeks after starting your cholesterol-lowering therapy can give you a lot of confidence that the medicine is working well. Recently, BTMs have entered that space for osteoporosis. They are an easy way to show people with osteoporosis, “Hey, this medicine is effective for you.”
How else do you use bone turnover markers?
Because bisphosphonates are incorporated in the skeleton and continue to exert their anti-fracture effect for a considerable period of time after stopping the drug, a concept of a “drug holiday” has emerged when taking this group of medications. During this period, a person’s risk of fracture continues to remain low because the medicine is still working for them. On the plus side, stopping the medication for a brief period does tend to lower the individual’s long-term risk of adverse effects.
BTMs are great monitoring tools for people who are on a “drug holiday” from bisphosphonate therapy. Once the medication is stopped, a measurement of the BTM is taken as a new baseline after the end of treatment and again periodically. A significant increase would indicate that the effect of the medicine is wearing off and it may be time to think about restarting treatment to further lower the fracture risk. Serial DXA scans can also be used to monitor this, but the marker tends to rise earlier than a density change via DXA scan. Often, both measurement tools are used together.
If I feel an individual is at high risk of fracture, I tend to offer re-treatment if the markers start rising significantly and I may not wait for the bone density to change. On the other hand, if an individual is just at a moderate risk of fractures, has never had a fracture in the past, and is otherwise doing well, I may wait until I see a little bit of both. And the individual’s preference matters too.
Who is not a good candidate for monitoring bone turnover markers?
BTMs are not of much help in monitoring people on anabolic therapy. Anabolic therapies — such as teriparatide (Forteo), abaloparatide (Tymlos) and romosozumab (Evenity) — work by stimulating bone formation, which leads to increases in bone mass and density. Since new bone is being built, the markers are expected to increase and are not helpful in the decision-making process. There is also no role for monitoring after completion of anabolic treatment, as all these agents should be followed by treatment with anti-resorptive drugs without a pause in treatment.
And then there are other scenarios in which specific BTMs may not be useful. Some markers are cleared through the kidneys, and so in those with chronic kidney disease you can rely on some, but not all, markers.
Drugs can also affect bone turnover markers. For example, glucocorticoids such as prednisone or hydrocortisone suppress bone turnover markers, especially bone formation markers. Therefore, bone turnover markers can only be helpful if a person’s glucocorticoid dose remains the same.
Do these markers need to be measured in a specific way?
Yes, absolutely. Since bone turnover varies during the day, and can be affected by food intake, a morning collection after fasting is preferred for blood measurements. If this is not possible, collecting the baseline and subsequent specimens under the same circumstances is advisable (for example, at the same time of day). Markers can also vary with different laboratories; therefore, I encourage my patients to have their measurements done in the same lab.
How commonly are bone turnover markers used?
Bone density tests using DXA scans are still much more commonly used in current clinical practice, but markers are kind of making their mark, so to speak, particularly in the area of bisphosphonate treatment monitoring.
In the U.S., current clinical guidelines say to use bone turnover markers in the right clinical setting, if necessary. They don’t mandate it, and they don’t strongly recommend it. This is because compared with bone density tests, the markers have not been validated to the same extent by big clinical studies, and guidelines are evidence based.
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