Bone is composed of a living protein framework upon which mineral crystals are placed. As bone breaks down, bits of this living protein framework appear in the urine or the blood. Tests of bone breakdown, called bone resorption tests, measure the amount of one specific bone protein in the urine or in the blood, and thus gauge the current rate of bone breakdown. Markers of bone breakdown (known as markers of bone resorption) are simple tests that can help determine if you are currently losing bone or not. Such bone breakdown testing can also indicate if your bone-building program is effective at reducing and normalizing the bone breakdown process.
As bone is broken down, certain bone protein by-products are excreted in the urine or blood. Measurement of the amount of these bone breakdown by-products can determine the rate of bone breakdown. A high rate of bone breakdown is strongly suggestive of current, ongoing bone loss and a greater risk for osteoporotic fracture. A low rate of bone resorption is generally thought to suggest that one’s rate of bone loss is that of the ideal young adult. Most ongoing bone loss is associated with high bone turnover. There is, however, also a situation of “low turnover osteoporosis.” Here, bone testing shows that bone breakdown is low similar to that of healthy young adults, but the rate of new bone formation is even lower.
Two common markers of bone breakdown
The two most widely used bone resorption markers are the N-Telopeptides test (known as NTx) and the C-terminal cross-linked telopeptide test (known as CTx).
Urine NTx test for bone breakdown: This simple urine test looks at the number of cross-linked N-telopeptides of bone type I collagen (NTx) in the urine.
The standard laboratory range for the urine NTx test is very wide. The ideal for post-menopausal women would be an NTx urine level in the high 30s or low 40s. The healthy average for pre-menopausal women, for instance, is around 36 bone collagen equivalent units/mmol creatinine (nM BCE/mM creatinine). The average for men is 27 nM BCE/mM creatinine.
Serum NTx bone breakdown marker: This is a simple blood test that measures the amount of cross-linked N-telopeptides of bone type I collagen (NTx) in the blood. The amount of NTx in the blood is used also to assess the degree of current bone breakdown. The blood draw for this test is to be done first thing in the morning in a fasting state.
For serum NTx, the pre-menopausal mean is 12.6 nM BCE and the male mean is 14.8 nM BCE. The post-menopausal range is very wide and not very useful. The goal for post-menopausal women is to reduce the NTx to as close to the pre-menopausal level as possible without taking bone drugs.
Serum CTx bone breakdown test: CTx is a blood test used to monitor the rate of bone breakdown and the effectiveness of anti-resorptive natural or drug bone therapies. It tests for the C-terminal telopeptide of type I collagen, which is a peptide fragment derived from the carboxy terminal end of the bone protein matrix.
Similar to the urine NTx and the serum NTx, the range for serum CTx is very wide. For instance, Labcorp uses the range of 34 to 635 pg/mL for pre-menopausal women. Unfortunately, the pre-menopausal mean is not documented like with the NTx test, so it is hard to know what the post-menopausal goal should be. Summarizing the research I suggest that 400 or 450 is probably a good level for post-menopausal women not using bone drugs. But we don’t know for sure.
If a woman is on bone drugs that suppress bone breakdown, this marker reflects the degree to which the drug is reducing bone breakdown. If the CTx goes down to the range of 150 to 200 pg/mL, there is a reported risk of osteonecrosis of the jaw.
With any of these tests, values above the ideal range could indicate that bone loss is occurring. In our studies, we like to see more than a 30% reduction in these markers, or normalization to young adult levels.
All these bone breakdown tests should be done first thing in the morning before eating anything (in a fasting state). For at least twelve hours before these tests do not take multivitamins or dietary supplements containing biotin or vitamin B7, which are commonly found in hair, skin, and nail supplements, and multivitamins.
Your physician can order either of these tests or you can order them online and self-pay.
Other tests of interest
In addition to the NTx and CTx tests, three other tests look at calcium levels to determine whether calcium is being lost from the bone:
- the 24-hour urine calcium excretion test,
- the serum blood calcium test, and
- the ionized blood calcium level test.
The 24-hour urine calcium excretion test looks at how much calcium is being excreted in the urine—usually, among other things, this is a sign that the body is too acid. For this test, you collect all your urine over a 24-hour period for laboratory analysis to measure the amount of calcium in the urine. For more information on calcium loss in the urine, see my article Are you losing too much calcium in your urine?
The serum blood calcium test and the ionized blood calcium level test require a blood draw to determine the level of calcium in the blood. Of the two, the ionized calcium level test is more precise. Although blood calcium stays within a fairly tightly controlled range in the blood, small variations in blood calcium levels can provide useful information for your physician.
It’s never too late
It is never too early nor too late to begin building and rebuilding bone, and these tests can, at times, help assure that you are on the right path or uncover a hidden cause for ongoing bone loss. Remember, that bone resorption tests exhibit wide within-subject day-to-day variation. Even with proper collection, shipping, and processing, there is a substantial day-to-day variation in these bone breakdown markers. No single test result should be taken as a “bad sign” or an indication that all is not well; instead, the various tests should be used in concert to get an accurate picture of current bone health.