Bone Biomarkers in Osteoporosis

Diagnosis of osteoporosis depends almost exclusively on bone density tests with the doctor’s judgment informed by history of bone breaks, changes in height and stature, etc. Here is one way osteoporosis is different from other common diseases – blood and urine tests are not a big part of the diagnostic work-up. Patients are usually given these tests, as part of their routine trips to the doctor, but routine tests do not include chemical analysis that specifically looks for bone metabolism markers.

Although imaging is the first line of diagnosis there is scientific and medical interest in blood or urine tests to aid in uncovering osteoporosis, osteopenia, and other metabolic diseases of the bone.  "Bone turnover markers" are chemicals in the bloodstream that may be useful in determining the rate of bone demineralization.  BTMs can help tell whether bone disease is happening or immanent and whether treatment – antiresorptive or anabolic - is doing any good.

BTMs are useful in development and proof of efficacy of new drugs.  They have other research uses but have not found wide use in clinical diagnostics.  Which is too bad because they may have some advantages to the bone mineral density tests currently used.

Bone mineral density (BMD) has its own problems with repeatability, and even with a foolproof method that is lock-tight reliable, BMD can identify a density at a snapshot in time, but to see if things are getting better or worse you have to wait 6 months or a year.  BTMs can theoretically (if the test is precise) get at whether the conditions are favorable for bone desorption or deposit of minerals in the bony tissue.

Biomarkers could potentially be useful for choosing treatments.  Given the number of different drugs available to manage bone loss, such markers would come in handy.

Biomarkers could also be useful for predicting who is at risk for fracture or for low bone density in the future.  They might also prove useful for determining possible causes of secondary osteoporosis.

Deoxypyridinoline is one such physiological marker that shows up in the urine and has been talked about as a useful BTM.

Possible markers that scientists have looked at include soluble receptor activator of nuclear factor-?B ligand-(sRANKL), osteoprotegerin (OPG), and bone alkaline phophatase (BAP),

The sex hormone estradiol. which is tied up with menopause, has also bee mentioned as has the bone protein osteocalcin which is found in the blood in greater concentration when bones are remodeling.

Trace minerals in the blood and bone (zinc, magnesium) have been proposed, and blood, calcium levels are already part of laboratory blood tests when bone disease is known or suspected.

If the doctor orders the tests and the lab is capable, blood levels of bone building enzymes and proteins (alkaline phosphatase, osteocalcin, procollagen +(C1NP or P1NP)) can be measured. The products of bone breakdown can also be measured. These include cross-linked C-telopeptide (CTX) in the blood or urine and collagen fragments (hydroxyproline or pyridinoline) and protein-collagen fragment complexes in the urine.

CTX is getting a lot of attention partly because of a relatively new test called Serum CrossLaps® which is sensitive and can tell doctors a lot about the dynamic state of the skeleton. A high CTX level in the blood indicates rapid bone breakdown, although there is not yet a widespread consensus on what levels constitute high risk and call for additional treatment.

Scientists have begun to speak of bone turnover markers (BTMs) as an insight into remodeling of the tissue in the skeleton, especially in times of rapid (by bone standards) gain or loss. BTMs could be used in an initial diagnosis, but they would also find use in monitoring response to treatment, where changes in bone density would take a long time to show up and which might be limited by the accuracy and consistency of the DEXA scans.

The application of bone turnover markers in clinical use is something the osteoporosis research and advocacy movement has been pushing for.

Improvements in automation and standardization of analyses may make clinical use of bone markers viable.  Some British scientists claim "BTM levels respond rapidly to both anabolic and antiresorptive treatments" although their paper did not specify which biomarkers they are referring to.

An article in the Global Library of Women’s Medicine stated that “biochemical tests are inadequate to diagnose low BMD.” 1 However, it did list some biomarkers:

A recent review identifies low 25-hydroxyvitamin D and hemoglobin A1c as biomarkers.

Bone resorption

Lysylpyridinoline (LP)
Deoxylysylpyridinoline (Dpd)
Urinary C-telopeptide of collagen cross-links (PICP)
Urinary N-telopeptide of collagen cross-links (uNTX)
Serum C-telopeptide of type 1 collagen (sCTX)
Serum N-telopeptide of type 1 collagen (sNTX)

Bone formation

Bone-specific alkaline phosphatase (BSAP)
Carboxy-terminal propeptide of type 1 collagen (P1CP)
N-terminal propeptide of type 1 collagen (P1NP)

The protease Cathepsin Z has attracted attention as a potential biomarker for bone thinning.

There is also interest in use of bone biomarkers for diagnosis and treatment of other diseases, such as arthritis. See also: biomarkers of aging.

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