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.

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.

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.

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

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