Bone Markers

Below is a list of some of the known bone resorption and bone formation bone markers determined in blood and/or urine specimens. Research is ongoing for new biomarkers that can predict abnormal bone loss in various disease states. For many of these markers, caution is required in interpreting test results due to intraindividual variability from diet, exercise, and time of day sample collected.

Urine or blood tests for bone resorption include:

• C-telopeptide (C-terminal telopeptide of type 1 collagen (CTx)) – a peptide fragment from the carboxy terminal end of the protein matrix; aids in monitoring antiresorptive therapies, such as bisphosphonates and hormone replacement therapy, in postmenopausal women and people with low bone mass (osteopenia)
• N-telopeptide (N-terminal telopeptide of type 1 collagen (NTx)) – a peptide fragment from the amino terminal end of the protein matrix; it is recommended that the test be performed at baseline before starting osteoporosis therapy and again 3 to 6 months later
• Deoxypyridinoline (DPD) - a collagen breakdown product with a ring structure
• Pyridinium Crosslinks - a group of collagen breakdown products that includes DPD; used to monitor therapy response; not as specific for bone collagen as the telopeptides
• Tartrate-resistant acid phosphatase (TRAP) 5b – 5b is the isoform of TRAP produced by osteoclasts during bone resorption

Bone formation blood tests include:

• Bone-specific alkaline phosphatase (ALP) – one of the isoenzymes (types) of ALP; it is associated with osteoblast cell function and thought to have a role in bone mineralization; it is recommended that the test be performed at baseline before starting osteoporosis therapy and again 3 to 6 months later; results may be affected by levels of liver ALP
• Osteocalcin (bone gla protein) – a protein formed by osteoblasts; part of the non-collagen portion of the new bone structure; some of it also enters the bloodstream; osteocalcin helps to predict the rate of bone loss in postmenopausal women and can serve as an indicator of the rate of bone remodeling; somewhat helpful in choosing most effective treatment for osteoporosis but not as sensitive to change as are the telopeptides; it is recommended that the test be performed at baseline before starting osteoporosis therapy and again 3 to 6 months later. This test may be affected by use of the drug warfarin.
• P1NP (Procollagen Type 1 N-Terminal Propeptide) – formed by osteoblasts; reflects rate of collagen and bone formation; may be ordered along with bone resorption marker such as C or N-telopeptide; most sensitive marker of bone formation and particularly useful for monitoring bone formation therapies and antiresorptive therapies; it is recommended that the test be performed at baseline before starting osteoporosis therapy and again 3 to 6 months later.

Increased levels of bone markers in urine or blood suggest an increased rate of resorption and/or formation of bone, but they do not indicate the cause. When they are used to monitor anti-resorptive therapy, decreasing levels of the bone resorption markers reflect a response to therapy.

If you are having one or more of these tests performed, you may be asked to fast before having your blood sample taken. Be sure to carefully follow any instructions you are given for the timing of sample collection, such as collecting a second morning void of urine.

There are limitations to the clinical utility of many of these bone markers, but researchers continue to explore ways to improve their clinical use. Their principal use is to gauge the effectiveness of the many therapies used to treat metabolic bone disease and to properly adjust the dose for maximal effect.