What are they?
Bone markers are blood and urine tests that detect products of bone remodeling to help determine if the rate of bone resorption and/or formation is abnormally increased, suggesting a potential bone disorder. The markers can be used to help determine a person’s risk of bone fracture and to monitor drug therapy for patients receiving treatment for skeletal disorders, including osteoporosis.
Bone is a living, growing tissue that turns over at a rate of about 10% a year. It is made up largely of type-I collagen, a protein network that gives the bone its tensile strength and framework, and calcium phosphate, a mineralized complex that hardens the skeletal framework. This combination of collagen and calcium gives bone its hardness, and yet bones are flexible enough to bear weight and to withstand stress. More than 99% of the body’s calcium is contained in the bones and teeth. The remaining 1% is found in the blood. Throughout a person’s lifetime, old bone is constantly being removed (resorption) and replaced with new bone (formation) to maintain a healthy bone structure. During bone resorption, cells called osteoclasts dissolve small amounts of bone, while enzymes dissolve the protein network. Bone formation is then initiated by cells called osteoblasts. They secrete a variety of compounds that help form a new protein network, which is then mineralized with calcium and phosphate to produce new bone. This on-going remodeling process takes place on a microscopic scale throughout the body to keep bones alive and sturdy.
During early childhood and in the teenage years, new bone is added faster than old bone is removed. As a result, bones become larger, heavier, and denser. Bone formation happens faster than bone resorption until you reach your peak bone mass (maximum bone density and strength), between the ages of 25 and 30 years. After this peak period, bone resorption occurs faster than the rate of bone formation, leading to net bone loss. Bone loss is most rapid in women in the first few years after menopause but continues into the postmenopausal years. In men, appreciable bone loss does not usually occur until the middle 70’s.
How are they used?
One or more of the bone marker tests may be ordered to help your doctor determine if you have increased rates of bone resorption and/or formation. Bone markers are sometimes used as an adjunct to bone density testing when doctors are evaluating whether or not your bones are thinning or if you have a bone disease. They are used primarily to monitor response to anti-resorptive therapy for bone disease and to help your doctor determine if the dose of the drug you are receiving is adequate. These tests can enable your doctor to quickly tell if you are responding to anti-resorption or bone formation therapies in a much shorter time period than the X-ray types of bone density testing (three to six months versus one to two years). This way, your therapy can be altered if you are not responding properly to it.
Since breast and prostate cancer patients have a high incidence of bone metastases, there is also some evidence that bone markers can help doctors predict which breast and prostate cancer patients may be at high risk for complications from bone metastases and thus eligible for bone resorption sparing medications such as the bisphosphonates. Bone markers may also be able to predict a patient’s response to therapy for a bone loss condition.
Bone Marker Tests
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.
[Image source: Wikimedia Commons]