

Bone Markers

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Formal name: Biochemical Markers of Bone Remodeling

The Test Sample

What is being tested?

Bone is the rigid, hard connective tissue that comprises the majority of the skeleton in humans. It is a living, growing tissue that turns over at a rate of about 10% a year. 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 people receiving treatment for skeletal disorders including osteoporosis.

Bone 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 withstand stress. More than 99% of the body's calcium is contained in the bones and teeth. Most of the remaining 1% is found in the blood.

Throughout a person's lifetime, bone is constantly being remodeled to maintain a healthy bone structure that conforms to the person's needs. There are two major types of cells within bone: osteoblasts and osteoclasts. Osteoblasts are the cells that lay down new bone, but they first initiate bone resorption by stimulating osteoclasts, which dissolve small amounts of bone in the area that needs strengthening using acid and enzymes to dissolve the protein network.

Osteoblasts then initiate new bone formation by secreting a variety of compounds that help form a new protein network, which is then mineralized with calcium and phosphate. 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 a person reaches their 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. The age at which an individual begins to experience symptoms of bone loss depends on the amount of bone that was developed during their youth and the rate of bone resorption. Traditionally, women exhibit these symptoms earlier than men because they may not have developed as much bone during the peak years and, after menopause, rate of bone loss is accelerated in some women.

Several diseases and conditions can cause an imbalance between bone resorption and formation, and bone markers can be useful in detecting the imbalance and bone loss. Most often, the markers have been studied in the evaluation and monitoring of osteoporosis, including age-related osteoporosis or secondary osteoporosis, which is bone loss due to an underlying condition. Bone loss may result from conditions such as rheumatoid arthritis, hyperparathyroidism, Cushing disease, chronic kidney disease, multiple myeloma, or from prolonged use of drugs such as anti-epileptics, glucocorticoids, or lithium.

Below is a list of some bone resorption and formation markers measured in blood and/or urine samples. 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 as they can be affected by diet, exercise, and time of day the sample is collected.

The International Osteoporosis Foundation (IOF) and the International Federation for Clinical Chemistry (IFCC) recommend two blood tests for evaluating bone turnover:

  • A blood test for C-telopeptide (C-terminal telopeptide of type 1 collagen (CTx)) as a marker for bone resorption
  • A blood test for P1NP (Procollagen type 1 N-terminal propeptide) as a marker for bone formation

Other bone marker tests that may sometimes be used include:

  • N-telopeptide (N-terminal telopeptide of type 1 collagen (NTx))
  • Deoxypyridinoline (DPD)
  • Pyridinium Crosslinks
  • Tartrate-resistant acid phosphatase (TRAP) 5b
  • Bone-specific alkaline phosphatase (ALP)
  • Osteocalcin (bone gla protein)

For further discussion of these tests, see the section on How is it used?

How is the sample collected for testing?

A blood sample is obtained by inserting a needle into a vein in the arm. Sometimes, a random or timed urine sample is collected in a clean container provided by the laboratory.




It may be necessary to fast prior to testing. Many of the bone markers vary in the blood and urine depending upon the time of day (diurnal variation), so sample timing can be important. Carefully follow any instructions given for the timing of sample collection, such as collecting a second morning void of urine.