One or more of the bone marker tests may be used to help determine if a person has increased rates of bone turnover (resorption and/or formation). Bone markers are sometimes used as an adjunct to bone mineral density (BMD) testing (e.g., by DEXA scan) to help evaluate bone loss and detect some bone diseases. They often are used to monitor response to anti-resorptive therapy for bone disease, primarily osteoporosis, and to help a doctor determine if the dose of the drug a person is receiving is effective.

These tests can detect response to anti-resorption or bone building therapies in a much shorter time period than BMD testing (three to six months versus one to two years). This way, therapy can be adjusted or altered in a more timely manner if a person is not responding as expected.

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

• C-telopeptide (C-terminal telopeptide of type 1 collagen (CTx), Crosslaps) – a marker for bone resorption. It is a peptide fragment from the carboxy terminal end of the collagen protein; used to monitor anti-resorptive therapies, such as bisphosphonates and hormone replacement therapy, in postmenopausal women and people with low bone mass (osteopenia)
• P1NP (Procollagen type 1 N-terminal propeptide) – a marker for bone formation. It is 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 anti-resorptive therapies; it is recommended that the test be performed at baseline before starting osteoporosis therapy and again 3 to 6 months later.

Other urine or blood tests used less commonly for bone resorption include:

• N-telopeptide (N-terminal telopeptide of type 1 collagen (NTx)) – a peptide fragment from the amino terminal end of the protein matrix; another marker used to monitor therapy.
• 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) is the version of acid phosphatase produced by osteoclasts, the cells that dissolve small amounts of bone, during bone resorption.

Other bone formation blood tests that may sometimes be used include:

• Bone-specific alkaline phosphatase (ALP) – one of the isoenzymes (types) of ALP; it is associated with osteoblast cell function, the type of cell involved in bone formation. It is 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 the level of liver ALP.
• Osteocalcin (bone gla protein) – a protein formed by osteoblasts; part of the non-collagen portion of the bone structure; some of it also enters the bloodstream; the level of osteocalcin in the blood reflects the rate of bone formation, thus it is a useful indicator of the function of osteoblasts. This test may be affected by use of the drug warfarin (Coumadin®).

Testing may be performed along with other tests such as a calcium, vitamin D, thyroid testing, and parathyroid hormone when bone loss is detected during a bone mineral density test (diagnostic imaging) and/or when a person has a history of unexpected bone fracture.

One or more bone marker tests may be performed prior to anti-resorptive or bone formation therapy and then typically 3 to 6 months later to monitor the effectiveness of treatment.

A high level of one or more bone markers in urine and/or blood suggests an increased rate of resorption and/or formation of bone, but it does not indicate the cause (it is not diagnostic). An elevated level of bone markers may be seen in conditions such as:

• Osteoporosis
• Paget disease
• Cancer that has spread to the bone (metastatic bone disease)
• Hyperparathyroidism
• Hyperthyroidism
• Osteomalacia in adults and rickets in children—lack of bone mineralisation, often due to vitamin D or calcium deficiency
• Chronic kidney failure (renal osteodystrophy)
• Excess use or high doses of glucocorticoids or Cushing syndrome

A low or normal level suggests no excessive bone turnover.

When used to monitor anti-resorptive therapy, decreasing levels of the bone resorption markers over time reflect a response to therapy.

Samples must be consistently collected, and test results must be interpreted with caution. There is both day-to-day variability in bone marker concentrations and diurnal variation (changes throughout the day). Most bone marker concentrations will be the highest in the morning, and some, in particular, C-telopeptide, are affected by eating.
Concentrations of bone markers are affected by a variety of factors, particularly during childhood development. These include age, sex, growth velocity, nutritional status, and puberty. Therefore, interpretation of bone marker results requires use of appropriate reference intervals.

Most people with bone loss are not aware of it. The condition may not cause any symptoms until a person has an unexpected bone fracture.

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 therapies used to treat metabolic bone disease and to properly adjust the dose for maximal effect.

Bone marker testing is typically only indicated in those who have been diagnosed with or are at risk of bone loss. The tests are not intended to be used to screen the general public. They offer additional information to the doctor but do not take the place of bone mineral density screening.

Typically, no one will have all of the tests done that are described here. Most doctors use one or a few particular bone markers, including one or two that evaluate bone resorption and one or two that evaluate bone formation. The choice of bone markers will depend on many factors, including your medical history, signs and symptoms, and physical examination, and these all vary from person to person. Your doctor will make the selection based on the usefulness of the tests for your condition. In general, if a test is ordered as a baseline prior to therapy, then the same test will be ordered later so that the two results can be compared.

In general, no. While a blood or urine sample may be collected in your doctor's office, the sample will be sent to a laboratory for testing. Bone marker testing is not offered by all laboratories and will often be sent to a reference laboratory.

People can and should take steps to maintain bone health throughout their life, but bone markers themselves are not affected by lifestyle changes. If you have bone loss, work with your healthcare practitioner to determine the best treatment for you.

Hormone replacement therapy (HRT) and related drugs such as raloxifene can help maintain bone density in women after the menopause. Bisphosphonates, such as alendronate, also help to maintain bone density and prevent fractures, and the hormone calcitonin can be used to prevent bone resorption. Alternative treatments such as strontium ranelate taken as a daily drink increase bone mass, zoledronic acid given as a once yearly infusion and denosumab given as a 6 monthly injection, are also effective treatments. The most appropriate option will need to be discussed with your doctor.

The condition may affect up to 2 million people in Australia but many will not know they have the disease. Of the people with osteoporosis, 80% are women.