• Bone is constantly rebuilding itself, replacing old weak bone with new strong bone.
• To do this, old bone is broken down and absorbed by the body and new bone is formed. This is called remodelling.
• Bone markers are substances released into your blood and urine when bone is remodelled.
• Bone markers can be measured to help in diagnosing and monitoring treatment in osteoporosis (when bones get too weak) and in diseases that affect bones.
• By themselves, bone markers cannot predict your risk of having a fracture as a result of osteoporosis but can help to make this prediction when used with other risk assessment tools.

Bone is a living, growing tissue that is constantly rebuilding itself, replacing old weak bone with new fresh bone. To do this your body breaks down and dissolves old bone into minerals and collagen and then recycles these products into the growing new bone.

In order to keep bones healthy, it is important tmatrihat the amount of bone that is removed is replaced with the same amount of new bone. This is called remodelling.

Throughout your lifetime, your bones are constantly being remodelled to maintain a healthy bone structure. Bone turns over at a rate of about 10 per cent a year. This constant remodelling keeps your bones strong, as it repairs the microscopic cracks that are made as part of daily activity. Bone remodelling takes place all the time throughout your body.

In young, healthy people, the amount of bone formed is usually more than the amount removed but as we age, more bone is removed than formed causing a gradual loss of bone structure and strength. This can lead to the bone disorder known as osteoporosis (which means porous bones).

Bone turnover markers are substances that are made as bones remodel themselves as part of the natural regeneration cycle. They can be found in your blood and urine.

How does bone rebuild itself?

Bone begins as a flexible scaffold made by special cells which lay down type-1 collagen, a tough fibrous type of protein that acts as a framework. Next, minerals which circulate in the bloodstream, calcium and phosphate start to crystalise within the framework. This gives the bone its structure and strength.

There are two main types of cells involved in maintaining bone: osteoclasts and osteoblasts.

• Osteoclasts – bone resorption: These are cells that dissolve small amounts of bone in the area that needs strengthening. To do this they use acid and enzymes to dissolve the protein scaffolding. (Resorption is the process by which bone is dissolved and then absorbed by the body.)
• Osteoblasts – bone building: These are the cells that lay down new bone. They do this by releasing substances that help form a new protein scaffolding which is then hardened and strengthened by adding the minerals calcium and phosphate.

What causes bone loss?

During early childhood and in the teenage years, new bone is added faster than old bone is removed. People generally reach their peak bone density and strength between the ages of 25 and 30. The age at which someone starts to see some bone loss depends on the amount of bone that was developed during their youth and the rate of bone resorption.

After this peak period, bone loss occurs faster than the rate of bone formation, leading to bone loss. Women, who generally have smaller, lighter bones than men, experience bone loss earlier than men and after menopause the rate of bone loss speeds up due to a drop in oestrogen levels.

Each remodelling cycle leaves the bone a little thinner than before. Anything that speeds up the breakdown of bones or slows down the rebuilding process raises your risk of having osteoporosis.

In osteoporosis, your bones lose too much density and become fragile, making them more likely to break. The spongy inner mesh develops larger gaps and thinner struts, making it less able to absorb force. The hard outer shell of bone becomes thinner and more porous.

As well as ageing, several diseases and conditions can cause bone loss. These include:

• rheumatoid arthritis
• hyperparathyroidism
• Cushing disease
• chronic kidney disease
• multiple myeloma
• Paget’s disease
• long-term use of medications such as antiepileptics, glucocorticoids, or lithium.

Diagnosing bone loss

If you are being investigated for bone loss you will have a bone density scan, also known as a DEXA scan which measures the density of bones in the spine and hip. If the scan detects bone loss and/or if you have a history of unexpected bone fracture, a range of blood and urine tests will be needed.

Bone turnover markers

Bone turnover markers are substances measured in blood or urine that show how actively your bone is being formed and broken down. They help understand how fast bone tissue is turning over.

Sample

Blood or urine.

Any preparation?

Fasting may be required before testing and samples are typically collected in the morning. Many bone markers in the blood and urine vary in concentrations depending on the time of day (diurnal variation), so sample timing can be important. Carefully follow any instructions given for the timing of blood and urine sample collections, especially if you are having a Fasting Bone Metabolic Study.

Reading your test report

Your results will be presented along with those of your other tests on the same form. You will see separate columns or lines for each of these tests.

Reference intervals - comparing your results to the healthy population

Your results will be compared to reference intervals (sometimes called a normal range).

• Reference intervals are the range of results expected in healthy people.
• They are used to provide a benchmark for interpreting a patient's test results.
• When compared against them, your results may be flagged high or low if they sit outside this range.
• Some reference intervals are harmonised or standardised, which means all labs in Australia use them.
• Others are not because for these tests, labs are using different instruments and chemical processes to analyse samples.
• Always compare your lab results to the reference interval provided on the same report.

If your results are flagged as high or low this does not necessarily mean that anything is wrong. It depends on your personal situation.

Reference intervals for bone turnover markers vary between labs so you will need to go through your results with your doctor.

Fracture risk assessment

Bone turnover markers are currently not recommended for fracture risk assessment and therefore not included in fracture risk calculators. However, they are valuable tools for monitoring, particularly for people with osteoporosis.

Bone turnover markers are used to provide further information. They are most useful when used in conjunction with other established risk assessment tools, such as the FRAX® or Garvan calculators and BMD (bone mineral density) measurements.

High levels of bone turnover markers, such as CTx, can indicate a higher fracture risk, especially if you have a low BMD. The highest risk is seen in people with both low BMD and high bone turnover. Bone turnover markers cannot show the cause of the problem.

Important considerations

Caution is needed in interpreting test results as they can be affected by diet, exercise, and the time of day the sample is collected.

Your results need to be interpreted by your doctor. Usually, you will be having these tests when seeing a specialist doctor. Concentrations of bone markers are affected by many factors, particularly during childhood development. These include age, sex, growth velocity, nutritional status and puberty. Other clinical risk factors, such as age, history of fractures and medication use (such as glucocorticoids), should always be considered alongside BMD and bone turnover marker levels.

Very high bone turnover marker levels can be a sign of conditions other than postmenopausal osteoporosis, such as hyperparathyroidism, hyperthyroidism, Paget's disease or malignancy (cancer).

The choice of tests your doctor makes will be based on your medical history and symptoms. It is important that you tell them everything you think might help.

You play a central role in making sure your test results are accurate. Do everything you can to make sure the information you provide is correct and follow instructions closely.

Talk to your doctor about any medications you are taking. Find out if you need to fast or stop any particular foods or supplements. These may affect your results. Ask:

• Why does this test need to be done?
• Do I need to prepare (such as fast or avoid medications) for the sample collection?
• Will an abnormal result mean I need further tests?
• How could it change the course of my care?
• What will happen next, after the test?

Pathology and diagnostic imaging reports can be added to your My Health Record. You and your healthcare provider can now access your results whenever and wherever needed.

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