- Also Known As:
- Bone Resorption Markers
- Bone Formation Markers
- Bone Turnover Tests
- Pyridinium Crosslinks
- Tartrate-resistant Acid Phosphatase
- Bone-specific Alkaline Phosphatase
- Procollagen Type 1 N-Terminal Propeptide
- Formal Name:
- Biochemical Markers of Bone Remodeling
At a Glance
Why Get Tested?
To help evaluate and monitor the rate of bone resorption and formation; to monitor some metabolic bone diseases such as osteoporosis; to help detect metabolic bone disorders such as Paget disease
When To Get Tested?
When a bone mineral density scan indicates reduced bone density; before and periodically during treatment for bone loss to evaluate effectiveness, to determine if the rate of loss has decreased or the rate of bone formation has increased
A blood sample drawn from a vein in your arm or sometimes a urine sample
Test Preparation Needed?
Fasting may be required before testing; samples are typically collected in the morning.
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’…
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 bone disorders, such as osteoporosis and Paget disease.
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. 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.
In children, bone markers are also useful in helping to diagnose metabolic bone diseases and in monitoring treatment of these conditions. Examples include rickets, juvenile Paget disease, osteogenesis imperfecta, sometimes called brittle bone disease, and hypophosphatemic rickets, a type of rickets associated with low phosphate levels and hypophosphatasia (HPP), a disorder causing abnormal development of bones and teeth. To learn more about these, see the links in the Related Content section.
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.
Is any test preparation needed to ensure the quality of the sample?
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.
How is it used?
One or more of the bone marker tests may be used to help determine if a person has an increased rate of bone turnover (resorption and/or formation). Bone markers are sometimes used as an adjunct to bone density testing (e.g., BMD, DEXA scan) to help evaluate bone loss and detect some bone diseases.
In adults, bone markers often are used to monitor response to anti-resorptive therapy for bone disease, primarily osteoporosis, and to help determine if the dose of the drug a person is receiving is effective.
In children, these tests are primarily used to help detect and manage metabolic bone disorders, such as secondary osteoporosis, rickets, Paget disease, and osteogenesis imperfecta.
These tests can detect response 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, 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 for Clinical Chemistry (IFCC) recommend two blood tests for evaluating bone turnover:
- C-telopeptide (C-terminal telopeptide of type 1 collagen (CTx)) – a marker for bone resorption. It is a peptide fragment from the carboxy terminal end of the protein matrix; 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®).
When is it ordered?
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.
In children, testing may be done when they have signs and symptoms suggesting a metabolic bone disorder, such as:
- Bone and/or joint pain
- Increased frequency of fractures
- Delayed growth and bone development
- Deformed bones
- Brittle teeth
For managing and treating bone diseases, 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.
What does the test result mean?
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:
- Paget disease
- Cancer that has spread to the bone (metastatic bone disease)
- Osteomalacia in adults and rickets in children—lack of bone mineralization, often due to vitamin D or calcium deficiency
- Chronic kidney disease (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.
Is there anything else I should know?
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, alkaline phosphatase, 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 values require 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.
Since people with breast or prostate cancer have a high incidence of bone metastases, there is also some evidence that bone markers can help healthcare practitioners predict which breast and prostate cancer patients may be at a high risk for complications from bone metastases and thus eligible for bone resorption sparing medications such as the bisphosphonates.
There are limitations to the clinical utility of many of these bone markers, but researchers continue to explore ways to improve their clinical use.
Should everyone have bone marker testing performed?
Bone marker testing is typically only indicated for 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 but do not take the place of bone mineral density screening.
Will I have all or just some of these bone markers tested?
Typically, no one will have all of the tests done that are described here. Most healthcare practitioners 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 healthcare practitioner 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.
Can testing be performed in my healthcare practitioner's office?
In general, no. While a blood or urine sample may be collected in your healthcare practitioner’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.
What can I do to increase or decrease bone marker results?
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.
On This Site
Elsewhere On The Web
NIH Osteoporosis and Related Bone Diseases National Resource Center
MedlinePlus: Bone Diseases
National Osteoporosis Foundation
RadiologyInfo.org: Bone Densitometry (DEXA)
Mayo Clinic: Osteomalacia
WomensHealth.gov: Osteoporosis fact sheet
Mayo Clinic: Paget disease of bone
MedlinePlus: Osteogenesis Imperfecta
Soft Bones, Inc., The US Hypophosphatasia Foundation
Sources Used in Current Review
Talwar, S. (2017 January 12, Updated). Bone Markers in Osteoporosis. Medscape Drugs and Diseases. Available online at http://emedicine.medscape.com/article/128567-overview. Accessed on 02/18/17.
Meikle, A. W. and Straseski, J. (2017 January). Osteoporosis. ARUP Consult. Available online at https://arupconsult.com/content/osteoporosis. Accessed on 02/18/17.
Vasikaran, S. (2013 July 1). Bone Turnover Markers, The Impact of Assay Standardization on Assessing and Monitoring Osteoporosis. Clinical Laboratory News. Available online at https://www.aacc.org/publications/cln/articles/2013/july/bone-turnover-markets. Accessed on 02/18/17.
Bethel, M. et. al. (2016 September 21, Updated). Osteoporosis. Medscape Drugs and Diseases. Available online at http://emedicine.medscape.com/article/330598-overview. Accessed on 02/18/17.
(© 1995–2017). Beta-CrossLaps (Beta-CTx), Serum. Mayo Clinic Mayo Medical Laboratories. Available online at http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/83175. Accessed on 02/18/17.
Alikhan, M. et. al. (2016 November 21). Paget Disease. Medscape Drugs and Diseases. Available online at http://emedicine.medscape.com/article/334607-overview. Accessed on 02/18/17.
Greenblatt, M. et. al. (2017 February). Bone Turnover Markers in the Diagnosis and Monitoring of Metabolic Bone Disease. Clin Chem. 2017 Feb;63(2):464-474. Abstract. Available online at https://www.ncbi.nlm.nih.gov/pubmed/27940448. Accessed on 02/18/17.
(© 1995–2017). Mayo Clinic. Pediatric Metabolic Bone Disorders Clinic. Available online at http://www.mayoclinic.org/departments-centers/childrens-center/overview/specialty-groups/pediatric-metabolic-bone-disorders-clinic. Accessed March 2017.
Sources Used in Previous Reviews
Interview with Laurence M. Demers, PhD. Distinguished Professor of Pathology and Medicine, The Pennsylvania State University College of Medicine, The M. S. Hershey Medical Center, Hershey, PA. Additionally, conducted article review March 2009.
Srivastava, A. (2005 July 22). Clinical Use of Serum and Urine Bone Markers in the Management of Osteoporosis. Medscape from Curr Med Res Opin 2005;21(7): 1015-1026 [On-line journal]. Available online at http://www.medscape.com/viewarticle/508542_print.
Vesper, H. (2005 August 10). Analytical and Preanalytical Issues in Measurement of Biochemical Bone Markers. Medscape from Lab Med. 2005;36(7):424-429 [On-line journal]. Available online at http://www.medscape.com/viewarticle/509097.
(© 2005). Bone Turnover, Biochemical Markers. ARUP’s Guide to Clinical Laboratory Testing [On-line information]. Available online at http://www.aruplab.com/guides/clt/tests/clt_a125.jsp#1145643.
(2005 June, Revised). Osteoporosis Overview. NIAMS [On-line information]. Available online at http://www.niams.nih.gov/bone/hi/overview.htm.
Bone Disease in Chronic Kidney Failure (July 2006- Online information). National Kidney Foundation. Available online at http://www.kidney.org/atoz/atozItem.cfm?id=49.
Hyperparathyroidism: What It Is and How It’s Treated (July 2006-Online information). American Association of Family Physicians. Available online at http://familydoctor.org/251.xml.
Rickets (July 2006-Online information). MedlinePlus, NIH. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/000344.htm.
Coleman, Robert et al. Predictive Value of Bone Resorption and Formation Markers in Cancer Patients With Bone Metastases Receiving the Bisphosphonate Zoledronic Acid. Journal of Clinical Oncology, Vol 23, No 22 (August 1), 2005; Pp. 4925-4935.
Rosen, C.J. et al. The Predictive Value of Biochemical Markers of Bone Turnover for Bone Mineral Density in Early Postmenopausal Women Treated with Hormone Replacement or Calcium Supplementation. Journal of Clinical Endocrinology & Metabolism Vol. 82, No. 6 1904-1910, 1997.
N.H Bjarnasona, C Christiansena. Early response in biochemical markers predicts long-term response in bone mass during hormone replacement therapy in early postmenopausal women. Bone. Vol 26, Issue 6, Pp 561-569 (2000).
Lein M et al. Bone Turnover Markers As Predictive Tools For Skeletal Complications In Men With Metastatic Prostate Cancer Treated With Zoledronic Acid Prostate. Prostate Feb. 2009.
Shidara K et al. Serum levels of TRAP5b, a new bone resorption marker unaffected by renal dysfunction, as a useful marker of cortical bone loss in hemodialysis patients. Calcif Tissue Int. 2008 Apr;82(4):278-87.
Centers for Disease Control and Prevention. Improving the Clinical Use of Biochemical Bone Marker in Metabolic Bone Diseases. Available online at http://www.cdc.gov/NCEH/DLS/osteoporosis.htm. Accessed March 2009.
Hubert W. Vesper, PhD. Analytical and Preanalytical Issues in Measurement of Biochemical Bone Markers. Medscape Today from Lab Med. 2005;36(7):424-429. Available online at http://www.medscape.com/viewarticle/509097_2. Accessed March 2009.
ARUP Consult. Osteoporosis. Available online at http://www.arupconsult.com/Topics/EndocrineDz/Osteoporosis.html#. Accessed March 2009.
Vesper, H. (2005 August 10). Analytical and Preanalytical Issues in Measurement of Biochemical Bone Markers. Medscape from Laboratory Medicine [On-line information]. Available online at http://www.medscape.com/viewarticle/509097.
Srivastava, A. (2005 July 22). Clinical Use of Serum and Urine Bone Markers in the Management of Osteoporosis. Medscape Current Medical Research and Opinion [On-line information]. Available online at http://www.medscape.com/viewarticle/508542.
(2006 July). Procollagen Type 1 N-Terminal Propeptide. ARUP Technical Bulletin [On-line information]. PDF available for download through http://www.aruplab.com.
Cundy, T. et. al. (2007 April 13). Bone Formation Markers in Adults with Mild Osteogenesis Imperfecta. Clinical Chemistry 2007; 53:1109-1114. [On-line abstract]. Available online at http://www.clinchem.org/cgi/content/abstract/53/6/1109.
Garnero, P. et al. Evaluation of a Fully Automated Serum Assay for Total N-Terminal Propeptide of Type I Collagen in Postmenopausal Osteoporosis. Clinical Chemistry 2008; 54:1, Pp. 188-196.
Talwar, S. and Aloia, J. (Updated 2012 January 3). Bone Markers in Osteoporosis. Medscape Reference [On-line information]. Available online at http://emedicine.medscape.com/article/128567-overview. Accessed February 2013.
Staros, E. (Updated 2012 September 7). N-Terminal Telopeptide. Medscape Reference [On-line information]. Available online at http://emedicine.medscape.com/article/2093977-overview#showall. Accessed February 2013.
Medscape Editorial Staff (Updated 2012 October 1). C-Terminal Telopeptide. Medscape Reference [On-line information]. Available online at http://emedicine.medscape.com/article/2093999-overview#showall. Accessed February 2013.
Jacobs-Kosmin, D. and Shanmugam, S. (Updated 2012 December 10). Osteoporosis. Medscape Reference [On-line information]. Available online at http://emedicine.medscape.com/article/330598-overview. Accessed February 2013.
Meikle, A. W. (Update 2013 January). Osteoporosis. ARUP Consult [On-line information]. Available online at http://www.arupconsult.com/Topics/Osteoporosis.html#tabs=0. Accessed February 2013.
Bolster, M. (Revised 2012 December). Osteoporosis. Merck Manual for Healthcare Professionals [On-line information]. Available online through http://www.merckmanuals.com. Accessed February 2013.
Singer, F. and Eyre, D. (2008). Using biochemical markers of bone turnover in clinical practice. [On-line information]. Cleveland Clinic Journal of Medicine October 2008 vol. 75 10 739-750. Available online at http://www.ccjm.org/content/75/10/739.full. Accessed February 2013.
(© 2013). NOF’s Newly Revised 2013 Clinician’s Guide to Prevention and Treatment of Osteoporosis. National Osteoporosis Foundation [On-line information]. Available online at http://nof.org/hcp/practice/practice-and-clinical-guidelines/clinicians-guide. Accessed March 2013.
Clarke, W., Editor (© 2011). Contemporary Practice in Clinical Chemistry 2nd Edition: AACC Press, Washington, DC. Pp 522-523.
McPherson, R. and Pincus, M. (© 2011). Henry’s Clinical Diagnosis and Management by Laboratory Methods 22nd Edition: Elsevier Saunders, Philadelphia, PA. Pp 205-206.
Srivastava A, et.al. Clinical Use of Serum and Urine Bone Markers in the Management of Osteoporosis. Medscape news, Curr Med Res Opin. 2005;21(7):1015-1026. Available online at http://medscape.com/viewarticle/508542_1. Accessed March 3013.
Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. Burtis CA, Ashwood ER, Bruns DE, eds. 4th edition, St. Louis: Elsevier Saunders; 2006, Pp 1932-1943.
Vasikarin S, et. al. International Osteoporosis Foundation and International Federation of Clinical Chemistry and Laboratory Medicine Position on bone marker standards in osteoporosis. Clin Chem Lab Med 2011;49(8):1271–1274.