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Bone Markers

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Also known as: Bone Resorption Markers; Bone Formation Markers; Bone Turnover Tests; N-telopeptide; NTx; C-telopeptide; CTx; Deoxypyridinoline; DPD; Pyridinium Crosslinks; Tartrate-resistant Acid Phosphatase; TRAP; Bone-specific Alkaline Phosphatase; Osteocalcin; P1NP; Procollagen Type 1 N-Terminal Propeptide
Formal name: Biochemical Markers of Bone Remodeling
Related tests: Calcium, Phosphorus, Vitamin D, PTH, ALP

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 detect 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

Sample Required?

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.

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.

NOTE: If undergoing medical tests makes you or someone you care for anxious, embarrassed, or even difficult to manage, you might consider reading one or more of the following articles: Coping with Test Pain, Discomfort, and Anxiety, Tips on Blood Testing, Tips to Help Children through Their Medical Tests, and Tips to Help the Elderly through Their Medical Tests.

Another article, Follow That Sample, provides a glimpse at the collection and processing of a blood sample and throat culture.

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.

The Test

Common Questions

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Article Sources

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NOTE: This article is based on research that utilizes the sources cited here as well as the collective experience of the Lab Tests Online Editorial Review Board. This article is periodically reviewed by the Editorial Board and may be updated as a result of the review. Any new sources cited will be added to the list and distinguished from the original sources used.

Sources Used in Current Review

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 through http://emedicine.medscape.com. 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 through http://emedicine.medscape.com. 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 through http://emedicine.medscape.com. 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 through http://emedicine.medscape.com. 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 through http://www.arupconsult.com. 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 through http://www.ccjm.org. 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 through http://nof.org. 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 through http://medscape.com. 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.

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 through http://www.medscape.com.

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 through http://www.medscape.com.

(© 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 through http://www.aruplab.com.

(2005 June, Revised). Osteoporosis Overview. NIAMS [On-line information]. Available online at http://www.niams.nih.gov/bone/hi/overview.htm through http://www.niams.nih.gov.

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 through http://www.kidney.org.

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 through http://familydoctor.org.

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 through http://www.cdc.gov. 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 through http://www.medscape.com. Accessed March 2009.

ARUP Consult. Osteoporosis. Available online at http://www.arupconsult.com/Topics/EndocrineDz/Osteoporosis.html# through http://www.arupconsult.com. 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 through http://www.medscape.com.

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 through http://www.medscape.com.

(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 through http://www.clinchem.org.

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.

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