Medscape is available in 5 Language Editions – Choose your Edition here.


C-Terminal Telopeptide 

  • Author: Carlos Solano Loran, MD; Chief Editor: Eric B Staros, MD  more...
Updated: Mar 16, 2015

Reference Range

The reference ranges for C-terminal telopeptide electrochemiluminescence assays in blood are below.

Reference ranges for males are as follows:

  • < 18 years - Not established
  • 18-30 years - 155-873 pg/mL
  • 31-50 years - 93-630 pg/mL
  • 51-70 years - 35-836 pg/mL
  • >70 years - Not established

The reference ranges for females are as follows:

  • < 18 years - Not established
  • Premenopausal - 25-573 pg/mL
  • Postmenopausal - 104-1008 pg/mL


C-terminal telopeptide levels may indicate the following:

  • Elevated levels of C-terminal telopeptide indicate increased bone turnover.
  • Elevated levels are found in osteoporosis patients with elevated bone turnover who are at increased risk for rapid disease progression.
  • Increased levels are also associated with osteopenia, Paget disease of the bone, hyperthyroidism, and hypothyroidism.
  • This test can be used to monitor and assess how effective antiresorptive therapy has been in patients treated for disorders such as osteopenia, osteoporosis, and Paget disease.
  • This test can also serve as an adjunct means of monitoring patient response to other treatments for diseases with increased bone turnover, such as rickets, osteomalacia, and hyperthyroidism.
  • Using pretreatment beta-CTX levels as a baseline, adequate therapeutic response is indicated by a decrease of 25% or more 3-6 months after the initiation of therapy.

Collection and Panels

Specimen details are as follows:

  • Specimen type - Serum
  • Collection container/tube - Red top preferred, serum gel acceptable
  • Submission container/tube - Plastic vial
  • Specimen volume - 1 mL, minimum volume 0.4 mL
  • Collection instructions - Fasting; draw specimen before 10 am
  • Reject in cases of gross hemolysis
  • Specimen stability - 14 days frozen (preferred), 72 hours refrigerated



Degradation products derived from the enzymatic hydrolysis of type 1 collagen, particularly peptides related to regions of cross-linking with PYD, are the best markers of bone resorption. Released collagen fragments are responsible for many bone markers, since more than 90% of protein in bone consists of collagen type 1.

Although urinary hydroxyproline was previously one of the primary bone resorption markers used, specificity and sensitivity were lacking in this assay. A component of bone collagen, hydroxyproline is released into the serum during degradation of bone, reaching the urine in free and bound forms. However, because it is derived from the degradation of newly synthesized collagens, from collagens of nonbone tissues, and from diet, serum hydroxyproline is now considered to be a nonspecific marker of bone turnover. Urinary hydroxyproline has consequently been replaced by more specific techniques.

The pyridinium compounds PYD and DPD, as well as hydroxypyridinium cross-links collagen, are among the more specific markers. Formed during the extracellular maturation of fibrillar collagens, PYD and DPD are released when mature collagens degrade. PYD and DPD measurement values do not change in association with the degradation of newly synthesized collagens and are not influenced by dietary sources.

Testing can also be performed without directly using cross-links as markers. Assays have been developed based on specific antibodies raised in an immune response against isolated collagen peptides containing cross-links. Detected by radioimmunoassay technique, fragments exist for C-telopeptide of type 1 collagen (CTX, CrossLaps) and cross-linked N-terminal telopeptide of type 1 collagen by ELISA technique (NTX, Osteomark).[2]

The NTX assay employs a monoclonal antibody directed against a urinary pool of collagen cross-links (originating from a patient with Paget disease). Serum CrossLaps assay measures only β-isomer of CTX, while the urine CrossLaps assay measures α- and β-isomers of CTX. Urine from healthy individuals has produced a detectable reaction from these assays, and elevated turnover has produced large increases.

The 2 categories of C-telopeptide methods are C-telopeptide of type 1 collagen (CTX) and type 1 collagen cross-linked C-telopeptide (ICTP). They differ with regard to which segment domains they recognize in the C-terminal telopeptide region of the α1 chain of type 1 collagen and also differ in their response to bone metabolic processes.

CTX shows remarkable response to antiresorptive therapies, while serum ICTP is insensitive to osteoporosis and other normal metabolic bone processes. However, in bone pathologic conditions such as bone metastasis and rheumatoid arthritis, serum ICTP may be a marker of bone degradation.[1]


In addition to the traditional evaluation of bone mineral density, biochemical markers of bone resorption provide additional predictive information on a patient’s fracture risk. Preventive therapy with antiresorptive agents is warranted for patients with low BMD or high marker values, because they would be at risk for osteoporosis.

Although results of prospective studies assessing the relationship between the rate of bone loss and biochemical markers of bone turnover have been conflicting, the following guidelines apply to the use of bone markers in prediction of fragility fractures:

  • Bone resorption markers elevated more than +2 SD/T score more than 2 above the premenopausal normal range is associated with approximately 2-fold increase in osteoporotic fracture risk.
  • In selected patients whose clinical risk factors and BMD assessment are not sufficient to allow treatment decision, resorption markers can be used to assess fracture risk. [5]
  • A high level of bone turnover marker (T score >3) is highly suggestive of alternative metabolic bone diseases, including malignancy, in patients with osteoporosis.
  • Normal values are reference values derived from the evaluation of healthy, premenopausal women aged 30-45 years.

See also the Fracture Index WITH known Bone Mineral Density (BMD) calculator.

The lists below summarize recommendations for monitoring antiresorptive treatment in postmenopausal women with osteoporosis, using bone markers.

Types of marker include the following:

  • Bone resorption - Urine NTX, serum CTX, or urine CTX
  • Bone formation - Bone-specific alkaline phosphatase or osteocalcin (use 1 marker or 1 resorption and 1 formation marker.)

Intervals of measurement include the following:

  • Resorption markers - Prior to starting treatment and 3 or 6 months after treatment initiation
  • Formation markers - Prior to starting treatment and 6 months after treatment initiation


Reduced urinary excretion of beta-CTX and a consequent rise in the apparent serum beta-CTX concentration may result from reduced renal function.

In patients undergoing treatment with high doses of biotin (ie, >5 mg/day), a specimen should not be drawn until at least 8 hours after the biotin was last administered, to avoid assay interference from the biotin.

Erroneous results may be derived from any test containing monoclonal mouse antibodies in a patient who has been treated with monoclonal mouse antibodies or has received them for diagnostic purposes.

Contributor Information and Disclosures

Carlos Solano Loran, MD Resident Physician, Department of Internal Medicine, Albert Einstein Medical Center

Carlos Solano Loran, MD is a member of the following medical societies: American College of Physicians

Disclosure: Nothing to disclose.

Chief Editor

Eric B Staros, MD Associate Professor of Pathology, St Louis University School of Medicine; Director of Clinical Laboratories, Director of Cytopathology, Department of Pathology, St Louis University Hospital

Eric B Staros, MD is a member of the following medical societies: American Medical Association, American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology

Disclosure: Nothing to disclose.

  1. Garnero P, Borel O, Delmas PD. Evaluation of a fully automated serum assay for C-terminal cross-linking telopeptide of type I collagen in osteoporosis. Clin Chem. 2001 Apr. 47(4):694-702. [Medline].

  2. Christgau S, Bitsch-Jensen O, Hanover Bjarnason N, et al. Serum CrossLaps for monitoring the response in individuals undergoing antiresorptive therapy. Bone. 2000 May. 26(5):505-511.

  3. Baim S, Miller PD. Assessing the clinical utility of serum CTX in postmenopausal osteoporosis and its use in predicting risk of osteonecrosis of the jaw. J Bone Miner Res. 2009 Apr. 24(4):561-74. [Medline].

  4. Bone HG, Downs RW Jr, Tucci JR, Harris ST, Weinstein RS, Licata AA. Dose-response relationships for alendronate treatment in osteoporotic elderly women. Alendronate Elderly Osteoporosis Study Centers. J Clin Endocrinol Metab. 1997 Jan. 82(1):265-74. [Medline].

  5. Brown JP, Albert C, Nassar BA, Adachi JD, Cole D, Davison KS. Bone turnover markers in the management of postmenopausal osteoporosis. Clin Biochem. 2009 Jul. 42(10-11):929-42. [Medline].

  6. Clowes JA, Hannon RA, Yap TS, Hoyle NR, Blumsohn A, Eastell R. Effect of feeding on bone turnover markers and its impact on biological variability of measurements. Bone. Jun 2002. 30(6):886-90.

  7. Garnero P. Markers of bone turnover for the prediction of fracture risk. Osteoporos Int. 2000. 11 Suppl 6:S55-65. [Medline].

  8. Garnero P, Hausherr E, Chapuy MC, Marcelli C, Grandjean H, Muller C. Markers of bone resorption predict hip fracture in elderly women: the EPIDOS Prospective Study. J Bone Miner Res. 1996 Oct. 11(10):1531-8. [Medline].

  9. Hadji P, Ziller M, Kieback DG, Menschik T, Kalder M, Kuck J. The effect of exemestane or tamoxifen on markers of bone turnover: results of a German sub-study of the Tamoxifen Exemestane Adjuvant Multicentre (TEAM) trial. Breast. 2009 Jun. 18(3):159-64. [Medline].

  10. Lewiecki EM, Baim S, Bilezikian JP, Eastell R, LeBoff MS, Miller PD. 2008 Santa Fe Bone Symposium: update on osteoporosis. J Clin Densitom. 2009 Apr-Jun. 12(2):135-57. [Medline].

  11. Miazgowski T, Noworyta-Zietara M, Safranow K, Ziemak J, Widecka K. Serum adiponectin, bone mineral density and bone turnover markers in post-menopausal women with newly diagnosed Type 2 diabetes: a 12-month follow-up. Diabet Med. 2012 Jan. 29(1):62-9. [Medline].

  12. Miller PD. Diagnosis and treatment of osteoporosis in chronic renal disease. Semin Nephrol. 2009 Mar. 29(2):144-55. [Medline].

  13. Miller PD, Baran DT, Bilezikian JP, et al. Practical clinical application of biochemical markers of bone turnover: Consensus of an expert panel. J Clin Densitom. 1999. 2(3):323-342.

  14. Ott SM, Bauer DC, Santora A. Ability of biochemical markers to predict 4 year changes in bone density in postmenopausal women. Bone. 1998. s159.

  15. Rosen CJ, Chesnut CH 3rd, Mallinak NJ. The predictive value of biochemical markers of bone turnover for bone mineral density in early postmenopausal women treated with hormone replacement or calcium supplementation. J Clin Endocrinol Metab. 1997 Jun. 82(6):1904-10. [Medline].

  16. Ross PD, Knowlton W. Rapid bone loss is associated with increased levels of biochemical markers. J Bone Miner Res. 1998 Feb. 13(2):297-302. [Medline].

  17. Roy DK, O'Neill TW, Finn JD, Lunt M, Silman AJ, Felsenberg D. Determinants of incident vertebral fracture in men and women: results from the European Prospective Osteoporosis Study (EPOS). Osteoporos Int. 2003 Jan. 14(1):19-26. [Medline].

  18. Sarkar S, Reginster JY, Crans GG, Diez-Perez A, Pinette KV, Delmas PD. Relationship between changes in biochemical markers of bone turnover and BMD to predict vertebral fracture risk. J Bone Miner Res. 2004 Mar. 19(3):394-401. [Medline].

  19. Yavropoulou MP, Tomos K, Tsekmekidou X, Anastasiou O, Zebekakis P, Karamouzis M. Response of biochemical markers of bone turnover to oral glucose load in diseases that affect bone metabolism. Eur J Endocrinol. 2011 Jun. 164(6):1035-41. [Medline].

All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.