NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
1. An adjunct in the diagnosis of medical conditions associated with increased bone turnover
2. The differential diagnosis of osteomalacia versus osteoporosis
3. Identifying individuals with osteoporosis with elevated bone turnover and consequent increased risk for rapid disease progression
4. Prediction of bone densitometry response to antiresorptive therapy of osteoporosis
5. Monitoring and assessing effectiveness of therapy in patients treated for osteopenia, osteoporosis, Paget disease, or other disorders treated with antiresorptive therapy
6. An adjunct in monitoring response to other therapeutic intervention in diseases with increased bone turnover (eg, rickets, osteomalacia, hyperthyroidism)
Indications 3 through 5 have been endorsed by the Negotiated Rulemaking Committee of HCFA and are therefore federally reimbursed.
Profile Information A profile is a group of laboratory tests that are ordered and performed together under a single Mayo Test ID. Profile information lists the test performed, inclusive of the test fee, when a profile is ordered and includes reporting names and individual availability.
|Test ID||Reporting Name||Available Separately||Always Performed|
Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
NTXUR/124091: VITROS Competitive Chemiluminscence Immunoassay
NTXCT/300188: Enzymatic Colorimetric Assay
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Crosslinked N-telopeptide of Type I Collagen (NTX), Urine
Crosslinked N-telopeptide of Type I Collagen (NTX), Urine
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Collection Container/Tube: Clean, plastic urine collection container
Submission Container/Tube: Plastic, 10-mL urine tube (Supply T068)
Specimen Volume: 4 mL
1. Collect urine for 24 hours.
2. No preservative.
3. Refrigerate specimen during collection.
1. 24-Hour collection is preferred, but second-morning voided or random specimen is also acceptable.
2. See Urine Preservatives in Special Instructions for multiple collections.
Urine Preservative Collection Options
50% Acetic Acid
Forms: If not ordering electronically, submit a General Request Form (Supply T239) with the specimen.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Specimen with pH <5
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
|Urine||Frozen (preferred)||30 days|
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Human bone is continuously remodeled through a process of osteoclast-mediated bone formation and resorption. This process can be monitored by measuring serum and urine markers of bone formation and resorption. Approximately 90% of the organic matrix of bone is type I collagen, a helical protein that is cross-linked at the N- and C-terminal ends of the molecule. The amino acid sequences and orientation of the cross-linked alpha 2 N-telopeptide of type 1 collagen make it a specific marker of human bone resorption. N-terminal telopeptide (NTx) molecules are mobilized from bone by osteoclasts and subsequently excreted in the urine. Elevated levels of NTx indicate increased bone resorption.
Bone turnover markers are physiologically elevated during childhood, growth, and during fracture healing. The elevations in bone resorption markers and bone formation markers are typically balanced in these circumstances and of no diagnostic value. By contrast, abnormalities in the process of bone remodeling can result in changes in skeletal mass and shape. Many diseases, in particular hyperthyroidism, all forms of hyperparathyroidism, most forms of osteomalacia and rickets (even if not associated with hyperparathyroidism), hypercalcemia of malignancy, Paget's disease, multiple myeloma, and bony metastases, as well as various congenital diseases of bone formation and remodeling can result in accelerated and unbalanced bone turnover. Unbalanced bone turnover, usually without increase in bone turnover, is also found in age-related and postmenopausal osteopenia and osteoporosis.
Disease-associated bone turnover abnormalities should normalize in response to effective therapeutic interventions, which can be monitored by measurement of serum and urine bone resorption and formation markers.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
All units are reported in nmol Bone Collagen Equivalents/mmol creatinine.
<6 years: 576-1,763
6-13 years: 307-1,367
14-17 years: 102-1,048
> or =18 years: 21-66
<6 years: 576-1,763
6-13 years: 307-1,367
14-17 years: 55-378
> or =18 years: 19-63
Values are based on Mayo in-house studies of 75 children and adolescents age 3.5 to 18.5 and >100 adults.
Elevated levels of N-terminal telopeptide (NTx) indicate increased bone resorption.
Most patients with osteopenia or osteoporosis have low, but unbalanced, bone turnover, with bone resorption dominating over bone formation. While this may result in mild elevations in bone turnover markers in these patients, finding significantly elevated urine NTx levels is atypical. Therefore, if levels are substantially elevated above the young adult reference range (>1.5- to 2-fold), the likelihood of coexisting osteomalacia, or of an alternative diagnosis as described in the Clinical Information section, should be considered.
When alternative causes for elevated NTx have been excluded in an osteopenia/osteoporosis patient, the patient must be considered at increased risk for accelerated progression of osteopenia/osteoporosis.
A 50% or greater reduction in this resorption marker 3 to 6 months after initiation of therapy indicates a probably adequate therapeutic response.
The Negotiated Rulemaking Committee of HCFA also recommends:
"Because of significant specimen to specimen collagen crosslink physiologic variability (15%-20%), current recommendations for appropriate utilization include: 1 or 2 baseline assays from specified urine collections on separate days; followed by a repeat assay about 3 months after starting antiresorptive therapy; followed by a repeat assay in 12 months; thereafter not more than annually, if medically necessary."
Patients with diseases such as hyperthyroidism, which can be cured, should have a return of bone NTx levels to the reference range within 3 to 6 months after complete cure.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
The intraindividual coefficient of variation of urine N-terminal telopeptide (NTx) measurements is approximately 30%. Part of this variation is due to diurnal fluctuations, and a 24-hour collection is preferred. However, a second-morning void and other random collections are acceptable. In the latter case, it is recommended that the measurement is repeated at least once in order to allow a more accurate estimation of the true average bone turnover in a patient.
Very dilute specimens may not allow measurement of a urine creatinine level and, therefore, reporting of NTx values normalized to creatinine becomes impossible.
Inadvertent collection of urine for NTx measurements in a collection bottle that contains an acidic preservative results in substantial artifactual elevations of apparent NTx concentrations; such specimens are unacceptable.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Harper KD, Weber TJ: Secondary osteoporosis. Diagnostic considerations. Endocrinol Metab Clin North Am 1998;27:325-348
2. 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
3. Delmas PD, Eastell R, Garnero P, et al: The use of biochemical markers of bone turnover in osteoporosis. Committee of Scientific Advisors of the International Osteoporosis Foundation. Osteoporos Int 2000;11(6):S2-S17
4. Harris SS, Soteriades E, Dawson-Hughes B, et al: Secondary hyperparathyroidism and bone turnover in elderly blacks and whites. J Clin Endocrinol Metab 2001 August;86(8):3801-3804
Method Description Describes how the test is performed and provides a method-specific reference
The Vitros N-terminal telopeptide (NTx) assay is a competitive immunoassay technique, which depends on competition between NTx in the sample with a synthetic NTx peptide coated on the wells, for binding by a horseradish peroxidase (HRP)-labeled antibody conjugate (mouse monoclonal anti-NTx). The conjugate is captured by the peptide coated on the wells and unbound materials are removed by washing.
A reagent containing luminogenic substrates (a luminol derivative and a peracid salt) and an electron transfer agent (a substituted acetanilide) are added to the wells. The HRP in the bound conjugate catalyzes the oxidation of the luminol derivative, producing light. The electron transfer agent increases the level of light produced and prolongs the duration of light produced. The light signals are read by the Vitros System. The amount of HRP conjugate bound is inversely proportional to the concentration of NTx in the sample. Assay values are corrected for urinary dilution by urinary creatinine analysis and expressed in nanomoles bone collagen equivalents per liter (nM BCE/L) per millimole creatinine per liter (mM creatinine/L).(Vitros Instructions for Use, N-Telopeptide. Ortho-Clinical Diagnostics, Inc. version 1.0; 100 Indigo Creek Drive, Rochester, NY 14626-1501 version 2.16/30/12)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Monday through Friday, varies
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location The location of the laboratory that performs the test
Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
This test has been cleared or approved by the U.S. Food and Drug Administration and is used per manufacturer's instructions. Performance characteristics were verified by Mayo Clinic in a manner consistent with CLIA requirements.
CPT Code Information Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
|Result ID||Reporting Name||LOINC Code|