Intact N-Terminal Propeptide of Type 1 Procollagen

CPT: 82523
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  • PINP

Special Instructions

This test may exhibit interference when sample is collected from a person who is consuming a supplement with a high dose of biotin (also termed as vitamin B7 or B8, vitamin H or coenzyme R). It is recommended to ask all patients who may be indicated for this test about biotin supplementation. Patients should be cautioned to stop biotin consumption at least 72 hours prior to the collection of a sample.

Expected Turnaround Time

3 - 5 days

Related Documents

Specimen Requirements




0.5 mL

Minimum Volume

0.4 mL (Note: This volume does not allow for repeat testing.)


Red-top tube or gel-barrier tube


Separate serum from cells within 45 minutes of collection. If a red-top tube is used, transfer separated serum to a plastic transport tube.

Storage Instructions

Maintain specimen at room temperature.

Stability Requirements



Room temperature

14 days


14 days


14 days

Freeze/thaw cycles

Stable x3

Causes for Rejection

Nonserum sample received

Test Details


This test is used for measurement of Intact N-Terminal Propeptide of Type 1 Procollagen (PINP) levels in serum.


This test was developed and its performance characteristics determined by Labcorp. It has not been cleared or approved by the Food and Drug Administration.

When evaluating subsequent samples, collect the samples at the same time of the day, as there is a diurnal variation of P1NP with the values being higher at night.

The measurement of P1NP has limited specificity as it is reflective of the rate of bone turnover in general.1-3

Type I collagen is synthesized by fibroblasts and therefore can be found in loose connective tissues together with other collagen types. However, since bone is the major collagenous organ and also metabolically active throughout life, the majority of the circulating P1NP is of osteoblast origin.

PINP is metabolized in the liver. Severe liver disease may affect clearance from the circulation and give rise to elevated serum P1NP levels.

As with most assays utilizing secondary antibodies, samples containing antibodies (such as heterophilic antibodies) that react with rabbit/goat IgG may cause erroneous results.


Immunochemiluminometric assay (ICMA)

Reference Interval

See table.4

Pre-menopausal females

13.9–89.1 ng/mL

Post-menopausal females

10.4–97.8 ng/mL

Males ≤ 45 years of age

21.8–96.0 ng/mL

Male > 45 years of age

18.3–86.1 ng/mL

Additional Information

Type I collagen, which is synthesized by fibroblasts and osteoblasts, is the most abundant collagen type in the body and the only collagen type found in mineralized bone, where it accounts for more than 90% of the organic matrix. Since bone is the major collagenous organ and metabolically highly active throughout life, the majority of the synthesized type I collagen stems from bone osteoblasts. Bone collagen is derived from a larger protein, type I procollagen, which consists of three amino acid chains that are intertwined to form a rod-like triple helix. Type I procollagen has propeptide extensions at both ends of the molecule, which are removed by specific proteinases before the collagen molecules thus formed are assembled into collagen fibers. Both propeptides can be found in the circulation, where their concentration reflects the synthesis rate of type 1 collagen. The P1NP assay measures the serum concentration of the amino-terminal propeptide of type I procollagen (P1NP).1 As the concentration of this extension propeptide is directly proportional to the amount of new collagen laid down in bone, it can be used to assess bone formation. During bone formation, the bone matrix is produced before mineralization occurs; hence P1NP is an early marker of bone formation.

Bone tissue is metabolically active and throughout life undergoes constant remodeling. Bone remodeling is achieved by two counteracting processes: bone formation and bone resorption, which under normal conditions are tightly coupled to each other. Metabolic bone diseases are characterized by imbalances in bone turnover and often lead to an uncoupling between bone formation and resorption.2 P1NP is a byproduct produced from the bone formation (osteoblast) activity that can be measured in serum as a biomarker reflecting the rate of bone turnover.3,5 An indicator of type I collagen turnover, such as P1NP, is useful for investigating skeletal remodeling under normal and abnormal conditions. P1NP has very low circadian and biological variation, is not affected by food intake, and is very stable in serum after venipuncture.6

The International Osteoporosis Foundation (IOF) and International Federation of Clinical Chemistry (IFCC) has recommended serum P1NP as bone formation for use in fracture risk prediction and monitoring of osteoporosis treatment.7 The National Bone Health Alliance, working in association with the American Association for Clinical Chemistry, established that the preferred bone formation marker is P1NP in clinical studies of bone turnover.8 The application of P1NP as a biomarker of bone turnover in various clinical applications has been reviewed extensively.9-13 The P1NP assay provides a sensitive tool for assessing increased bone turnover in postmenopausal women.14-19 Unlike bone density measurements, P1NP levels can show appreciable, rapid response to changes in turnover rate, supporting its clinically use for monitoring treatment response and adherence in osteoporotic patients from the onset of treatment initiation.13 P1NP has been applied for monitoring the effect of antiresorptive and anabolic therapy on bone metabolism20-43 and in hormone replacement therapy.31,32,34,44,45 The determination of PINP concentrations has also been used to detect increases in type I collagen turnover in disease states such as renal osteodystrophy,46 primary hyperparathyroidism47 and Paget’s disease of bone.48-51 P1NP determination may be useful in assessing bone metastatic activity in malignancy and in predicting survival.52-54

When monitoring response to osteoporosis treatment, a change of greater or equal to 21% (Reference Change Value - RCV) from baseline PINP levels (i.e., prior to the start of therapy), three to six months after initiation of therapy indicates an adequate therapeutic response.55


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3. Williams C, Sapra A. Osteoporosis markers. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan. 2023 May 1.32644732
4. Reference intervals were established at the Powell Center for Esoteric Testing in Burlington, NC, by the Esoteric Immunoassay department.
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19. Scariano JK, Glew RH, Bou-Serhal CE, Clemens JD, Garry PJ, Baumgartner RN. Serum levels of cross-linked N-telopeptides and aminoterminal propeptides of type I collagen indicate low bone mineral density in elderly women. Bone. 1998 Nov;23(5):471-477.9823455
20. Blumsohn A, Marin F, Nickelsen T, et al. Early changes in biochemical markers of bone turnover and their relationship with bone mineral density changes after 24 months of treatment with teriparatide. Osteoporos Int. 2011 Jun;22(6):1935-1946.20938767
21. Chen P, Satterwhite JH, Licata AA, et al. Early changes in biochemical markers of bone formation predict BMD response to teriparatide in postmenopausal women with osteoporosis. J Bone Miner Res. 2005 Jun;20(6):962-970.15883636
22. Tsujimoto M, Chen P, Miyauchi A, Sowa H, Krege JH. PINP as an aid for monitoring patients treated with teriparatide. Bone. 2011 Apr 1;48(4):798-803.21168536
23. Bauer DC, Black DM, Garnero P, et al. Change in bone turnover and hip, non-spine, and vertebral fracture in alendronate-treated women: the fracture intervention trial. J Bone Miner Res. 2004 Aug;19(8):1250-1258.15231011
24. Naylor KE, Jacques RM, Paggiosi M, et al. Response of bone turnover markers to three oral bisphosphonate therapies in postmenopausal osteoporosis: the TRIO study. Osteoporos Int. 2016 Jan;27(1):21-31.25990354
25. Bell KJ, Hayen A, Glasziou P, et al. Potential usefulness of BMD and bone turnover monitoring of zoledronic acid therapy among women with osteoporosis: secondary analysis of randomized controlled trial data. J Bone MinerRes. 2016 Sep;31(9):1767-1773.27027655
26. Eastell R, Rosen CJ, Black DM, Cheung AM, Murad MH, Shoback D. Pharmacological management of osteoporosis in postmenopausal women: an Endocrine Society* clinical practice guideline. J Clin Endocrinol Metab. 2019 May 1;104(5):1595-1622.30907953
27. Naylor KE, McCloskey EV, Jacques RM, et al. Clinical utility of bone turnover markers in monitoring the withdrawal of treatment with oral bisphosphonates in postmenopausal osteoporosis. Osteoporos Int. 2019 Apr;30(4):917-922.30613868
28. Garnero P, Stevens RE, Ayres SA, Phelps KV. Short-term effects of new synthetic conjugated estrogens on biochemical markers of bone turnover. J Clin Pharmacol. 2002 Mar;42(3):290-296.11865965
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30. Fink E, Cormier C, Steinmetz P, Kindermans C, Le Bouc Y, Souberbielle JC. Differences in the capacity of several biochemical bone markers to assess high bone turnover in early menopause and response to alendronate therapy. Osteoporos Int. 2000;11(4):295-303.10928218
31. Hannon R, Blumsohn A, Naylor K, Eastell R. Response of biochemical markers of bone turnover to hormone replacement therapy: impact of biological variability. J Bone Miner Res. 1998 Jul;13(7):1124-1133.9661076
32. Peris P, Alvarez L, Monegal A, et al. Biochemical markers of bone turnover after surgical menopause and hormone replacement therapy. Bone. 1999 Sep;25(3):349-353.10495139
33. Reginster J-Y, Sarkar S, Zegels B, et al. Reduction in PINP, a marker of bone metabolism, with raloxifene treatment and its relationship with vertebral fracture risk. Bone. 2004 Feb;34(2):344-351.14962813
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38. Ettinger B, San Martin J, Crans G, Pavo I. Differential effect of teriparatide on BMD after treatment with raloxifene and alendronate. J Bone Miner Res. 2004 May;19(5):745-751.15068497
39. Eastell R, Krege JH, Chen P, Glass EV, Reginster J-Y. Development of an algorithm for using PINP to monitor treatment of patients with teriparatide. Curr Med Res Opin. 2006 Jan;22(1):61-66.16393431
40. Liberman U, Weiss SR, Bröll J, et al. Effect of oral alendronate on bone mineral density and the incidence of fractures in post menopausal osteoporosis. N Engl J Med. 1995 Nov 30;333(22):1437-1443.7477143
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43. Finkelstein JS, Leder BZ, Burnett SM, et al. Effects of teriparatide, alendronate, or both on bone turnover in osteoporotic men. J Clin Endocrinol Metab. 2006 Aug;91(8):2882-2887.16684825
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45. Heikkinen J, Vaheri RT, Ahomäki SM, Kainulainen PM, Viitanen AT, Timonen UM. Optimizing continuous-combined hormone replacement therapy for postmenopausal women: A comparison of six different treatment regimens. Am J Obstet Gynecol. 2000 Mar;182(3):560-567.10739508
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52. Diaz-Martin MA, Traba ML, De La Piedra C, Guerrero R, Méndez-Dávila C, De La Peña EG. Aminoterminal propeptide of type I collagen and bone alkaline phosphatase in the study of bone metastases associated with prostatic carcinoma. Scand J Clin Lab Invest. 1999 Apr;59(2):125-132.10353326
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54. Jukkola A, Bloigu R, Holli K, et al. Postoperative PINP in serum reflects metastatic potential and poor survival in node positive breast cancer. Anticancer Res. 2001 Jul-Aug;21(4B):2873-2876.11712779
55. Reference Change Value or RCV (also known as Least Significant Change) calculator. European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Biological Variation Database website: Updated March 29, 2024. Accessed May 2024.


Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
140850 Propeptide Type I Collagen 47255-5 140856 Propeptide Type I Collagen ng/mL 47255-5

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