Intact N-Terminal Propeptide of Type 1 Procollagen

Serum

0.5 mL

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

Red-top tube or gel-barrier tube

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)

See table.⁴

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 metabolism^20-43 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