Procollagen I Intact N-Terminal, Serum
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Procollagen type I propeptides are derived from collagen type I, which is the most common collagen type found in mineralized bone. In bone, collagen is synthesized by osteoblasts in the form of procollagen. This precursor contains a short signal sequence and terminal extension peptides: amino-terminal propeptide (PINP) and carboxy-terminal propeptide. These propeptide extensions are removed by specific proteinases before the collagen molecules form. Both propeptides can be found in the circulation and their concentration reflects the synthesis rate of collagen type I. Although collagen type I propeptides may also arise from other tissues (such as the skin, vessels, fibrocartilage, and tendons), most nonskeletal tissues exhibit a slower turnover than bone, and contribute very little to the circulating pool of PINP. PINP is considered the most sensitive marker of bone formation and it is particularly useful for monitoring bone formation therapies and antiresorptive therapies; it is recommended that the test be performed at baseline before starting osteoporosis therapy and again 3 to 6 months later. PINP could be detected in the circulation as the "intact" or trimeric molecule and the monomer. In osteoporosis subjects with normal renal function, the predominant form of PINP detected in circulation is the trimeric form. However, monomeric PINP fragments may accumulate in patients with renal failure or metastatic bone disease.
An aid in monitoring antiresorptive and anabolic therapy in patients with osteoporosis
An adjunct in the assessment of conditions associated with increased bone turnover such as Paget disease
This test should be performed before beginning osteoporosis treatment (ie, prior to the start of therapy) to establish a baseline procollagen I intact N-terminal (PINP) level. Three to 6 months after initiation of therapy, a change of > or =21% (least significant change) from baseline PINP levels indicates an adequate therapeutic response. This assay is specific for the intact trimeric form of PINP.
The direction of the change in PINP levels (decrease or increase) will depend on the type of osteoporosis treatment. In patients taking bisphosphonates, PINP levels have been shown to decrease up to 70% from baseline after 6 months of therapy. Treatment with hormone replacement therapy also shows a decrease in PINP levels, but to a lesser degree than bisphosphonates therapy. In patients treated with teriparatide (recombinant human parathyroid hormone 1-34), PINP levels increase from baseline reflecting the stimulatory effect of teriparatide on osteoblasts and bone formation. PINP levels have been shown to significantly increase as early as 1 month after teriparatide treatment, peaking at 6 months following treatment. Increases of >10 mcg/L have been reported in 77% to 79% of teriparatide-treated patients after 3 months of therapy and are considered a successful response.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Procollagen I intact N-terminal (PINP) values should not be used as a screening test for osteoporosis in the general population.
There is diurnal variation of PINP levels, with the values being higher at night. When serial measurements of PINP are performed, specimens should be collected at the same time of the day.
PINP is metabolized in the liver. In individuals with severe liver disease, clearance from the circulation might be affected resulting in elevated PINP levels.
Some patients who have been exposed to mouse antigens, whether in the environment or as part of treatment or imaging procedures, may have circulating antimouse antibodies. These antibodies may interfere with the assay reagents to produce unreliable PINP assay results.
This test should not be requested in patients who have recently received radioisotopes, therapeutically or diagnostically, because of potential assay interference. A recommended time period before collection cannot be made because it will depend on the isotope administered, the dose given and the clearance rate in the individual patient. Specimens will be screened for radioactivity prior to analysis. Radioactive specimens received in the laboratory will be held and assayed after the radioactivity has sufficiently decayed. This will result in a test delay
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.
Reference values have not been established for patients who are <18 years of age.
Adult male: 22-87 mcg/L
Adult female premenopausal: 19-83 mcg/L
Adult female postmenopausal: 16-96 mcg/L
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Liberman UA, Weiss SR, Broll J, et al: Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. The Alendronate Phase III Osteoporosis Treatment Study Group. N Engl J Med 1995;333(22):1437-1443
2. McClung MR, San Martin J, Miller PD, et al: Opposite bone remodeling effects of teriparatide and alendronate in increasing bone mass. Arch Intern Med 2005 Aug 8-22;165(15):1762-1768
3. Eastell R, Krege JH, Chen P, et al: Development of an algorithm for using PINP to monitor treatment of patients with teriparatide. Curr Med Res Opin 2006 ;22(1):61-66
4. Vasikaran S, Eastell R, Bruyere O, et al: IOF-IFCC Bone Marker Standards Working Group. Markers of bone turnover for the prediction of fracture risk and monitoring of osteoporosis treatment: a need for international reference standards. Osteoporos Int 2011;22(2):391-420