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Procollagen Type 1 Intact N Terminal Propeptide

Bone remodeling allows for bone growth, bone repair and elimination of microfractures. Osteoclasts resorb old bone, while osteoblasts synthesize new protein, known as osteoid. Within several months, osteoid becomes calcified. After the age of 40 years, bone destruction begins to exceed formation, leading to osteoporosis. For every 10% of bone that is lost, the risk of fracture doubles.

The medications most commonly used to treat osteoporosis are estrogen, calcitonin and biphosphonates (etidronate, alendronate, risedronate). Their mechanism of action is to inhibit osteoclastic activity and decrease bone resorption. Treatment with biphosphonates must be continuously monitored because overdosage can eventually weaken bone.

More than 90% of the osteoid matrix of bone consists of type I collagen. Noncollagenous proteins, such as osteocalcin, comprise the remaining 10%. Osteoblasts synthesize procollagen, which is the precursor of collagen. Procollagen contains a short signal sequence as well as amino and carboxy terminal propeptides. Propeptides are cleaved from procollagen by proteinases to form collagen. Both propeptides enter the circulation in a concentration that reflects the synthesis rate of collagen type I. Procollagen Type 1 N-terminal propeptide (PINP) is considered to be the most sensitive biomarker of bone formation.

Procollagen I intact N-terminal propeptide (PINP) values should not be used as a screening test for osteoporosis in the general population. PINP is used to monitor bone formation and antiresorptive therapies. PINP should be measured prior to the start of therapy to determine a baseline value and again at 3 to 6 months after initiation of therapy. Therapeutic response is evaluated by comparing pre and post-treatment values. The direction and degree of the change vary with the type of osteoporosis treatment. PINP levels have been shown to decrease as much as 70% during biphosponate therapy. Hormone replacement therapy also decreases PINP levels, but to a lesser extent. Recombinant human parathyroid hormone 1-34 (teriparatide) stimulates osteoblasts and bone formation. An increase in PINP can be seen as early as one month after initiation or treatment and peaks at 6 months. Increases of 10 ug/L or more at 3 months of therapy is considered an adequate response.

PINP exhibits diurnal variation, with higher values occurring at night. Serial measurements should be collected at the same time of the day. PINP is metabolized in the liver. Individuals with severe liver disease have decreased clearance and elevated PINP levels.

Reference ranges using a radioimmunoassay are listed below.




Adult male

20-100 ug/L

Adult female premenopausal

20-85 ug/L

Adult female postmenopausal

15-95 ug/L


Specimen requirement is a red top tube of blood.

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