**3.1 Procollagen type 1 N-peptide (P1NP)**

Osteoblasts synthesize a large amount of type I procollagen, and its carboxyl and amino termini extend to both ends respectively to form the precursor of type I collagen. The propeptides extending toward the carboxyl end are C-propeptides. During bone formation, type I procollagen is secreted to the outside of the cell, and is cleaved 1: 1:1 into procollagen type I N-peptide (PINP), type I collagen and procollagen type I C-peptide (PICP), mature type I collagen mainly constitutes the main component of osteoid, while PINP and PICP enter into the blood and urine as metabolites, so the detection of PINP and PICP can reflect the level of bone

## *Advances in Clinical Application of Bone Mineral Density and Bone Turnover Markers DOI: http://dx.doi.org/10.5772/intechopen.109074*

formation [60, 61]. Both P1NP and P1CP are metabolized in the liver. Because the half-life of serum PICP fluctuates greatly, the research evidence that P1NP reflects bone formation is more abundant than that of P1CP. Clinically, it is recommended to use PINP as an indicator of bone formation to reflect the synthesis rate of type I collagen and bone turnover [62].

Most studies suggest that elevated PINP can predict fractures. In postmenopausal osteoporotic patients, the P1NP of fracture patients is significantly higher than that of non-fracture groups, and PINP can be used as an important indicator to predict postmenopausal osteoporotic fractures [63]. A meta-analysis of postmenopausal women and men over 50 years of age showed that the hazard ratio (HR) of osteoporotic fractures was 1.18 for every one standard deviation increase in serum PINP [64]. Further studies have shown that high PINP is primarily associated with spine and hip fracture risk, predicting fractures with greater accuracy in the short term (5 years) than in the long term (10 years or more) [65]. After adjusting for BMI, smoking, frequency of falls, previous fracture history, vitamin D intake and other confounding factors, the Crandall study included 800 postmenopausal women with an average follow-up time of 7.13 years was found that serum PINP levels were not correlated with the risk of incidence of hip fractures [66]. Another Meta-analysis, with a total of 11,572 participants, showed that serum PINP levels were not significantly associated with fractures before confounding factors were adjusted. After adjusting for confounding factors (including age, BMI, previous fracture history and BMD, etc.) Raising one standard deviation level, the HR for fracture was 1.28. Whether PINP has a predictive effect on fracture occurrence is still inconsistent due to different statistical methods and different confounding factors in PINP research. At the same time, studies have found that PINP has a good predictive effect on the occurrence of fractures in non-diabetic patients, but has no predictive effect on the occurrence of fractures in patients with type 2 diabetes, suggesting that PINP will have different effects on fracture prediction under different health conditions [66]. Therefore, the correlation between PINP and osteoporotic fractures still needs to be further confirmed by large sample and prospective studies.
