## 1 Introduction  
Saliva has been proposed in the medical field as a biological fluid collected with non-invasive methods, suitable for discreet monitoring of health conditions [1]. Saliva is an \"ultra-filtered\" blood and salivary biomarkers can virtually be applied to evaluate the physiological conditions of the patient, to track the progression of a disease and to monitor the efficacy of therapies [2]. Saliva analysis is a potential substitute for blood analysis, sampling is non-invasive and can also be performed by the patient himself; it is particularly suitable for long-term monitoring, for screening large numbers of patients [3, 4], as well as for the development of point-of-care salivary technology [5]. However, saliva sampling requires a standardization phase with the choice of a suitable device and an indication of the factors that can influence the salivary composition, such as blood contamination, a factor capable of invalidating the determination of the salivary biomarker [6]. The literature reports various applications of salivary dosages with a different clinical value in the diagnosis, in the monitoring of oncological, cardiovascular, autoimmune, viral and bacterial diseases, or in the assessment of the risk to of exposure to toxic substances [7]. Levels of bone turnover markers (BTM) that provide an estimate of bone resorption and formation can also be measured non-invasively using saliva. Numerous proteins or derived biomarkers are released during remodeling by osteoblasts or osteoclasts and are generically described as bone turnover markers (BTM) [8; 9]. The most used markers are N-terminal collagen extension propeptide type I (PINP), osteoclastin and bone alkaline phosphatase for indicators of the process of bone formation and crosslinking C-terminal collagen telopeptide type I (bCTX-I), N- terminal telopeptide of collagen type I (NTX), resistant to acid tartrate phosphatase isoform 5b (TRAP5b) for bone resorption. Each bone marker has distinct characteristics that reflect particular aspects of bone physiology. [10]. Bone is a dynamic and metabolically active tissue that is continuously remodeled by the coordinated actions of osteoclasts and osteoblasts in cellular packages. In particular, PINP is an indicator of bone formation and is produced during the formation of the bone matrix by cleavage of type I collagen; TRAcP 5b reflects the number of osteoclasts and is correlated to bone resorption; Parathyroid hormone-related protein (PTHrP) instead intervenes in the physiological regulation of bone remodeling (an endocrine mechanism) but it is also locally produced (paracrine function) by osteoblast progenitors; it promotes the differentiation of mature osteoblasts by inhibiting the apoptosis process that allows bone formation; moreover it stimulates the differentiation of the osteoclasts that is responsible of the bone resorption [11]. PTHrP is present in the enamel organ and is responsible for the formation of the eruptive pathway [11]. This observation has inspired various studies that have focused on the role of PTHrP in mediating osteoclastengenesis. Parathyroid hormone-related protein (PTHrP) is also a protein, which has several biologically active domains, and plays a vital role in regulating bone metabolism. [12]. Such as Parathyroid hormone-related protein (PTHrP) is also a protein, which has several biologically active domains and plays a vital role in regulating bone metabolism. Some studies have evaluated the bone turnover markers CTX and B-ALP in particular using the salivary matrix and have correlated them with the concentrations on serum samples [11; 12; 13; 14]. Others found significant correlations between concentrations and age, body mass index, and bone mineral density concluding that saliva could be used as a fluid sample to evaluate bone remodeling [13; 15].