One objective of orthodontic treatment during adolescence in those with skeletal discrepancies is to take advantage of the patient’s residual growth status. It is assumed that through effective management of the growing craniofacial complex during adolescence, optimal results can be achieved within a relatively shorter period of treatment. Adolescence is a period during which the rate of growth accelerates, reaches a peak velocity, and then decelerates until adulthood is achieved. This pattern can be found in all subjects, but there are marked individual variations in the initiation, duration, rate, and amount of growth during this period of life.

Many investigators have shown that human development is best represented by the stages of skeletal maturation. Skeletal maturation refers to the degree of ossification in bones. During growth, every bone goes through a series of consistent changes that can be seen radiographically.

Fishman and Hägg and Taranger developed a system of skeletal maturation assessment based on a sequence of events at different anatomic sites on hand-wrist radiographs. Lamparski introduced a method that used the cervical vertebrae from lateral cephalometric radiographs to assess skeletal maturity, and this has been especially appealing to orthodontists. Baccetti et al used longitudinal data from the Michigan Growth Study and related the timing of peak mandibular growth to the 6 cervical vertebral stages by examining the second, third, and fourth cervical vertebrae.

Skeletal morphogenesis at the growth plate (highly organized cartilage structure), is a result of chondrocyte proliferation, differentiation, and endochondral ossification. It is regulated by many genetic, hormonal, and growth factors, as well as the environment and nutrition.

Stutzmann and Petrovic hypothesized and Rabie and Hägg established the orchestrated influence of various systemic and local factors in the regulation of craniofacial growth, reflecting a close association between growth factors and craniofacial growth.

Systemic factors include growth hormone, insulin-like growth factor (IGF-1), thyroid hormones, glucocorticoids, estrogen, and androgens such as testosterone. IGF-1 was discovered by Salmon and Daughaday as a mediator of growth hormone function and since then has been extensively studied and shown to play a principal role in systemic and local regulation of both prenatal and postnatal longitudinal bone growth. Masoud et al studied serum IGF-1 levels and correlated the values with various skeletal stages as determined by cephalometric radiographic techniques. They concluded that serum IGF-1 level could be used as a skeletal maturity indicator for detecting residual mandibular growth in humans. Juul et al in a cross sectional study found that mean serum IGF-1 levels increased slowly in prepubertal children from 80 to 200 μg per liter, with a further steep increase during puberty to approximately 500 μg per liter. After puberty, circulating IGF-1 levels continued to fall to approximately 250 μg per liter at age 25 years.

However, there is still a debate about the effect of IGF-I, IGF-II, and growth hormone on the growth plate chondrocytes and the somatotrophic axis in the regulation of longitudinal bone growth; it is still unclear to what extent local IGF-1 contributes to longitudinal bone growth. Furthermore, it was summarized that systemic hormones involved in the regulation of the growth plate exert their influence on the growth plate and condylar cartilage chondrocytes by influencing the expression or the activity of locally active growth factors, stressing the importance of local factors in orchestrating the skeletal morphogenesis at the growth plate.

Local factors involved in regulation of chondrocyte activity and subsequent endochondral bone growth include Indian hedgehog protein (Ihh); parathyroid hormone-related protein (PTHrP); FGF; BMPs; VEGF; Wnt5a; Wnt5b; SOX 5, 6, and 9; Runx2; HIF-1 alpha; RANKL; and OPG, of which the biochemical signaling pathway of PTHrP-Ihh is the best known system.

PTHrP, initially purified from a lung cancer cell line, has been identified as the primary mediator of humoral hypercalcemia of malignancy. PTHrP is translated as a preprohormone that is posttranslationally processed to yield a family of mature secretary hormones that subserve different biologic functions through autocrine, paracrine, and classic endocrine functions.

PTHrP and Ihh have been reported to regulate multiple steps in the development of the growth plate and the secondary cartilage at the head of the condyle during skeletal morphogenesis.

Kindblom et al reported increased levels of expression of Ihh and PTHrP in the early stages of puberty than in the later stages in the postnatal human growth plate. However, the relationship between circulating PTHrP levels and the various stages of circumpubertal development for skeletal maturation assessment has not been examined. A biologic indicator required for the appraisal of individual skeletal maturity and consequently for the detection of the pubertal growth spurt should satisfy the following criteria : (1) the method should have biologic validity in describing individual skeletal maturity, (2) the information provided should agree with that derived from a reliable indicator, and (3) it should be efficient in detecting the peak in mandibular growth.

Hence, we hypothesized that correlating serum PTHrP levels and the cervical vertebral maturation stages of Baccetti et al could establish the usefulness of serum PTHrP levels as biomarkers in assessing the various stages of the circumpubertal growth spurt period.

The purposes of this cross-sectional study were to assess the serum levels of PTHrP at different pubertal stages, to correlate the PTHrP levels to skeletal maturity by using the the cervical vertebral maturation stages of Baccetti et al, and to evaluate the viability of serum PTHrP levels as skeletal maturity indicators in regular orthodontic practice.