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Table 3.

Results Associated with Variation in Mediator Levels in Different Skeletal Maturation Stages.

Mediator	Criteria	Results
Insulin-like growth factor-1 (IGF-1)	Upregulation/downregulation	Level in pubertal stage (CS3, CS4) greater than in pre-pubertal (CS1, CS2)/pubertal (CS5, CS6) stages20–22,37,43,46,48,53,56,62 Levels in high velocity stages (SMI 6–8) greater than in accelerating stage (SMI 4–5)/pre-pubertal (SMI 1–3)/decelerating velocity (SMI 9–10)/post-pubertal stages (SMI 11)38,61 Salivary IGF-1 at QCVM II (high velocity) greater than in QCVM I (accelerating velocity)/QCVM III (decelerating)/QCVM IV (completed)52
	Peak levels	CS3 stage20,37,43,46,55 CS4 stage37,43,48,58,62
	Sex predilection	Peak IGF-1 levels in F at CVMI 3;20–22,44,46,49,55 CVMI 448 Peak IGF-1 levels in M at CVMI 420,22,49,53,56 Peak IGF-1 levels in M and F at CVMI 456 Peak levels in F greater than in M,49 and in M greater than in F23,37,38
	Significant correlations	Positive correlation btw BALP and IGF-1 across various skeletal stages20 Positive correlation btw OC and IGF-1 in CVMI 1–6 (M) and CVMI 3–6,4–6 (F)22 Positive correlation btw IGF-1 and IGFBP-3 across CVMI 1–337,38,46 Positive correlation of IGF-1 levels in serum and urine across CVMI 1–448 Positive correlation of IGF-1 with age till CS3 and negative correlation until CS4, CS553 Negative correlation of IGF-1 with time of pubertal onset and age62 IGF-1 peak levels at CS3 in correlation with peak IGF-1 levels at MP3G stage45
	Craniofacial parameters	Negative correlation of annual change in IGF-1% with mandibular length20 Positive correlation of IGF-1 increase with increasing mandibular length50 Positive correlation of AFH and mandibular plane change with % change in IGF-1 levels50 Moderate to high correlation of ascending IGF-1 levels (> 250 μg/L) to greater mandibular growth (5.6 mm)57
	Growth predictive model	Regression model with IGF-1, ALP, and chronological age provided the best skeletal growth prediction (P<0.001)40
Bone-specific alkaline phosphatase (BALP)	Upregulation/downregulation	BALP levels peak at CVMI 3 in both sexes20,21 Negative correlation of annual % change in BALP with mandibular length20 Salivary BALP levels in pre-pubertal stage greater in the pubertal stage greater than in post-pubertal stage21
Bone-specific alkaline phosphatase (BALP)	Association with other parameters	BALP levels peak at CVMI 3 earlier than IGF-120,21 BALP more accurate than IGF-1 for skeletal maturation20
Osteocalcin (OC)	Upregulation/downregulation	Mean serum OC levels reach peak at CVMI 5 in M, and from CVMI 322 OC levels in M greater than in F22
Osteocalcin (OC)	Correlations	Significant correlation btw IGF-1 and OC in CVMI 1–6 (M) (P<0.05), and CVMI 3–6, 4–6 (F) (P<0.05)22
Vitamin D binding protein (DBP) and serotransferrin (TF)	Upregulation/downregulation	DBP and TF % in GCF in pubertal greater than in pubertal/post-pubertal stage24,45 In post-pubertal stage, mandibular TF greater than maxillary TF24 In pre-pubertal and post-pubertal stages, maxillary DBP greater than mandibular DBP24 No difference in TF and DBP levels in malocclusion class or sex24
Vitamin D binding protein (DBP) and serotransferrin (TF)	Pubertal predictive model	Maxillary TF levels and age important variables, maxillary TF more accurate btw pubertal and non-pubertal stages, with 100% specificity and 68.2% sensitivity24
Dehydroepiandrosterone sulfate (DHEAS)	Upregulation/downregulation	Levels of DHEAS in pubertal greater than in pre-pubertal39,44 Mean DHEAS levels steady increase from pre-pubertal to post-pubertal stage39,47,58
Dehydroepiandrosterone sulfate (DHEAS)	Sex predilection	Peak in M at CS4, and in F at CS344 Levels in M greater than in F at all stages except CS2, 344
Alkaline phosphatase (ALP)	Upregulation/downregulation	Peak in early pubertal stage27 ALP protein concentration peaked at CVM stage 3 (1.44 [0.65] mg/mL) and CVM stage 5 (1.50 [0.46] mg/mL)27 GCF ALP levels in pubertal greater than in pre-pubertal/post-pubertal stage25,60 Total GCF ALP activity in pubertal greater than in non-pubertal stages60
	Correlations	Significant positive correlation btw salivary ALP and age27 Negative correlation of GCF ALP levels with pre-pubertal/post-pubertal phase25,60
	Pubertal predictive model	ALP and age combined proved better predictive accuracy for pubertal peak than ALP alone27
	Sex predilection	Levels in M greater than in F27
Parathormone-related protein (PTHrP)	Upregulation/downregulation	Serum PTHrP increase across CS1–5 with a correlation coefficient of 10.68 (P<0.001)54 Peak levels seen at CS5, then decline at CS6 (coefficient 0.676)54

AFH, anterior facial height; ALP, alkaline phosphatase; BALP, bone alkaline phosphatase; btw, between; CS, cervical stage; CVMI, cervical vertebral maturation index; DBP, vitamin D binding protein; F, female(s); GCF, gingival crevicular fluid; IGF-1, insulin-like growth factor; IGFBP-3, insulin-like growth factor binding protein-3; M, male(s); MP3G, middle phalanx of third finger (G stage); OC, osteocalcin; PTHrP, parathormone-related protein; QCVM, quantitative cervical vertebral maturation; SMI, skeletal maturity indicators; TF, serotransferrin.