Participant and Study Characteristics of Included Studies.
Participant and Study Characteristics of Included Studies.
| # | Reference | Study Design | Participants | X-ray | Skeletal Maturity Method | Biomarker(s) | Body Fluid | Results |
|---|---|---|---|---|---|---|---|---|
| 1. | Almalki, 202237 | CSS | 105 (62 F, 43 M), 6–25 y | LCR | Cervical vertebral maturation stages (CVM stages):9 6 CS | IGF-1, IGFBP-3, IGF-1/ IGFBP-3 ratio | Saliva | Highest mean IGF-1 at peak puberty (CS3 and 4): F=1.57 ng/mL; M=2.57 ng/mL
Lowest mean IGF-1 at pre-puberty (CS 1 and 2): F=0.85 ng/mL; M=1.22 ng/mL Significant difference between M and F at puberty (P<0.01) but no significant difference in pre- and post-puberty Significant interaction of stages and sex on IGF-1 (P<0.05) but not on IGFBP-3 and IGF-1/IGFBP-3 molar ratio (P>0.05) |
| 2. | Almalki et al., 202238 | CSS | 90 (34 M, 56 F), 6–25 y | Hand-wrist | 5 SMI stages36 | IGF-1, IGF-1/IGFBP-3 ratio | Saliva | IGF-1 levels low at pre-puberty, then increase at puberty onset and peak, followed by a decrease at growth deceleration stage to growth completion.
Strong positive correlation (r=0.98, P<0.01) btw IGF/IGFBP-3 ratio and SMI staging |
| 3. | Al Meshari and Aldweesh, 202239 | CSS | 141 (70 M, 71 F), 7–23 y | LCR | CVM:9 6 CS | DHEAS | Saliva | DHEAS levels increased progressively from CS1 to CS2, sharp increase at CS3, followed by a gradual increase to reach peak at CS6
Strong positive correlation coefficient of 0.94 btw CS and DHEAS levels |
| 4. | Sookhakian et al., 202240 | CSS | 55, 7–20 y | LCR | CVM:9 6 CS | IGF-1, ALP | Saliva | Strong positive correlation btw chronological age and CVM staging (r=0:836, P<0.001)
Regression model with IGF-1, ALP, and chronological age provided best skeletal growth prediction (P<0.001) Predictive potential of model for pre-puberty (95%), puberty (80%), post-puberty (90%) |
| 5. | Tsagkari, 202241 | CSS | 54 | LCR | CVM:9 3 groups: pre-puberty (CS1, CS2), puberty (CS3, CS4), post-puberty (CS5, CS6) | Metabolomics | Saliva | 61 endogenous compounds identified
Significant difference for glycerol (P<0.01), glyceric acid (P<0.05), btw pre-puberty and puberty; mannose differed (P=0.12) btw pre-puberty and post-puberty, glucose differed btw puberty and post-puberty, and glutamic acid btw pre-puberty and puberty groups, puberty and post-puberty groups Metabolite differences with dental and chronological age also identified |
| 6. | Carelli et al., 202142 | CSS | 37 (17 M, 20 F), 10-16.3 y, class II patients with retrognathic mandible | CBCT, hand-wrist | CVM:31 6 CS on LCR and 11 SMI6 on hand-wrist: stage 1, SMI 1–3 (pre-puberty); stage 2, SMI 4–5 (toward peak puberty); stage 3, SMI 6–8 (peak puberty); stage 4, SMI 9–10 (decelerating growth), stage 4, SMI 11 (post-puberty) | IGF-1 | Serum | Strong correlation btw CVM staging and hand-wrist staging, but moderate correlation btw IGF-1 levels and CVM/SMI staging |
| 7. | Kahlon et al., 202143 | CSS | 240 (120 M, 120 F), 8-16 y, 20 subjects in each grp | LCR | CVM:11 3 groups: pre-puberty (CS1, CS2); puberty (CS3, CS4); post-puberty (CS5, CS6) | IGF-1 | Serum | IGF-1 levels increase from CVM stage 1 to reach peak at CVM 3 and fall later till CVM 6 in both M and F |
| 8. | Wen et al., 202124 | CSS | 66 (35 M, 31 F) (32 class I, 11.8±2.4 y), (34 class II, 12.2±2.4 y) | LCR | CVM:9 3 grp: pre-puberty (CS1, CS2); puberty (CS3, CS4); post-puberty (CS5, CS6) | TF, DBP | GCF | Percentage TF, DBP in GCF is significantly higher in puberty than pre-pubertal or post-pubertal stage both in maxilla and mandible |
| 9. | Anusuya et al., 202044 | CSS | 90 (45 M, 45 F), 7-21 y | LCR | CVM:9 6 CS, pre-puberty (CS1, CS2); puberty (CS3, CS4); post-puberty (CS5, CS6) | DHEAS, IGF-1 | Serum | DHEAS, IGF-1 levels reach peak in males at CS4 and in females at CS3 (IGF-1, DHEAS levels in puberty significantly higher than pre-puberty stages). Serum DHEAS in males significantly higher than in females for all CS except CS2 and CS3. Serum IGF-1 in males significantly higher than females in all CS except CS1 and CS3 |
| 10. | Alhazmi et al., 201927 | CSS | 79 (31 M, 48 F), 7-23 y | LCR | 5 CS:10 CS 1,2,3,4,5 | ALP activity, protein conc. | Saliva | Salivary ALP higher in CS1
Salivary ALP significantly different btw CS1-2 and CS1-5, peak at early puberty stage IQR protein conc. peak at CS3 and CS5 Positive significant correlation btw chronological age and CS |
| 11. | Tripathi et al., 201920 | Longitud. | 63, 11–17 y | LCR | 6 CVMI stages12 (CVMI 1-6) | BALP, IGF-1 | Serum | Peak IGF-1, BALP levels at CVMI 3, BALP reaches peak earlier than IGF-1
Positive correlation btw IGF-1 and BALP, but BALP more accurate for skeletal maturity IGF-1 and BALP annual % changes in negative correlation with mandibular length |
| 12. | Wijaya et al., 201923 | CSS | 136 (64 M, 72 F), 8-18 y | LCR | CVM.9 3 grps: pre-puberty/pre-peak puberty (CS1, CS2), puberty/peak puberty (CS3, CS4), post-puberty/post-peak puberty (CS5, CS6) | BALP and total protein | Saliva | Pubertal phase prediction using multinomial logistic regression including chronological age, salivary BALP levels, and body mass index percentile
Salivary BALP level in pre-peak puberty grp is greater than in peak puberty grp, which in turn is greater than in post-puberty grp |
| 13. | Wen et al., 201845 | CSS | 40 (20 M, 20 F); puberty grp (10 M, 10 F) mean age (9.2±1.4 y); post-puberty grp (10 M, 10 F) mean age (23.3±0.64 y) | LCR | CVM:10 puberty (CS3 and 4), post-puberty (CS5 and 6) | Protein conc., DBP, TF | GCF | Of 537 total identified proteins in GCF, 25 were upregulated and 18 downregulated in puberty versus post-puberty grp
DBP and TF in puberty grp are significantly higher in than post-puberty grp |
| 14. | Tripathi et al., 201821 | CSS | 150 (75 M, 75 F), 8–20 y | LCR | 6 CVMI stages12 (CVMI 1–6) | BALP and IGF-1 | Serum | Peak serum IGF-1 levels: M=CVMI 4; F=CVMI 3
Peak serum BALP: CVMI 3 for both sexes Statistically significant correlation btw serum IGF-1 and serum BALP across CVMI 1–3 and 4–6 (P<0.01) |
| 15. | Tripathi et al., 201722 | CSS | 150 (75 M, 75 F), 8–20 y | LCR | 6 CVMI stages12 (CVMI 1–6) | OC, IGF-1 | Serum | Peak IGF-1 at CVMI 4 and 3, peak OC at CVMI 5 and 3 in M and F, respectively
Statistically significant correlation btw IGF-1 and OC in CVMI 1–6 in M (P<0.05), and CVMI 3-6, 4–6 in F (P<0.05) |
| 16. | Jain et al., 201746 | CSS | 90 F, 8–20 y | LCR | 6 CVMI stages12 (CVMI 1–6) | IGF-1, IGFBP-3, and its ratio | Serum | Serum IGF-1 increase across CVMI 1-3, peak levels (403.3±12.3 ng/mL), then decrease across CVMI 3-6; serum IGFBP-3 increase across CVMI 1-4 (peak values 5186.8±1384.2 ng/mL), then decrease across CVMI 4-6
High positive correlation btw IGF-1 and IGFBP-3 to CVMI 1–3 |
| 17. | Venkatagiriappa et al., 201647 | CSS | 107 (45 M, 62 F) 5–25 y | Hand-wrist | 11 SMI:6 Stage 1, SMI 1–3 (pre-puberty); stage 2, SMI 4–5 (toward peak puberty); stage 3, SMI 6–8 (peak puberty); stage 4, SMI 9–10 (decelerating growth); stage 4, SMI 11 (post-puberty) | DHEAS | Blood | Mean DHEAS levels increase from pre-puberty (75.95 μg/dL), to post-puberty (102.24 μg/dL), but not statistically significant at P<0.05 |
| 18. | Giuseppe et al., 201625 | CSS | 100 (38 M, 62 F), mean age, 11.5±2.4 y; range, 7.6–17.7 y) | LCR | CVM:9 3 grps: Grp A, pre-puberty (CS1, CS2); Grp B, puberty (CS3, CS4); Grp C, post-puberty (CS5, CS6) | ALP | GCF | GCF ALP levels in puberty grp two times greater than in pre-puberty/post-puberty grp (P<0.001)
Intermediate mixed dentition only noted in pre-puberty grp (P<0.001) Negative correlation of GCF ALP levels with pre-puberty and post-puberty grp |
| 19. | Sinha et al., 201648 | CSS | 72 F, 8–20 y | LCR | 6 CVMI stages12 (CVMI 1–6) | IGF-1 | Serum and urine | Median serum IGF-1 levels increased across CVMI 1–4 (statistically significant peak at 408.59 ng/mL), decreased later
Urine IGF-1 levels also showed peak at CVMI 4 (5.12 ng/mL) |
| 20. | Gupta et al., 201549 | CSS | 60 (30 M, 30 F), 8–23 y | LCR | CVM:9 6 CS (CS1–6) | IGF-1 | Serum | M: serum IGF-1 increased across CS1–4, then decreased
F: increased across CS1–3, then decreased Greatest mean IGF-1 value in F (397 ng/mL) greater than in M (394.8 ng/mL) |
| 21. | Masoud et al., 201550 | Longitud. | 25 (13 M, 12 F), 9.2–17.4 y, 43 yearly samples | LCR | CVM:9 3 grps: Grp A, pre-puberty (CS1, CS2); Grp B, puberty (CS3, CS4); Grp C, post-puberty (CS5, CS6); single observer | IGF-1 | Blood | Average IGF-1 level and IGF-1 change were significantly associated with increase in mandibular length across the grps |
| 22. | Masoud et al., 201551 | Longitud. | 25, (13 M, 12 F) 9.2–17.4 y; 43 yearly samples | LCR | CVM:9 3 grps: Grp A, pre-puberty (CS1, CS2); Grp B, puberty (CS3, CS4); Grp C, post-puberty (CS5, CS6); single observer | IGF-1 | Blood | Moderate positive correlation btw total AFH change and annual % change in blood spot IGF-1 levels (P<0.01) |
| 23. | Nayak et al., 201452 | CSS | 45 (21 M, 24 F), 7–23 y | LCR | QCVM staging:32 QCVM I/accelerating velocity (n=13); QCVM II/high velocity (n=15); QCVM III/decelerating velocity (n=10); QCVM IV/completing velocity (n=7) | IGF-1 and salivary secretion rate | Saliva | IGF-1 levels in QCVM II greater than QCVM I (P<0.0001), and QCVM II greater than QCVM III/IV (P<0.001), at completing velocity stage |
| 24. | Jain et al., 201353 | CSS | 45 M | LCR | CVM:9 CS3, 4, 5 (n=15 for each CS) divided into 3 grps: advanced, average, and delayed maturers | IGF-1 | Serum | Peak IGF-1 level in CS4, in CS5 IGF-1 level low in all 3 maturity grps |
| 25. | Hussain et al., 201354 | CSS | 90 (47 M, 43 F), 5–20 y | LCR | CVM:9 CS1–6 (n=15 for each CS) | PTHrP | Serum | Serum PTHrP increased across CS1-5, peaks at CS5, declines sharply at CS6 |
| 26. | Gupta et al., 201255 | CSS | 30 F, 8–23 y | LCR and IOPA | CVM:9 CS1–6, MP333 (MP3F, MP3FG, MP3G, MP3H, MP3HI, MP3I) | IGF-1 | Serum | Mean IGF-1 in CS1 (216±7.53 ng/mL) increased to peak levels in CS3 (397±20.76 ng/mL), then declined
Mean IGF-1 in MP3F stage (218±8.73 ng/mL), increased to peak in MP3G stage (397±20.76 ng/mL), then declined |
| 27. | Ishaq et al., 201256 | CSS | 120 (60 M, 60 F); M, 10–18 y; F, 8–16 y | LCR | 6 CS12 (CS1–6) | IGF-1 | Serum | M: peak mean IGF-1 value in CS4 (mean age 14.5 y, 893±171 ng/mL)
F: peak mean IGF-1 value in CS4 (mean age 14 y, 794±217 ng/mL) Sex-related differences at CS3 and 5 |
| 28. | Masoud et al., 201257 | Longitud. | 25 (13 M, 12 F); 9.2–17.4 y; 43 yearly samples | LCR | CVM:9 3 grps: Grp A: pre-puberty (CS1, CS2), Grp B: puberty (CS3, CS4), Grp C: post-puberty (CS5, CS6) | IGF-1 | Blood | Significant mild to moderate correlation btw change in mandibular length and mean IGF-1 change in levels (r=0.4; P=0.008)
Grp with ascending IGF-1 levels had moderate to high correlation with change in mandibular length (r=0.655; P=0.015) |
| 29. | Srinivasan et al., 201258 | CSS | 60 (30 F, 30 M); 7–30 y | Hand-wrist | Grp A: pre-puberty, Grp B: puberty, Grp C: post-puberty34,35 (n=20, 10 M, 10 F in each grp) | DHEAS | Serum | Mean DHEAS values in pre-puberty grp (0.43 μg/mL) is less than puberty grp (2.17 μg/mL) which in turn is lower than post-puberty grp (4.60 μg/mL)
No significant difference btw M and F |
| 30. | Perinetti et al., 201259 | CSS | 50 (19 M, 31 F), 7.8-17.7 y | LCR | CVM:9 6 CS; 3 grps: pre-puberty (CS1, CS2), puberty (CS3, CS4), post-puberty (CS5, CS6) | ALP activity, protein conc. | GCF | Total GCF ALP activity greatest in puberty grp compared to pre- and post-puberty grps
Total protein and normalized GCF ALP activity showed no association with stages |
| 31. | Perinetti et al., 201160 | CSS | 72 (27 M, 45 F); 7.8–17.7 y | LCR | CVM:9 6 CS; 3 grps: pre-puberty (CS1, CS2), puberty (CS3, CS4), post-puberty (CS5, CS6) | ALP activity | GCF | Two-fold peak of GCF ALP activity in puberty compared to pre- and post-puberty grps
Sites: ALP activity in CS4 in maxillary sites and CS3 in mandibular sites is significantly greater than in CS2 stage |
| 32. | Masoud et al., 200961 | CSS | 84 (45 F, 39 M); 5–25 y | Hand-wrist | 11 SMI:6 stage 1, SMI 1–3 (pre-puberty); stage, SMI 4–5 (toward peak puberty); stage 3, SMI 6–8 (peak puberty); stage 4, SMI 9–10 (decelerating growth); stage 5, SMI 11 (post-puberty) | IGF-1 | Blood | IGF-1 in high velocity/peak puberty stage greater than accelerating (stage 2)/pre-puberty (stage 1)/post-puberty (stage 5) |
| 33. | Masoud et al., 200862 | CSS | 83 (39 M, 44 F); 5–25 y | LCR | CVM:9 6 CS; 3 grps: pre-puberty (CS1, CS2), puberty (CS3, CS4), post-puberty (CS5, CS6) | IGF-1 | Blood | Mean blood spot IGF-1 levels in CS4 is significantly higher than in CS1, CS2, CS6
IGF-l levels show positive correlation upon progress from pre-pubertal to pubertal stages followed by negative correlation on attaining post-pubertal stage Negative correlation of IGF-1 levels with time of puberty onset and chronological age |
AFH, anterior facial height; ALP, alkaline phosphatase; BALP, bone alkaline phosphatase; btw, between; CBCT, cone beam computed tomography; conc., concentration; Class I, normal upper and lower jaw relation; Class II, mandible retrognathic or maxilla prognathic or combination of both; CS, cervical stage(s); CSS, cross-sectional study; CVM, cervical vertebral maturation; CVMI, cervical vertebral maturation index; CVS, cervical vertebral staging; DBP, vitamin D binding protein; DHEAS, dehydroepiandrosterone sulfate; F, Female; grp(s), group(s); GCF, gingival crevicular fluid; IGF-1, insulin growth factor-1; IGFBP-3, insulin-like growth factor binding-protein-3; IOPA, intra-oral periapical radiograph; IQR, interquartile range; LCR, lateral cephalometric radiograph; Longitud., longitudinal; M, male;); MP3F, middle phalanx of third finger (F stage); MP3FG, middle phalanx of third finger (FG stage); MP3G, middle phalanx of third finger (G stage); MP3H, middle phalanx of third finger (H stage); MP3HI, middle phalanx of third finger (HI stage); MP3I,middle phalanx of third finger (I stage); OC, osteocalcin; PTHrP, parathormone-related protein; QCVM, quantitative cervical vertebral maturation; SMI, skeletal maturity indicators; TF, serotransferrin; y, year(s); X-ray, radiograph.