Authors Study design | Study title | Sample size/sex/age | Health status/ drug intake | Type of orthodontic treatment | Observation period | Method of GCF collection | Tooth site of collection | Control group | Biomarker assessed |
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Castroflorio et al. 2017 [16] RCT/ Split mouth | Biochemical markers of bone metabolism during early orthodontic tooth movement with aligners | 10 (5 F, 5 M) Mean age 22.3 ± 3.3 years | No anti-inflammatory or antibiotic therapy in the previous 6 months | Aligners (Invisalign) | • 1 h before placement • 1 h after aligner placement • 7 days after • 21 days after | Periopaper strips | Distobuccal and mesiobuccal sites of second molar under distalization | Contralateral second molar | Osteopontin (OPN) |
Al Swafeeri et al. 2015 [17] RCT/ Split mouth | Crevicular alkaline phosphatase activity during the application of two patterns of orthodontic forces | 12 (7 F, 5 M) Mean age 17.5 ± 2.4 years | Healthy medical status/ drug intake not reported | Fixed appliances/ extraction of 1st premolar/ distalization of canine | Baseline (before the activation) and every week for 3 weeks after the initial activation | Paper strips | Constant orthodontic force 150cN for 3 weeks mesial side of maxillary canine and distal site of maxillary first molar | Increasing orthodontic force 50 cN throughout the first week, 100 cN throughout the second week and 150 cN the third week. | Alcaline phosphatase (ALP) |
Wahab et al. 2014 [18] RCT/ Split mouth | Enzyme activity profiles and ELISA analysis of biomarkers from human saliva and GCF during orthodontic tooth movement using self-ligating brackets | 19 (14 F, 5M) Between 16 and 28 years old | No drug intake during the study or 1 month before | Fixed appliances/ extraction of 1st premolar/ distalization of canine | Baseline and every week for 5 weeks after the initial application | Periopaper strips | 100-g force on tested canine | 150-g force on contralateral canine | Tartrate-resistant acid phosphatase (TRAP) Alkaline Phosphatase (ALP) |
Barbieri et al. 2013 [19] RCT/ Split mouth | Biochemical markers of bone metabolism in GCF during early orthodontic treatment | 10 (5 F, 5 M) Aged from 22–29 years | No anti-inflammatory or antibiotic therapy in the previous 6 months | Separators | • Baseline • 24 h • 7 days after the placement of separators | Periopaper strips | Mesiobuccal and distobuccal sides of tested molars | Mesiobuccal and mesiolingual of contralateral molars | Osteopontin (OPN) |
Kalha et al. 2010 [20] RCT | Redefining orthodontic space closure: sequential repetitive loading of the periodontal ligament—a clinical study | 10 (6 F, 4 M) Mean age 20.6 ± 3.2 years | Healthy medical status/ drug intake not reported | Fixed appliances/ extraction of 1st premolar/ distalization of canine | • 1 h before • 1 h after the activation • On days 7, 14, 21, and 28 | Sterile paper strips | Distogingival margin of the four canines (5 patients with hycon-screw) | Distogingival margin of the four canines (5 patients with active tie-backs) | Alcaline phosphatase (ALP) |
Bitra et al. 2017 [21] Prospective | Gingival crevicular fluid turnover markers in premenopausal vs. postmenopausal women receiving orthodontic treatment | 25 F Postmenopausal (mean age 57 years) | No drug intake 1 month before the study | Fixed appliances | • Baseline • 24 h | Periopaper strips | NA | 25 F Premenopausal (mean age > 30 years) | Osteopontin (OPN) |
Smuthkochorn et al. 2017 [22] Prospective | Gingival crevicular fluid bone turnover biomarkers: how postmenopausal women respond to orthodontic activation | 16 F Postmenopausal (mean age 63 years) | No drug intake 1 month before the study | Fixed appliances | • Baseline • 24 h | Periopaper strips | 2 Anterior and 2 posterior teeth | 12 F Premenopausal (mean age 32 years) | Osteopontin (OPN) |
Yang et al. 2014 [23] Prospective | Preliminary study on the best-exerted force chance in the female menstrual cycle | 12 F Aged 18–28 years | Not reported | Fixed appliances/ extraction of 1st premolar/ distalization of canine | • Baseline • 15 days • 30 days • 45 days after | Paper strips | Distal site of canine that is distalized | NA | Osteocalcin (OC) |
Alfaqeeh et al. 2011 [24] Prospective | Osteocalcin and N-telopeptides of type I collagen marker levels in gingival crevicular fluid during different stages of orthodontic tooth movement | 20 (10 F, 10 M) Aged 15–25 years | No regimen or antibiotic therapy the last 3 months | Fixed appliances/ extraction of 1st premolar/ distalization of canine | • 1 h, 1 day, 7, 14, and 21 days after application | Periopaper strips | Buccal and palatal, mesial, and distal sites of tested canines | Contralateral canine with fixed appliance but not activated | Osteocalcin (OC) N-telopeptides (NTX) |
Batra et al. 2006 [25] Prospective | Alkaline phosphatase activity in gingival crevicular fluid during canine retraction | 10 F Aged 12–21 years | Healthy medical status/ drug intake not reported | Healthy medical status/ drug intake not reported | • Baseline (before the activation) • Immediately after • 1 day • 7 days • 14 days • 21 days after | Micropipettes of 1 μl capacity | Mesial and distal sites of tested canine | Contralateral canine (no forced applied) | Alcaline phosphatase (ALP) |
Isik et al. 2005 [26] Prospective | Bone marker levels in GCF during orthodontic intrusive tooth movement. A preliminary study. | 9 (5 F, 4 M) Mean age: 14.6 ± 2.08 years | Not reported | Fixed appliances/ intrusion of 1st premolar | • 1 h • 24 h • 168 h after 1st activation • 22nd day • 28th day after 2nd activation | Periopaper strips | Mesiobuccal, distobuccal, palatinal crevicular region of maxillary first premolars | NA | Deoxypyridinoline (DPD) Osteocalcin (OC) N-telopeptide (NTX) Bone alkaline phosphatase (BALP) |
Perinetti et al. 2004 [27] Prospective | Longitudinal monitoring of sub-gingival colonization by Actinobacilllus actinomycetemcomitans and crevicular alkaline phosphatase and asparate aminotransferase activities around orthodontically treated teeth | 21 (11 F, 10 M) Mean age 17.1 ± 3.3 years | No drug intake 1 month before the study | Fixed appliances/ extraction of 1st premolar/ distalization of canine | • Baseline • On day 28 | Standardized sterile paper strips | Mesial and distal sites of experimental canine | Mesial and distal sites of contralateral and antagonist canine | Alcaline phosphatase (ALP) |
Perinetti et al. 2002 [28] Prospective | Alkaline phosphatase activity in GCF during human orthodontic tooth movement | 16 (10 F, 6 M) Mean age 15.5 ± 3.5 years | No drug intake 1 month before the study | Fixed appliances/ distal retraction of 1st molar | • 1h after activation • 1, 2, 3, and 4 weeks after | Sterile paper strips | Mesial & distal sites of maxillary 1st molar | Contralateral molar with fixed appliance but not activated and antagonist molar without appliance | Alcaline phosphatase (ALP) |
Griffiths et al. 1998 [29] Prospective | Evaluation of osteocalcin and pyridinium crosslinks of bone turnover in gingival crevicular fluid during different stages of orthodontic treatment | 20 (12 F, 8 M) Mean age 13.5 years | Not reported | Fixed appliances/ extraction of 1st premolar/ distalization of canine | T1 prior to orthodontic appliance, T2 post appliance fit but prior to activation, T3 during active retraction, T4 during retention | Paper strips | Distal surface of maxillary canines | NA | Osteocalcin (OC) Pyridinoline (PYD) Deoxypyridinoline (DPD) |
Insoft et al. 1996 [30] Cross-sectional | The measurement of acid and alkaline phosphatase in GCF during orthodontic movement | 30 (sex NA) Aged 8–12 years | Not reported | 3 Groups: 1) Bionator 2) Headgear 3) Control group | One collection time point | Periopaper strips | Mesial and distal sites of 1st molars | Control group | Acid and alcaline phosphatase (ALP) |