Table 5 Outcomes of included studies

Castroflorio et al. 2017 [16]

RCT/

Split mouth

OPN test sites:

T0: 28.1 ± 15.5

T1: 35.6 ± 19.9

T2: 35.2 ± 18.5

T3: 46.0 ± 22.7

Control sites:

T0: 31.2 ± 15.7

T1: 26.2 ± 13.6

T2: 32.9 ± 14.5

T3: 31.3 ± 14.7

ng/μl

Invisalign aligners release an initial force of about 1 N on distalizing a maxillary molar. This force delivery produces an increased concentration of OPN at tension sites.

Not reported

Al Swafeeri et al. 2015 [17]

RCT/

Split mouth

Constant force group

Canine

A0 9.16 ± 5.22

A1 12.10 ± 7.86

A2 23.19 ± 9.83

A3 21.73 ± 12.16

Molar

B0 7.19 ± 6.26

B1 9.32 ± 6.57

B2 21.23 ± 9.70

B3 13.95 ± 8.05

Gradually increasing force group

Canine

C0 10.66 ± 6.99

C1 19.50 ± 12.41

C2 35.73 ± 10.10

C3 20.22 ± 12.88

Molar

D0 5.70 ± 6.39

D1 11.42 ± 5.05

D2 18.74 ± 5.48

D3 27.03 ± 9.32

IU/μl

The use of a gradually increasing orthodontic force could induce an increase in osteoblastic activity during initial stage of orthodontic tooth movement compared with that induced by a relatively constant orthodontic force.

Gradually increasing force systems could be recommended for clinical use in orthodontics.

Wahab et al. 2014 [18]

RCT/

Split mouth

The LDH activity for 100 g of force exhibited significant differences at weeks 2 and 3, while the activities of AST and TRAP were significantly different from control values at week 5. For 150 g of force, there were significant differences in the LDH activities at weeks 3, 4, and 5 but no significant differences in the TRAP activities.

U/mg

The activity of LDH in the GCF increased significantly at 2 and 3 weeks for 100 g of force and at 1, 2, 3 weeks for 150 g of force. These findings showed that inflammation occurred earlier when 150 g of force was applied, which might induce a painful sensation that starts earlier and lasts longer. The 150-g force is a heavy force, and it produced significant AST-specific activity or necrosis earlier than the application of 100-g force. TRAP activity shows no differences for 150g of force throughout the treatment, this finding indicates that heavy force results in undermining resorption

The movements of the canines showed no significant differences between 100 and 150 g of force throughout the 5 weeks of treatment. LDH, TRAP, and AST from the GCF may be used as biomarkers for monitoring orthodontic tooth movement

Barbieri et al. 2013 [19]

RCT/

Split mouth

At the control sites there were no differences between the values recorded for buccal/palatal sites or between values recorded at different visits. In contrast, the concentration of OPG significantly decreased at the compression site by 24 h and the amount, and concentration of RANK differed significantly between control, compression, and tension sites after 7 days. A significant increase in absolute TGF-β1 levels was also detected at the compression site versus the control and tension sides after 7 days.

pg/ml or pg

Both increased expression of bone resorptive mediators (RANK, TGFβ1) and decreased expression of a bone-forming mediator (OPG) on the compression side were detected.

Bone metabolism is affected by application of force to the teeth by elastic separators.

Kalha et al. 2010 [20]

RCT

There was a 200% increase in the alkaline phosphatase level between days 21 and 28 in the active tie-back group at all sites, while that in the retraction screw group was more than 260%.

IU/l

Alkaline phosphatase levels increased more in the Hycon-screw group between 14 and 28 days. That can be explained by the fact that elastomeric modules generally lose 50–70% of their initial force after 3 weeks of loading.

Sequential repetitive loading of the periodontal ligament with small and controlled activations is effective for space closure as indicated by a significantly higher increase in the GCF alkaline phosphatase level if a retraction screw is used instead of active tie-backs.

Bitra et al. 2017 [21]

Prospective

OPN:

Baseline:

Premenopausal 241.52 pg/μl and postmenopausal 317.15 pg/μl

24 h after:

Premenopausal 540.97 pg/μl and postmenopausal 492.73 pg/μl

pg/μl

No difference is observed in GCF levels of OPN while comparing the mean premenopausal and postmenopausal women.

Orthodontic treatment appears to be equally safer for both premenopausal and postmenopausal subjects.

Smuthkochorn et al. 2017 [22]

Prospective

OPN

Premenopausal

T0 238.92 ± 66.88

T1 531.72 ± 465.98

Postmenopausal

T0 323.26 ± 157.27

T1 489.61 ± 280.38

pg/μl

There are OPN baseline differences in GCF bone turnover markers in premenopausal vs. postmenopausal groups.

Reactions to orthodontic activation are not significantly different between the groups.

Yang et al. 2014 [23]

Prospective

The OCN levels were significantly higher in the ovulation period group than in the menstrual period group (P < 0.05).

pg/nl

The OCN levels affected from the menstrual period

Exerted force on teeth during the menstrual period may promote rapid tooth movement.

Alfaqeeh et al. 2011 [24]

Prospective

At the experiment sites, the GCF NTX level steadily increased from day 7 to day 21. The control side did not show any statistically significant variation throughout the observation period.

The OC levels in the GCF showed no difference at the control site. At the experimental site where pressure was applied, the levels of OC showed higher values on day 7 and onward.

nmol of bone collagen equivalents per litre (nmol BCE/L)

Statistically significant changes in NTX and OC levels on days 7, 14, and 21 when we compared the experimental and control sides. The peak in all activity of the variables occurred on day 14 after retraction.

The GCF NTX and OC markers showed statistically significant increases in the levels on days 14 and 21 at the side that had orthodontic tooth movement.

Batra et al. 2006 [25]

Prospective

Significant changes on ALP activity on 7, 14, and 21 days at mesial & distal sides compared with experimental and control teeth

IU/l

The peak in enzyme activity occurred on the 14th day of initiation of retraction followed by a significant fall in activity.

ALP activity could possibly be a biological indicator of the activity in the periodontium and orthodontic tooth movement.

Isik et al. 2005 [26]

Prospective

OC:

Initial 500.22 ± 360.67

1 h 500.22 ± 360.67

1 day 451.86 ± 330.07

7 days 505.85 ± 236.15

22 days 326.98 ± 240.58

28 days 309.22 ± 173.85

BALP:

Initial 102.08 ± 63.62

1 h 91.82 ± 65.07

1 day 57.39 ± 33.48

7 days 75.14 ± 49.56

22 days 44.60 ± 24.17

28 days 52.35 ± 27.10

DPD:

Initial 1.54 ± 0.57

1 h 1.16 ± 0.66

1 day 0.95 ± 0.56

7 days 0.85 ± 0.50

22 days 0.52 ± 0.12

28 days 0.75 ± 0.48

NTX:

Not detectable

pmol/mg

DPD, OC, and BALP values decrease with force application.

The applied forces may have caused the hyalinization process and decrease of bone turnover.

Perinetti et al. 2004 [27]

Prospective

ALP:

Test tooth:

Mesial

• T0 60 ± 36

• 28 days 159 ± 83

Distal

• T0 52 ± 18

• 28 days 102 ± 43

Contralateral tooth:

Mesial

• T0 59 ± 33

• 28 days 80 ± 31

Distal

• T0 61 ± 23

• 28 days 81 ± 26

Antagonist tooth:

Mesial

• T0 46 ± 26

• 28 days 47 ± 24

Distal

• T0 43 ± 19

• 28 days 44 ± 24

mU/sample

GCF ALP is sensitive in distinguishing between tension and compression sites on day 28.

Factors as clinical condition changes may affect the enzymatic activities. GCF ALP should be considered as a reliable biomarker of tissue responses to orthodontic treatment only when oral hygiene is kept under control.

Perinetti et al. 2002 [28]

Prospective

Distalized molar:

Baseline 60 ± 33

1 h 79 ± 53

7 days 138 ± 95

14 days 160 ± 82

21 days 147 ± 101

28 days 153 ± 84

Contralateral molar:

Baseline 43 ± 25

1 h 69 ± 52

7 days 74 ± 44

14 days 90 ± 52

21 days 73 ± 43

28 days 75 ± 38

Antagonist molar:

Baseline 50 ± 24

1 h 46 ± 30

7 days 45 ± 18

14 days 50 ± 15

21 days 37 ± 21

28 days 46 ± 23

mU/sample

High levels of ALP activity have been described after 7 days when bone deposition begins, greater in dental sites of tension than in sites of compression.

Increased ALP activity in teeth-bearing orthodontic appliances might be due to gingival inflammation independently of clinically detectable movement.

Griffiths et al. 1998 [29]

Prospective

PYD, DPD not detected

OC showed variation between subjects and within subject at different stages

pg/ml or pg

OC has been shown to be present in the GCF of adolescents, but there was a wide variation between subjects in the amount and concentration.

GCF volume is the most sensitive indicator of gingival inflammation.

Insoft et al. 1996 [30]

Cross-sectional

Acid phosphatase activities were constantly higher in all groups.

There was a substantial peak in acid phosphatase at month 11, followed by a smaller second peak at month 16, and an even smaller at month 19.

ALP demonstrated a large first peak at month 15 and a second smaller at month 17.5.

sigma units/min

Changes in GCF phosphatase activities during orthodontic tooth movement may reflect bone remodeling.

ALP in GCF is partly influenced by gingival inflammation.