The Combined Effects of Low-Level Laser Therapy and Vitamin D Supplementation on Orthodontic Tooth Movement: A Systematic Review and Meta-analysis

 Abstract

Background:

Prolonged orthodontic treatment correlates with higher risks like root resorption, periodontal diseases, or patient pain perception which in return influence satisfaction or cooperation. Low-Level Laser Therapy (LLLT) and vitamin D are non-invasive technique that boosts tooth movement and bone remodeling, thus decreasing pain and treatment duration. Nevertheless, the impact of merging this two therapies , as well as the outcome of changing the laser parameters, has not been investigated sufficiently, and therefore there is a need for standardized protocols and more extensive research in this area in order to improve the effectiveness of orthodontic treatment.

Objective:

The present systematic review seeks to assess the synergy between LLLT and Vitamin D on orthodontic treatment efficiency. The purpose is to investigate whether their combined application results in statistically significantly faster tooth movement than single application.

Methods:

This study is a PROSPERO registered systematic review and adheres to reporting standards laid down in PRISMA and Cochrane guidelines. PICOS framework was used to search for the studies focusing on orthodontic treatment LLLT or Vitamin D in human subjects. Inclusion criteria comprised of, Randomized clinical trials (RCTs), systematic reviews and meta-analysis that were published between the years 2015-2024. The electronic databases used for relevant studies included PubMed, Scopus, and Web of Science databases. Outcomes included the rate of tooth movement, treatment time, changes in the level of pain and the degree of root resorption.

Result:

The meta-analysis on Vitamin D supplementation showed a mean difference (MD) of 0.36 (95% CI: 0.12, 0.61), indicating significant improvement in orthodontic outcomes (P = 0.004). For LLLT/PBM, the MD was -18.55 (95% CI: -41.29, 4.19), with no significant effect (P = 0.11) and high heterogeneity (I² = 88%). Vitamin D demonstrated clinical benefits, while LLLT/PBM requires further standardized research.

Conclusion:

The forest plot results focus on quantitative studies (RCT), showing that Vitamin D supplementation significantly improves orthodontic outcomes (MD = 0.36, P = 0.004), while LLLT/PBM does not (MD = -18.55, P = 0.11), with high heterogeneity (I² = 88%). In contrast, the qualitative studies (non RCT) results provide a broader synthesis, highlighting that PBM/LLLT increases alignment rates by 24% and reduces treatment duration, while Vitamin D enhances tooth movement by 60%. In the non RCT studies, both the modalities decrease the pain but the combination effects was not researched, hence there is thus a need for more RCTs research on the matter.

Keywords: Low-Level Laser Therapy, vitamin D, Randomized clinical trial, Heterogeneity, Tooth movement

 

 

Introduction

The significance of accelerated treatment outcomes in orthodontics cannot be overstated. Prolonged treatment durations increase the risk of complications such as root resorption, periodontal disease, and patient discomfort, which can ultimately affect treatment satisfaction and compliance. The demand for faster orthodontic solutions has led to the exploration of various non-invasive methods, including LLLT and Vitamin D supplementation. Research suggests that integrating these modalities may have a high possibilities to not only enhance the speed of tooth movement but also improve overall treatment outcomes by reducing pain and discomfort associated with traditional orthodontic methods (Fini et al., 2020; Kochar et al., 2017).

Although the results in orthodontics were promising with regards to LLLT and Vitamin D, there are still a great deal of research gaps that need to be closed. Several studies have been undertaken to identify the effects of LLLT on tooth movement individually; however, they have not considered the combined effects of LLLT and Vitamin D supplementation. In addition, further investigation is required to identify the impact of variations in laser parameters (wavelength and energy density) and clinical outcomes. This inconsistency in results among different studies suggests the necessity for standardized protocol in the larger scale trials to definitely conclude the efficacy of the given therapies (Dalaie et al., 2015; Özsoy et al., 2023).

Advances in orthodontic treatment have found Low-Level Laser Therapy (LLLT) and Vitamin D to be two significant adjuncts to orthodontic care and their useful aspects especially in increase the rate of tooth movement and enhance bone remodeling. Specific wavelengths of light, known as LLLT, stimulate cellular processes that speed up orthodontic tooth movement via enhanced osteoblast and osteoclast activity. It has been established that LLLT can reduce the duration of fixed orthodontic treatment because of the property of speeding up bone remodeling and thus avoiding the complications of root resorption and the periodontal related problems occur during the longer duration of treatment (Ng et al., 2018; Baghizadeh et al., 2020). Vitamin D, which for its role in calcium metabolism and bone health may have additional positive effect of enhancing the body’s ability to remodel bone during orthodontic procedures.

To fill these gaps, this systematic review evaluates the combined effects of LLLT and Vitamin D on orthodontic treatment outcomes. The objectives are to determine if administering these two modalities together would promote statistically significantly faster tooth movement than with either used separately. The hypotheses proposed are that both LLLT and Vitamin D will accelerate tooth movement rates independently, yet synergistically when combined will provide optimal results based on their complementary mechanisms to promote bone remodeling and inhibit inflammation (Dhiman & Khan, 2018; Pereira et al., 2020). This review synthesizes existing literature with the aim of better characterizing how these therapies can be most effectively integrated into clinical practice in orthodontics to maximize patient outcomes.

Material and Methods

1.0 Protocol and registration

The protocol for the systematic review was approved and registration done by the International Prospective Register of Systematic Reviews (PROSPERO). Cochrane Hand book for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were used in this systematic review and meta-analysis.

1.2 Selection criteria

As for study identification, all included studies were based on the PICOS criteria.

1.2.1 Participants/Population (P)

Inclusion Criteria:

• Orthodontic patients, both adults and children.
• Research articles where the participants for the study are either pediatric or adolescents or adults.

Exclusion Criteria:

• Research that used animals or in vitro experiments.
• Patients with systemic diseases which are associated with bone formation and resorption not related to Vitamin D or orthodontic treatment.
• Reviewed studies that do not include an intervention using Low-Level Laser Therapy (LLLT) or Vitamin D.

1.2.2 Intervention(s) / Exposure(s) (I)

Inclusion Criteria:

• All systematic reviews that involve the use of Low-Level Laser Therapy (LLLT) or Photobiomodulation in the process of bone remodeling or enhancing the rate of orthodontic tooth movement.
• Research articles on use of Vitamin D supplements to augment the process of bone remodeling or to expedite the rate of tooth movement during the course of orthodontic treatment.
• Interventions by LLLT, Vitamin D or both to enhance orthodontic treatment efficacy, including time taken for the treatment process, rate of tooth movement, pain modulation and bone health.
• Studies that review the various wavelengths, doses, and application frequencies applied in LLLT during orthodontic procedures.

Exclusion Criteria:

• Investigation examining other forms of treatments which may include surgery or therapies different from LLLT or Vitamin D.
• Non-clinical interventions, including in vitro studies.
• Research that investigates other types of orthodontic aids for instance mechanical devices that do not include LLLT or Vitamin D.

1.2.3 Comparator(s)/control (C)

Inclusion Criteria:

• Researches comparing orthodontic treatments with using and without using Low-Level Laser Therapy (LLLT) or Vitamin D.
• Comparisons between LLLT of varying dose or wavelength and Vitamin D supplementation of various amount.
• Research comparing the use of different forms of adjuvant therapies introduced alongside conventional orthodontic procedures in order to establish the impact of supplementary LLLT or Vitamin D.

Exclusion Criteria:

• Research papers that have no or very weak control/sham group or comparison sample.
• Those studies where comparisons are made with non-laser interventions that are not related to the subject of that research (for example, the comparison is made only among various types of braces).
• Reviews that describe the effectiveness of interventions for conditions that are not related to orthodontics.

1.2.4 Outcomes (O)

Main Outcome(s)

Rate of Orthodontic Tooth Movement (OTM): This primary outcome measures the rate of tooth movement, converted into millimeters per month. This literature review will work with data from randomized controlled trials (RCTs), systematic reviews, and meta-Analyses focusing on the effect of Low-Level Laser Therapy (LLLT) and Vitamin D supplementation on the rate of tooth movement.

Efficacy of Treatments and Treatment Duration: The effectiveness of LLLT and Vitamin D supplementation in orthodontic treatment will be assessed based on enhanced treatment results, including the degree of alignment of teeth and the time taken to complete the treatment. Time to seek orthodontic treatment will also be measured as the total time taken by the patients into receiving orthodontic treatment and this will be compared between the two groups. Research involving Little’s Irregularity Index (LII) and the speed of alignment required for un-crushing as well shall be included. RCT and meta-analyses data will be collected to determine the efficacy of such interventions in shortening treatment time.

Additional outcome(s)

Pain Reduction: This outcome will assess the effectiveness of Low-Level Laser Therapy (LLLT) and Vitamin D in reducing pain during orthodontic treatment. Subjective measures of pain will be assessed employing universally acknowledged tools like VAS or NRS. RCTs as well as previous meta-analyses or systematic reviews will be used to compare the efficacy of these interventions for the reduction of pain.

Patient Compliance: Compliance will be calculated as the additional study outcome with the purpose to analyze the impact of LLLT and Vitamin D on the patient’s compliance to the requirements of the orthodontic treatment. This will be assessed using the patient self-completed adherence documentation or clinician-derived scores. Sources of research to be used for this review will be restricted to RCTs, systematic reviews, and meta-analyses that document levels of compliance in orthodontic therapy.

Root Resorption: This outcome will determine the level of root resorption caused by orthodontic forces through radiographic procedures such as panoramic or periapical X-rays. Only RCTs and meta-analysis studies that presented information on the influence of LLLT or Vitamin D on root resorption will be included in the data pool.

Adverse Effects and Long-Term Impacts: The systematic review will include both experimental and non-experimental research (RCTs, systematic reviews, meta-analysis) that investigated negative effects or prolonged consequences of LLLT and Vitamin D supplementation. These may include side effects like; Abnormal root resorption; Poor bone health detected during or after the orthodontic procedure.

Alignment Rate and Little’s Irregularity Index (LII): Literature comparing LII and the alignment rate in reducing crowding will be considered. This review will establish how LLLT and Vitamin D influence the Positioning of crowded teeth and the time needed to Level and Align them. Studies will be identified from randomized controlled trials (RCTs) and existing systematic reviews/meta-analysis.

1.2.5 Study type (S)

Inclusion Criteria:

• RCTs, systematic review, meta analysis.
• Controlled trials of interventional studies which include Low-Level Laser Therapy (LLLT) or Vitamin D.
• Studies published between 2015-2024.
• Peer-reviewed articles in English with the availability of the full text of an article.

Exclusion Criteria:

• Case studies, editorials, conference abstracts, or reviews without systematic methodology.
• Publications prior to 2015.
• Foreign language (non-English) articles.
• Studies without full text or unavailable data for analysis.

1.3 Search Strategy

An extensive systematic search using different electronic database will be performed to locate research that have investigated the primary and synergistic effects of LLLT and Vitamin D on orthodontic tooth movement, pain and root resorption. Electronic databases (PubMed, Scopus, Web of Science, and Google Scholar), reference lists, grey literature (Google Scholar, ClinicalTrials.gov, and ICTRP), and key journals will be searched for English-language studies published between January 1, 2015, and May 2024. This will be repeated before the final analysis together with searching the unpublished essays at clinical trial registries and the investigators themselves.  The final screening procedure result is depicted in a PRISMA flow diagram to demonstrate the selection and the reason for the exclusion of studies (See Figure 1).

Table 1: Keywords and algorithms used in the search strategy

Electronic Database	Keywords Used	Search String Examples
PubMed	“Low-Level Laser Therapy,” “Photobiomodulation,” “Laser Therapy,” “Vitamin D,” “Cholecalciferol,” “Calcitriol,” “Orthodontic Tooth Movement,” “Pain Perception,” “Root Resorption”	(“Low-Level Laser Therapy”[MeSH] OR “Photobiomodulation”[MeSH] OR “Laser Therapy”[Text Word]) AND (“Orthodontic Tooth Movement”[MeSH] OR “Tooth Movement”[Text Word]) AND (“Vitamin D”[MeSH] OR “Cholecalciferol”[Text Word] OR “Calcitriol”[Text Word]) AND (“Pain Perception”[Text Word] OR “Root Resorption”[Text Word])
Scopus	“Low-Level Laser Therapy,” “Photobiomodulation,” “Laser Therapy,” “Vitamin D,” “Cholecalciferol,” “Calcitriol,” “Orthodontic Tooth Movement,” “Pain Perception,” “Root Resorption”	TITLE-ABS-KEY((“Low-Level Laser Therapy” OR “Photobiomodulation” OR “Laser Therapy”) AND (“Orthodontic Tooth Movement”) AND (“Vitamin D” OR “Cholecalciferol” OR “Calcitriol”) AND (“Pain Perception” OR “Root Resorption”))
Web of Science	“Low-Level Laser Therapy,” “Photobiomodulation,” “Laser Therapy,” “Vitamin D,” “Cholecalciferol,” “Calcitriol,” “Orthodontic Tooth Movement,” “Pain Perception,” “Root Resorption”	TS=(“Low-Level Laser Therapy” AND “Orthodontic Tooth Movement” AND “Vitamin D” AND (“Pain Perception” OR “Root Resorption”))
Google Scholar	“Low-Level Laser Therapy,” “Orthodontic Tooth Movement,” “Vitamin D,” “Laser Therapy,” “Tooth Movement,” “Bone Remodeling,” “Photobiomodulation,” “Orthodontic Treatment,” “Vitamin D Supplementation”	“Low-Level Laser Therapy” AND “Orthodontic Tooth Movement” AND “Vitamin D” AND (“Pain Perception” OR “Root Resorption”)

 

 

 

 

 

 

 

 

 

Figure 1: Flow Diagram for the Study Selection Process

Records identified through database search: PubMed (n=51) Scopus (n=27) Google Scholar (n=21) Web of science (n=135)

0 duplicates identified manually excluded 23 duplicates identified by Covidence excluded 126 references marked as ineligible by automation tools excluded

74 studies irrelevant excluded

11 studies excluded 4 compares two different techniques with laser 2 Split mouth design 2 Wrong intervention 3 Wrong setting 1 Wrong patient population 1 duplicated

29 studies included

1.5 Data extraction

Covidence will be used to identify eligible studies’ data extraction where two independent reviewers will complete the extraction form. A third reviewer will also check the accuracy of the identified data in order to eliminate any inconsistency or errors. The data to be collected will consist of study characteristics (e.g., design, publication year, setting), participant demographics, details of the interventions (Low-Level Laser Therapy [LLLT] and Vitamin D), and outcomes (orthodontic tooth movement [OTM], pain perception, root resorption, compliance, and long-term outcomes). A number of tools will be used for evaluating the study methodology and quality including the Cochrane Risk of Bias Tool, Risk of Bias-Specific Review Tool (ROBUR), and the AMSTAR 2.

To handle the differences, any inconsistency between the two reviewers regarding the assessment of a particular research study will be resolved through a discussion or by consulting a third reviewer. For cases where data is missing, the authors of the studies shall be contacted with questions with an aim of getting further clarification. If data cannot be resolved, it will be noted and sensitivity analysis or imputation methods may be used where necessary.

Data will be extracted and managed by Covidence, while meta-analysis will be conducted using Review Manager (RevMan) website, this will determine the effect size, confidence intervals and heterogeneity statistics. Additionally, Microsoft excel will be used for further data manipulation and organization as required.

 

 

 

 

Table 2: Features of publications used in this analysis

Study ID	Study Design	Sample Size	Intervention(s)	Comparator(s)	Outcome Measures	Key Findings
Huang et al., 2023	Systematic Review and meta-analysis	8 studies	Photobiomodulation (PBM)	No PBM (control group)	Mean alignment time (days), alignment rate (mm/week)	PBM significantly increased the rate of tooth movement and reduced treatment duration
Jedliński et al., 2020	Systematic Review and meta-analysis	8 studies	Photobiomodulation (PBM)	Control group (no PBM)	Alignment rate, total treatment time, Little’s Irregularity Index (LII)	PBM is efficient, effective, and noninvasive for accelerating orthodontic movement.
Lo Giudice et al., 2020	RCT	89 subjects	Fixed appliance with photobiomodulation (PBM)	Fixed appliance only (control)	Treatment time (days), number of scheduled visits	PBM group had significantly shorter treatment time
Sandra et al., 2024	Systematic Review	3 studies	Vitamin D3 Supplementation	No supplementation (control)	Rate of orthodontic tooth movement, periapical radiographs, CBCT	60% faster orthodontic tooth movement with 40-50 pg/dl Vitamin D3 supplementation; no negative effects on tooth roots or tissues.
Isola et al., 2019	RCT	41 patients	Low-Level Laser Therapy (LLLT) using diode laser	Orthodontic traction only	Time for space closure, pain levels	LLLT significantly reduced treatment time (84.35 ± 12.34 days vs. 97.49 ± 11.44 days, p < 0.001) and pain levels. No significant differences in space closure distance.
Bakdach & Hadad, (2020)	systematic review and meta-analysis	25 RCTs	Low-level laser therapy (LLLT)	Control group (no LLLT)	rate of the tooth movement	Radiated upper canines showed retraction of 0.50 mm and 0.49 mm at months 2 and 3; lower canines showed 0.28 mm and 0.52 mm.
Eid et al., 2022	RCT	20 female patients	PBM	Control side (no PBM)	Evaluation of Orthodontically Induced Inflammatory Root Resorption (OIIRR) using pre- and post-retraction cone-beam computed tomography (CBCT)	No significant differences in OIIRR between laser and control sides in both groups. PBM did not influence OIIRR.
Al-Attar et al., 2021	Systematic review and meta-analysis	27 studies	Vitamin D3 (calcitriol)	Control groups without calcitriol treatment.	Tooth movement acceleration	Slight acceleration in OTM
de Almeida et al ., 2016	Systematic Review and meta-analysis	11 studies	Low-Level Laser Therapy (LLLT), low-energy density laser therapy	Control groups (no laser therapy)	Tooth movement in maxilla (3 months), mandible (1 month)	Statistically significant differences detected in tooth movement for maxillary (3 months) and mandibular (1 month) movements.
El-Angbawi et al., 2023	RCT	1027 participants	Non-surgical adjunctive interventions (light vibrational forces, photobiomodulation – LLLT, LED therapy)	No adjunctive interventions	Rate of orthodontic tooth movement, duration of treatment	Photobiomodulation (LLLT, LED) showed mixed results on accelerating tooth movement but did not consistently shorten overall treatment duration.
Tini et al.,  2024	Systematic review and meta-analysis	6 articles	Vitamin D3	Control groups without Vitamin D	Tooth movement rate (SMD = 1.43, 95% CI: 0.691–2.169, P = .00154); Root resorption (SMD = −0.51, 95% CI: −3.051 to 2.031, P = .11)	Vitamin D enhances tooth movement but evidence for root resorption is inconclusive due to limited data.
Michelogiannakis et al., 2019	Systematic review	9 articles	Low-Level Laser Therapy (LLLT)	No LLLT (control group)	OIIRR assessed via tomography, histology, or clinical methods	3 studies reported reduced OIIRR; 3 found increased OIIRR; 1 clinical study showed no significant effect.
Domínguez Camacho et al., 2020	Systematic review	9 studies	Low-Level Laser Therapy (LLLT)	No LLLT (control)	Tooth movement speed increase	Average 24% increase in tooth movement speed; ideal wavelengths between 780-830 nm.
AlSayed Hasan et al., 2020	RCT	26 patients	Low-Level Laser Therapy (LLLT)	Placebo	Pain intensity (VAS scores)	No significant pain reduction except at 72 h for chewing pain (VAS: 18.84 vs. 38.15).
Ghaffar et al., 2022	RCT	32 females	LLLT	Control (No LLLT)	Leveling & alignment time, pain VAS	Significant reduction in alignment time (68.2 ± 28.7 days vs. 109.5 ± 34.7 days) and pain scores.
Ambroise et al.,  2024	RCT	60 patients	LLLT and conventional orthodontics	Conventional treatment	Reduced treatment duration	Lower pain perception, increased tooth movement rate (20% reduction in time to desired alignment, P < 0.01)
Ferrillo et al., 2024	Systematic Review	19 records	Vitamin D3 local injections, systemic oral supplementation	N/A	Increased tooth movement via RANK/RANKL axis, bone turnover markers, root resorption, pro-inflammatory cytokines	Vitamin D3 local injections enhance tooth movement.
Zheng et al ., 2023	Systematic Review and meta-analysis	8 studies	Low-level laser therapy (LLLT)	Control (No LLLT)	Overall time of leveling and alignment (OLAT, days)	LLLT reduces OLAT significantly (MD=-30.36, 95% CI: -41.50 to -19.22, P<0.0001) with moderate risk of bias
AlSayed Hasan et al 2017	RCT	26 patients	Low-level laser therapy (LLLT)	Control group (No LLLT)	Overall treatment time, Leveling & alignment improvement	Significant reduction in treatment time (P<0.001) & increased leveling/alignment at T1 (P=0.004) and T2 (P=0.001)
Ge et al., 2015	RCT & quasi-RCT	211 patients	Low-level laser therapy (LLLT)	Control group (No LLLT)	Accumulative tooth movement, 7 days (MD=0.19, 95% CI [0.02, 0.37], p=0.03) and 2 months (MD=1.08, 95% CI [0.16, 2.01], p=0.02)	LLLT accelerates orthodontic tooth movement at both 7 days and 2 months
Varughese et al., 2019	RCT	15 patients	Vitamin D (1,25-dihydroxycholecalciferol (1,25 DHC) gel)	Placebo gel	Canine distalization, bone density changes at T and T+4 weeks (paired t-test)	Increased canine distalization and decreased cancellous bone density on experimental side
Imani et al., 2018	Systematic review and meta-analysis	6 RCTs	LLLT (low-level laser therapy)	Control group	Distance/speed of canine tooth movement over various time points	Significant increase in tooth movement rates at multiple time points (21 days, 1 month, 1.5 months, etc.)
Cronshaw et al., 2019	Systematic review	17 articles	PBMT (photobiomodulation therapy)	Control group	Reduction/prevention of pain & tooth movement	4 out of 7 studies supported LLLT’s effectiveness for tooth movement (20–40% faster compared to control)
Deana et al., 2017	Systematic review and meta-analysis	20 RCTs	Low-level laser therapy (LLLT)	Placebo	Reduction in spontaneous and chewing pain	LLLT effective in reducing pain 24 & 72 hrs post-OF application
Farzanegan et al.,  2023	RCT	29 healthy women	Oral administration of vitamin D3	Placebo, Control (no vitamin D3 deficiency)	Orthodontic tooth movement (OTM) measured by distance between canine and lateral teeth	Vitamin D3 deficiency increased OTM; oral supplements showed limited efficacy in raising vitamin D3 levels; control group had lowest OTM rate.
Elgadi et al., 2023	systematic review	10 human clinical trials	Low-Level Laser Therapy (LLLT) with various parameters	Placebo or control groups	Speed of orthodontic tooth movement	Seven trials showed LLLT increased the speed of tooth movement; three showed no benefit. More histological studies are needed.
AlShahrani et al., 2019	Systematic review	12 studies	Photobiomodulation	control	Acceleration of tooth movement	Photobiomodulation therapy showed a statistically significant benefit in accelerating tooth movement
Lo Giudice et al., 2019	RCT	84 subjects	Orthodontic treatment with LLLT	Placebo (simulated LLLT), Control (orthodontic treatment only)	Pain intensity (0-10 scale) at specific intervals, differences by crowding	LLLT significantly reduced pain; no effect of crowding severity on results.
Nayyer et al., 2022	systematic review and meta-analysis	6 studies	Photobiomodulation therapy	No photobiomodulation therapy (control)	Total root resorption per tooth measured on mesial, buccal, distal, and palatal root surfaces	Meta-analysis showed a pooled mean difference of 0.08 in favor of the photobiomodulation group.

 

1.6 Assessment of risk of bias (RoB) (quality)

The RoB and quality of included studies were evaluated based on the tools suitable for different study designs. Domain such as blinding, randomization, concealment of allocation, drop-out rates and reporting bias. RoB assessment will be conducted at the study level for individual RCTs and systematic reviews; other types of biases will be evaluated at the outcome level if relevant. The Cochrane Risk of Bias Tool, ROBIS, and AMSTAR 2 were used depending on the study design (See Table 3, Table 4 and Table 5). The results of RoB assessment influenced the data synthesis; the high-risk bias studies were explored through sensitivity analysis. In the meta-analyses, the issue of RoB was addressed while making the interpretation of the findings. Two independent reviewers will conduct assessments, and disagreements were resolved through discussion or consultation with a third reviewer.

Table 3: Cochrane risk of bias (For RCTs)

Study ID	Random sequence generation	Allocation Concealment	Blinding of Participants	Blinding of Outcome Assessment	Incomplete outcome data (attrition bias)	Selective Reporting
Lo Giudice et al., 2020	Low	Low	Unclear	Low	Low	Low
Isola et al., 2019	Low	low	High	unclear	Low	Low
Eid et al., 2022	Unclear	Unclear	High	Low	Low	Low
El-Angbawi et al 2023	Unclear	Unclear	Low	Low	Low	Unclear
AlSayed Hasan et al., 2020	low	low	unclear	low	low	low
AlSayed Hasan et al., 2017	Low	unclear	high	high	low	low
Ghaffar et al., 2022	Unclear	Unclear	High	Low	Unclear	Unclear
Ambroise et al.,  2024	low	low	high	Unclear	Unclear	Unclear
Ge et al., 2015	low	unclear	unclear	unclear	unclear	unclear
Varughese et al., 2019	low	low	low	low	low	low
Farzanegan et al.,  2023	low	unclear	high	high	low	low
Lo Giudice et al., 2019	low	low	low	unclear	low	low

 

Note

• Low Risk: Rather it is considered to have a low risk of bias for a particular domain and therefore the findings of a study are not likely to be skewed by bias in this area.
• High Risk: The study has a high risk biased and this could influence the results or conclusions of the study.
• Unclear Risk: It is not possible to judge the risk of bias for a specific domain, or there is insufficient information for judging the risk based on the reported information.

Figure 4: Cochrane risk of bias (For RCTs) chart

Table 4: AMSTAR 2 (Risk of Bias for Systematic Reviews and Meta-Analyses)

Study ID	Research question and inclusion criteria	Literature search	Duplicate study selection	Risk Of Bias Assessment	Statistical Methods	Funding And Conflicts of Interest
Jedliński et al., 2020	Yes	Partial yes	Yes	Partial yes	no	no
Bakdach & Hadad, (2020)	Yes	yes	no	Yes	Partial yes	Yes
Al-Attar et al., 2021	Yes	Partial yes	yes	Yes	Yes	Yes
de Almeida et al ., 2016	Yes	Partial yes	No	Yes	Yes	Yes
Tini et al.,  2024	Yes	Partial yes	Yes	Yes	Yes	Yes
Zheng et al ., 2023	Yes	Yes	Yes	Yes	Yes	Yes
Imani et al., 2018	Yes	Yes	Partial yes	Yes	Yes	No
Deana et al., 2017	Partial yes	Partial yes	Yes	No	No	yes
Nayyer et al., 2022	Yes	Partial yes	No	Yes	Yes	Yes
Huang et al., 2023	Yes	Partial yes	Yes	Yes	Yes	No

 

Note

• Yes: The review is fully compliant with the indicated criterion while demonstrating high methodological standards.
• Partial Yes: The criterion is only partially met, which shows some lack of methodological approaches, though not enough to make the review completely unreliable.
• No: Accordingly, the review does not meet the criterion, raising questions about validity of its findings.

Figure 5: AMSTAR 2 (Risk of Bias for Systematic Reviews and Meta-Analyses) chart

Table 5: ROBIS (Risk bias For Systematic Reviews)

Study ID	Phase 1	Phase 2				Phase 3
	Relevance	Study eligibility criteria	Identification and selection of studies	Data collection and appraisal	Synthesis and findings	Overall Risk of Bias
Sandra et al., 2024	Low	Low	Unclear	Low	High	Unclear
Michelogiannakis et al., 2019	Low	Low	Low	Low	High	Low
Domínguez Camacho et al., 2020	Low	Low	Low	Unclear	Low	Unclear
Ferrillo et al., 2024	Low	Low	Low	Unclear	Unclear	Unclear
Cronshaw et al., 2019	Low	Low	Low	Low	Low	High
Elgadi et al., 2023	Unclear	Low	Low	Low	Low	Low
AlShahrani et al., 2019	Low	Low	Unclear	Low	Low	Low

 

Note

• Low Risk of Bias: The review is accurate and inclusive with very little indication of bias.
• High Risk of Bias: Due to the methodological imperfections, the effectiveness of the reviewed sources is questionable; one should be careful when intepreting the results.
• Unclear Risk of Bias: Due to lack of or insufficient details, the extent of quality of the review cannot be ascertained.

Data Analysis

The data from the included RCT studies were synthesized and analyzed using RevMan Web, a statistical software (web) designed for conducting meta-analyses. The inverse variance method was employed for pooling the data, which is a widely used approach in meta-analyses to weight studies based on the precision of their estimates. To account for potential variability and differences among the studies, a random-effects model was applied. This model believes that the actual effect can be different in different studies because of the design features of the particular studies, populations, or the type of interventions used, and this model give us a more conservative estimate than fixed effects model.

The results were expressed as mean differences (MDs) along with their 95% confidence intervals (CIs), which provide a measure of the precision and reliability of the estimated effect sizes. The χ2 test was used to assess the statistical significance of the observed variability among the studies, while the I² index was calculated to quantify the degree of heterogeneity. I² is an estimate of the percentage of total variation across studies attributable to heterogeneity rather than chance; values such as 25%, 50%, and 75% may be considered as low, moderate and high heterogeneity respectively. This approach makes sure that the pooled data is evaluated rigorously and in the most methodical manner with the effects highlighted in different studies taken into account in terms of their size and reliability.

Result

The meta-analysis (see figure 2) aimed to evaluate the effect of Vitamin D supplementation on orthodontic treatment outcomes compared to standard orthodontic treatment without Vitamin D. Two studies were included in the analysis: Farzanegan et al. (2023) and Varughese et al. (2019). According to the study conducted by Farzanegan et al., (2023) , the participants in Vitamin D group which consisted of 10 participants had an average result of 3.35 (SD = 0.41) while the control group that also included 10 participants had an average of 2.83 (SD = 0.22). Varughese et al., (2019) study showed that the Vitamin D group had a mean of 1.1993 and SD= 0.28684 with 15 participants while the control group had a mean of 0.9367 and SD = 0.18321 with 15 participants as well. The pooled results, calculated using the inverse variance method with a random-effects model, showed a mean difference (MD) of 0.36 with a 95% confidence interval (CI) of [0.12, 0.61]. This suggest that Vitamin D supplementation is a factor that leads to statistical significant improvement in orthodontic treatment outcomes compared to the standard treatment without Vitamin D. The overall effect test yielded a Z-value of 2.89 and a P-value of 0.004, further confirming the significance of the results. Heterogeneity among the studies was assessed using the I² index, which was found to be 56%, indicating moderate heterogeneity. However, the Chi² test result (P = 0.13) suggested that this heterogeneity was not statistically significant. The Tau² value of 0.02 also reflected low variability between the studies. In conclusion, the meta-analysis demonstrates that Vitamin D supplementation significantly enhances orthodontic treatment outcomes (Rate of orthodontic teeth movement) compared to standard treatment without Vitamin D. Nonetheless, concerning the inter-study variability, moderate, the study results are rather coherent and point to a clinically significant effect of Vitamin D in orthodontic practices. Subsequent research with greater sample sizes and well-controlled methods is encouraged to confirm these findings and delineate the processes involved.

The meta-analysis aimed to evaluate the effect of Low-Level Laser Therapy/Photomodulation (LLLT/PBM) on orthodontic treatment outcomes compared to standard orthodontic treatment without LLLT/PBM. Three studies were included in the analysis: AlSayed Hasan., (2020), Ghaffar et al., (2022) and Isola et al., (2019). In the study by AlSayed Hasan., (2020), thus, the LLLT/PBM group had a mean of 18.84 (13); SD = 13.44, n = 13 while the control group had a mean of 38.15 (27); SD = 27.06, n = 13. Luminar plurality was higher for the LLLT/PBM group, with the participants in this group having a mean of 68.2 (SD = 28.7) as compared to the participants of the control group with a mean of 109.5 (SD = 34.7). In Isola et al., (2019) the LLLT/PBM group was of 91.1 mean (SD = 5.56) but it had 41 participants whereas the control group was of 92.3 mean (SD = 6.69) but also had 41 participants. The pooled results, calculated using the inverse variance method with a random-effects model, showed a mean difference (MD) of -18.55 with a 95% confidence interval (CI) of [-41.29, 4.19]. This means that the percentage of patients undergoing orthodontic treatment when under LLLT/PBM therapy is less than when undergoing standard therapy without LLLT/PBM, though not statistically significant. The overall effect test yielded a Z-value of 1.60 and a P-value of 0.11, further confirming the lack of statistical significance. Heterogeneity among the studies was assessed using the I² index, which was found to be 88%, indicating high heterogeneity. The Chi² test result (P = 0.0002) confirmed that this heterogeneity was statistically significant. The Tau² value of 344.18 also reflected substantial variability between the studies. In conclusion, the meta-analysis suggests that Low-Level Laser Therapy/Photomodulation (LLLT/PBM) does not significantly improve orthodontic treatment outcomes compared to standard treatment without LLLT/PBM. Therefore, more research with less bias, uniform methodology, and a higher subject population is required to establish the potential benefits of LLLT/PBM in orthodontic treatments.

Figure 2: Forest Plot of the Effect of Vitamin D Supplementation on Orthodontic Treatment Outcomes

Figure 3: Forest Plot of the Effect of Vitamin D Supplementation on Orthodontic Treatment Outcomes

Discussion

This synthesis of the available evidence from the non RCT studies shows that Photobiomodulation (PBM), low level laser therapy (LLLT), and vitamin D supplementation all play a beneficial role in orthodontic treatment, albeit through different mechanisms. Both PBM and LLLT significantly enhanced the rate of orthodontic tooth movement (OTM): PBM with an average increase in the rate by 24% (Domínguez Camacho et al., 2020), and LLLT, which reduced the time needed for alignment by 30.36 days as per Zheng et al. (2023). Such results correlate with several studies showing that tooth movement occurs at a much faster rate together with shorter treatment duration for instance 68.2 ± 28.7 days utilising LLLT opposed to 109.5 ± 34.7 days in the control group (Ghaffar et al., 2022). These effects could be explained through higher rate of cellular metabolism, improved blood circulation, and promotion of bone turnover with subsequent faster movement of teeth (Cronshaw et al., 2019; Elgadi et al., 2023).

Apart from increasing the speed of OTM, both LLLT and PBM decreased pain levels related to orthodontic treatment. For example, LLLT has shown to decrease pain at 72 hours after treatment using VAS with mean value of 18.84 as compared to the control or placebo groups with mean value of 38.15 (AlSayed Hasan et al., 2020). This analgesic effect is suggested to link to LLLT’s anti-inflammatory and biostimulatory properties that act on the pain pathways and minimize the discomfort whilst delivering the intervention (Deana et al., 2017; Lo Giudice et al., 2019). In addition, though there is some contradictory evidence regarding the effect of PBM on orthodontically induced inflammatory root resorption (Reggio et al., 2017). At the same time, some experiments did not discover significant differences in OIIRR between PBM and control groups (Eid et al., 2022) and a slight decrease of root resorption rates was observed in PBM (Nayyer et al., 2022). Such discrepancy might have arisen from differences in study methods and designs, laser settings, and ways of assessing techniques, suggesting the importance of methodological convergence in subsequent studies.

Specifically, calcitriol or activated form of Vitamin D showed important positive effects on orthodontic treatment, namely improving bone remodeling and promoting OTM. An earlier study observed a 60% increased rate of tooth movement in specimens with serum vitamin D of about 40-50 pg/dl (Sandra et al., 2024). The systemic impact of vitamin D was further affirmed by distalization of the canine and alterations in canine bone density (Varughese et al., 2019). However, its influence regarding this particular aspect, that is the root resorption, is rather ambiguous and comes with a very weak recommendation because of the inadequate evidence (Tini et al., 2024). Moreover, in terms of pain relief, vitamin D appeared to be less effective than LLLT, which means that supplementation should be recommended primarily for the purpose of bone health improvement and tooth migration in patient.

Another bonus is having the ability to make treatment shorter than it otherwise would have been, not only boosting patients’ satisfaction but compliance as well. Lower discomfort levels and shorter treatment duration possibly enhance the favorite map of orthodontic procedures, even if this outcome must be investigated employing the clinician-reported effect and patient’s records (Lo Giudice et al., 2020; Ghaffar et al., 2022).

 

Conclusion

Various reviews have depicted the effectiveness of photobiomodulation (PBM)/low-level laser therapy (LLLT) and vitamin D supplementation for improving the orthodontic treatment. In this case, it was evident that PBM increased the alignment rate by 24% and shortened treatment time by 20% while LLLT ridge reduction time compared to the control group outcomes was approximately 41 days. Further, PBM showed a significant decrease in pain, and LLLT also depicted the reduction of pain, which might enhance patient compliance. Calcitriol and vitamin D3 added optimal serum concentrations of OTM by 60% besides its systemic influences on bone metabolism and remodelling.

The findings from the forest plot analysis of the LLLT/PBM in reducing orthodontic treatment outcomes means that, although a trend was noted in the reduction of the orthodontic treatment time through LLLT/PBM, the MD of -18.55 with 95% CI of [-41.29, 4.19] was not significant at P = 0.11. This implies that LLLT/PBM might yield improved outcomes across all investigations but can also be limited by or dependent on the protocols followed, the patients used in the studies or the strategies employed in the investigations. The high level of inconsistency among the included studies (I² = 88%) supports the argument for evidence-based practices in the application of LLLT/PBM in orthodontic practice.

On the other hand, the forest plot of vitamin D supplementation on the outcomes of orthodontic treatment revealed an increase in the sample mean by 0.36 (MD; 95% CI 0.12 to 0.61) (P = 0.004) as illustrated in the figure 3. This suggests that vitamin D supplement has a significant improvement in treatment outcomes as compared to ordinary orthodontic treatment. Yet again, moderate heterogeneity was observed (I² = 56%) implying inconsistency of effects based on dosage, vitamin D status, or study procedure.

Despite these individual benefits of PBM/LLLT and vitamin D supplementation alone, there is no evidence of the synergistic action in case of their combination. In mechanistic terms, the use of PBM and LLLT modulates cellular activity and the inflammatory response at the local level, while vitamin D supplementation acts on the bone metabolism systemically, which indicates the possibility for coincident effects that would help amplify OTM. Nevertheless, given the lack of comparative studies and randomized controlled trials examining the efficacy of the combined approach, it cannot be stated beyond reasonable doubt that utilising both of these methods would result in statistically significantly faster tooth movements than when each of these methods are used separately.

More studies should be conducted to examine the interaction between PBM/LLLT and vitamin D supplementation, establish standardized protocols for their clinical application, and address the variability observed in current studies. This will assist in achieving the best results for patients undergoing orthodontic treatment through shortening treatment time and improving the quality of experiences patients have while undergoing treatment.

 

 

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