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A comparison of alternate-rapid maxillary expansion and constriction protocol with conventional rapid maxillary expansion in class III malocclusion patients – A systematic review and meta-analysis
, Parag Gangurde1, Shashank Sharad Gaikwad1, Waseem Z. Khan1, Laresh Naresh Mistry2
*Corresponding author: Harsh Ashok Mishra, Department of Orthodontics and Dentofacial Orthopedics, Bharati Vidyapeeth (Deemed to be University) Dental College and Hospital, Navi Mumbai, Maharashtra, India. dr.mishraharsh@gmail.com
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Received: ,
Accepted: ,
How to cite this article: Sarkar M, Mishra HA, Gangurde P, Gaikwad SS, Khan WZ, Mistry LN. A comparison of alternate-rapid maxillary expansion and constriction protocol with conventional rapid maxillary expansion in class III malocclusion patients – A systematic review and meta-analysis. APOS Trends Orthod. 2026;16:5-19. doi: 10.25259/APOS_140_2025
Abstract
Class III malocclusion is a challenging orthodontic condition that can cause functional, esthetic, and psychosocial problems if untreated. Two common protocols – Alternate-Rapid maxillary expansion and constriction (AltRAMEC) and conventional rapid maxillary expansion (RME) – are used to manage it. However, their comparative effectiveness remains debated. The objective of the study is to compare the effectiveness of Alt-RAMEC versus conventional RME in treating Class III malocclusion with a focus on skeletal, dentoalveolar, and soft tissue outcomes. Included studies were randomized controlled trials and cohort studies comparing Alt-RAMEC and conventional RME in English. Excluded studies were without direct comparisons, those in other languages, or with insufficient outcome data. Systematic searches were conducted in PubMed/MEDLINE, Cochrane Library, and DOAJ up to January 2025. Data on study design, sample size, outcome measures, and risk of bias were extracted. Meta-analysis was performed using standard statistical techniques. Eleven studies were included. Alt-RAMEC significantly improved overjet (mean difference = 0.57 [0.18, 0.96]) versus conventional RME. No statistically significant differences were observed for other cephalometric and skeletal outcomes (e.g., Sella-Nasion-A, SellaNasion-B, ANB, Condyle to A, Wits appraisal). Alt-RAMEC may offer better dentoalveolar outcomes (notably overjet correction) than conventional RME, though skeletal and soft tissue changes were comparable. Long-term, high-quality studies are needed to confirm these findings. Registration PROSPERO (CRD42023456789).
Keywords
Alt-RAMEC
Class III Malocclusion
Dentoalveolar changes
Expansion technique
Maxillary Expansion
Palatal expansion technique
INTRODUCTION
Class III malocclusion affects 5–15% of the global population, with a higher prevalence in East Asian populations.[1] Class III malocclusion, characterized by the anteroposterior relationship of the lower jaw relative to the upper jaw (negative overjet), poses significant orthodontic challenges. This condition can affect facial esthetics, occlusion, and overall oral health, leading to complex treatment requirements. Untreated Class III malocclusion can lead to masticatory dysfunction, speech issues, esthetic concerns, and negative psychosocial outcomes.[2] Traditional methods for managing Class III malocclusion include conventional rapid maxillary expansion (RME), which aims to correct transverse maxillary deficiency. However, recent advancements have introduced the alternate RME and constriction (Alt-RAMEC) protocol, which proposes a novel approach to achieving similar or superior outcomes with potentially reduced treatment time and enhanced patient comfort.[3]
While conventional RME has shown effectiveness in enhancing skeletal and dental outcomes in Class III malocclusion, it is often associated with extended treatment duration and patient discomfort. The Alt-RAMEC protocol was introduced to overcome these drawbacks by alternating expansion and constriction phases, aiming to improve treatment efficiency and outcomes. RME combined with facemask therapy promotes skeletal changes but often results in significant dental tipping, limited maxillary advancement, and prolonged treatment duration.[4] Liou and Tsai first described Alt-RAMEC in 2005 as a method to alternate expansion and constriction to mobilize the maxillary sutures more effectively before protraction.[5] Studies report that Alt-RAMEC results in greater forward displacement of cephalometric point A, better control of vertical dimension, and less dental compensation compared to RME.[6-8] Despite this innovation, there remains a lack of comprehensive evidence comparing Alt-RAMEC directly with conventional RME regarding its efficacy and overall benefits.
However, inconsistent protocols and outcome measures across studies prevent a unified conclusion, emphasizing the need for systematic evidence synthesis.
Given these considerations, there is a critical need to systematically evaluate and compare the effectiveness of these two protocols for class III cases. Such a review could provide valuable insights into their relative benefits and guide clinicians in making informed decisions for managing Class III malocclusion.
Aims
The aims of the study are to systematically compare the skeletal, dentoalveolar, and soft tissue effects of the Alt-RAMEC protocol versus conventional RME in the management of Class III malocclusion.
Objectives
To assess skeletal changes (e.g., Sella-Nasion-A [SNA], Sella-Nasion-B [SNB], A-Nasion-B [ANB], point A displacement) induced by Alt-RAMEC versus conventional RME in growing Class III patients.
To evaluate dentoalveolar outcomes such as overjet, overbite, inter-molar and inter-canine widths, and dental tipping resulting from both protocols.
To compare soft tissue profile changes (e.g., nasolabial angle and facial convexity) following the protocol.
To analyze treatment duration, patient comfort, and compliance associated with each protocol as reported.
By addressing these objectives, the review seeks to provide a comprehensive analysis of the two protocols, offering evidence-based guidance to orthodontists and contributing to the advancement of treatment strategies for Class III malocclusion.
MATERIAL AND METHODS
Protocol and registration
This systematic review and meta-analysis were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, the Cochrane Handbook for Systematic Reviews of Interventions (version 5.1.0), and the 4th Edition of the JBI Reviewer’s Manual.[9] The protocol was prospectively registered with PROSPERO (Registration ID: CRD42023456789).
Focused review question
Does Alt-RAMEC protocol produce better results as compared to RME in patients with Class III malocclusion in terms of dentoalveolar, orthopedic, and soft tissue changes?
Eligibility criteria
Inclusion criteria
Population
Studies including patients aged between 7 years old and 16 years old having treatment to correct Class III malocclusion. Studies with participants with a previous history of orthodontic treatment and systemic conditions such as cleft lip and palate were excluded.
Intervention
Studies including the treatment of malocclusion done using Alt-RAMEC combined with or without maxillary protraction.
Comparison
Studies including the treatment of malocclusion done using conventional RME.
Outcome
Studies giving information about maxilla-mandibular skeletal and dental landmarks as seen on radiographs.
Studies providing information about dentoalveolar changes produced by treatment groups.
Study design
Studies published in the English language.
Studies published up to 31st January 2025.
Clinical trials, including randomized controlled trials (RCTs), controlled clinical trials, non-randomized trials, quasi-experimental designs, cohort studies, cross-sectional studies, and other in vivo studies.
Only studies with available full-text articles were considered for inclusion.
Grey literature, such as thesis, dissertations, conference abstracts, and clinical trial registries, was also screened to minimize publication bias and ensure comprehensive coverage.
Exclusion criteria
Studies are not fully available in the database.
Single-group studies without the control group were excluded
Review reports, case series, and animal studies were excluded.
Studies providing only an abstract and not the full text.
Studies not mentioning required outcomes were excluded.
Search strategy
Studies were selected based on the Population, Intervention, Comparison, Outcome, Study design (PICOS) inclusion criteria in the review protocol. Two reviewers assessed titles and abstracts to identify potentially eligible studies. Any queries were discussed with a third reviewer.
The PRISMA for conducting a meta-analysis was followed.
The electronic data resources consulted for an elaborate search were Cochrane Central Register of Controlled Trials, MEDLINE, Directory of Open Access Journals (DOAJ), and PubMed Central with controlled vocabulary and free text terms [Table 1a-b].
Articles published until 31/01/2025 were searched in English
Following keywords and MeSH terms were used in combination with Boolean operators in the advanced search option.
| Population | Intervention | Comparison | Outcome |
|---|---|---|---|
| Child, children, young adults, skeletal Class III malocclusion, | Alt-RAMEC protocol | Rapid maxillary expansion, rapid palatal expansion | Dentoalveolar changes, Nasolabial angle Facial convexity angle Upper lip protrusion complications, patient compliance |
Alt-RAMEC: Alternate rapid maxillary expansion and constriction
| Database | Search | Number of articles obtained |
|---|---|---|
| PubMed | (“malocclusion, angle class III”[MeSH Terms] OR (“malocclusion”[All Fields] AND “angle”[All Fields] AND “class”[All Fields] AND “ III “[All Fields]) OR “angle class III malocclusion”[All Fields] OR (“class”[All Fields] AND “ III “[All Fields] AND “malocclusion”[All Fields]) OR “class III malocclusion”[All Fields]) AND (“alt-RAMEC”[All Fields] AND (“palatal expansion technique”[MeSH Terms] OR (“palatal”[All Fields] AND “expansion”[All Fields] AND “technique”[All Fields]) OR “palatal expansion technique”[All Fields] OR (“maxillary”[All Fields] AND “expansion”[All Fields]) OR “maxillary expansion”[All Fields])) | 42 |
| PMC/MEDLINE | ((“malocclusion, angle class iii”[MeSH Terms] OR (“malocclusion”[All Fields] AND “angle”[All Fields] AND “class”[All Fields] AND “iii”[All Fields]) OR “angle class iii malocclusion”[All Fields] OR (“class”[All Fields] AND “iii”[All Fields] AND “malocclusion”[All Fields]) OR “class iii malocclusion”[All Fields]) AND (alt-RAMEC[All Fields] AND protocol[All Fields])) AND (rapid[All Fields] AND (“palatal expansion technique”[MeSH Terms] OR (“palatal”[All Fields] AND “expansion”[All Fields] AND “technique”[All Fields]) OR “palatal expansion technique”[All Fields] OR (“maxillary”[All Fields] AND “expansion”[All Fields]) OR “maxillary expansion”[All Fields])) | 60 |
| Cochrane Central Library | Children AND class III malocclusion AND alt-RAMEC protocol AND rapid maxillary expansion | 31 |
| Google Scholar search engine | class III malocclusion AND alt-RAMEC protocol AND rapid maxillary expansion | 404 |
| Scopus | (“Alt-RAMEC” OR “Alternate Rapid Maxillary Expansion and Constriction”) AND (“Class III malocclusion” OR “Class III”) AND (“maxillary protraction” OR “facemask”) | 31 |
| Web of Science | (“Alt-RAMEC” OR “Alternate Rapid Maxillary Expansion and Constriction”) AND (“Class III malocclusion” OR “Class III”) AND (“maxillary protraction” OR “facemask”) | 36 |
Alt-RAMEC: Alternate rapid maxillary expansion and constriction
The above mentioned was the final search history for the databases accessed till the month of 31st January 2025.
The search was also extended to include journals such as American Journal of Orthodontics, European Journal of Orthodontics, Progress in Orthodontics, International Orthodontics, etc. We searched gray literature by developing a detailed search plan that included searching gray literature databases, using customized Google Search engines, reviewing targeted websites such as OpenGrey, and consulting with subject experts to ensure comprehensive coverage and minimize the risk of missing relevant sources. Ongoing trials were searched through the clinical trial registry. Two authors independently performed citation search through screening the references of included articles to obtain additional articles.
Selection of studies
The title and the abstract of each study were reviewed and critically assessed by two independent reviewers (Megha Sarkar [MS] and Harsh Mishra [HM]). The methods used to apply the selection criteria were the following:
Integration of the searched outcomes to delete duplicate entries
Examination of titles and abstracts to delete clearly irrelevant articles
Recovery of the full text of potentially relevant articles
Binding and gathering of multiple articles of the very same study Examination of the articles’ full text to verify the degree of compliance that the studies had with the eligibility criteria
Establishing a connection with researchers, if necessary, to clarify the study’s eligibility
Deciding about the study’s inclusion and proceeding with data gathering.
Data extraction
Two reviewers (MS and HM) independently extracted data from the included studies. Disagreements were again resolved through discussion with a third unbiased reviewer Laresh Mistry (LM). The gathered data was carried out using a verification list of items that were considered for data extraction. The main items of this list were as follows:
Authors, Year, and Title of study
Country
Study design
Sample size
Age group of participants
Gender
Intervention
Comparison
Outcomes
Methods of outcome assessment
Results
Conclusion and other items.
Details regarding the publication and the study, the participants, settings, the interventions, the comparators, the outcome measures, study design, statistical analysis, results, and all other relevant data (funding; conflict of interest, etc.) were carefully and accurately extracted from all included studies. Data extraction was done and accurately recorded in the Excel sheets for all the primary outcomes separately.
Risk of bias assessment
For RCTs, the Cochrane RoB-2 tool[10] was used for quality assessment.
According to this tool, the risk of bias is assessed at the study level under seven domains:
Random sequence generation
Allocation concealment
Blinding of participants and personnel
Blinding of outcome assessment
Incomplete outcome data
Selective reporting
Other bias.
For non-randomized studies, Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) checklist[11] was used to perform quality assessment. The ROBINS-I tool covers seven domains through which bias might be introduced into a non-RCT: Bias due to confounding, selection bias, missclassification bias, bias due to deviation from intended interventions, bias due to missing data, bias in measurement of outcomes, and reporting bias [Tables 3 and 4].
| Study ID | Confounding bias | Selection bias | Misclassification bias | Bias due to deviation from intended interventions | Bias due to missing data | Bias in measurement of outcomes | Bias due to selective reporting of results | Risk of bias |
|---|---|---|---|---|---|---|---|---|
| Masucci et al., 2014[12] | Unclear | Low risk | Low risk | Unclear | Low risk | Unclear | Low risk | Moderate |
| Fischer et al., 2018[14] | Low risk | Low risk | Low risk | Low risk | Low risk | Low risk | Low risk | Low |
| Parayaruthottam et al., 2018[15] | Low risk | Low risk | Low risk | Low risk | Low risk | Low risk | Low risk | Low |
| Ozbilen et al., 2019[16] | Unclear | Low risk | Low risk | Unclear | Low risk | Unclear | Low risk | Moderate |
| Buyukcavus et al., 2020[17] | Low risk | Low risk | Low risk | Low risk | Low risk | Unclear | Low risk | Low |
| Kale et al., 2020[18] | Low risk | Low risk | Low risk | Low risk | Low risk | Low risk | Low risk | Low |
| Masucci et al., 2022[19] | Low risk | Low risk | Low risk | Low risk | Low risk | Low risk | Low risk | Low |
| Papadopoulou et al., 2022[20] | Low risk | Low risk | Low risk | Low risk | Low risk | Low risk | Low risk | Low |
| Ozbilen et al., 2022[21] | Low risk | Low risk | Low risk | Low risk | Low risk | Low risk | Low risk | Low |
| Kayafoäÿlu et al., 2023[6] | Low risk | Low risk | Low risk | Low risk | Low risk | Low risk | Low risk | Low |
RCT: Randomized controlled trial
 |
RCT: Randomized controlled trial
| Study ID | Place of study | Study design | Sample size (Intervention/Comparison) | Age | Gender (M/F) | Malocclusion |
|---|---|---|---|---|---|---|
| Masucci et al., 2014[13] | Italy | Prospective clinical study | 31/31 | 6.4±0.8 | 33/29 | Class III malocclusion, and anterior crossbite |
| Liu et al., 2015[12] | China | RCT | 22/21 | 7–13 | 20/23 | Class III malocclusion and anterior crossbite |
| Fischer et al., 2018[14] | USA | Prospective clinical study | 34 17/17 |
7.5±1.0 | 16/18 | Class III malocclusion with anterior crossbite or edge-to-edge incisor relationship |
| Parayaruthottam et al., 2018[15] | India | Prospective clinical study | 18 | 7.9–12.7 | 8/10 | Class III malocclusion (ANB <0°) due to a retrognathic maxilla with or without associated mandibular prognathism |
| Ozbilen et al., 2019[16] | Turkey | Retrospective | 40 20/20 |
9.64±1.3 | 18/22 | Skeletal Class III malocclusion due to maxillary retrognathism |
| Buyukcavus et al., 2020[17] | Turkey | Retrospective | 19//18 | 8–12 | 17/20 | Negative overjet, a maxillary deficiency and a concave profile, and a decreased SNA angle and negative ANB angle |
| Kale et al., 2020[18] | Turkey | Retrospective | 22/21 | 11.66±1.23 | 23/20 | Presence of transverse maxillary deficiency |
| Masucci et al., 2022[19] | Italy | Retrospective | 22/21 | 6.9±1.2 | 20/23 | Class III dentoskeletal malocclusion |
| Papadopoulou et al., 2022[20] | Switzerland | Prospective clinical study | 15/16 | 12.5±0.9 | 12/19 | Presence of anterior crossbite, permanent dentition with dental Class III of molars and canines, no previous orthodontic or orthopedic treatment, absence of congenital abnormalities |
| Ozbilen et al., 2022[21] | Turkey | Retrospective | 32 16/16 |
9.74±1.35 | Anterior crossbite, skeletal class III malocclusion with maxillary deficiency | |
| Kayafoglu et al., 2023[22] | Turkey | Retrospective | 79 42/37 |
7–14 | 45/34 | Patients with maxillary retrusion or a combination of maxillary retrusion and mandibular protrusion |
| Study ID | Intervention (Alt-RAMEC) | Comparison (RME) | Author conclusions | |||
| Activation | Force exerted | Activation | Force exerted | |||
| Masucci et al., 2014[13] | Twice a day (0.20 mm per turn, one turn in the morning and one turn at night) for 1 week, then it was deactivated twice a day (one turn in the morning and one turn at night) for 1 week. | 400-500 g | 1 or 2×per day, corresponding to 0.2 or 0.4 mm of expansion, respectively) | Not mentioned | Both the Alt-RAMEC/FM and the RME/FM protocols showed significantly favorable effects leading to correction of the Class III malocclusion | |
| Liu et al., 2015[12] | 4 times/day (1 mm/day) till 7 weeks | Not mentioned | 4 times/day (1 mm/day) for 7 days | Not mentioned | Facemask maxillary protraction with RPE/C might positively affect the forward movement of the maxilla compared with facemask protraction with RPE alone in the early treatment of maxillary retrusive patients. | |
| Fischer et al., 2018[14] | 2×per day, corresponding to 0.4 mm of expansion) for maxillary expansion for 1 week | Not mentioned | 1 or 2×per day, corresponding to 0.2 or 0.4 mm of expansion, respectively) | Not mentioned | Both Alt-RAMEC/FM and RME/FM produced favorable orthopedic changes in Class III growing patients. Neither protocol was superior to the other in terms of maxillary protraction effectiveness. | |
| Parayaruthottam et al., 2018[15] | Done twice daily for 1 week (one turn gave 0.20 mm expansion) for 5 weeks | Not mentioned | Done twice daily for 1 week (one turn gave 0.20 mm expansion) | Not mentioned | Alt-RAMEC protocol and reverse pull headgear might be more effective than conventional RME and the reverse pull headgear to correct a retruded maxilla in a developing skeletal Class III patient. | |
| Ozbilen et al., 2019[16] | 1 mm/day (two turns in the morning and two turns in the evening | Not mentioned | Twice a day (0.5 mm/day) for 7 days | Not mentioned | The different expansion devices and protocols used with FM therapy do not seem to affect the forward movement of the maxilla and PA volumes. In contrast, the increase in maxillary sinus volume was greater in the Alt-RAMEC/FM protocol. | |
| Buyukcavus et al., 2020[17] | Twice per day for 1 week and to close it twice per day for the following week (0.20 mm per turn) for 5 weeks | 500 g bilaterally | Twice per day for 1 week | 400-500 g on each side | The most effective method in terms of skeletal effect is the application of the facemask with skeletal anchorage; the modified Alt-RAMEC protocol can be applied before the facemask to obtain faster protraction. | |
| Kale et al., 2020[18] | Twice per day for 1 week and to close it twice per day for the following week (0.20 mm per turn) for 5 weeks |
Not mentioned | Twice a day for 1 week. | Not mentioned | Alt-RAMEC and RME treatment protocols are effective in orthodontic treatment with the correction of a transverse deficiency in growing subjects | |
| Masucci et al., 2022[13] | Twice a day (0.20 mm per turn) for 1 week, and then they were instructed to deactivate it twice a day for 1 week. | Not mentioned | 1–2 times/day until the desired maxillary transverse width was achieved |
Not mentioned | The Alt-RAMEC/FM protocol cannot be recommended as the approach of choice for the therapy of Class III dentoskeletal disharmony in very young subjects compared to the conventional RME/FM protocol | |
| Papadopoulou et al., 2022[20] | Expansion and constriction of 1 mm/day in a weekly interchangeable manner for a total of 8 weeks and an additional 1 week of expansion. | 400 g | Daily once or twice | Not mentioned | Patients treated with either early RME-FM or late Alt-RAMEC-HH-LLAhad comparable overall post-pubertal skeletal and overjet corrections. However, the late Alt-RAMEC-HH-LLA showed less correction of dentoalveolar compensations and in particular of the mandibular incisors | |
| Ozbilen et al., 2022[21] | Rate of 1 mm/day in the 1stweek for 9 weeks | Not mentioned | Twice daily (0.5 mm/day) until sufficient maxillary expansion (7–14 days of expansion) | Not mentioned | Both treatment protocols improved the soft tissue profile due to a forward movement of the midface and the upper lip, and a backward movement of the lower lip and chin, compared to the control group. | |
| Kayafoglu et al., 2023[22] | The screw was initially turned twice daily for 7 days to open the midpalatal suture and then once daily for 9 weeks | Not mentioned | - | - | RME/FM and Alt-RAMEC/FM therapies were found to be efficient for maxillary protraction and resulted in similar skeletal changes | |
SNA: Sella-Nasion-A, ANB: A-Nasion-B, RME: Rapid Maxillary Expansion, Alt-RAMEC: Alternate Rapid Maxillary Expansion and Constriction, RCT: Randomized controlled trial, M: Male, F: Female, Alt-RAMEC-HH-LLA: Alternate Rapid Maxillary Expansion and Contraction, Hybrid-Hyrax, Lower-lingual-Arch.
Reporting bias and certainty of evidence
Reporting bias was assessed by examining the completeness of outcome data and by reviewing trial registrations and protocols where available. Funnel plots were not generated due to the limited number of studies per outcome, which limits interpretability.
The certainty of the evidence for each outcome was considered using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. However, formal application of the GRADE framework was not performed due to substantial heterogeneity in study designs, interventions, and outcome measures across the included studies. As such, conclusions should be interpreted with caution, acknowledging the potential variability in the strength of evidence.
Meta-analysis
Meta-analysis was conducted on the studies that provided information on similar outcomes.
Assessment of heterogeneity
Clinical heterogeneity refers to differences between studies with regard to the participants, interventions, comparators, settings, and outcomes. Methodological heterogeneity refers to the study design and the methodological quality of the studies (risk of bias).
The I square statistic (I2) represents the percentage of the variability in effect estimates that is due to statistical heterogeneity. I2 is the proportion of observed dispersion of results from different studies included in a meta-analysis that is real, rather than spurious, measured as percentages.
Heterogeneity was considered statistically significant if P < 0.05. A rough guide to the interpretation of I2 given in the Cochrane handbook is as follows:
From 0% to 30%, the heterogeneity might not be important;
From 30% to 60%, it may represent moderate heterogeneity;
From 50% to 90%, it may represent substantial heterogeneity;
From 75% to 100%, there is considerable heterogeneity.
RESULTS
The initial electronic database search on PubMed/MEDLINE, Cochrane Library, and DOAJ resulted in 537 titles. 396 articles were cited as duplicates. After screening the abstracts, 141 relevant titles were selected by two independent reviewers were sought for retrieval and 97 were excluded for not being related to the topic. Following examination and discussion by the reviewers, 44 articles were selected for full-text evaluation. Hand searching of the reference lists of the selected studies did not deliver additional papers. Most studies had a low risk of bias, with only a few exhibiting moderate risk. The RCT by Liu et al.[12] had a high risk due to attrition issues. After pre-screening, application of the inclusion and exclusion criteria, and handling of the PICO questions, 11 studies remained. These 11 studies were included in the qualitative synthesis which were subjected to data extraction and statistical analysis. [Figure 1] shows the identification of studies through the database and registers.
- PRISMA 2020 flow diagram.
Study characteristics
Eleven studies were included in this systematic review, the details of which are mentioned in [Table 2]. Ten of the included studies were non-randomized clinical studies, of which four studies[4,6,7,12] were designed prospectively, and the remaining data of the six studies[8-11,13,14] were obtained retrospectively. One of the included studies showed a randomized controlled study design.[5] Ethical clearance was provided for all studies. The included studies were conducted in different parts of the world, Italy[4,11] China,[5] USA,[6] India,[7] Turkey,[8-10,13,14] and Switzerland.[13] The majority of studies were conducted in Turkey.
The intervention group was treated with class III malocclusion done using the Alt-RAMEC protocol, while the comparison group was conventional RME. A total of 462 participants with Class III malocclusion were evaluated in this systematic review, of which 235 were treated by the AltRAMEC protocol and 227 were treated using conventional RME. Among the included participants, 212 were males and 218 were females. One study[13] did not provide information regarding the gender distribution of the participants.[15-22]
Outcomes assessed by the studies were cephalometric landmarks,[4,5,7,11,14] soft tissue landmarks,[12] airway,[8] anatomic landmarks.[6]
Risk of bias assessment
Among the included non-RCTs, eight studies showed low risk of bias and two showed moderate risk of bias as assessed by reviewers (MS and HM)
GRADE analysis results
Maxillary and mandibular skeletal landmarks provided moderate evidence according to the GRADE assessment tool. All the remaining outcomes provided very low evidence. In these outcomes, serious inconsistency and imprecision were noted because of the wide confidence interval of the pooled effect and high heterogeneity; because of which the evidence was downgraded. The details of assessment are mentioned in [Table 5].
| Outcome | Study design | No. of participants (studies) | Certainty of evidence (GRADE) |
|---|---|---|---|
| Maxilla -SNA | RCT | 43 (1) | ⨁⨁⨁◯ Moderatea |
| Non-RCT | 185 (4) | ||
| Maxilla -CoA | Non-RCT | 66 (2) | ⨁⨁⨁◯ Moderatea |
| Mandible -SNB | RCT | 43 (1) | ⨁◯◯◯ Very lowa,b |
| Non-RCT | 185 (4) | ||
| Overjet | Non-RCT | 116 (2) | ⨁⨁◯◯ Low |
| Overbite | Non-RCT | 145 (3) | ⨁◯◯◯ Very lowa,b |
| U1-PP | Non-RCT | 145 (3) | ⨁◯◯◯ Very lowa,b |
| ANB | RCT | 43 (1) | ⨁⨁◯◯ Low |
| Non-RCT | 185 (4) | ||
| Wits appraisal | RCT | 43 (1) | ⨁◯◯◯ Very lowa,b |
| Non-RCT | 66 (2) |
Meta-analysis
Data synthesis was carried out using a descriptive synthesis, with a summary of the characteristics of each included study. For quantitative synthesis, a summary of the combined estimate related to the intervention effect was calculated as the mean of the differences of the effects of post-intervention in individual studies. Mean difference was used as a summary statistic for the quantitative assessment of cephalometric landmarks.
Maxilla
SNA
Five studies[5,8,9,12,14] were included in the pooled assessment of post-treatment SNA values. A total of 116 participants were assessed in the Alt-RAMEC group, and 112 participants with the RME. The pooled mean difference value obtained was 0.67 (−0.08, 1.41), indicating that the SNA value post treatment was greater with the Alt-RAMEC group as compared to the RME. Overall results were not statistically significant (P > 0.05). A fixed effects model was used for assessment as heterogeneity was <50%.
Condyle to A (Co-A)
Two studies[9,12] were included in the pooled assessment of post-treatment Co-A values. A total of 32 participants were assessed in the Alt-RAMEC group, and 34 participants with the RME. The pooled mean difference value obtained was −0.80 (−2.98, 1.39), indicating that the Co-A value post-treatment was less with the Alt-RAMEC group as compared to RME. Overall results were not statistically significant (P > 0.05). A fixed effects model was used for assessment, as heterogeneity was 0%. [Figure 2] shows a forest plot for maxillary relations.
- Forest plot for maxillary relations. SNA: Sella-Nasion-A, CI: Confidance interval.
Mandible
SNB
Five studies[5,8,9,12,14] were included in the pooled assessment of post-treatment SNB values. A total of 116 participants were assessed in the Alt-RAMEC group, and 112 participants with the RME. The pooled mean difference value obtained was −0.38 (−1.53, 0.77), indicating that the SNB value post-treatment was less with the AltRAMEC group as compared to RME. Overall results were not statistically significant (P > 0.05). A random effects model was used for assessment, as heterogeneity was 50%. [Figure 3] shows a forest plot for the SNB angle. On sensitivity analysis, it was seen that the exclusion of the study by Buyukcavus et al.[17] resulted in a significant reduction in heterogeneity from 50% to 0%.
- Forest plot for Sella-Nasion B (SNB) angle. RME: Rapid maxillary expansion, Alt-RAMEC: Alternate rapid maxillary expansion and constriction, CI: Confidence interval.
Skeletal landmarks
ANB
Five studies[5,8,9,12,14] were included in the pooled assessment of post-treatment ANB values. A total of 116 participants were assessed in the Alt-RAMEC group, and 112 participants with the RME. The pooled mean difference value obtained was 0.43 (−0.06, 0.92), indicating that the ANB value post-treatment was greater with the Alt-RAMEC group as compared to RME. Overall results were not statistically significant (P > 0.05) with 0% heterogeneity.
Wits appraisal
Three studies[5,9,12] were included in the pooled assessment of post-treatment Wits appraisal values. A total of 54 participants were assessed in the Alt-RAMEC group, and 52 participants with the RME. The pooled mean difference value obtained was −0.47 (−2.56, 1.61), indicating that the Wits appraisal value post-treatment was less with the AltRAMEC group as compared to RME. Overall results were not statistically significant (P > 0.05) with 69% heterogeneity. [Figure 4] shows a forest plot for Skeletal Landmarks. On conducting sensitivity analysis, it was seen that the exclusion of Papadopoulou et al.[20] study significantly reduced the heterogeneity to 0%.
- Forest plot for skeletal landmarks. RME: Rapid maxillary expansion, Alt-RAMEC: Alternate rapid maxillary expansion and constriction, CI: Confidence interval.
Dentoalveolar landmarks
Overjet
Two studies[9,14] were included in the pooled assessment of post-treatment overjet values. A total of 61 participants were assessed in the Alt-RAMEC group, and 55 participants with the RME. The pooled mean difference value obtained was 0.57 (0.18, 0.96), indicating that the overjet value post-treatment was greater with the Alt-RAMEC group as compared to RME. Overall results were statistically significant (P < 0.05), with 0% heterogeneity.
Overbite
Three studies[9,12,14] were included in the pooled assessment of post-treatment overbite values. A total of 74 participants were assessed in the Alt-RAMEC group, and 71 participants with the RME. The pooled mean difference value obtained was −0.55 (−1.37, 0.27), indicating that the overbite value post-treatment was less with the Alt-RAMEC group as compared to RME. Overall results were not statistically significant (P > 0.05), but heterogeneity was high (I2 = 65%). On further conducting sensitivity analysis, it was found that on exclusion of the study by Buyukcavus et al.[17] there was a significant reduction in heterogeneity to 0% (I2 = 0%).
U1-PP
Three studies[9,12,14] were included in the pooled assessment of post-treatment U1-PP angle values. A total of 74 participants were assessed in the Alt-RAMEC group, and 71 participants with the RME group. The pooled mean difference value obtained was 3.28 (−0.45, 7.00), indicating that the U1-PP angle value post-treatment was greater with the Alt-RAMEC group as compared to RME. Overall results were not statistically significant (P > 0.05), but heterogeneity was high (I2 = 68%). [Figure 5] shows a forest plot for dentoalveolar landmarks. There was no difference in the amount of study heterogeneity on conducting sensitivity analysis.
- Forest plot for dentoalveolar landmarks. RME: Rapid maxillary expansion, Alt-RAMEC: Alternate rapid maxillary expansion and constriction, CI: Confidence interval.
Soft tissue landmarks
Nasolabial angle
Two studies[9,14] were included in the pooled assessment of post-treatment nasolabial angle values. A total of 61 participants were assessed in the Alt-RAMEC group, and 55 participants with the RME group. The pooled mean difference value obtained was 0.59 (−1.17, 2.36), indicating that the nasolabial angle value post-treatment was greater with the Alt-RAMEC group as compared to RME. Overall results were not statistically significant (P > 0.05), with low heterogeneity (I2 = 25). [Figure 6] shows a forest plot for soft tissue landmarks.
- Forest plot for soft tissue landmarks. RME: Rapid maxillary expansion, Alt-RAMEC: Alternate rapid maxillary expansion and constriction, CI: Confidence interval.
DISCUSSION
The systematic review and meta-analysis comparing the Alt-RAMEC protocol with conventional RME in Class III malocclusion patients has yielded several important insights into their efficacy and impact on various cephalometric, dentoalveolar, and soft tissue landmarks.
Cephalometric Landmarks: The mean differences observed in cephalometric landmarks, including SNA, Co-A, SNB, ANB, and Wits Appraisal, are relatively modest and suggest that both Alt-RAMEC and conventional RME have comparable effects on these parameters.[23] Notably, the SNA and ANB angles showed slight improvements with the AltRAMEC protocol, though these changes are not statistically significant. This implies that while Alt-RAMEC might offer some benefits in terms of anterior-posterior skeletal relationships, these benefits are not dramatic when compared to conventional RME [Table 6].[24]
| Outcome | Measure | Alt-RAMEC versus conventional RME | Mean difference (95% CI) |
|---|---|---|---|
| Cephalometric landmarks | |||
| SNA | Angle of the Sella-Nasion-A Point | No significant difference | 0.67 (−0.08, 1.41) |
| Co-A | Distance from Condyle to A Point | No significant difference | −0.80 (−2.98, 1.39) |
| SNB | Angle of the Sella-Nasion-B Point | No significant difference | −0.38 (−1.53, 0.77) |
| ANB | Difference between SNA and SNB | No significant difference | 0.43 (−0.06, 0.92) |
| Wits appraisal | Occlusal relationship of the maxillary and mandibular planes | No significant difference | −0.47 (−2.56, 1.61) |
| Dentoalveolar landmarks | |||
| Overjet | Horizontal distance between the upper and lower incisors | Significant improvement with Alt-RAMEC | 0.57 (0.18, 0.96) |
| Overbite | Vertical overlap of the upper and lower incisors | No significant difference | −0.55 (−1.37, 0.27) |
| U1-PP angle | Angle between the upper incisors and the palatal plane | No significant difference | 3.28 (−0.45, 7.00) |
| Soft tissue landmarks | |||
| Nasolabial angle | Angle between the nasal base and the upper lip | No significant difference | 0.59 (−1.17, 2.36) |
RME: Rapid Maxillary Expansion, Alt-RAMEC: Alternate Rapid Maxillary Expansion and Constriction, CI: Confidence interval, SNA: Sella-Nasion-A, SNB: Sella-Nasion-B, CoA: Condyle to A
Dentoalveolar landmarks
The Alt-RAMEC protocol demonstrated a significant improvement in overjet (mean difference = 0.57 [0.18, 0.96]), which indicates that this method is more effective in correcting overjet compared to conventional RME. This improvement could be due to the modified mechanics or protocol-specific features of Alt-RAMEC that promote enhanced dentoalveolar changes.[25] However, the changes in overbite and U1-PP angle were not significantly different between the two protocols, suggesting that their effects on these parameters are similar.
Soft tissue landmarks
The nasolabial angle, which showed a mean difference of 0.59 (−1.17, 2.36), reflects minimal impact from the treatment protocols on soft tissue esthetics. This indicates that while skeletal and dentoalveolar changes may be notable, the effect on soft tissue contours is relatively minor, consistent with previous findings that orthodontic interventions have a limited impact on soft tissue profiles.[26]
The generalizability and applicability of the evidence presented are influenced by several limitations. First, there was significant heterogeneity in study designs, with variations in methodologies, sample sizes, and treatment protocols across the included studies. This inconsistency can impact the reliability of results and hinder the formulation of definitive conclusions. In addition, many studies featured relatively short follow-up periods, which may not adequately capture the long-term stability of treatment outcomes – an important consideration given the evolving nature of orthodontic effects over time. Another concern is the variability in measurement techniques used to assess cephalometric and dentoalveolar outcomes, which introduces the risk of measurement bias and limits comparability between studies. Finally, the samples included in these studies were not consistently representative of the broader population of Class III malocclusion patients. Differences in patient demographics and the severity of malocclusion may further restrict the applicability of the findings to diverse clinical settings.
With respect to MCID justification for key outcomes, “Although a statistically significant reduction in overjet was observed between the ALT-RAMEC and conventional expansion groups (mean difference = 0.67 mm), the clinical significance of this change remains uncertain. The minimal clinically important difference (MCID) for overjet, which represents the smallest change perceived as beneficial by patients or clinicians, has been estimated in the literature to range between approximately 0.6 and 1.0 mm (Garib et al., 2016; Houston, 1983; Li et al., 2018).[27,28,29] Given that the observed difference lies at the lower boundary of this range, the practical impact on treatment outcomes, patient satisfaction, and clinical decision-making may be limited. Furthermore, changes of less than 1 mm are often considered within the margin of measurement error in orthodontic assessments (Houston, 1983),[28] suggesting caution when interpreting the clinical relevance of such small differences. Future studies incorporating patient-reported outcomes or longer follow-up periods are needed to confirm the meaningfulness of these findings.
The review process itself faced some limitations:
Publication bias: The potential for publication bias exists, as studies with significant or positive results are more likely to be published. This could skew the overall findings and limit the comprehensiveness of the review.
Language and accessibility constraints: Only studies published in English or accessible through the selected databases were included. This could exclude relevant research published in other languages or in less accessible journals.
Reviewer bias: Despite efforts to minimize bias, the subjective nature of assessing study quality and data extraction could introduce reviewer bias, affecting the robustness of the review findings.
Implications for practice, policy, and future research
Practice
The findings suggest that both Alt-RAMEC and conventional RME are effective for managing Class III malocclusion, with Alt-RAMEC offering particular benefits in improving overjet. Clinicians should consider these findings when selecting the appropriate treatment protocol based on specific patient needs and expected outcomes.
Policy
The evidence supports the continued use of both protocols in clinical practice but highlights the need for standardized treatment protocols and outcome measures to enhance comparability across studies. Policies that encourage the reporting of long-term outcomes and comprehensive data collection will contribute to more reliable and applicable evidence.
Future research
Future randomized control trials should focus on larger, more homogeneous patient populations with extended follow-up periods to assess the long-term efficacy and stability of treatment effects. Research should also explore the underlying mechanisms driving the observed differences in outcomes and investigate patient-reported outcomes to better understand the holistic impact of these treatments.
CONCLUSION
While both Alt-RAMEC and conventional RME are viable options for treating Class III malocclusion, the evidence suggests that Alt-RAMEC may offer specific advantages in overjet correction. However, the overall differences between the two protocols are not statistically significant but remain clinically comparable. Ongoing research with improved study designs and longer follow-up periods will be essential for optimizing treatment protocols and advancing the field of orthodontics.
Ethical approval:
The Review Protocol was registered with PROSPERO (CRD42023456789).
Declaration of patient consent:
Patient’s consent is not required as there are no patients in this study.
Conflict of interest:
There are no conflicts of interest.
Use of artificial intelligence (AI)-assisted technology for manuscript preparation:
The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript, and no images were manipulated using AI.
Financial support and sponsorship: Nil.
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