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Original Article

Korean J Orthod 2024; 54(1): 26-47   https://doi.org/10.4041/kjod23.064

First Published Date September 22, 2023, Publication Date January 25, 2024

Copyright © The Korean Association of Orthodontists.

Role of vitamin D for orthodontic tooth movement, external apical root resorption, and bone biomarker expression and remodeling: A systematic review

Martina Ferrilloa , Dario Calafioreb , Lorenzo Lippic,d , Francesco Agostinie,f , Mario Migliariog , Marco Invernizzic,d , Amerigo Giudicea , Alessandro de Sireh

aDentistry Unit, Department of Health Sciences, Magna Graecia University of Catanzaro, Catanzaro, Italy
bPhysical Medicine and Rehabilitation Unit, Department of Neurosciences, ASST Carlo Poma, Mantova, Italy
cPhysical and Rehabilitative Medicine, Department of Health Sciences, University of Eastern Piedmont “A. Avogadro”, Novara, Italy
dTranslational Medicine, Dipartimento Attività Integrate Ricerca e Innovazione (DAIRI), Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo, Alessandria, Italy
eDepartment of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza University, Rome, Italy
fDepartment of Neurological and Rehabilitation Science, IRCCS San Raffaele, Rome, Italy
gDentistry Unit, Department of Translational Medicine, University of Eastern Piedmont “A. Avogadro”, Novara, Italy
hPhysical Medicine and Rehabilitation Unit, Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, Catanzaro, Italy

Correspondence to:Alessandro de Sire.
Professor, Physical Medicine and Rehabilitation Unit, Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, Viale Europa 88100 Catanzaro, Italy.
Tel +390961712819 e-mail martina.ferrillo@unicz.it

How to cite this article: Ferrillo M, Calafiore D, Lippi L, Agostini F, Migliario M, Invernizzi M, Giudice A, de Sire A. Role of vitamin D for orthodontic tooth movement, external apical root resorption, and bone biomarker expression and remodeling: A systematic review. Korean J Orthod 2024;54(1):26-47. https://doi.org/10.4041/kjod23.064

Received: April 10, 2023; Revised: August 4, 2023; Accepted: September 18, 2023

Abstract

Objective: This systematic review aimed to evaluate the correlation between vitamin D levels and the rate of tooth movement, external apical root resorption, bone biomarker expression, and bone remodeling. Methods: Three databases (PubMed, Scopus, and Web of Science) were systematically searched from inception until 14th March 2023 to identify studies investigating the correlation between orthodontic tooth movement and vitamin D in animals and humans. The quality assessment was made in accordance with the Joanna Briggs Institute Critical Appraisal Checklist. Results: Overall, 519 records were identified, and 19 were selected for the qualitative synthesis. Eleven studies investigated the effect of local administration (injections in the periodontal ligament, to the gingiva distal to the teeth, or submucosae palatal area) and systemic administration (oral supplementation) of vitamin D on tooth movement, external apical root movement, pro-inflammatory cytokines, and bone remodeling factors. The remaining eight studies investigated the correlation between serum vitamin D levels and salivary vitamin D levels on bone turnover markers and tooth movement. Conclusions: The findings of this systematic review support that vitamin D3 local injections might increase the rate of tooth movement via the receptor activator of the nuclear factor-kB/osteoprotegerin axis. However, the non-uniform study designs and the different protocols and outcome methods make it challenging to draw reliable conclusions.

Keywords: Vitamin D, Calcitriol, Orthodontic tooth movement, External apical root resorption

Article

Original Article

Korean J Orthod 2024; 54(1): 26-47   https://doi.org/10.4041/kjod23.064

First Published Date September 22, 2023, Publication Date January 25, 2024

Copyright © The Korean Association of Orthodontists.

Role of vitamin D for orthodontic tooth movement, external apical root resorption, and bone biomarker expression and remodeling: A systematic review

Martina Ferrilloa , Dario Calafioreb , Lorenzo Lippic,d , Francesco Agostinie,f , Mario Migliariog , Marco Invernizzic,d , Amerigo Giudicea , Alessandro de Sireh

aDentistry Unit, Department of Health Sciences, Magna Graecia University of Catanzaro, Catanzaro, Italy
bPhysical Medicine and Rehabilitation Unit, Department of Neurosciences, ASST Carlo Poma, Mantova, Italy
cPhysical and Rehabilitative Medicine, Department of Health Sciences, University of Eastern Piedmont “A. Avogadro”, Novara, Italy
dTranslational Medicine, Dipartimento Attività Integrate Ricerca e Innovazione (DAIRI), Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo, Alessandria, Italy
eDepartment of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza University, Rome, Italy
fDepartment of Neurological and Rehabilitation Science, IRCCS San Raffaele, Rome, Italy
gDentistry Unit, Department of Translational Medicine, University of Eastern Piedmont “A. Avogadro”, Novara, Italy
hPhysical Medicine and Rehabilitation Unit, Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, Catanzaro, Italy

Correspondence to:Alessandro de Sire.
Professor, Physical Medicine and Rehabilitation Unit, Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, Viale Europa 88100 Catanzaro, Italy.
Tel +390961712819 e-mail martina.ferrillo@unicz.it

How to cite this article: Ferrillo M, Calafiore D, Lippi L, Agostini F, Migliario M, Invernizzi M, Giudice A, de Sire A. Role of vitamin D for orthodontic tooth movement, external apical root resorption, and bone biomarker expression and remodeling: A systematic review. Korean J Orthod 2024;54(1):26-47. https://doi.org/10.4041/kjod23.064

Received: April 10, 2023; Revised: August 4, 2023; Accepted: September 18, 2023

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective: This systematic review aimed to evaluate the correlation between vitamin D levels and the rate of tooth movement, external apical root resorption, bone biomarker expression, and bone remodeling. Methods: Three databases (PubMed, Scopus, and Web of Science) were systematically searched from inception until 14th March 2023 to identify studies investigating the correlation between orthodontic tooth movement and vitamin D in animals and humans. The quality assessment was made in accordance with the Joanna Briggs Institute Critical Appraisal Checklist. Results: Overall, 519 records were identified, and 19 were selected for the qualitative synthesis. Eleven studies investigated the effect of local administration (injections in the periodontal ligament, to the gingiva distal to the teeth, or submucosae palatal area) and systemic administration (oral supplementation) of vitamin D on tooth movement, external apical root movement, pro-inflammatory cytokines, and bone remodeling factors. The remaining eight studies investigated the correlation between serum vitamin D levels and salivary vitamin D levels on bone turnover markers and tooth movement. Conclusions: The findings of this systematic review support that vitamin D3 local injections might increase the rate of tooth movement via the receptor activator of the nuclear factor-kB/osteoprotegerin axis. However, the non-uniform study designs and the different protocols and outcome methods make it challenging to draw reliable conclusions.

Keywords: Vitamin D, Calcitriol, Orthodontic tooth movement, External apical root resorption

Fig 1.

Figure 1.PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 flow diagram.
Korean Journal of Orthodontics 2024; 54: 26-47https://doi.org/10.4041/kjod23.064

Table 1 . Search strategy.

PubMed:
((“vitamin d”[MeSH Terms] OR “vitamin d”[All Fields] OR “cholecalciferol”[MeSH Terms] OR “cholecalciferol”[All Fields] OR “ergocalciferols”[MeSH Terms] OR “ergocalciferols”[All Fields] OR “calcifediol”[MeSH Terms] OR “calcifediol”[All Fields] OR “25 oh d3”[All Fields])) AND (“Orthodontics”[Mesh Terms] OR “Orthodontics”[All Fields]) OR ((“tooth”[MeSH Terms] AND “movement”[MeSH Terms]) OR (“tooth”[All Fields] AND “movement”[All Fields])) OR (“malocclusion”[MeSH Terms] OR “malocclusion"”[All Fields]) OR (“dental occlusion”[MeSH Terms] OR (“dental”[All Fields] AND “occlusion”[All Fields]) OR “dental occlusion”[All Fields]) OR (“oral health”[MeSH Terms] OR “oral health”[All Fields]) OR (“oral status” [All Fields]))
Scopus:
TITLE-ABS-KEY (((vitamin d) OR (cholecalciferol) OR (25 oh d3)) AND ((Orthodontics) OR (tooth movement) OR (malocclusion)))
Web of Science:
ALL = ((“vitamin d” OR “cholecalciferol” OR “25 oh d3”) AND (“Orthodontics” OR “tooth movement” OR “malocclusion”))

Table 2 . Main characteristics of the studies included in the present systematic review.

AuthorsJournalDesignNatio-nalityPopulationAge (yr)InterventionComparatorOutcomeTime pointsMain findings
Al-Attar and Abid (2022)36International Journal of DentistryRandomized controlled trialIraq

Total: n = 33; M/F = N/A.

Group 1: n = 17; M/F = N/A.

Group 2: n = 16; M/F = N/A.

Total: 20.13 ± 1.81; (18–30).

Group 1: 20.5 ± 1.61.

Group 2: 19.70 ± 1.95.

Group 1: vitamin D3 level was measured before orthodontic intervention; if the level was below the normal value (30 ng/mL), then the participants were referred to an endocrine specialist to optimize the level of vitamin D3 to normal before bonding the appliance. Patients were treated with a fixed orthodontic appliance.

Group 2: orthodontic treatment was performed without measuring the level of vitamin D3 until completion of the alignment phase..

Patients were treated with fixed orthodontic appliance..

- Vitamin D3 level.

- Mandibular incisor crowding.

- EARR.

- Pain perception.

T0 (baseline), T1 (4 wk), T2 (8 wk), T3 (12 wk), T4 (16 wk), and T5 (20 wk)The results showed that there were statistically significant improvements in time elapsed for the complete alignment of the mandibular incisor crowding (P ≤ 0.001), which was 1 mo shorter in normal vitamin D3 group (23.53% faster), and the improvement percentage was significantly higher in all periods when compared to the CG (P ≤ 0.001). The amount of EARR was not significantly different between groups; however, pain during the first three days of alignment was significantly less in normal vitamin D3 group (P < 0.05).
Al-Hasani et al. (2011)22International Journal of Pharmacy and Pharmaceutical SciencesProspective studyIraqTotal: n = 15; M/F = N/ATotal: range, 17–28

Group 1: injection of 0.2 mL of calcitriol in DMSO containing 15 pg/mL of calcitriol into the periodontal ligament of the left canines (distal side). The injections were repeated 3 times for every subject (T0, T1, T2). The distalizing orthodontic forces were about 150 g..

Group 2: injection of 0.2 mL of calcitriol in DMSO containing 25 pg/mL of calcitriol into the periodontal ligament of the left canines..

Group 3: injection of 0.2 mL of calcitriol in DMSO containing 40 pg/mL of calcitriol into the periodontal ligament of the left canines..

Right canine: injection of 0.2 mL of DMSO.Tooth movementT0 (baseline), T1 (7 days), T2 (14 days), T3 (21 days), T4 (28 days)The results showed no statistically significant differences in OTM between control and experimental sides, and among the 3 groups. From a clinical point of view, the dose of 25 pg of calcitriol produced about 51% faster rate of experimental canine movement compared to control, whereas 15 pg and 40 pg doses resulted in about 10% accelerated OTM.
Azizi et al. (2022)37International Journal of DentistryRetrospective cohort studyIranTotal: n = 80; M/F = N/ATotal: range, 12–30Fixed orthodontic treatment

- Serum level of vitamin D.

- EARR.

- Root length.

T0 (baseline)A reduction in root length was noted in all patients, which was significant (P < 0.0001); 75% of patients showed EARR in at least one maxillary incisor. The EARR had no significant correlation with the serum level of vitamin D (P = 0.423).
Iosub Ciur et al. (2016)23Revista medico-chirurgicala˘˘ a Societa˘˘ţii de Medici şi Naturalişti din IaşiProspective studyFranceTotal: n = 6; M/F = 3/3Total: 18Injection of 0.2 mL of vitamin D3 in DMSO containing 42 pg/mL of vitamin D3 into the periodontal ligament of the experimental canine was administered, once a week, for 3 wk. Canine distalization was achieved using a closed Niti spring of 12 mm which generated a force of 150 g.The control canine received only conventional orthodontic treatment.Tooth movementT0 (baseline), T1 (1 mo)Results showed an average of 70% more tooth movement for the experimental teeth compared to control ones. The differences between the control and the experimental sides were statistically significant (P = 0.0313).
Collins and Sinclair (1988)24American Journal of Orthodontics and Dentofacial OrthopedicsAnimal studyUSA

Young adult cats.

Total: n = 5; M/F = N/A.

Total: N/AInjection of 0.1 mL of 1.25 D in DMSO containing 50 pg/mL of 1.25(OH)2D3 into the periodontal ligament of the left canines. The orthodontic forces were delivered using a light-wire retraction spring.The right canines received an injection of 0.1 mL of DMSO only. The orthodontic forces were delivered using a light-wire retraction spring.Cumulative amounts of tooth movement, weekly increments of tooth movement, numbers of mononuclear osteoclastsT0 (baseline), and T1 (21 days)After 21 days of canine retraction with a light-wire retraction spring, the teeth that had received weekly intraligamentous injections of 1.25 D had moved 60% further than matched control teeth (P < 0.05). At the histologic level, increased numbers of mononuclear osteoclasts were recruited and activated, resulting in greater amounts of alveolar bone resorption on the pressure side of the periodontal ligament.
Cui et al. (2016)25Journal of Molecular HistologyAnimal studyChina

Wistar rats.

Total: n = 30; M/F = 30/0.

Group 1: n = 12; M/F = 12/0.

Group 2: n = 12; M/F = 12/0.

Group 3: n = 6; M/F = 6/0.

7-week-old

Group 1: experimental group to examine the effect of 1α,25(OH)2D3 (n = 6) and normal saline (n = 6) on HMGB1 at day 7..

Group 2: experimental group to examine the effect of 1α,25(OH)2D3 (n = 6) and normal saline (n = 6) on HMGB1 at day 28..

The orthodontic forces were delivered using a nickel-titanium coil spring with (force level of 0.5 N) for 5 days..

Vitamin D administration: (100 ng/kg body weight) by gavage once every other day..

Saline: identical volume and frequency..

Group 3: control group to determine basal HMGB1 protein expressionTNF-α, IL-6, and HMGB1T0 (after 5 days of application of mechanical loading to the tooth), T1 (after 7 days), and T2 (after 28 days)Expression of IL-6 and TNF-α were time-dependently reduced in the 1α,25(OH)2 vitamin D group compared with the control group at each time point (P < 0.01). Similarly, expression of HMGB1 was decreased over time in both the 1α,25(OH)2 vitamin D and normal saline groups, and 1α,25(OH)2 vitamin D administration enhanced this decline (P < 0.01).
Fontana et al. (2012)26American Journal of Orthodontics and Dentofacial OrthopedicsProspective studyBrazil

Total: n = 377; M/F = 169/208.

Group 1: n = 160; M/F = 74/86.

Group 2: n = 179; M/F = 80/99.

Group 3: n = 38; M/F = 15/23.

Total: 14.9; range, 8–21.

Group 1: 14.50 ± 3.01 (8–21).

Group 2: 15.33 ± 2.64 (9.9–20).

Group 3: 16.46 ± 1.93 (11–19).

Group 1: patients treated with edgewise or straight-wire techniques, with EARR ≤ 1.43 mm..

Group 2: patients treated with edgewise or straight-wire techniques, with EARR > 1.43 mm..

EARR of the maxillary incisors was evaluated on periapical radiographs..

Group 3: untreated subjectsEARR, genotype and allele distribution of the VDR TaqI polymorphism, protective effect of allele CT0 (baseline), and T1 (6 mo)Differences were observed in VDR Taq1 polymorphism genotype frequency (P = 0.051) between groups. It was observed a weak protective effect of allele C against EARR (CC + CT × TT [OR, 0.29; 95% CI, 0.07–1.23; P = 0.091]) in treated patients compared with control group.
Gratton et al. (2022)38American Journal of Orthodontics and Dentofacial OrthopedicsAnimal studyCanada

Sprague Dawley rats.

Total: n = 32; M/F = 32/0.

Group 1: n = 8; M/F = 8/0.

Group 2: n = 8; M/F = 8/0.

Group 3: n = 8; M/F = 8/0.

Group 4: n = 8; M/F = 8/0.

N/A

Group 1: experimental gavage - daily solution of vitamin D (50 ng/mL) by gavage..

Group 2: experimental injection-submucosal injection of solution of vitamin D solution, every 2 days in the anterior and palatal region of the maxillary right first molar (volume of 20 mL, vitamin D 1 × 10-10 M, injected at each dose)..

A closed nickel-titanium coil of 50 cN force was bonded between the maxillary right first molar and the incisors of each rat at T1, for 7 days..

Group 3: control gavage - daily solution of PBS solution (0.1 M, pH 7.2) by gavage.

Group 4: control injection - submucosal injection of solution of PBS solution, every 2 days in the anterior and palatal region of the maxillary right first molar (volume of 20 mL injectedat each dose)..

A closed nickel-titanium coil of 50 cN force was bonded between the maxillary right first molar and the incisors of each rat at T1, for 7 days..

- Tooth movement.

- Bone morphometry.

T0 (baseline), T1 (10 days), T2 (17 days), T3 (24 days), T4 (47 days)

The systemic vitamin D group showed a lower OTM rate and a lower relapse than the control (P < 0.05)..

It also demonstrated increased bone mineral density, bone volume/total volume, and a decrease in total porosity (P < 0.05). The bone structure appeared more fragmented and presented a lower connectivity density than the control (P < 0.05). No statistical difference was found between vitamin D local administration and the other groups for the rate and stability of OTM or bone morphometry..

Kale et al. (2004)27American Journal of Orthodontics and Dentofacial OrthopedicsAnimal studyTurkey

Sprague Dawley rats.

Total: n = 37; M/F = 37/0.

Group 1: n = 8; M/F = 8/0.

Group 2: n = 8; M/F = 8/0.

Group 3: n = 8; M/F = 8/0.

Group 4: n=8; M/F= 8/0.

Group 5: n = 5; M/F = 5/0.

6-week-old

Group 1: appliance control group; orthodontic appliances alone.

Group 2: DMSO group; 20 µL injection of DMSO on days 0, 3, and 6..

Group 3: 1.25-dihydroxy-cholecalciferol (1.25-DHCC) group; orthodontic appliances + single injection of 20 µL of 10–10 mol/L, given on days 0, 3, and 6..

Group 4: PGE2 group; orthodontic appliances + a single injection of 0.1 mL of 0.1 µg PGE2 on the day of appliance placement..

Injections were administered with a microsyringe to the gingiva distal to the maxillary incisors..

Group 5: no treatmentTooth movement, numbers of Howship’s lacunae and capillaries, number of osteoblastsT0 (baseline), and T1 (9 days)There was no significant difference in tooth movement between the PGE2 and the 1.25-DHCC groups (P > 0.05). Both PGE2 and 1.25-DHCC enhanced the amount of tooth movement significantly when compared with the control group (P < 0.001). The numbers of Howship’s lacunae and capillaries on the pressure side were significantly greater in the PGE2 group than in the 1.25-DHCC group (Howship’s lacunae: P < 0.001; capillaries: P < 0.005). Compared to the DMSO group and Control, the number of capillaries in the pressure side in the 1.25-DHCC group remains significantly higher (P < 0.001). On the other hand, the number of osteoblasts on the external surface of the alveolar bone on the pressure side was significantly greater in the 1.25-DHCC group than in the PGE2 group (P < 0.001).
Kawakami and Takano-Yama-moto (2004)28Journal of Bone and Mineral MetabolismAnimal studyJapan

Wistar rats.

Total: n = 16; M/F = 16/0.

Group 1: n = 8; M/F = 8/0.

Group 2: n = 8; M/F = 8/0.

7-week-old

Group 1: a piece of orthodontic elastic band (0.5-mm thickness) was inserted bilaterally between the first and second maxillary molars..

Twenty microliters of 10-10 M.

1.25(OH)2D3 was injected locally in the submucosal palatal area of the root furcation of the right molar, using a 30-gauge needle, once every 3 days (tooth movement [TM] 1.25(OH)2D3). The left side was injected with vehicle (TM phosphate-buffered saline-PBS)..

Group 2: rats without the insertion of elastic bands were injected with the same dose of 1.25(OH)2D3 on the right side (non-TM 1.25(OH)2D3) and with vehicle on the left side (non-TM PBS).Histomor-phometric indices on the distal and mesial sides of the inter radicular septum of the maxillary first molarT0 (baseline), T1 (7 days), and T2 (14 days)Histomorphometric analysis revealed that tooth movement without application of 1.25(OH)2 vitamin D decreased the mineral appositional rate (MAR) on the compression area at 7 days (P < 0.05). Repeated injections of 1.25(OH)2 vitamin D in the orthodontically treated animals distinctly stimulated alveolar bone formation on the mesial side at 14 days. There was a significant increase in MAR associated with elevated osteoblast surface value on the tension surface (P < 0.05).
Khalaf and Almudhi (2022)29Saudi Dental JournalAnimal studySaudi Arabia

Wistar rats.

Total: n = 16; M/F = 16/0.

Group 1: n = 8; M/F = 8/0.

Group 2: n = 8; M/F = 8/0.

8–9-week-old

Group 1: rats with induced vitamin D deficiency..

This condition was achieved using an injection of 0.1 mL of Saline and paricalcitol injected 3 times per week for 2 wk for each rat..

An additional week of inactivity was observed, totaling the time to three weeks before commencement of the OTM procedures..

Orthodontic appliances were fixed to initiate tooth movement..

Group 2: rats with average vitamin D serum level. Orthodontic appliances were fixed to initiate tooth movement at T0.Tooth movementT0 (baseline, for Group 1 after 3 wk from first injection), T1 (7 days), T2 (14 days), and T3 (21 days)The overall OTM was compared between groups and showed no statistically significant differences at 0–7 days (P = 0.709), 0–14 days (P = 0.313), or 0–21 days (P = 0.359). The OTM over time was compared separately, and for both groups significant changes were observed over time. In group 1 the pairwise comparisons found significant differences between 0–7 days and 0–14 days (P = 0.013), 0–7 days, and 0–21 days (P < 0.001). Similar results were found in the 2 groups, with significant differences between 0–7 days and 0–14 days (P = 0.014), 0–7 days, and 0–21 days (P = 0.001). The repeated measures ANOVA found the differences to be significant when considered for time (F = 29.9, P < 0.001). There was a significant drop in the OTM over time in both groups. Results showed that vitamin D deficiency did not affect rate of OTM.
Khalaf and Almudhi (2022)30Journal of Oral Biology and Craniofacial ResearchAnimal studySaudi Arabia

Wistar rats.

Total: n = 16; M/F = 16/0.

Group 1: n = 8; M/F = 8/0.

Group 2: n = 8; M/F = 8/0.

Total: N/A

Group 1: rats with induced vitamin D deficiency..

This condition was achieved using injection of 0.1 mL of Saline and paricalcitol injected 3 times per week for 2 wk..

An additional week of inactivity was observed, totaling the time to three weeks before commencement of the OTM procedures..

Orthodontic appliances were fixed to initiate tooth movement..

Group 2: normal rats. Orthodontic appliances were fixed to initiate tooth movement at T0.Vitamin D, serum level of RANKL concen-tration, OPG concen-tration, and RANKL/OPG ratioT0 (baseline, for Group 1 after 3 weeks from first injection), and T1 (21 days)A statistically significant decrease in serum RANKL concentration (P < 0.001) and RANKL/OPG ratio (P < 0.001) on day 21 were seen in the experimental group compared to the control group.
Lesz-czyszyn et al. (2021)31NutrientsProspective studyPoland

Total: n = 114; M/F = 61/53.

Group 1: n = 86; M/F = 57/29.

Group 2: n = 28; M/F = 4/24.

Total: 36.5 ± 11.8 (18–50)Group 1: vitamin D deficiencyGroup 2: no vitamin D deficiency25(OH) vitamin D serum levels, malocclusion development ratioT0 (baseline)In about 42.1% of patients, the presence of a skeletal defect was found, and in 46.5% of patients, dentoalveolar malocclusion. The most common defect was transverse constriction of the maxilla with a narrow upper arch (30.7%). The concentration of vitamin 25(OH) D in the study group was on average 23.6 ± 10.5 (ng/mL). Vitamin D deficiency was found in 86 subjects (75.4%). Our research showed that vitamin D deficiency could be one of the important factors influencing maxillary development. Patients had a greater risk of a narrowed upper arch (OR = 4.94), crowding (OR = 4.94), and crossbite (OR = 6.16).
Marañón-Vásquez et al. (2023)39European Journal of Oral SciencesRetrospective studyGer-manyTotal: n = 143; M/F = 71/72Total: 13.5 ± 4.5

Orthodontic treatment.

A sample of cheek cells (buccal cells) was collected for DNA analysis.

- Vitamin-D-related genes (VDR, GC, CYP27B1, and CYP24A1).

- EARR.

- Root length.

T1 (initial treatment.

radiograph), and T2 (final treatment adiograph).

Individuals carrying the AA genotype in VDR rs2228570 had a 21% higher EARRmol than those having AG and GG genotypes (95% CI: 1.03,1.40)..

EARRmol in heterozygous rs2228570, was 12% lower than for homozygotes (95% CI: 0.78–0.99). Participants with the CCG haplotype (rs1544410-rs7975232-rs731236) in VDR had an EARRmol 16% lower than those who did not carry this haplotype..

Regarding CYP27B1 rs4646536, EARRinc in participants who had at least one G allele was 42% lower than for homozygotes AA (95% CI: 0.37–0.93)..

Mora-dinejad et al. (2022)40American Journal of Orthodontics and Dentofacial OrthopedicsAnimal studyIran

Wistar rats.

Total: n = 32; M/F = 32/0.

Group 1: n = 8; M/F = 8/0.

Group 2: n = 8; M/F = 8/0.

Group 3: n = 8; M/F = 8/0.

Group 4: n = 8; M/F = 8/0.

N/A

Group 1: vitamin D3 intraperitoneal injection, once every 2 wk for 3 times (2 times [21 days and 7 days] before the appliance placement and 1 time [7 days] after it), each dose of 0.6 mg/kg body weight equivalent to 24,000 IU/kg..

Group 2: alendronate solution, once a week and for a total of 5 times (21, 14, and 7 days before the appliance placement, the day of placement, and 7 days after placement) at a dosage of 7 mg/kg of body weight per week by gavage..

Group 3: alendronate + vitamin D (same doses) Orthodontic appliances: the incisors were distalized at 30 g of force for 2 weeks..

Group 4: only orthodontic appliances

- Tooth movement.

- Capillaries, lacunae, osteoclasts, and osteoblasts.

T0 (21 days before the appliance placement).

T1 (14 days before the appliance placement).

T2 (7 days before the appliance placement).

T3 (the day of placement).

T4 (7 days after placement).

The OTMs in the groups vitamin D3, ALN+D3, ALN, and control were 1.900 ± 0.237, 1.629 ± 0.219, 0.975 ± 0.145, and 1.565 ± 0.324 mm (P < 0.001), respectively..

The OTM in the ALN group was smaller than all other groups (P < 0.001). The OTM in the D3 group was greater than in the control group (P = 0.054). The ALN+D3 group had greater OTM than the ALN group (P < 0.001) but was not significantly different from the D3 (P = 0.153) or control (P = 0.951) groups. All histologic variables were significantly different across groups (P < 0.001). All the markers in the D3 group were more frequent than those of the other groups (P < 0.001). There were fewer markers in the ALN group than in the control group (P ≤ 0.001). The ALN + D3 group had more markers than the ALN group in terms of capillaries, osteoclasts, and osteoblasts (P ≤ 0.007). The ALN + D3 group was similar to the control group regarding capillaries, osteoclasts, and osteoblasts (P ≥ 0.382)..

Takano-Yama-moto et al. (1992)32Journal of Dental ResearchAnimal studyJapan

Wistar rats.

Total: n = 60; M/F = 60/0.

Group 1: n = 30; M/F = 30/0.

Group 2: n = 30; M/F = 30/0.

Group 1: 7-week-old.

Group 2: 28-week-old.

The right maxillary first molar was moved buccally with a fixed appliance. The appliances delivered forces ranging from 5 to 20 g..

Twenty gL of 1.25(OH)2D3 (10-10 and 10-8 mol/L) was injected locally into the submucosal palatal area of the root bifurcation of the right first molar..

The left side was injected with PBS.Tooth movement, calcium, phosphate, and alkaline phosphatase activityT0 (baseline), and T1 (21 days)

In young rats receiving 10-10 mol/L 1.25(OH)2D3 every three days, tooth movement significantly increased to 126% of that in PBS-injected control rats on day 20. In 1.25(OH)2D3-injected mature rats, tooth movement was stimulated markedly and increased by 245% after 10-10 mol/L of 1.25(OH)2D3, while a dose of 10-8 mol/L of 1.25(OH)2D3 increased of 154% tooth movements compared to PBS-injected controls..

PBS-injected rats had a plateau stage where tooth movement did not occur at all, while there was no such lag-time in the 1.25(OH)2D3-injected group which showed continuous tooth movement. The local injection of 1.25(OH)2D3 did not change serum calcium, phosphate, and alkaline phosphatase activity, and there were no apparent clinical or microscopic side effects..

Tashkandi et al. (2021)33BMC Oral HealthProspective studyUSA

Total: n = 73; M/F = 30/43.

Group 1: n = 18; M/F = 9/9.

Group 2: n = 37; M/F = 15/22.

Group 3: n = 18; M/F = 6/12.

Total: 21.5 ± 11.1 (8–63).

Group 1: 22.78 ± 7.89.

Group 2: 20.05 ± 11.74.

Group 3: 23.72 ± 12.39.

Group 1: low VitDBP

Group 2: normal VitDBP.

Group 3: high VitDBP.

VitDBP, ALPT0 (baseline), and T1 (6 mo)VitDBP is a biological marker for bone apposition and clinical tooth movement. Both low (< 2.75 ng/mL) and high (> 6.48 ng/mL) VitDBP levels were associated with reduced tooth movement. Significant (P < 0.05) seasonal changes in VitDBP using a 2-season year model was found with lower levels observed in the summer (Apr–Sep) than in the winter (Oct–Mar).
Tehranchi et al. (2017)34Dental Research JournalCross-sectional studyIranTotal: n = 34; M/F = 8/26Total: 16.63 ± 2.84 (12–23)

Group 1: mild vitamin D deficiencies (25-OHD 20–30 ng/mL).

Patients were treated with fixed orthodontic treatment..

Group 2: moderate vitamin D deficiencies (25-OHD 10–20 ng/mL).

Group 3: severe vitamin D deficiencies (25-OHD < 10 ng/mL).

Vitamin D status, EARRT0 (baseline), and T1 (end of orthodontic treatment)The Pearson coefficient between vitamin D status and observed EARR was determined about 0.15 (P = 0.38). Regression analysis revealed that vitamin D status of the patients demonstrated no significant statistical correlation with EARR, after adjustment of confounding variables using linear regression model (P > 0.05).
Varughese et al. (2019)35The Journal of Contemporary Dental PracticeRandomized controlled trialIndiaTotal: n = 15; M/F = N/ATotal: 22.5; range, 15–30Injection of 0.2 mL of 1.25 vitamin D in DMSO containing 50 pg/mL of 1.25 D into the periodontal ligament of the experimental canine was administered at monthly intervals for duration of three months. Canine distalization was achieved using a closed Niti spring, which generated a force of 150 g.Injection of 0.2 mL placebo gel into the periodontal ligament of the control canine.Tooth movement and anchorage lossT0 (baseline), T1 (4 wk), and T2 (8 wk), T3 (12 wk)

About total amount of canine distalization the results showed statistically significant difference (P = 0.000) between experimental and control sides over a period of 3 mo..

About the amount of anchorage loss, no statistically significant results were shown..

Values are presented as mean ± standard deviation and maximum-minimum (range)..

M, male; F, female; N/A, not applicable; DMSO, dimethylsulfoxide; OTM, orthodontic tooth movement is correct; HMGB1, high mobility group box 1; EARR, external apical root resorption; VDR, vitamin D receptor; PBS, phosphate-buffered saline; PGE2, prostaglandin E2; RANKL, receptor activator of nuclear factor-kappa B ligand; OPG, osteoprotegerin; OR, odds ratio; EARRmol, external apical root resorption of lower first molars; EARRinc, external apical root resorption of upper central incisors; CI, confidence interval; ALN, alendronate; VitDBP, vitamin D binding protein; ALP, alkaline phosphatase..


Table 3 . Joanna Briggs Institute Critical Appraisal for quasi-experimental studies.

AuthorsQ1Q2Q3Q4Q5Q6Q7Q8Q9Total score
Al-Hasani et al. (2011)22YYYYYYYYY9
Azizi et al. (2022)37YYYNNYYYY7
Iosub Ciur et al. (2016)23YYYYYYYYY9
Collins and Sinclair (1988)24YYYYYYYYY9
Cui et al. (2016)25YYYYYYYYY9
Fontana et al. (2012)26YYYYYYYYY9
Gratton et al. (2022)38YYYYYYYYY9
Kale et al. (2004)27YYYYYYYYY9
Kawakami and Takano-Yamamoto (2004)28YYYYYYYYY9
Khalaf and Almudhi (2022)29YYYYYYYYY9
Khalaf and Almudhi (2022)30YYYYYYYYY9
Leszczyszyn et al. (2021)31YYYYNYYYY8
Marañón-Vásquez et al. (2023)39YYYNYYYYY8
Moradinejad et al. (2022)40YYYYYYYYY9
Takano-Yamamoto et al. (1992)32YYYYYYYYY8
Tashkandi et al. (2021)33YYYYYYYYY9
Tehranchi et al. (2017)34YYYNYYYYY8

Q1 = Is it clear in the study what is the ‘cause’ and what is the ‘effect’ (i.e. there is no confusion about which variable comes first)?; Q2 = Were the participants included in any comparisons similar?; Q3 = Were the participants included in any comparisons receiving similar treatment/care, other than the exposure or intervention of interest?; Q4 = Was there a control group?; Q5 = Were there multiple measurements of the outcome both pre and post the intervention/exposure?; Q6 = Was follow up complete and if not, were differences between groups in terms of their follow up adequately described and analyzed?; Q7 = Were the outcomes of participants included in any comparisons measured in the same way?; Q8 = Were outcomes measured in a reliable way?; Q9 = Was appropriate statistical analysis used?.

N, no; Y, yes..


Table 4 . Joanna Briggs Institute Critical Appraisal Checklist for randomized controlled trials.

AuthorsQ1Q2Q3Q4Q5Q6Q7Q8Q9Q10Q11Q12Q13Total score
Al-Attar and Abid (2022)36YYYYYYYYYYYYY13
Varughese et al. (2019)35YYYYYYYYYYYYY13

Q1 = Was true randomization used for assignment of participants to treatment groups?; Q2 = Was allocation to treatment groups concealed?; Q3 = Were treatment groups similar at the baseline?; Q4 = Were participants blind to treatment assignment?; Q5 = Were those delivering treatment blind to treatment assignment?; Q6 = Were outcomes assessors blind to treatment assignment?; Q7 = Were treatment groups treated identically other than the intervention of interest?; Q8 = Was follow up complete and if not, were differences between groups in terms of their follow up adequately described and analyzed?; Q9 = Were participants analyzed in the groups to which they were randomized?; Q10 = Were outcomes measured in the same way for treatment groups?; Q11 = Were outcomes measured in a reliable way?; Q12 = Was appropriate statistical analysis used?; Q13 = Was the trial design appropriate, and any deviations from the standard randomized controlled trial design (individual randomization, parallel groups) accounted for in the conduct and analysis of the trial?.

Y, yes..