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Introduction

Vitamin D3 (cholecalciferol) plays a fundamental role in calcium-phosphate metabolism, skeletal growth and mineralization during childhood and adolescence⁽¹⁾. Over the last decade, there has been growing recognition of its involvement in orofacial development, including tooth eruption, craniofacial bone maturation and the regulation of immune responses in the oral cavity^(2,3). Despite these well-established physiological functions, vitamin D3 deficiency remains a widespread public health problem, affecting up to 50% of children in some populations⁽⁴⁾.

Recent studies have associated insufficient levels of 25-hydroxyvitamin D3 (25-OH cholecalciferol), the major circulating form used to assess status, with an increased risk of dento-maxillary anomalies such as delayed eruption, hypomineralization and malocclusion^(5,6). These alterations may significantly impact both function and esthetics, with long-term consequences on mastication, speech and psychosocial development⁽⁷⁾.

While the orthodontic and surgical management of dento-maxillary anomalies has advanced considerably, the integration of nutritional and metabolic assessments into treatment planning is still limited⁽⁸⁾. Pediatricians, general practitioners and dental professionals often overlook routine screening of vitamin D3 status, resulting in delayed diagnosis and missed opportunities for preventive intervention⁽⁹⁾.

This review aims to synthesize current evidence regarding the epidemiology, pathophysiological mechanisms and potential therapeutic implications of vitamin D3 deficiency in pediatric dento-maxillary anomalies. By highlighting recent findings and emphasizing the need for interdisciplinary collaboration, this article seeks to raise awareness among clinicians and support the development of integrated management protocols⁽¹⁰⁾.

Biological and clinical background

Vitamin D3, also known as cholecalciferol, is a seco­ste­roid hormone synthesized in the skin under ultraviolet B exposure or acquired from dietary sources⁽¹¹⁾ (Figure 1). Once absorbed, it undergoes hepatic hydroxylation to form 25-hydroxyvitamin D3 [25(OH)D3], the main circulating metabolite and the most reliable indicator of vitamin D status⁽¹²⁾. A subsequent hydroxylation step in the kidneys generates the biologically active form, 1,25-dihydroxyvitamin D3, which binds to vitamin D receptors (VDRs) expressed in multiple tissues, including osteoblasts and chondrocytes⁽¹³⁾.

At the craniofacial level, vitamin D3 regulates calcium and phosphate homeostasis, supports mineralization of alveolar bone, and modulates the expression of matrix proteins involved in odontogenesis^(14,15). Animal studies have shown that VDR knockout models develop defective dentin and enamel formation, delayed tooth eruption and impaired mandibular growth⁽¹⁶⁾. Clinical investigations in pediatric populations have demonstrated associations between low serum 25(OH)D3 concentrations and increased prevalence of malocclusion, delayed exfoliation of primary teeth, and greater risk of hypomineralization defects^(17,18).

Beyond skeletal effects, vitamin D3 also exerts immunomodulatory and anti-inflammatory functions in the oral environment, which may influence periodontal status and healing capacity during orthodontic or surgical interventions⁽¹⁹⁾. These multifaceted biological roles provide the rationale for integrating vitamin D3 assessment into the comprehensive management of children with dento-maxillary anomalies⁽²⁰⁾.

Epidemiological data and literature review

Vitamin D3 deficiency is widely prevalent among children and adolescents worldwide. Epidemiological surveys have reported deficiency rates ranging from 30% to over 50% in various populations, depending on geographic location, sun exposure, diet and socioeconomic status^(4,21). In Europe, the prevalence of serum 25(OH)D3 levels below recommended thresholds is estimated to affect approximately 40% of children⁽²²⁾.

Evidence linking vitamin D3 deficiency to dento-maxillary anomalies has progressively accumulated in recent decades. Cross-sectional studies have associated low vitamin D3 concentrations with delayed exfoliation of primary teeth, delayed eruption of permanent teeth and an increased risk of malocclusion^(2,18). A cohort study conducted in Sweden observed that children with inadequate vitamin D3 status during early childhood had significantly higher prevalence of posterior crossbite and class II malocclusion during adolescence⁽²³⁾. Moreover, recent research has suggested that hypovitaminosis D may contribute to defective mineralization of craniofacial bones and enamel hypoplasia, further complicating orthodontic treatment and predisposing to dental caries⁽²⁴⁾.

Despite these findings, awareness of the implications of vitamin D3 deficiency remains low among pediatric practitioners and dental professionals. Screening for vitamin D3 status is rarely included in standard protocols for children presenting with dento-maxillary anomalies⁽¹⁷⁾. This gap underscores the need for integrated preventive approaches and improved interprofessional collaboration.

Diagnostic challenges

Identifying vitamin D3 deficiency in children with dento-maxillary anomalies poses several challenges. Firstly, clinical manifestations such as delayed tooth eruption, malocclusion or enamel hypoplasia are often attributed solely to genetic factors or mechanical influences without consideration of metabolic contributors⁽⁵⁾. Secondly, serum 25(OH)D3 measurement is not routinely recommended in pediatric dental protocols or orthodontic evaluations⁽²⁵⁾.

Pediatricians and general practitioners frequently limit vitamin D3 assessment to cases with overt skeletal deformities or recurrent fractures, overlooking the subtle effects on craniofacial development⁽²⁶⁾. Moreover, lack of standardized screening guidelines and variability in cutoff values further complicate consistent diagnosis⁽²⁷⁾.

A survey of dental practitioners revealed limited awareness regarding the association between hypovitaminosis D and malocclusion risk, highlighting the need for continuing education and updated protocols⁽²⁸⁾. Integrating vitamin D3 status assessment into the diagnostic workflow of children presenting with dento-maxillary anomalies could enable early identification of modifiable risk factors and support a more comprehensive management strategy⁽²⁹⁾.

Therapeutic implications

Addressing vitamin D3 deficiency as part of the therapeutic management of dento-maxillary anomalies offers significant potential benefits. Supplementation with cholecalciferol has been shown to improve bone mineral density, enhance alveolar bone healing and support the stability of orthodontic movements^(30,31) (Figure 2). In children undergoing orthodontic treatment, maintaining adequate vitamin D3 levels may reduce the risk of root resorption and improve treatment outcomes⁽³²⁾.

Moreover, surgical interventions such as alveolar bone grafting or orthognathic procedures may benefit from preoperative correction of hypovitaminosis D to optimize bone regeneration and reduce postoperative complications⁽³³⁾. Recent guidelines recommend individualized dosing based on baseline serum 25(OH)D3 concentrations, age and weight to achieve and maintain sufficient levels⁽³⁴⁾.

Despite these recommendations, there is still limited integration of vitamin D3 assessment and supplementation protocols into routine pediatric dental practice. Collaborative strategies involving pediatricians, orthodontists and maxillofacial surgeons are essential to implement effective prevention and management plans⁽³⁵⁾. Including vitamin D3 optimization as part of an interdisciplinary approach could improve long-term functional and esthetic outcomes in affected children.

Vitamin D3 binds to nuclear receptors in osteoblasts and preosteoclasts, stimulating RANKL expression, which promotes osteoclast differentiation. It also enhances calcium and phosphate absorption, supports matrix protein synthesis and facilitates bone mineralization. These actions improve alveolar bone density, tooth eruption, and stability during orthodontic treatment.

Discussion

The evidence reviewed underscores the multifactorial impact of vitamin D3 deficiency on craniofacial development and dental health. While genetic factors, environmental influences and functional habits remain central in the etiology of dento-maxillary anomalies, the role of metabolic contributors such as hypovitaminosis D has gained increasing recognition⁽⁶⁾. Recent studies have demonstrated that low 25(OH)D3 levels are associated not only with impaired bone mineralization but also with altered tooth eruption patterns and an increased susceptibility to malocclusion^(23,24).

Despite these findings, vitamin D3 assessment remains largely absent from standard diagnostic protocols. Pediatricians and dental professionals often limit their focus to the mechanical and hereditary determinants of malocclusion, missing opportunities for early preventive interventions⁽²⁾. Integrating serum 25(OH)D3 measurement into the evaluation of children with dento-maxillary anomalies could enable targeted supplementation strategies and improve orthodontic and surgical outcomes.

Furthermore, interdisciplinary collaboration is critical. Coordinated care involving pediatricians, orthodontists, maxillofacial surgeons and nutrition specialists can facilitate comprehensive management plans tailored to each patient’s metabolic and structural profile⁽³⁶⁾. Educational initiatives aimed at increasing awareness among healthcare providers may also play a pivotal role in bridging existing gaps.

Future research should focus on longitudinal studies to elucidate causal relationships between vitamin D3 deficiency and specific dento-maxillary patterns, as well as on randomized trials to establish standardized supplementation protocols. In the interim, clinicians are encouraged to consider vitamin D3 status as a modifiable factor in the management of craniofacial anomalies⁽⁸⁾.

Conclusions

Vitamin D3 deficiency represents a potentially modifiable factor in the complex etiology of dento-maxillary anomalies in children. Although genetic and environmental influences remain central to craniofacial development, accumulating evidence underscores the significant impact of vitamin D3 on bone mineralization, tooth eruption and orthodontic stability.

Integrating serum 25(OH)D3 assessment into routine diagnostic workflows can support early detection of deficiency and guide targeted supplementation strategies. Interdisciplinary collaboration among pediatricians, orthodontists and oral surgeons is essential to optimize the therapeutic outcomes and reduce the long-term functional and esthetic consequences.

Future efforts should focus on increasing awareness among healthcare providers and establishing standardized protocols to incorporate vitamin D3 optimization into comprehensive pediatric oral health care.  

Corresponding author: Diana-Monica Preda E-mail: diana_monica_preda@yahoo.com

Conflict of interest: none declared.

Financial support: none declared.

This work is permanently accessible online free of charge and published under the CC-BY licence.