Vitamin D Deficiency and Oral Health: A Comprehensive Review

2.1. Vitamin D Deficiency in Tooth Mineralization and Caries

Teeth are mineralized organs, surrounded by alveolar bone, and formed by three distinctive hard tissues: enamel, dentin, and cementum. The tooth mineralization process occurs parallel to skeletal mineralization, yet if mineral metabolism is disturbed then failures will occur similarly to those that occur in bone tissue. Vitamin D plays a key role in bone and tooth mineralization, and when levels are unregulated it can lead to the “rachitic tooth”, which is a defective and hypomineralized organ highly susceptible to fracture and decay [35,36].

The mechanisms by which VDD affects tooth mineralization are well debated elsewhere [35,36]. The main biological basis relies on the fact that severe VDD (<10 ng/mL) causes hypocalcemia and hypophosphatemia with secondary hyperparathyroidism (driven by hypocalcemia) [37,38]. This hyperparathyroidism promotes intestinal absorption of calcium (Ca²⁺), and renal production of 1 α,25-dihydroxyvitamin D (1,25[OH]2D), increasing bone turnover leading to elevated serum levels of Ca²⁺ and low serum levels of inorganic phosphate (Pi) [37,38]. The initial hypophosphatemia is then severely worsened. Ultimately, the loss of vitamin D signaling pathways in tooth cells with low concentrations of Ca²⁺ and phosphate ions inhibit proper mineralization of teeth and mineralization defects occur [35].

Apart from its mineralization homeostasis role, circulating vitamin D can initiate a signaling pathway through vitamin D receptors (VDR). VDR is a ligand-activated transcription factor that controls gene expression through vitamin D elements (VDRE) [39]. For instance, some of these responsive genes affect bone, mineral metabolism, immune response, cell life cycle and migration, skeletal muscle, detoxification, and energy metabolism [8,39,40,41,42,43]. Vitamin D upregulates VDR which, in turn, can induce structural gene products, including calcium-binding proteins and various extracellular matrix proteins (e.g., enamels, amelogenins, dentin sialoglycoproteins, and dentin phosphoproteins), resulting in the formation of dentin and enamel [35,44].

Beyond the typical VDD causes, nutritional deficiency or reduction of sunlight exposure, there are genetic deficiencies originating from mutations encoding elements of the vitamin D metabolic machinery. The main causes of VDD, second to genetic mutations, are abnormal enzyme secretion (i.e., vitamin D-dependent rickets type 1, VDDR-I) and anomalous VDR function or signaling (vitamin D-dependent rickets type 2, VDDR-IIa; hereditary defects in the vitamin D receptor-effector system, HDVDR) [35]. These genetic conditions cause defective mineralized tissues, despite normal vitamin D consumption or sunlight exposure and, ultimately, will increase the risk of mineralized tooth tissue hypoplasia (i.e., amelogenesis imperfecta, dentinogenesis imperfecta, enamel hypoplasia) or higher risk of caries [35].

Remarkably, deciduous dentition can be influenced by maternal 25(OH)D levels, despite the influence of inherited defects of the fetus [45,46]. Fetal serum-circulating levels of vitamin D follow the maternal concentration and can be used as a standard surrogate marker to the fetus [47]. Therefore, if maternal 25(OH)D levels turn unbalanced, this may have direct repercussions on the baby’s health [48] and, in particular, on tooth development [45,46,49,50,51]. The pattern of mineralization defect depends on the specific week of gestation when maternal VDD occurred. For example, approximately at the 13th week from conception, the human primary maxillary central incisor begins its calcification, and if there is a VDD status, there could be a hypoplasia/mineralization defect on the incisal third of the crown. Nowadays, it is known that maternal VDD at 12–16, 20–32 and 36–40 weeks results in defects at the incisal third, middle third and cervical third, respectively [51]. In a randomized clinical trial (RCT), vitamin D supplementation during pregnancy revealed that pregnant women with < 15 ng/mL of vitamin D had a 14% higher risk of deciduous dentition [51]. In contrast, high-dose vitamin D supplementation during pregnancy was associated with an approximately 50% reduced odds of enamel defects [49,52]. In another RCT, high-dose Vitamin D supplementation during pregnancy was linked to 50% lower risk of enamel defects in the newborn, underlying once more the likely preventive role of Vitamin D for enamel defects [49].

Furthermore, untreated caries in deciduous and permanent teeth were the most prevalent condition, affecting 9% and 35% of global population, respectively [53]. Moreover, according to WHO, caries is the fourth-most expensive chronic disease to treat [54]. This infectious disease has a complex and multifactorial etiology. Environmental factors, such as cariogenic diet with a high carbohydrate content, cariogenic bacteria, and poor oral hygiene were the most widely studied risk factors [55,56,57]. Nevertheless, when exposed to the same environmental risk factors, some patients are more susceptible or resistant to caries than others, so that environmental factors alone are insufficient to explain the prevalence and incidence of caries [58,59,60]. Currently the evidence highlights the association of low levels of vitamin D and the high prevalence of caries in both children and adults, although the mechanism remains unclear [61,62,63,64,65,66,67,68].

Additionally, vitamin D exerts several roles in the control of the human immune system, and an optimal vitamin D concentration (≥75 nmol/L) is associated with lower odds for dental caries in children [29,69,70]. However, the studies’ results are contradictory [45,62,71,72]. A recent systematic review of controlled clinical trials, with data from 2827 children, investigated the impact of vitamin D supplementation on dental caries prevention [28,73]. The results of this study show that vitamin D supplementation reduced the risk of caries in about 47%, but with low certainty [28]. Another research supports that caries-free children were twice as likely to have optimal vitamin D concentrations (≥75 nmol/L) and those with severe early childhood caries were at nearly three times the odds of having deficient levels (<35 nmol/L) [29]. On the one hand, it is important to clarify that serum vitamin D does not change the major structure of teeth since this structure remains constant until some extrinsic factor causes its wear. Notwithstanding, apparently vitamin D prevents caries lesions through immune regulation, promoting microbial eradication with peptide activity as discussed above.

The roles of both UVB and antimicrobial peptides (AMPs) in cariogenic bacteria reduction have been studied [74,75,76,77,78,79,80,81]. The mechanism through which UVB reduces the risk of dental caries is likely to be through the production of vitamin D and followed by the induction of AMPs, which have antimicrobial properties [74,76,77,78,79,80,81]. AMPs are host defense peptides, mostly cationic and amphiphilic molecules, that are essential elements of the innate immunity against several bacteria, fungi and viruses [75,78]. Investigations seem to point to a combination of AMPs rather than a specific role of a single AMP [79], and they have been proposed as potential application for the prevention and treatment of dental caries [80,81]. Remarkably, Streptococcus mutans, a primary etiological agent of dental caries, may resist host salivary AMPs explaining its virulence in dental caries pathophysiology [74,77,80].

Hence, we can conclude that vitamin D control levels prior to conception may be important to reduce the risk of enamel defects in deciduous teeth and should be controlled throughout pregnancy and after delivery.