The Role of Vi tamın D i n Implant Success

Vitamin D is a multifunctional hormone that is mostly produced in the skin following exposure to ultraviolet B sunlight. It coordinates the physiological functions by controlling calcium and phosphate metabolism, promotes growth, and induces necessary remodeling of the bones and teeth. As known high serum vitamin D levels have beneficial effects on oral health and that exposure to safe sunlight can reduce the risk of periodontal disease and thus affect implant success. In order to prove this hypothesis, we conducted a detailed literature review. In the literature review, 3 clinical studies and 2 case reports of implant and vitamin D were found. Although vitamin D is highly correlated with bone metabolism, and expected a very close relationship with implant success, a large number of experimental studies and few clinical studies unfortunately showed contradictory results and no direct studies showing vitamin D and implant success were found. Therefore, it is necessary to demonstrate the existence or absence of this relationship by conducting much broader studies.


Introduction
Vitamin D is a multifunctional hormone that is mostly produced in the skin following exposure to ultraviolet (UV) B sunlight. A negligible amount comes from exogenous sources (foods and supplements). It coordinates the physiological functions by controlling calcium and phosphate metabolism, promotes growth, and induces necessary remodeling of the bones and teeth [1]. The important role of vitamin D in the regulation of musculoskeletal health by maintaining mineral ion homeostasis is elaborated elsewhere [1] [2]. To assess the vitamin D level in the individual, the 25 (OH) D level with a half-life of 2 -3 weeks, indicating both vitamin D intake and endogenous production, should be considered. Many studies have been conducted to identify deficiency of vitamin D and to determine the normal range of 25 (OH) D level. In the light of these studies; Vitamin D deficiency if 25 (OH) D is less than 20 ng/mL, vitamin D insufficiency between 21 and 29 ng/mL, sufficient level if preferred is greater than 30 ng/mL (preferred range is 40 -60 ng/mL) and higher than 150 ng/mL [3] [4].
Vitamin D, on the other hand, stimulates osteoclast differentiation and activity, resulting in increased bone resorption. Furthermore, parathyroid hormone (PTH), and vitamin D can induce skeletal fibroblast growth factor 23 (FGF23) production to regulate serum phosphate levels and can thereby influence bone resorption. FGF23, a member of the FGF19 subfamily of fibroblast growth factors, has been shown to play a key role in balancing mineral ion homeostasis [2] [5]. The effect of vitamin D and calcium supplements in the treatment of Bone Mineral Density (BMD) reduction depends on the regulation of calcium and phosphorus concentration in the blood [6].
Directly or indirectly, the 1,25(OH) 2 D 3 /Vitamin D Receptor (VDR) pathway may influence bone remodeling by mediating differentiation and maturation of osteoblasts and osteoclasts. 1,25(OH) 2 D 3 /VDR pathways in osteoblasts; type I enhances expression of osteogenic genes such as those encoding collagen, alkaline phosphatase, osteocalcin and osteopontin, and accelerates bone formation. In addition, VDR polymorphism has been shown to be associated with an increased risk of chronic periodontitis and other inflammatory conditions in the presence of exogenous etiological factors [7].

The Importance of Vitamin D in Jaws
Mandibular bone is one of the four tissues that make up the periodontium. It is therefore closely associated with osteoporosis and periodontal disease. Low levels of vitamin D and calcium lead to a negative calcium balance, disruption of bone mineralization, and loss of bone structure. Vitamin D deficiency causes rashitzm in children and osteoporosis in adults and increased risk of bone fracture [6]. Alshouibi et al. in a study conducted on 562 patients, they found that total vitamin D intake was associated with improved periodontal health compared to measurements of alveolar bone loss, pocket depth and attachment loss [8]. Syed  Also periodontal health, additional vitamin D and calcium taken can improve peridontal health, increase bone mineral density in mandible and decrease alveolar bone resorption [11]. Systemic increase in cytokines affecting bone resorption in the entire skeletal and jawbone can be seen in people with low BMD. This information shows that vitamin D may be useful in the treatment of peridontitis not only with its effect on bone but also with its anti-inflammatory effect [6].
It is known that there is a correlation between bone loss and intraoral bone and tooth loss, and calcium, vitamin D supplementation and intraoral bone modulation are affected and dental retention is increased to prevent this [10].
To summarize, as known high serum vitamin D levels have beneficial effects on oral health and that exposure to safe sunlight can reduce the risk of periodontal disease and thus affect implant success. In order to prove this hypothesis, we conducted a detailed literature review.

Implant and Vitamin D
Vitamin D deficiency is a risk factor affecting the jaw bones [8]. In a study, the criteria such as periodontal pocket depth, bone level and attachment loss were examined in patients receiving daily vitamin D, and the progression of periodontal diseases was decreased in patients receiving high vitamin D. Calcium intake leads to a similar effect; periodontal, ginjivitis disease decreases with antiinflammatory effect, the success of periodontal surgery increases, decrease of bleeding [10] [12] [13]. There was an association between periodontal health status, BMD and implant success [14].
Uwitonze et al. (2018) reported that, inadequate vitamin D status can compromise osseous healing in the oral cavity and beyond [1]. Sufficient osseous healing is main factor for osseointegration hence implant success. Long-term stable implants are the primary target of dental implantology and implant survival and hence osseointegration are known to be dependent on a number of factors. Current research describing the mechanism of implant failure includes tobacco use, diabetes, bone preparation, and local bone necrosis due to heat generation during implant placement. Failures, especially due to lack of osseointegration, are serious problems and may be related to the patient's systemic health status. Recognition of systemic risk factors has shown that failure rates can be reduced and predictability can be increased [15] [16]. Since osseointegration of dental implants also depends on bone metabolism, there is a possibility that low levels of vitamin D in the blood may adversely affect healing processes and new bone formation on the implant surface [16]. Current case reports have raised the question of the effect of vitamin D deficiency on the survival of the implant during early stage recovery [15].
As known, good bone metabolism is indispensable for successful in bone regeneration procedures in osseointegration of implants [17].
Vitamin D is known to increase osteocalcin, osteopontin, calbindin and 24 hydroxylase levels in bone metabolism, increase extracellular matrix protein for-

Experimental Research on Implant and Vitamin D
In an experimental study, Satué  be included in human studies [28]. Vitamin D deficiency is a common condition in chronic kidney disease (CKD) which adversely affects bone regeneration and fracture healing. In a study by Liu et al., It was aimed to investigate the effect of vitamin D supplementation on implant osseointegration in CKD mice. Uremia was induced by nephrectomy in mice; The animals received 1,25(OH) 2 D 3 intraperitoneally three times a week for four weeks, and titanium implants were placed into the femur two weeks later. Serum measurements confirmed that 1,25(OH) 2 D 3 levels decreased in CKD mice, which was successfully corrected with vitamin D injections. Histomorphometric analyzes showed that the bone implant contact ratio and bone volume around the implant increased significantly in the vitamin D supplementation group [29].
As a result, in order to investigate the relationship between implant osseointegration and vitamin D, implants were applied in animals such as dogs, rats, rabbits and mice carrying diseases associated with vitamin D metabolism such as chronic kidney disease, osteoporosis, diabetes, and the rate of bone and implant contact with vitamin D supplementation and bone stability was observed. Animal experiments have also been performed on topical application of vitamin D, and bone formation is stimulated in cases where implant surfaces are covered with vitamin D, and crestal bone loss is reported to be less. With the positive effects observed in animal experiments in general, it is revealed that further studies are needed for the effect of vitamin D on humans.

Clinical Research on Implant and Vitamin D
In the literature review, 3 clinical studies and 2 case reports of implant and vitamin D were found [15]  ng/mL levels, 16 (3.9%) in patients with levels between 10 and 30 ng/mL and 2 (9%, in patients with levels < 10 ng/mL). The incidence of premature failure almost doubled in patients with inadequate serum vitamin D levels (10 -30 ng/mL) and was even higher in patients with severe vitamin D deficiency (9.0%).
According to the statistical analysis, the incidence of failure in patients with severe vitamin D deficiency increased, but as a result, there was no statistically sig- or nicotine use. Both patients lost their teeth a few years before implant placement, and the first patient (48 years old) underwent a crestal bone graft with autologous material prior to implant placement. 3 months after the graft procedure, 2 implants were applied to the 36 and 37 regions, and the bone graft was completely revascularized and confluent. One day after the operation, the patient was reported to have pain. After 3 days the pain increased and both implants were removed. While the implants were removed, large osteolysis areas surrounding them and debris of the region were seen and wound closure was completed. The second implant surgery was performed 6 months later by placing 2 implants in 36 and 37 regions, and the mandible was well vascularized and no granulation tissue was seen in the resettlement. After 3 days, the two implants had to be removed because of severe pain that persisted without any signs of soft tissue swelling, swelling or abscess. At this point, relevant parameters of bone metabolism were screened and diagnosed as vitamin D deficiency (vitamin D serum level 11 ng/ml). After the vitamin D supplementation and six-month re-Open Journal of Stomatology covery period, a third surgical intervention was planned, with an implant placed in the 36 region at a serum D level of 46 ng/ml. It was observed that the old area completely re-ossified during implant placement. Second stage surgery was successfully completed and prosthetic restoration started [15].
In 2014, Bryce and Macbeth published a 29-year-old patient with an immediate implant. Five months after the operation, no osseointegration of the implant was found. Tests showed that the patient had severe vitamin D deficiency, which may have been a factor in implant failure. The patient was then supplemented with vitamin D until normal levels were reached [18].
In a randomized, double-blind, controlled study in 2016, Schulze-Späte et al.

Conclusion
Growing awareness by dental health care providers for keeping the optimal vitamin D status is necessary for maintaining disease-free oral health is of the vital importance [1]. Although vitamin D is highly correlated with bone metabolism,  [31]. This is probably due to the fact that two of the five published clinical trials on implant and vitamin D were case reports, two were retrospective studies and one was related to sinus augmentation. Therefore, it is necessary to demonstrate the existence or absence of this relationship by conducting much broader studies. That kind of prospective studies should design as long-term and case-control.