|Year : 2017 | Volume
| Issue : 2 | Page : 89-95
Reconnoitering the relationship between “The sunshine Vitamin” and periodontal disease
Himani Sharma, Ritika Arora, Mrinalini A Bhatnagar
Department of Periodontology, Subharti Dental College and Hospital, Meerut, Uttar Pradesh, India
|Date of Web Publication||26-Jul-2017|
Department of Periodontology, Subharti Dental College and Hospital, Swami Vivekanand Subharti University, Subharti Puram, NH-58, Delhi Haridwar Bypass Road, Meerut - 250 005, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
According to anthropological records, with a reduction in dietary intake of Vitamin D and reduced sun exposure, the prevalence of Vitamin D deficiency is increasing day by day. About 30%–50% of the general adult population has serum Vitamin D levels below the recommended values. Since its discovery of Vitamin D is always associated with regulation of calcium metabolism. Recently, it has been discovered that Vitamin D plays a role beyond this. Numerous evidences have indicated that the participants with Vitamin D deficiency are at a higher risk of bone loss, but they are also prone to many infectious and chronic inflammatory diseases. Through its effect on bone and mineral metabolism, innate immunity, and several Vitamin D receptor gene polymorphisms, it is now believed that Vitamin D benefits periodontal health and its deficiency is associated with the periodontal disease. This review will examine these actions of Vitamin D, in particular, the role of Vitamin D in periodontal diseases.
Keywords: Bone, periodontitis, Vitamin D receptor, Vitamin D deficiency
|How to cite this article:|
Sharma H, Arora R, Bhatnagar MA. Reconnoitering the relationship between “The sunshine Vitamin” and periodontal disease. J Oral Res Rev 2017;9:89-95
|How to cite this URL:|
Sharma H, Arora R, Bhatnagar MA. Reconnoitering the relationship between “The sunshine Vitamin” and periodontal disease. J Oral Res Rev [serial online] 2017 [cited 2021 Jun 24];9:89-95. Available from: https://www.jorr.org/text.asp?2017/9/2/89/211632
| Introduction|| |
Periodontitis is a chronic multifactorial disease caused primarily by dental plaque microorganisms along with other modifying local and systemic factors. Characterized by periods of exacerbation and remission, periodontitis results in the activation of immune-inflammatory responses against the infection, leading to the destruction of periodontal tissues., It affects approximately 50% of the adult population and is the major cause for adult tooth loss. Furthermore, it is associated with an increased risk of developing cardiovascular disease, Type 2 diabetes mellitus, and respiratory infections, thus making it an important public health problem.,,
Vitamin D refers to a group of fat-soluble secosteroids, which was first discovered in 1919–1924 as an antirachitic agent. It enters in the circulation of human body through diet or synthesized in skin from 7-dehydrocholestrol, by the means of ultraviolet (UV) light of the sun.,
The main function of Vitamin D is to support calcium homeostasis, but it also plays an important role in immunity, the cardiovascular system, diabetes, cancer, and chronic illness. Vitamin D has been found to be associated with bone growth and preservation. With the recent discovery of Vitamin D receptor (VDR) in the inflammatory cells, it has also been seen that the active form of Vitamin D, that is 1,25-dihydroxy Vitamin D (1,25(OH)2D), inhibits the cytokine production and inflammatory cell proliferation, thus playing a crucial role in various chronic inflammatory disease conditions. It affects the periodontal disease both by affecting the bone density and through its immune modulatory effects.,
| Activation and Metabolism of Vitamin D|| |
Vitamin D exists in two major forms, Vitamin D2 or ergocalciferol and Vitamin D3 or cholecalciferol, which are collectively known as calciferol. Chemically, Vitamin D is secosteroids, which means steroids with broken bonds in the steroid rings. The presence of a double bond between C22 and C23 and a methyl group on C24 on the side chain of Vitamin D2 differentiates it from D3 [Figure 1]. Vitamin D2 in humans is obtained from mushrooms, which are an excellent source of ergosterol or provitamin D2 or from yeast, in which it is synthesized through the irradiation of ergosterol by UV light.,, While Vitamin D3 is a product of UV irradiation, which causes the rupture of β ring of the canonical structure of 7-dehydrocholesterol, which is a metabolite in cholesterol synthesis and found in the epidermal layer of human skin or obtained through diet. Before 1967, it was believed that Vitamin D is active directly without any further modification; however, now, it has been proven that Vitamin D obtained from diet or by sunlight must be metabolized, before becoming an active form, [Figure 2].
|Figure 1: (a) Chemical structure of Vitamin D2(Ergocalciferol), (b) Chemical structure of Vitamin D3(Cholecalciferol)|
Click here to view
The formation of this active Vitamin D is strictly controlled mainly by plasma parathyroid hormone (PTH) levels and serum calcium levels.,, Whenever the blood calcium levels are low or there is hypophosphatemia, the stimulation of parathyroid glands to secrete PTH occurs, which causes the increase in the production and transportation of 1,25-(OH)2D through proximal convoluted tubule causing transportation of calcium and phosphorus into small intestine, mobilization of calcium and phosphorus from bone into the blood, and increase absorption of phosphorus and calcium from distal convoluted tubule of kidneys. Certain growth factors such as fibroblast growth factor-23 are also found to play an important role in this regulation process.,
These active molecules, whether produced extrarenally or in kidneys, are a ligand of VDR. These receptors can be highly seen in the cells of intestine, bone, kidneys, and parathyroid gland, which are the target tissues in the regulation of calcium and phosphate homeostasis and bone metabolism. The Vitamin D bound molecules then bind to the retinoic acid X-receptor and serve as a nuclear transcription factor. This causes an alteration in the gene function and induction of protein synthesis which influences the calcium transport and phospholipid metabolism.
| Vitamin D Effects on Periodontal Disease|| |
Recently, various studies have demonstrated that Vitamin D influences the periodontal disease status.,,,,,, Vitamin D has been found to affect bone metabolism by enhancing the calcium and phosphorus absorption and transportation and thus protects the strength of bone. It has anti-inflammatory and immune modulatory activities as well, which can cause suppression of inflammatory processes associated with the periodontal disease. It helps in the production of cathelicidin and other defensins to act against bacterial infection. Furthermore, polymorphism in VDR gene is found to be associated with the development of disease and alveolar bone loss and clinical attachment loss.
| Vitamin D – Bone Metabolism|| |
The interaction between 1,25(OH)2D and VDR causes the regulation of calcium and phosphate levels in the body. Through intestinal absorption, bone resorption, and renal resorption, Vitamin D helps to modulate the skeletal and mineral homeostasis. The decrease in serum Vitamin D levels below 30 ng/ml is seen to be associated with marked decrease in the intestinal absorption of calcium causing a significant increase in PTH which, in turn, increases the tubular reabsorption of calcium.,,,,,,, This causes increase in the production of 1,25-dihydroxyvitamin D and activation of osteoblasts. The activated osteoblasts stimulate the production of receptor activator of nuclear factor kappa B ligand (RANKL) production and binding of RANKL to RANK (expressed on the surface of osteoclast progenitor cells) causes differentiation of mature osteoclasts.
On the other hand, RANKL antagonist that is osteoprotegerin (OPG), acts as a soluble receptor for RANKL, and thus inhibits the maturation of osteoclast precursor cells. Vitamin D has shown to express transient downregulation of OPG, thus causing bone resorption. However, long-term usage of vitamin D causes the recovery of OPG expression. Therefore, the relative ratio of RANKL and OPG along with serum Vitamin D is the determinants of bone remodeling and helps in modulating the skeletal and mineral homeostasis.,,,
| Vitamin D and Anti-Inflammatory Properties|| |
Apart from maintaining the skeletal homeostasis, DeLuca reported about the immune modulatory activities of Vitamin D in its biologically active form, i.e., 1,25(OH)2D. In this form, Vitamin D causes the inhibition of B-cell-mediated antibody production, cytokine production, and T-cell proliferation. It also causes the inhibition of the maturation and differentiation of dendritic cells, thereby maintaining the immature, tolerogenic phenotype by downregulating the expression of Major Histocompatibility Complex Class II molecules, thus lowering its immune stimulating ability. However, anin vitro study reported the activation of monocytes under the influence of Vitamin D. Furthermore, it has shown to upregulate serum cathelicidin levels which is an antimicrobial peptide found in human body at the site constantly exposed to the attack of potential pathogens such as keratinocytes in the epithelial surfaces of the skin, respiratory tract, and gastrointestinal tract.,
| Vitamin D Receptor Polymorphisms and Periodontal Disease|| |
Various studies have demonstrated that 1,25(OH)D3 expresses its activities by the activation of VDR.,,, VDR is expressed widely in immune cells and studies have reported that genetic polymorphisms of VDR gene are associated with periodontitis., Apart from loss of function, VDR polymorphisms are also associated with various diseases including osteoporosis, cancer, diabetes, and periodontal diseases. Therefore, it can be said that 1,25(OH)2D - VDR system plays an important role in maintaining oral health by affecting bone and mineral metabolism and innate immunity.
| Deficiency of Vitamin D|| |
Due to the limitation of the dietary sources of Vitamin D and inconsistent or inadequate uptake of food, the main source of Vitamin D is sunlight. However, the amount of UVB rays from sunlight and its effectiveness is influenced by various factors, which include time, season, latitude, altitude, clothing, sunscreen use, pigmentation, and age. Furthermore, despite regular exposure to sunlight, elderly people produce 75% less cutaneous D3 than young adults. This makes Vitamin D deficiency a more common problem than previously thought. According to various studies, it is estimated that worldwide, approximately 1 billion people suffer Vitamin D deficiency or insufficiency. Furthermore, commonly recommended daily intake of Vitamin D is not sufficient if sunlight exposure is limited. The Vitamin D status is determined by measuring plasma 25(OH)D levels which is the prehormone of Vitamin D3 produced in liver. The plasma 25(OH)D levels >30 ng/mL are considered sufficient, with 40–60 ng/mL being the preferred range. Vitamin D deficiency is defined as plasma 25(OH)D levels below 25 nmol/l, and levels below 12 nmol/l are considered as a state of severe deficiency, which may cause frank osteomalacia and severe proximal myopathy. Most experts suggest that a state of insufficiency arises if the plasma 25(OH)D levels are below 50 nmol/l; however, increasing number of studies suggest that levels above 80 nmol/l are needed to ensure an optimal Vitamin D status.
| Effect of Vitamin D Deficiency on Periodontal Status|| |
Studies have suggested that patients with low serum concentration of 25(OH)D have higher inclination toward chronic inflammatory diseases. The periodontal disease is widely accepted as being a chronic host-mediated response causing periodontal destruction by the release of pro-inflammatory cytokines by local tissues and immune cells in response to the bacteria of dental plaque and their products and metabolites.
Furthermore, it was demonstrated that a strong negative association exists between serum Vitamin D concentration and gingival inflammation, and the prevalence of periodontitis is more in the patient suffering from Vitamin D deficiency. Recent studies reported that Vitamin D deficiency may play an evident role in periodontal disease and loss of teeth among nonpregnant adults.,,, However, this association was also found true with regard to pregnant females. This relationship exists may be because of the anti-inflammatory properties of Vitamin D, inhibiting the expression of inflammatory cytokines and stimulating monocytes/macrophages to secrete molecules with potent antibiotic effects. Vitamin D also plays an important role in bone formation and preservation,, and recently, it was observed that alveolar bone loss due to periodontal disease is more pronounced in osteoporotic bone.
However, in another study, Dietrich et al. did not attenuate the association between serum 25(OH)D concentrations and alveolar bone loss. Joseph et al. reported contrasting results in case of aggressive periodontitis where elevated levels of plasma 25(OH)D were reported.
| Treatment Strategy|| |
The traditional and most cost-effective way of obtaining Vitamin D is through sunlight. A 5–10 min of mid-day, mid-year exposure of arms and legs of a light-colored Caucasian individual can produce up to 3000 IU of Vitamin D3 in the epidermis of human skin, which can increase up to 10,000 IU in case of a whole body exposure. However, nowadays, various factors such as sunscreen, clothing, age, pollution, the zenith angle of the sun, and limited outdoor activity have caused reduction in the exposure to UV radiation.
Therefore, many patients and physicians have this fallacious thought in mind that the deficiency of Vitamin D can be cured by Vitamin D obtained only through diet. However, with fatty fish (100–1000 IU/3.5-oz) as the exception, the Vitamin D content of most of the foods, including fortified dairy products (100 IU/8-oz), is relatively low. Therefore, there arises a need for Vitamin D supplementation.
D2 and D3 forms of Vitamin D are available as dietary supplements containing 300–400 IU/capsule. The treatment of Vitamin D-deficient individuals should start by 50,000 IU of Vitamin D for 8–12 weeks. A single dose of 50,000 IU of D2 or D3 produces a similar increase in the total 25(OH)D concentration. However, D3 is considered more effective than D2 primarily to differences in serum half-life as D3 has a longer half-life; thus, it reduces the frequency of the doses required.,
After completion of the initial repletion phase, patient can be kept on maintenance dose which includes either 50,000 IU Vitamin D2/D3 every 2 weeks or 1000–2000 IU Vitamin D3 daily or the exposure of sunlight UVB rays for 5–10 minutes. According to various studies on an average, every 100 IU of Vitamin D supplementation administered causes a rise in the 25 (OH)D level by 0.5 to 1ng/ml.,
Furthermore, different individuals need different dosage of Vitamin D. The US government recommends 200 IU daily Vitamin D intake for individuals of more than 50 years, 400 IU for individuals between 50 and 7-years, and 600 IU for individuals more than 70 years of age. In addition, the requirement of Vitamin D uptake is more in case of obese individuals or patients suffering from malabsorption. Toxicity due to Vitamin D supplementation has not been observed for doses <10,000 IU/day.
| Vitamin D Supplementation and Periodontitis|| |
Various studies demonstrating the effect of Vitamin D on periodontal disease are conducted time to time. In a study, where the effect of Vitamin D supplementation was studied on tooth loss, it was observed that Vitamin D supplementation per day for 3 years reduced the risk of tooth loss by 60%. However, the major limitation of this investigation was that the study included the supplementation of calcium along with Vitamin D; therefore, the effects of Vitamin D alone could not be studied. Moreover, tooth loss was a secondary outcome in the study, and tooth counts were based on self-reports by participants who completed the study.
In another double-masked placebo-controlled trial, improved periodontal health was seen in the participants who received Vitamin D supplementation than placebos. However, this study also included the supplementation of calcium along with Vitamin D. In addition, no radiographic analysis was done and little information was provided regarding the assessment of periodontal health in this study.
Another study showed similar results to the above studies, in which periodontally healthy postmenopausal women who received calcium and Vitamin D supplementation per day were evaluated for 3 years. A significant improvement in both alveolar bone mass and alveolar crest height was observed. The limitations of this study are that the women were periodontally healthy and there was no control arm, for which women received only placebo.
In another examination where investigators used the National Health and Nutrition Examination Survey (NHANES) III data to examine the association between serum Vitamin D levels and attachment loss found that the participants with lower levels of Vitamin D demonstrated more attachment loss. Thus, they suggested that an inverse relationship exists between Vitamin D status and periodontal disease. However, it was a cross-sectional study and serum levels of Vitamin D were determined at only one point.
Eighty-five postmenopausal women were randomized to receive 400 IU/day of Vitamin D and increased calcium intake to 1000 mg/day. After 2 years, 83% of the women either maintained or gained mandibular bone mass although no significant difference was attributable to calcitriol alone. The major limitations of this study are that 20% of the participants were edentulous and data on periodontal disease status were not given.
In a cohort, in which analysis of periodontal status of the patients on vitamin and calcium supplements periodontal status was done, it was found that compared to participants who did not take Vitamin D and calcium supplementation, supplement takers had shallower probing depths, fewer bleeding sites, lower gingival index values, fewer furcation involvements, less attachment loss, and less alveolar crest height loss.
The analysis of cross-sectional data from the third NHANES III suggested that Vitamin D may reduce the risk of gingival inflammation by exerting anti-inflammatory effects, as it was found that the individuals with the highest 25(OH)D levels experienced 20% less bleeding on probing than those with the lowest levels.
A case–control study found that Vitamin D deficiency was associated with periodontal disease among pregnant women. Furthermore, a study done to evaluate the effect of presurgical Vitamin D status on periodontal surgery outcomes with or without concomitant administration of anabolic doses of a commercially available form of PTH (teriparatide, PTH 1-34) revealed that daily calcium and Vitamin D supplements and postsurgery caused greater resolution of infrabony defects. In addition, Vitamin D deficiency at the time of periodontal surgery negatively affects treatment outcomes for up to 1 year suggesting that Vitamin D status may be critical for postsurgical healing.
However, all of the above investigations had limitations. Most of the studies were observational and checked the effects of both calcium and Vitamin D on periodontal disease. In some studies, dental measurements were secondary outcomes while others did not presented the procedures for randomization, masking, and data collection were not presented. Certain studies lacked data on the cause of tooth loss and/or the periodontal disease status of the patients. There was also a great deal of variation among the studies with regard to the amounts of supplementation and the monitoring of intakes. Therefore, for the evaluation of the effects of Vitamin D on periodontitis, a clinical trial in which randomization and blinding were carefully controlled, and the periodontal disease status of patients known with periodontal disease measures as the primary outcomes, and levels of supplementation/intake optimized to produce maximal effects are required.
| Conclusion|| |
Apart from its activity in the prevention of rickets and osteomalacia, the active form of Vitamin D, 1,25 (OH)2D, has been seen to effect the periodontal status of human beings. This function of Vitamin D is on account of its anti-inflammatory, immune modulatory, and skeletal homeostasis maintaining activities. Various studies have demonstrated that its deficiency or dysfunction related to gene polymorphism may trigger the development of periodontal disease. Therefore, Vitamin D supplementation may cause decrease in the amount of bone destruction and inflammation, thus, can decline the rate of tooth loss due to periodontal diseases in deficient patients. However, furthermore, clinical trials are required to further establish its efficacy.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Tomar N, Gupta C, Kaushik M, Wadhawan A. Nutrigenomics: A perio-nutrition interrelationship. J Oral Rev Res 2017;9:32-6.
Shiva G, Deepa D. Applications of ozone therapy in dentistry. J Oral Rev Res 2016;8:86-91.
D'Aiuto F, Parkar M, Nibali L, Suvan J, Lessem J, Tonetti MS. Periodontal infections cause changes in traditional and novel cardiovascular risk factors: Results from a randomized controlled clinical trial. Am Heart J 2006;151:977-84.
Al-Shammari KF, Al-Ansari JM, Moussa NM, Ben-Nakhi A, Al-Arouj M, Wang HL. Association of periodontal disease severity with diabetes duration and diabetic complications in patients with type 1 diabetes mellitus. J Int Acad Periodontol 2006;8:109-14.
Scannapieco FA. Pneumonia in nonambulatory patients. The role of oral bacteria and oral hygiene. J Am Dent Assoc 2006;137 Suppl: 21S-5S.
Wolf G. The discovery of Vitamin D: The contribution of Adolf Windaus. J Nutr 2004;134:1299-302.
Jones G, Strugnell SA, DeLuca HF. Current understanding of the molecular actions of Vitamin D. Physiol Rev 1998;78:1193-231.
Anand N, Chandrasekaran SC, Rajput NS. Vitamin D and periodontal health: Current concepts. J Indian Soc Periodontol 2013;17:302-8.
] [Full text]
Adams JS, Hewison M. Update in Vitamin D. J Clin Endocrinol Metab 2010;95:471-8.
Walters MR. Newly identified actions of the Vitamin D endocrine system. Endocr Rev 1992;13:719-64.
D'Ambrosio D, Cippitelli M, Cocciolo MG, Mazzeo D, Di Lucia P, Lang R, et al.
Inhibition of IL-12 production by 1,25-dihydroxyvitamin D3. Involvement of NF-kappaB downregulation in transcriptional repression of the p40 gene. J Clin Invest 1998;101:252-62.
Holick MF. Vitamin D deficiency. N
Engl J Med 2007;357:266-81.
Horst RL, Omdahl JA, Reddy S. Rat cytochrome P450C24 (CYP24) does not metabolize 1,25-dihydroxyvitamin D2 to calcitroic acid. J Cell Biochem 2003;88:282-5.
Keegan RJ, Lu Z, Bogusz JM, Williams JE, Holick MF. Photobiology of Vitamin D in mushrooms and its bioavailability in humans. Dermatoendocrinol 2013;5:165-76.
Simon RR, Borzelleca JF, DeLuca HF, Weaver CM. Safety assessment of the post-harvest treatment of button mushrooms (Agaricus bisporus
) using ultraviolet light. Food Chem Toxicol 2013;56:278-89.
Holick MF. Resurrection of Vitamin D deficiency and rickets. J Clin Invest 2006;116:2062-72.
Holick MF, Schnoes HK, DeLuca HF, Suda T, Cousins RJ. Isolation and identification of 1,25-dihydroxycholecalciferol. A metabolite of Vitamin D active in intestine. Biochemistry 1971;10:2799-804.
DeLuca HF. The transformation of a vitamin into a hormone: The Vitamin D story. Harvey Lect 1979-1980;75:333-79.
DeLuca HF, Schnoes HK. Vitamin D: Recent advances. Annu Rev Biochem 1983;52:411-39.
DeLuca HF. The Vitamin D-calcium axis-1983. In: Rubin RP, Weiss GB, Putney JW Jr., editors. Calcium in Biological Systems. New York: Plenum; 1985. p. 491-511.
DeLuca HF. The Vitamin D story: A collaborative effort of basic science and clinical medicine. FASEB J 1988;2:224-36.
Fukumoto S. Physiological regulation and disorders of phosphate metabolism – Pivotal role of fibroblast growth factor 23. Intern Med 2008;47:337-43.
Perwad F, Zhang MY, Tenenhouse HS, Portale AA. Fibroblast growth factor 23 impairs phosphorus and Vitamin D metabolismin vivo
and suppresses 25-hydroxyvitamin D-1alpha-hydroxylase expression in vitro
. Am J Physiol Renal Physiol 2007;293:F1577-83.
Haussler MR, Whitfield GK, Haussler CA, Hsieh JC, Thompson PD, Selznick SH, et al.
The nuclear Vitamin D receptor: Biological and molecular regulatory properties revealed. J Bone Miner Res 1998;13:325-49.
Garcia N, Miley D, Dixon DA. Vitamin D and periodontal disease. In: Watson RR, editor. Handbook of Vitamin D in Human Health: Prevention, Treatment and Toxicity. Wageningen Academic Publishers; 2013. p. 243-53.
Boggess KA, Espinola JA, Moss K, Beck J, Offenbacher S, Camargo CA Jr. Vitamin D status and periodontal disease among pregnant women. J Periodontol 2011;82:195-200.
Dietrich T, Joshipura KJ, Dawson-Hughes B, Bischoff-Ferrari HA. Association between serum concentrations of 25-hydroxyvitamin D3
and periodontal disease in the US population1-3
. Am J Clin Nutr 2004;80:108-13.
Hildebolt CF. Effect of Vitamin D and calcium on periodontitis. J Periodontol 2005;76:1576-87.
Joseph R, Nagrale AV, Joseraj MG, Pradeep Kumar KM, Kaziyarakath JA, Chandini R. Low levels of serum Vitamin D in chronic periodontitis patients with type 2 diabetes mellitus: A hospital-based cross-sectional clinical study. J Indian Soc Periodontol 2015;19:501-6.
] [Full text]
Holick MF, Garabedian M. Vitamin D: Photobiology, metabolism, mechanism of action, and clinical applications. In: Favus MJ, editor. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. 6th
ed. Washington, DC: American Society for Bone and Mineral Research; 2006. p. 129-37.
Bouillon R. Vitamin D: From photosynthesis, metabolism, and action to clinical applications. In: DeGroot LJ, Jameson JL, editors. Endocrinology. Philadelphia: W.B. Saunders; 2001. p. 1009-28.
DeLuca HF. Overview of general physiologic features and functions of Vitamin D. Am J Clin Nutr 2004;80 6 Suppl: 1689S-96S.
Dusso AS, Brown AJ, Slatopolsky E. Vitamin D. Am J Physiol Renal Physiol 2005;289:F8-28.
Thomas MK, Lloyd-Jones DM, Thadhani RI, Shaw AC, Deraska DJ, Kitch BT, et al.
Hypovitaminosis D in medical inpatients. N
Engl J Med 1998;338:777-83.
Chapuy MC, Preziosi P, Maamer M, Arnaud S, Galan P, Hercberg S, et al.
Prevalence of Vitamin D insufficiency in an adult normal population. Osteoporos Int 1997;7:439-43.
Holick MF, Siris ES, Binkley N, Beard MK, Khan A, Katzer JT, et al.
Prevalence of Vitamin D inadequacy among postmenopausal North American women receiving osteoporosis therapy. J Clin Endocrinol Metab 2005;90:3215-24.
Heaney RP, Dowell MS, Hale CA, Bendich A. Calcium absorption varies within the reference range for serum 25-hydroxyvitamin D. J Am Coll Nutr 2003;22:142-6.
de Brito Júnior RB, Scarel-Caminaga RM, Trevilatto PC, de Souza AP, Barros SP. Polymorphisms in the Vitamin D receptor gene are associated with periodontal disease. J Periodontol 2004;75:1090-5.
Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, et al.
Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 1998;93:165-76.
Kitazawa S, Kajimoto K, Kondo T, Kitazawa R. Vitamin D3 supports osteoclastogenesis via functional Vitamin D response element of human RANKL gene promoter. J Cell Biochem 2003;89:771-7.
Kamen DL, Tangpricha V. Vitamin D and molecular actions on the immune system: Modulation of innate and autoimmunity. J Mol Med (Berl) 2010;88:441-50.
Mora JR, Iwata M, von Andrian UH. Vitamin effects on the immune system: Vitamins A and D take centre stage. Nat Rev Immunol 2008;8:685-98.
Dimeloe S, Nanzer A, Ryanna K, Hawrylowicz C. Regulatory T cells, inflammation and the allergic response-The role of glucocorticoids and Vitamin D. J Steroid Biochem Mol Biol 2010;120:86-95.
Wang TT, Nestel FP, Bourdeau V, Nagai Y, Wang Q, Liao J, et al.
Cutting edge: 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. J Immunol 2004;173:2909-12.
Inagaki K, Krall EA, Fleet JC, Garcia RI. Vitamin D receptor alleles, periodontal disease progression, and tooth loss in the VA dental longitudinal study. J Periodontol 2003;74:161-7.
Yoshie H, Kobayashi T, Tai H, Galicia JC. The role of genetic polymorphisms in periodontitis. Periodontol 2000 2007;43:102-32.
Amano Y, Komiyama K, Makishima M. Vitamin D and periodontal disease. J Oral Sci 2009;51:11-20.
Deng H, Liu F, Pan Y, Jin X, Wang H, Cao J. BsmI, TaqI, ApaI, and FokI polymorphisms in the Vitamin D receptor gene and periodontitis: A meta analysis of 15 studies including 1338 cases and 1302 controls. J Clin Nutr 2011;80:108-13.
Glerup H, Mikkelsen K, Poulsen L, Hass E, Overbeck S, Andersen H, et al.
Hypovitaminosis D myopathy without biochemical signs of osteomalacic bone involvement. Calcif Tissue Int 2000;66:419-24.
Singh G, Bonham AJ. A predictive equation to guide Vitamin D replacement dose in patients. J Am Board Fam Med 2014;27:495-509.
Singh G, Drees BM. Normal, healthy, and optimum level of 25-hydroxyvitamin D and required daily intake of Vitamin D. Austin J Nutr Food Sci 2015;3:1060.
Dawson-Hughes B, Harris SS, Krall EA, Dallal GE. Effect of calcium and Vitamin D supplementation on bone density in men and women 65 years of age or older. N
Engl J Med 1997;337:670-6.
Krall EA. The periodontal-systemic connection: Implications for treatment of patients with osteoporosis and periodontal disease. Ann Periodontol 2001;6:209-13.
Dietrich T, Nunn M, Dawson-Hughes B, Bischoff-Ferrari HA. Association between serum concentrations of 25-hydroxyvitamin D and gingival inflammation. Am J Clin Nutr 2005;82:575-80.
Specker BL, Ho ML, Oestreich A, Yin TA, Shui QM, Chen XC, et al.
Prospective study of Vitamin D supplementation and rickets in China. J Pediatr 1992;120:733-9.
Aksnes L, Aarskog D. Plasma concentrations of Vitamin D metabolites in puberty: Effect of sexual maturation and implications for growth. J Clin Endocrinol Metab 1982;55:94-101.
Wactawski-Wende J. Periodontal diseases and osteoporosis: Association and mechanisms. Ann Periodontol 2001;6:197-208.
Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ. Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr 2003;77:204-10.
Chen TC, Chimeh F, Lu Z, Mathieu J, Person KS, Zhang A, et al.
Factors that influence the cutaneous synthesis and dietary sources of Vitamin D. Arch Biochem Biophys 2007;460:213-7.
Bikle DD. Vitamin D and bone. Curr Osteoporos Rep 2012;10:151-9.
Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. Am J Clin Nutr 1999;69:842-56.
Whiting SJ, Calvo MS. Correcting poor Vitamin D status: Do older adults need higher repletion doses of Vitamin D3 than younger adults? Mol Nutr Food Res 2010;54:1077-84.
Krall EA, Wehler C, Garcia RI, Harris SS, Dawson-Hughes B. Calcium and Vitamin D supplements reduce tooth loss in the elderly. Am J Med 2001;111:452-6.
Wical KE, Brussee P. Effects of a calcium and Vitamin D supplement on alveolar ridge resorption in immediate denture patients. J Prosthet Dent 1979;41:4-11.
Civitelli R, Pilgram TK, Dotson M, Muckerman J, Lewandowski N, Armamento-Villareal R, et al.
Alveolar and postcranial bone density in postmenopausal women receiving hormone/estrogen replacement therapy: A randomized, double-blind, placebo-controlled trial. Arch Intern Med 2002;162:1409-15.
Kribbs PJ. Two-year changes in mandibular bone mass in an osteoporotic population. J Prosthet Dent 1992;67:653-5.
Miley DD, Garcia MN, Hildebolt CF, Shannon WD, Couture RA, Anderson Spearie CL, et al.
Cross-sectional study of Vitamin D and calcium supplementation effects on chronic periodontitis. J Periodontol 2009;80:1433-9.
Bashutski JD, Eber RM, Kinney JS, Benavides E, Maitra S, Braun TM, et al.
The impact of Vitamin D status on periodontal surgery outcomes. J Dent Res 2011;90:1007-12.
[Figure 1], [Figure 2]