The document provides a comprehensive overview of vitamin D, focusing on its classification as a hormone, its synthesis, metabolism, regulation, functions, and dietary sources. It details the health implications of deficiency, including diseases like rickets and osteomalacia, as well as the potential effects on periodontal health. The document also discusses how genetic factors can influence vitamin D's impact on bone density and periodontal conditions.

1. VITAMIN D
DR AKRITI
I MDS

2. CONTENTS
• Introduction
• Vitamin D - A Hormone
• Chemistry
• Synthesis, Metabolism
• Storage, Absorption,
Excretion
• Regulation
• Functions
• Dietary sources and RDA
• Diseases associated

3. Vitamin D (also known as CALCIFEROL) is a lipid soluble vitamin
and a polar hydrophobic compound that can be absorbed
efficiently when there is normal fat absorption. It resembles sterols
in structure and functions like a hormone.
Vitamin D first made its appearance in the simplest of plants and
animals, the phytoplankton and zooplankton that rest at the
bottom of the food chain for our ocean creatures. Brine shrimp and
krill contain both ergosterol and 7-dehydrocholesterol, the
precursors for vitamin D2 and vitamin D3, respectively..With UVB
radiation as in sunlight, these forms are converted to vitamin D.
Bikle DD. Vitamin D: an ancient hormone. Experimental dermatology. 2011 Jan;20(1):7-13.

4. VITAMIN D - A HORMONE
• Calcitriol is now considered calciotropic hormone while cholecalciferol is the
prohormone.
• The biologically active form of vitamin D- calcitriol is produced in the kidney.
• Calcitriol has target organs-intestine, bone and kidney, where it specifically acts.
• Only when sunlight is inadequate dietary source is required.
• Its actions are regulated by nuclear receptors that regulate gene expression.
• Calcitriol synthesis is self-regulated by a feedback mechanism i.e., calcitriol
decreases its own synthesis.
Bikle DD. Vitamin D: an ancient hormone. Experimental dermatology. 2011 Jan;20(1):7-13.
Verstuyf A, Carmeliet G, Bouillon R, Mathieu C. Vitamin D: a pleiotropic hormone. Kidney international. 2010
Jul 2;78(2):140-5.

5. CHEMISTRY: Ergocalciferol, Cholecalciferol
Ergocalciferol (vitamin D2) is formed
from ergosterol and is present in plants.
Cholecalciferol (vitamin D3) is found in
animals.
Both the sterols are similar in structure
except that ergocalciferol has an
additional methyl group and a double
bond.
Bikle DD. Vitamin D: an ancient hormone. Experimental dermatology. 2011 Jan;20(1):7-13.

6. CHEMISTRY: Calcitriol
• It is the active form of vitamin D.
• Contains 3 hydroxyl groups ( 1, 3 ,25
) hence called calcitriol.
• Calcitriol binds to vitamin D
receptors (VDR) present in nuclei of
target tissues
Bikle DD. Vitamin D: an ancient hormone. Experimental dermatology. 2011 Jan;20(1):7-13.

7. SYNTHESIS,
METABOLISM

8. SYNTHESIS, METABOLISM
Skin :
7 dehydrocholesterol 🡪 cholecalciferol (D3) (this is a ultravoilet light mediated nonenzymatic
photolysis reaction.)
D3 binds to D binding protein 🡪 intestine 🡪 liver.
Liver :
cholecalciferol 🡪 25-hydroxycholecalciferol (25 hydroxylation reaction occurs in
endoplasmic reticulum)
Kidney:
25OH D3 formed is a weak agonist (it is hydroxylated at C1)
25-hydroxycholecalciferol converts to 1,25 DHCC (by 25-hydroxycholecalciferol 1-hydroxylase)
Site: Mitochondria of the renal proximal convoluted tubule.
Verstuyf A, Carmeliet G, Bouillon R, Mathieu C. Vitamin D: a pleiotropic hormone. Kidney international.
2010 Jul 2;78(2):140-5.
Bikle DD. Vitamin D: an ancient hormone. Experimental dermatology. 2011 Jan;20(1):7-13.

9. ABSORPTION, STORAGE, EXCRETION
● Absorption:
○ Vitamin D is absorbed from small intestine for which bile is essential
● Storage:
○ Stored in adipose tissue
● Excretion
○ Excreted in bile.
○ Metabolized to water soluble metabolites and then excreted in urine
Verstuyf A, Carmeliet G, Bouillon R, Mathieu C. Vitamin D: a pleiotropic hormone. Kidney international.
2010 Jul 2;78(2):140-5.
Bikle DD. Vitamin D: an ancient hormone. Experimental dermatology. 2011 Jan;20(1):7-13.

10. REGULATION
● The concentration of 1,25- DHCC is regulated by plasma levels of calcium
and phosphate
● They control hydroxylation reaction at position 1.
● Low plasma phosphate increases the activity of
25-hydroxycholecalciferol 1- hydroxylase.
● Low plasma calcium enhances the production of parathyroid hormone
which in turn activates 1- hydroxylase.
● Thus the action of phosphate is direct while that of calcium is indirect on
kidney.
Sutton AL, MacDonald PN. Vitamin D: more than a “bone-a-fide” hormone. Molecular endocrinology. 2003
May 1;17(5):777-91.

11. Sutton AL, MacDonald PN. Vitamin D: more than a “bone-a-fide” hormone. Molecular endocrinology. 2003
May 1;17(5):777-91.

12. Action of calcitriol on the
intestine:
Calcitriol increases the intestinal
absorption of calcium and phosphate.
Calcitriol binds with the cytosolic
receptor in the intestinal cells to form
calcitriol receptor complex.The complex
interacts with the specific DNA leading
to synthesis of calcium binding protein.
This will increase the calcium uptake.
FUNCTIONS
DeLuca HF. Overview of general physiologic features and functions of vitamin D. The American journal of
clinical nutrition. 2004 Dec 1;80(6):1689S-96S.

13. Calcitriol action on bone:
The calcitriol stimulates calcium
uptake for deposition as calcium
phosphate thus it is important for
bone formation.
Calcitriol along with parathyroid
hormone increases mobilization of
calcium and phosphate from the
bone, leads to elevation of plasma
calcium and phosphate levels.
FUNCTIONS
DeLuca HF. Overview of general physiologic features and functions of vitamin D. The American journal of
clinical nutrition. 2004 Dec 1;80(6):1689S-96S.

14. Action of calcitriol on kidney:
It minimizes the excretion of calcium
and phosphate in the kidney by
enhancing their reabsorption.
All these actions of calcitriol on
kidney, bone and intestine ultimately
leads to elevation of plasma calcium
concentration.
FUNCTIONS
DeLuca HF. Overview of general physiologic features and functions of vitamin D. The American journal of
clinical nutrition. 2004 Dec 1;80(6):1689S-96S.

15. • Increases intestinal absorption of magnesium and phosphate.
• Insulin secretion.
• Synthesis and secretion of thyroid and parathyroid hormones.
• Inhibition of production of interleukin by activatedT lymphocytes.
• Inhibition of immunoglobulins by activated B lymphocytes.
• Stimulates differentiation of monocyte precursor cell.
• Modulation of cell proliferation.
FUNCTIONS
DeLuca HF. Overview of general physiologic features and functions of vitamin D. The American journal of
clinical nutrition. 2004 Dec 1;80(6):1689S-96S.

16. DIETARY SOURCES
Food sources of vitamin D include fatty fish, fish liver oils, egg yolk etc. Milk is
not a good source of vitamin D.
Vitamin D can be provided to the body in three ways :
1. Exposure of skin to sunlight for synthesis of vitamin D
2. Consumption of natural foods
3. By irradiating foods (like yeast) that contain precursors of vitamin D and
fortification of foods (milk, butter etc.).
Lamberg-Allardt C. Vitamin D in foods and as supplements. Progress in biophysics and molecular biology. 2006
Sep 1;92(1):33-8.

17. RECOMMENDED DIETARY ALLOWANCE

19. DEFICIENCY OF VITAMIN D
• Deficiency of vitamin D is relatively less common as it can be synthesized
by the body, insufficient exposure to sunlight and consumption of diet
lacking vitamin D results in its deficiency.
• Reports from across the world indicate that hypovitaminosis D is
widespread and is re-emerging as a major health problem globally
• Vitamin D deficiency occurs in strict vegetarians, chronic alcoholics,
individuals with Iiver and kidney diseases or fat malabsorption
syndromes. In some people, who cover the entire body (purdah) for
religious customs, vitamin D deficiency is also observed, if the
requirement is not met through diet.
Prentice A. Vitamin D deficiency: a global perspective. Nutrition reviews. 2008 Oct 1;66(suppl_2):S153-64.

20. RICKETS
● Common in children.
● Derived from the German word “wricken” meaning “twisted”
● Lack of phosphate at the growth plate and mineralising bone surfaces
due to inadequate vitamin D supply either from sunlight exposure or diet
remains the principal cause.
● The pathological definition of rickets, the failure to mineralise
newly-formed bone, means that preformed osteoid remains
unmineralised (osteomalacia) and there is a lack of, or reduced,
endochondral calcification at the growth plate, with associated growth
plate deformity.
Elder CJ, Bishop NJ. Rickets. The Lancet. 2014 May 10;383(9929):1665-76
Pettifor JM. Nutritional Rickets. In: Glorieux FH, editor. Pediatric Bone; Biology and Diseases. San Diego:
Academic Press; 2003:541-65.

21. ● Rickets in children is characterized
by bone deformities due to
incomplete mineralization,
resulting in soft and pliable bones
and delay in teeth formation.
● The weight bearing bones are bent
to form bow legs.

22. Dental findings that are often characteristic include dentin defects,
unusually large pulp chambers and enlarged pulp horns, in some cases the
enamel is hypoplastic.These dental problems are more commonly
associated with the primary than the permanent dentition.
The most common intraoral radiologic findings include large pulp chambers,
short roots, poorly defined lamina dura and hypoplastic alveolar ridge.
Shroff DV, McWhorter AG, Seale NS. Evaluation of aggressive pulp therapy in a population of vitamin
D-resistant rickets patients: a follow-up of 4 cases. Pediatr Dent. 2002;24:347–349.
Rabbani A, Rahmani P, Ziaee V, Ghodoosi S. Dental problems in hypophosphatemic rickets, a cross
sectional study. Iran J Pediatr. 2012;22(4):531–534.
Zambrano M, Nikitakis NG, Sanchez-Quevedo MC, Sauk JJ, Sedano H, Rivera H. Oral and dental
manifestations of vitamin D-dependent rickets type I: report of a pediatric case. Oral Surg Oral Med Oral
Pathol Oral Radiol Endod. 2003;95:705–709.

23. Souza AP, Kobayashi TY, LOURENÇO NETO N, Silva SM, Machado MA, Oliveira TM. Dental
manifestations of patient with vitamin D-resistant rickets. Journal of Applied Oral Science. 2013
Nov;21:601-6.

24. OSTEOMALACIA
● Osteomalacia is a generalized bone disorder characterized by
impairment of mineralization, leading to accumulation of unmineralized
matrix or osteoid in the skeleton.
● The classical clinical features of osteomalacia include musculoskeletal
pain, skeletal deformity, muscle weakness and symptomatic
hypocalcaemia.
● Vitamin D deficiency osteomalacia may also occur with malabsorption,
liver disease and anticonvulsant therapy. Less commonly, osteomalacia
may result from abnormal vitamin D metabolism, resistance to the
action of vitamin D, hypophosphataemia or toxic effects on osteoblast
function.
Francis RM, Selby PL. Osteomalacia. Bailliere's clinical endocrinology and metabolism. 1997 Apr 1;11(1):145-63.

26. HYPERVITAMINOSIS D
● Among the vitamins, vitamin D is the most toxic in overdoses (10-100 times
RDA).
● Excessive vitamin D causes marked and prolonged hypercalcemia by
accelerating intestinal calcium absorption and bone resorption.Vitamin D
induced hypercalcemia includes the toxic ingestion of excessive amount of
vitamin D preparations, granulomatous diseases and lymphoproliferative
malignancies.
● In vitamin D toxicity, the clinical courses vary depending on the vitamin D
preparation responsible for the hypercalcemia. Hypercalcemia state
continues for several months when D2 or D3 are responsible for the toxicity
whereas the hypercalcemia would subside in a week when 1 alpha(OH) D3
or 1,25 (OH)2D3 are responsible for the toxicity.
Morita R,Yamamoto I,Takada M, OhnakaY,Yuu I. Hypervitaminosis D. Nihon rinsho. Japanese Journal of Clinical
Medicine. 1993 Apr 1;51(4):984-8.

27. ● Prolonged hypercalcemia is associated with deposition of calcium in
many soft tissues such as kidney and arteries.
● Hypervitaminosis D leads to formation of stones in kidneys (renal
calculi).
● High consumption of vitamin D is associated with loss of appetite,
nausea, increased thirst, loss of weight etc.
● In adults, hypervitaminosis D results in muscle weakness, frequent and
rapid fatigue, functional dyspepsia (indigestion), sub febrile type of
fever, with progressive weight loss, constant headaches without clear
localization, hypertensive crises leading to stroke, development of
various forms of cardiomyopathies accompanied with bradyarrhythmic
disorders of cardiac activity and generalized icterus of the skin and
mucous membranes.
Morita R,Yamamoto I,Takada M, OhnakaY,Yuu I. Hypervitaminosis D. Nihon rinsho. Japanese Journal of Clinical
Medicine. 1993 Apr 1;51(4):984-8.
Roop JK. Hypervitaminosis-an emerging pathological condition. Int J Heal Sci Res. 2018;8:280.

28. VDR POLYMORPHISMS
Vitamin D deficiency induces a decreased bone mineral density at skeletal level including maxilla and
mandible, with an increased alveolar porosity and more rapid alveolar bone re-absorption following
invasion by periodontal pathogens.These evidences may explain a higher susceptibility to
periodontitis of patients showingVDRTT genotype, hypothesizing a more difficult host response to
periodontopathogenic bacteria and to a marked bone loss.
Inagaki et al. demonstrated an association between AA genotype and the highest rates of progression
of alveolar bone loss and tooth loss compared to Aa or aa genotypes.
Naito et al. found that AA genotype correlates with an increased risk of severe chronic periodontitis
among Japanese males.
Martelli FS, Martelli M, Rosati C, Fanti E. Vitamin D: relevance in dental practice. Clin Cases Miner Bone Metab. 2014;11(1):15-19.
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 Feb; 74(2):161-7.
Naito M, Miyaki K, Naito T, Zhang L, Hoshi K, Hara A, Masaki K, Tohyama S, Muramatsu M, Hamajima N, Nakayama T. Association between vitamin D
receptor gene haplotypes and chronic periodontitis among Japanese men.Int J Med Sci. 2007 Aug 22; 4(4):216-22
Sun JL, Meng HX, Cao CF, et al. Relationship between vitamin D receptor gene polymorphism and periodontitis.J Periodontal Res.2002;37(4):263-267

29. VITAMIN D AND PERIODONTAL HEALTH
In a recently published longitudinal study, Garcia et al.reported that calcium and vitamin D
supplementation may reduce the severity of periodontal disease if used at doses higher than
800-1,000 IU daily and supported the rationale for testing the potential beneficial role of vitamin
D on periodontal disease in randomized clinical trials.They also noted that vitamin D, in addition
to its role in bone and calcium homeostasis, acts as an anti-inflammatory agent because it
inhibits immune cell cytokine expression and causes monocyte/ macrophages to secrete
molecules that have a strong antibiotic effect.Indeed, vitamin D deficiency may be linked to
increased risk of infectious diseases.This suggests that vitamin D may be of benefit in the
treatment of periodontitis, not only because of its direct effects on bone metabolism, but also
because it may have antibiotic effects on periodontopathogens and inhibit inflammatory
mediators that contribute to periodontal destruction.
Garcia M, Hildebolt C, Miley D, et al. One-year Effects of Vitamin D and Calcium Supplementation on Chronic Periodontitis. J Periodontol
2011; 82: 25-32.
White JH. Vitamin D Signaling, Infectious Diseases, and Regulation of Innate Immunity. Infect Immun 2008; 76: 3837-3843.
Zittermann A. Vitamin D in Preventive Medicine: Are We Ignoring the Evidence? Br J Nutr 2003; 89: 552-572.
Cochran DL. Inflammation and Bone Loss in Periodontal Disease. J Periodontol 2008; 79(Suppl.8): 1569-1576.

30. VITAMIN D AND PERIODONTAL HEALTH
Jabbar et al., have noted that, like periodontal disease, osteoporosis is a chronic,
multifactorial disease and that the two diseases may share certain risk factors such as genetic
polymorphisms and hormonal and/or dietary deficiencies. Several studies have suggested an
association between systemic bone mineral density/low bone mass/osteoporosis and alveolar
bone density and tooth loss.
Recent studies showed significant associations between periodontal health and intake of
vitamin D and calcium and that dietary supplementation with calcium and vitamin D may
improve periodontal health, increase bone mineral density in the mandible and inhibit
alveolar bone resorption.
Jabbar S, Drury J, Fordham J, Datta H, Francis R, Tuck S. Plasma Vitamin D and Cytokines in Periodontal Disease and Postmenopausal Osteoporosis. J
Periodont Res 2011; 46: 97-104.
Taguchi A, Sanada M, Suei Y. Effect of Estrogen Use on Tooth Retention, Oral Bone Height and Oral Bone Porosity in Japanese Postmenopausal Women.
Menopause 2004; 11: 556-562.
Tezal M, Wactawski-Wende J, Grossi SG, Ho AW, Dunford R, Genco RJ. The Relationship Between Bone Mineral Density and Periodontitis in
Postmenopausal Women. J Periodontol 2000; 71: 1492-1498.
Famili P, Cauley J, Suzuki JB, Weyant R. Longitudinal Study of Periodontal disease and Edentulism with Rates of Bone Loss in Older Women. J Periodontol
2005; 76: 11-15.

31. VITAMIN D AND PERIODONTAL HEALTH
One of the defensins, beta-defensin 2, exhibits antimicrobial activity against oral pathogens,
including bacteria associated with the development of periodontitis (Porphyromonas gingivalis,
Fusobacterium nucleatum, and Aggregatibacter actinomycetemcomitans).
The analysis of observations demonstrated that vitamin D deficiency leads to less effective
outcomes after periodontal surgery (lower soft tissue attachment and changes in probing depth).
In addition to the above, some studies demonstrated that calcium and vitamin D supplementation
(1000 IU/day) had a moderate positive effect on periodontal health and improved clinical
parameters.
Many studies have confirmed that supplementation with vitamin D significantly raised its serum
level, improved such periodontal parameters as attachment loss and probing depth, and reduced
systemic inflammation.
Diachkova E, Trifonova D, Morozova E, Runova G, Ashurko I, Ibadulaeva M, Fadeev V, Tarasenko S. Vitamin D and Its Role in
Oral Diseases Development. Scoping Review. Dentistry Journal. 2021 Nov;9(11):129.

32. VITAMIN D AND IMMUNE RESPONSE
Vitamin D was implicated in the regulation of immune responses following the
discovery ofVDRs on most immune cells including activated CD4+ and CD8+T cells, B
cells, neutrophils and antigen presenting cells such as macrophages and dendritic cells.
In addition, vitamin D enhanced macrophage chemotactic and phagocytic capacity.
Importantly, toll like receptor activation of monocytes and macrophages results in the
up-regulation ofVDR andVDR target genes, with subsequent induction of cathelicidin
antimicrobial peptide (CAMP).
Provvedini DM, Tsoukas CD, Deftos LJ, Manolagas SC. 1,25-dihydroxyvitamin D3 Receptors in Human Leukocytes. Science 1983; 221
1181-1183.
Takahashi K, Nakayama Y, Horiuchi H, et al. Human Neutrophils Express Messenger RNA of Vitamin D Receptor and Respond to
1Alpha,25-dihydroxyvitamin D3. Immunopharmacol Immunotoxicol 2002; 24:335-347.
Xu H, Soruri A, Gieseler RK, Peters JH. 1,25-Dihydroxyvitamin D3 Exerts Opposing Effects to IL-4 on MHC Class-II Antigen
Expression, Accessory Activity, and Phagocytosis of Human Monocytes. Scand J Immunol 1993; 38:535-540.

33. VITAMIN D AND IMMUNE RESPONSE
Vitamin D was also reported to exert pro-differentiation effects on monocytes, stimulating
their acquisition of phenotypic features associated with macrophage.
Vitamin D also inhibited the expression of monocytic inflammatory cytokines including IL-1,
IL-6,TNFα, IL-8, and IL-12.
These findings support the active role of vitamin D in clearing bacterial infections through
augmented production of antimicrobial peptides
Griffin MD, Xing N, Kumar R. Vitamin D and Its Analogs as regulators of Immune Activation and Antigen Presentation. Annu Rev Nutr
2003; 23:117-145.
Almerighi D, Sinistro A, Cavazza A, Ciaprini C, Rocchi G, Bergamini A. 1Alpha,25-dihydroxyvitamin D3 Inhibits CD40L-induced
Pro-inflammatory and Immunomodulatory Activity in Human Monocytes. Cytokine 2009; 45:190-197.
D’Ambrosio D, Cippitelli M, Cocciolo MG, 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; 101:252-262.
Giulietti A, van Etten E, Overbergh L, Stoffels K, Bouillon R, Mathieu C. Monocytes From Type 2 Diabetic Patients Have a
Pro-inflammatory Profile. 1,25-Dihydroxyvitamin D(3) Works as an Anti-inflammatory. Diabetes Res Clin Pract 2007; 77:47-57.

34. VITAMIN D IN ORAL DISEASES
Vitamin D’s regulation of calcium phosphate metabolism and bone remodeling, as well as its
anti-inflammatory and immunomodulatory effects (regulation cell proliferation and
differentiation), can significantly affect the health of the oral cavity.
A number of studies and reviews have demonstrated the association between low vitamin D
levels and the course and frequency of recurrent aphthous stomatitis (RAS), the course and
response to treatment of squamous cell carcinoma in the oral cavity, the severity of
periodontal disease, and the processes of osseointegration and bone remodeling during
dental implantation and guided tissue regeneration.
Diachkova E, Trifonova D, Morozova E, Runova G, Ashurko I, Ibadulaeva M, Fadeev V, Tarasenko S. Vitamin D and Its Role in Oral
Diseases Development. Scoping Review. Dentistry Journal. 2021 Nov;9(11):129.

35. VITAMIN D SUPPLEMENTATION
The bone-centric guidelines recommend a target 25(OH)D concentration of 20 ng/mL (50 nmol/L), and
age-dependent daily vitamin D doses of 400-800 IU.
The guidelines focused on pleiotropic effects of vitamin D recommend a target 25(OH)D concentration of 30
ng/mL (75 nmol/L), and age-, body weight-, disease-status, and ethnicity dependent vitamin D doses
ranging between 400-2,000 IU/day.The wise and balanced choice of the recommendations to follow
depends on one's individual health outcome concerns, age, body weight, latitude of residence, dietary and
cultural habits, making the regional or nationwide guidelines more applicable in clinical practice.
For adults, the 5-μg (200 IU) vitamin D recommended dietary allowance may prevent osteomalacia in the
absence of sunlight, but more is needed to help prevent osteoporosis and secondary hyperparathyroidism.
Other benefits of vitamin D supplementation are implicated epidemiologically: prevention of some cancers,
osteoarthritis progression, multiple sclerosis, and hypertension.
Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. The American journal of clinical nutrition.
1999 May 1;69(5):842-56.
Pludowski P, Holick MF, Grant WB, Konstantynowicz J, Mascarenhas MR, Haq A, Povoroznyuk V, Balatska N, Barbosa AP,
Karonova T, Rudenka E. Vitamin D supplementation guidelines. The Journal of steroid biochemistry and molecular biology.
2018 Jan 1;175:125-35.

36. REFERENCES
1. Harpers illusterated biochemistry 26th
edition by Lange.
2. Textbook of biochemistry Satyanarayan 4th
edition.
3. Bikle DD. Vitamin D: an ancient hormone. Experimental dermatology. 2011 Jan;20(1):7-13.
4. Verstuyf A, Carmeliet G, Bouillon R, Mathieu C. Vitamin D: a pleiotropic hormone. Kidney
international. 2010 Jul 2;78(2):140-5.
5. Sutton AL, MacDonald PN. Vitamin D: more than a “bone-a-fide” hormone. Molecular endocrinology.
2003 May 1;17(5):777-91.
6. DeLuca HF. Overview of general physiologic features and functions of vitamin D. The American
journal of clinical nutrition. 2004 Dec 1;80(6):1689S-96S.
7. Lamberg-Allardt C. Vitamin D in foods and as supplements. Progress in biophysics and molecular
biology. 2006 Sep 1;92(1):33-8.
8. Prentice A. Vitamin D deficiency: a global perspective. Nutrition reviews. 2008 Oct
1;66(suppl_2):S153-64.
9. Elder CJ, Bishop NJ. Rickets. The Lancet. 2014 May 10;383(9929):1665-76
10. Pettifor JM. Nutritional Rickets. In: Glorieux FH, editor. Pediatric Bone; Biology and Diseases. San
Diego: Academic Press; 2003:541-65.

37. 11. Shroff DV, McWhorter AG, Seale NS. Evaluation of aggressive pulp therapy in a population of vitamin
D-resistant rickets patients: a follow-up of 4 cases. Pediatr Dent. 2002;24:347–349.
12. Rabbani A, Rahmani P, Ziaee V, Ghodoosi S. Dental problems in hypophosphatemic rickets, a cross
sectional study. Iran J Pediatr. 2012;22(4):531–534.
13. Zambrano M, Nikitakis NG, Sanchez-Quevedo MC, Sauk JJ, Sedano H, Rivera H. Oral and dental
manifestations of vitamin D-dependent rickets type I: report of a pediatric case. Oral Surg Oral Med
Oral Pathol Oral Radiol Endod. 2003;95:705–709.
14. Souza AP, Kobayashi TY, LOURENÇO NETO N, Silva SM, Machado MA, Oliveira TM. Dental
manifestations of patient with vitamin D-resistant rickets. Journal of Applied Oral Science. 2013
Nov;21:601-6.
15. Francis RM, Selby PL. Osteomalacia. Bailliere's clinical endocrinology and metabolism. 1997 Apr
1;11(1):145-63.
16. Morita R, Yamamoto I, Takada M, Ohnaka Y, Yuu I. Hypervitaminosis D. Nihon rinsho. Japanese
Journal of Clinical Medicine. 1993 Apr 1;51(4):984-8.
17. Roop JK. Hypervitaminosis-an emerging pathological condition. Int J Heal Sci Res. 2018;8:280.
18. Martelli FS, Martelli M, Rosati C, Fanti E. Vitamin D: relevance in dental practice. Clin Cases Miner
Bone Metab. 2014;11(1):15-19.
19. 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 Feb; 74(2):161-7.

38. 20. Naito M, Miyaki K, Naito T, Zhang L, Hoshi K, Hara A, Masaki K, Tohyama S, Muramatsu M,
Hamajima N, Nakayama T. Association between vitamin D receptor gene haplotypes and chronic
periodontitis among Japanese men.Int J Med Sci. 2007 Aug 22; 4(4):216-22
21. Sun JL, Meng HX, Cao CF, et al. Relationship between vitamin D receptor gene polymorphism and
periodontitis.J Periodontal Res.2002;37(4):263-267.
22. Garcia M, Hildebolt C, Miley D, et al. One-year Effects of Vitamin D and Calcium Supplementation on
Chronic Periodontitis. J Periodontol 2011; 82: 25-32.
23. White JH. Vitamin D Signaling, Infectious Diseases, and Regulation of Innate Immunity. Infect Immun
2008; 76: 3837-3843.
24. Zittermann A. Vitamin D in Preventive Medicine: Are We Ignoring the Evidence? Br J Nutr 2003; 89:
552-572.
25. Cochran DL. Inflammation and Bone Loss in Periodontal Disease. J Periodontol 2008; 79(Suppl.8):
1569-1576.
26. Jabbar S, Drury J, Fordham J, Datta H, Francis R, Tuck S. Plasma Vitamin D and Cytokines in
Periodontal Disease and Postmenopausal Osteoporosis. J Periodont Res 2011; 46: 97-104.
27. Taguchi A, Sanada M, Suei Y. Effect of Estrogen Use on Tooth Retention, Oral Bone Height and Oral
Bone Porosity in Japanese Postmenopausal Women. Menopause 2004; 11: 556-562.
28. Tezal M, Wactawski-Wende J, Grossi SG, Ho AW, Dunford R, Genco RJ. The Relationship Between
Bone Mineral Density and Periodontitis in Postmenopausal Women. J Periodontol 2000; 71:
1492-1498.

39. 29. Famili P, Cauley J, Suzuki JB, Weyant R. Longitudinal Study of Periodontal disease and Edentulism
with Rates of Bone Loss in Older Women. J Periodontol 2005; 76: 11-15.
30. Diachkova E, Trifonova D, Morozova E, Runova G, Ashurko I, Ibadulaeva M, Fadeev V, Tarasenko S.
Vitamin D and Its Role in Oral Diseases Development. Scoping Review. Dentistry Journal. 2021
Nov;9(11):129.
31. Provvedini DM, Tsoukas CD, Deftos LJ, Manolagas SC. 1,25-dihydroxyvitamin D3 Receptors in
Human Leukocytes. Science 1983; 221 1181-1183.
32. Takahashi K, Nakayama Y, Horiuchi H, et al. Human Neutrophils Express Messenger RNA of Vitamin
D Receptor and Respond to 1Alpha,25-dihydroxyvitamin D3. Immunopharmacol Immunotoxicol 2002;
24:335-347.
33. Xu H, Soruri A, Gieseler RK, Peters JH. 1,25-Dihydroxyvitamin D3 Exerts Opposing Effects to IL-4 on
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J Immunol 1993; 38:535-540.
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