5. Contents
History
What is vitamin D
Production and its metabolism
Sources
Functions
RDA
Biomarkers
Laboratory methods for testing vitamin d
Vitamin D deficiency General disorders
Dental considerations
Take home points
References
5
6. History
1600 1st description of rickets by Whistler & Glisson
1918 Sir Edward Mellanby linked with fat-soluble nutrient
1923 Goldblatt & Soames demonstrated exposure to
sunlight or UV light produced a substance with similar properties
1936 Identification of Vitamin D by Windaus
6
7. What is Vitamin D..??
Fat Soluble Vitamin
Known as calciferol
Absorbed through sunlight exposure
Converted to hormone form through liver and
kidney
7
8. Two Major Forms of Vitamin D
Vitamin D2, ergocalciferol
Vitamin D3, cholecalciferol
8
9. Other Forms of Vitamin D
Vitamin D1: molecular compound of
ergocalciferol with lumisterol, 1:1
Vitamin D4: 22-dihydroergocalciferol
Vitamin D5: sitocalciferol (made from 7-
dehydrosisterol)
9
19. What does Vitamin D do?
Maintain normal blood levels of Calcium and
Phosphorus
Aids in absorption of calcium
Promotes bone mineralization
Prevents rickets in children and Osteomalacia in
adults
19
22. Amount of vitamin D in foods…
Egg – 100 gms boiled egg – 871 IU
Sea fish – 100 gms - 759 IU
Mushrooms – 100gms - 446 IU
Cereals (fortified) – 100gms – 333 IU
Butter – 100 gms – 110 IU
Processed cheese(fortified) – 100 gms – 300 IU
Almond milk – 100 ml – 531 IU
Soy milk – 100 ml – 431 IU
Infant formula – 100 ml – 300-350 IU (depending on manufacturer)
22
23. Role in immunomodulation
Binds to nuclear Vitamin D receptors (VDR)
Immune enhancing and immunosuppressive
effects
Increase activity of NKCs
Increased production of cathelicidin
Therepeutic Clinical Applications
23
24. Vitamin D deficiency is epidemic in India despite of
plenty of sunshine.
All Indian studies uniformly point to low 25(OH)
All studies have uniformly documented low dietary
calcium intake compared to Recommended
Daily/Dietary Allowances (RDA) by Indian Council
of Medical Research (ICMR)
The vitamin D status of children is very low in both
urban and rural population studied.
Pregnant women and their new born had low vitamin
D status. The effect of short course of loading doses
of vitamin D doesn’t have a lasting effect and a
maintenance dose is needed
24Vitamin D in INDIA
25. 25
Decreased vitamin D synthesis Skin pigmentation, physical agents
blocking UVR exposure, clothing,
latitude, season, air pollution, cloud
cover, altitude
Decreased nutritional intake of
vitamin
Strict vegan diet
Age and physiology related Elderly, obese and institutionalised
Decreased maternal vitamin D stores Exclusive breast feeding
Malabsorption Celiac disease, pancreatic
insufficiency (cystic fibrosis), biliary
obstruction (biliary atresia)
Decreased synthesis Chronic liver disease
Increased degradation of 25 (OH) D Drugs such as rifampicin, isoniazid,
anticonvulsants, glucocorticoids.
TABLE I Etiology of Vitamin D Deficiency [19]
26. Vitamin D status Levels
US IOM classification [17]
Severe deficiency <5 ng/mL
Deficiency <15 ng/mL
Sufficiency >20 ng/mL
Risk of toxicity >50 ng/mL
US Endocrine Society classification [8]
Deficiency <20 ng/mL (50 nmol/L)
Insufficiency 21-29 ng/mL (52.5–72.5) nmol/liter
Sufficiency >30 ng/mL
Toxicity >150 ng/mL
1mcg = 40IU; 0.025 mcg is 1 IU
26
Vitamin D Status in Relation to 25 (OH) D Levels
27. Biomarkers for Vitamin D Sufficiency
25(OH)D
PTH
Bone mineral density (BMD)
Fracture + falls
Intestinal calcium absorption
Blood pressure
Dental health
Insulin sensitivity
Beta cell function
Immune function
Respiratory disease, wheezing.
27
28. When is it ordered?
25 OH Vitamin D test
1,25 di OH Vitamin D test
28
30. What does the test result
mean?
25 OH Vitamin D test
Low blood levels = not getting enough vitamin d,
problem with absorption from the intestines
High levels = supplementation from vitamin pills
or other nutritional supplements
30
31. Vitamin D Measurements
Interpretation Vit D Level Action
Deficiency < 25 Replace Vit D
Loading dose followed by
maintenance
Insufficient 25-50 Consider replacement if:
• Glucocorticoids
• Osteopenia/osteoporosis
• 2° HPTH
• Hypocalcaemia
• CKD
Maintenance dose
Replete >50 No need for replacement or continue
dose
Toxic >150 Check calcium
Stop treatment
31
36. Osteomalacia
Decalcification and softening of the bone
Caused mainly by: vitamin D deficiency
**Vitamin D is required for the absorption of calcium
from the intestine and calcium is responsible for
mineralization of bone
Etiology
Lack of exposure to sun
GI malabsorption, extensive burns, chronic diarrhea, pregnancy,
drugs such as Dilantin.
36
37. Osteomalacia
Signs & Symptoms
Most Common
Difficulty rising from a chair
Difficulty walking
Additional Signs and Symptoms
Low back pain, muscle weakness
Weight loss, progressive deformities
37
38. Diagnosis
Blood tests
Decreased serum calcium or phosphorus
Decreased serum 25-hydroxyvitamin D
Elevated alkaline phosphatase
X-Rays
Show loose’rs transformation zone –
ribbons of decalcification in bone
38
40. RICKETS
Rickets is consequence of the vitamin D deficit and
may occur due to calcium and phosphorus
metabolic disorders.
Blood analysis shows hypocalcemia and
hypophosphatemia.
Histology- Failure in mineralisation of the bone
and cartilaginous tissues .
Clinical- manifests as skeletal growth disorder.
40
41. History
Rickets ( from Greek word meaning spinal column )
It was described by Soran Efess (A.D) and by Galen
(134-211 A.D).
Described in detail by a British anatomist and
orthopedician, Glisson in 1650.
Incidence:
Rickets is frequently in premature children and the
children fed only wheat floor.
41
42. Biochemical stages of rickets
Stage 1: Low serum Ca level,
normal serum P;
normal serum PTH,
little raise AP Ca and P tubular reabsorption are
normal,
no amino acid loss in the urine.
42
43. Biochemical stages of rickets
Stage 2. Raised PTH in the serum, serum Ca
is normalized by bone demineralization.
Change in the ratio of Ca : P ( N=2:1), in this
stage become 3:1 or 4:1, high serum AP.
Raised Ca tubular re-absorption and decrease
phosphate tubular re-absorption.
As a result => hyper-aminoaciduria.
Phosphates are lost in the urine, Ph alkaline.
X-ray findings: Osteoporosis and meaphis-
epiphesial changes.
43
44. Biochemical stages of rickets
Stage 3. Severe deficiency of vit.D for a long
duration.
Laboratory reports:
Hypocalcemia, hypophosphatemia, serum
elevated of AP, PTH; hyperaminoaciduria,
Radiological changes more expressive.
44
45. CLASSIFICATION
Calcium deficiency rickets can be classified in to 3 grades
Depending on the duration, evolution and the complication:
1. I, evolution acute
2. II, subacute
3. III; recidivant.
45
46. Vitamin-D dependent rickets
type II (VDDRII)
Hereditary 1,25-dihydroxy vitamin D3 resistant
rickets.
Autosomal recessive inheritable disorder,
resulting from a failure of target organs to respond
to hormonal form of vitamin D i.e. 1,25-
dihydroxy vitamin D3 (1,25(OH)2D3)(1).
Characterised by an early onset refractory rickets,
hypocalcemia, hypophosphatemia, growth
retardation, hyper-parathyroidism, and elevated
circulating levels of 1,25- (OH)2D3 and total
scalp and body alopecia
46
47. Vitamin D resistant rickets
Resistance to vitamin D treatment used in deficiency
Signs- observed in first months of life
Radiological signs of defective mineralization on
cartilage growth (rickets) and bones (osteomalacia)
Alterations in phosphocalcic homeostasis inspite of
good vitamin D status
47
48. Hypophosphatemic resistant
rickets
Severe hypophosphatemia
Absence of radiological or biological signs of
secondary hyperthyroidism
Caused mainly due to alteration in x linked gene
Treatment with phosphates and derivates of
vitamin D prevents bone deformities
48
49. International journal of pediatric dentistry
Dental co-relations with hypophosphatemic resistant
rickets
Volume 8, Issue 1, pages 19–28, March 1998
49
50. Objective. To review a series of cases of hypophosphataemic vitamin D
resistant rickets.
Subjects included: Seventeen cases, aged between 2 years 1 month and 15 years 9
months at first referral, and with an established diagnosis of vitamin D resistant
rickets from twelve families were included in the review. Information was drawn
from patient records for follow-up periods between 9 months and 20 years 4
months.
Setting. All subjects had been referred to the Eastman Dental Hospital between
1973 and 1997.
Findings. Abscessed non-carious primary and/or permanent teeth were a presenting
feature in eleven of the seventeen cases. Although attrition and exposure of the
abnormally formed dentine accounted for the route of infection in primary teeth, the
route for microbial invasion of pulpal tissues in permanent teeth remained
unexplained in a number of patients. The possible part played by infractures of the
enamel as a portal of entry for infection is discussed. Enamel defects were observed
in only six patients, in three of whom these changes were limited to the primary
dentition. Taurodontism of permanent molar teeth was confirmed as a feature of the
condition in the more severely affected male subjects.
50
51. Pseudo deficiency rickets
Severe hypocalcemia with secondary
hypothyroidism
Charecterized by – Bone deformities, muscular
hypotonia, enamel hypoplasia.
Mode of inheritance is autosomal recessive.
51
53. CLINICAL MANIFESTATIONS
Rickets may develop in any age of an infant, more frequent at
3-6mo, early in prematures.
The first signs of hypocalcaemia are CNS changes-
excitation, restlessness, excessive sweated during sleep and
feeding, tremors of the chin and extremities.
Skin and muscle changes- pallor, occipital alopecia, fragile
nails and hair, muscular hypotony,motor retardation.
Complications- apnoea, stridor, low calcium level with
neuromuscular irritability (tetany).
53
54. ACUTE SIGNS
Craniotabes – acute sign of rickets,
Osteolyses detected by pressing firmly over the
occipital or posterior parietal bones, ping-pong
ball sensation will be felt.
Large anterior fontanellae with hyperflexible
borders,
Cranial deformation with asymmetric occipital
flattening.
54
55. SUBACUTE SIGNS
Subacute signs are all the following: frontal and temporal
bossing
False closure of sutures (increase protein matrix), in the X-ray
craniostenosis is absent.
Maxilla in the form of trapezium, abnormal dentition.
Late dental evolution, enamel defects in the temporary and
permanent dentition.
Enlargement of costo-chondral junctions-“rickets rosary”
Thorax, sternum deformation, softened lower rib cage at the site
of attachment of the diaphragm- Harrison groove.
55
56. Knowing how rickets affects
teeth
Rickets, a condition resulting from inadequate mineralization of all the bones,
can have a negative effect at every stage of the development of teeth. The
primary effects of rickets include the following:
Delayed formation: The baby teeth may not erupt until after one year. When
they erupt, they may be smaller than normal.
Periodontal disease: Calcitriol helps regulate the immune system and protect
against inflammation so some have suggested that low vitamin D status
increases periodontal disease by increasing gingivitis. Regardless of the
cause, when the teeth become loose in the mouth they may fall out.
Dental caries: Because the teeth don’t mineralize sufficiently in rickets
caused by low vitamin D status, this may increase a person’s chances of
getting cavities. In the absence of vitamin D, infection is established on the
tooth, leading to further loss of enamel and cavitation.
56
57. Radiological findings
Only in difficult diagnostic cases.
1. X-ray of the distal ulna and radius: concave (cupping)
ends; normally sharply,
2. Fraying rachitic metaphyses and a widened epiphyseal
plate.
3. Osteoporosis of clavicle, costal bones, humerus.
4. Greenstick fractures.
5. Thinning of the cortex, diaphysis and the cranial bones.
57
60. PROPHYLAXIS IN RICKETS
WHO recommendation for rickets
prophylaxis in a children coming from
unfavorable conditions and who have
difficult access to hospitals is 2 lac IU
vitamin D2 i/m
On the 7th day, 2nd , 4th , 6th month- total
dose 8 lac IU.
In case of the necessary prolongation
700IU/day till 24mo are given.
60
61. SPECIFIC TREATMENT IN RICKETS
The treatment is with vitamin D3 depending on
the grade.
In grade I- 2000-4000IU/day for 4-6weeks, totally
120000-180000IU.
In grade II- 4000-6000IU/day for 4-6 weeks,
totally 180000-230000IU.
In grade III- 8000-12000IU/day for 6-8 weeks,
totally 400000-700000IU.
61
62. Osteoporosis
* Normal mineralization
* Decrease bone mass
(amount of bone per unit volume)
* Age related
* Associated or manifestation of other conditions
62
68. 68Vitamin D and the Heart
Low levels of vitamin D associated with increased
risk of cardiovascular disease and mortality.
One study: Low vitamin D risk increase of
Coronary Artery Disease - 45%
Stroke - 78%
Heart attack - 50%
25-57% adults may be deficient
69. 69
Vitamin D and Critical Illness
For critically ill patients in the hospital, low vitamin D
levels have been found to be related to
Organ malfunction
Length of stay
Infection rates
70. 70Vitamin D and MS
Multiple Sclerosis: Vitamin D levels of 40 ng/ml or higher
may confer some protection against MS.
Patients receiving Magnesium, Calcium and 5000 IU
vitamin D significantly reduced MS exacerbations (14 vs
32).
71. 71Vitamin D and Cancer
Inverse correlation between incidence, mortality and or
survival rates for many cancers including breast,
colorectal, ovarian, and prostate cancers.
Emerging evidence that more than 17 cancers are
likely to be vitamin D sensitive.
1000 IU/day could reduce cancers 7% for men, 9% for
women in US.
25(OH)D level of 52 ng/ml reduced breast cancer by
50%
25(OH)D level increase from 29 to 39 reduced cancer
risk by 60% after 4 years.
72. 72Vitamin D and the Lungs
Lower respiratory tract infections are more
frequent in those with low 25(OH)D levels.
2000 IU Vitamin D abolished the seasonality of
influenza and dramatically reduced the self-
reported incidence.
Vitamin D reduces inflammation and viral
pathogens.
73. 73Vitamin D and the Lungs
One Vitamin D Influenza study showed:
334 children 6-15 years
50% -1200 D3 4 months vs placebo
Flu: 10.8% (with D) vs 18.6%
Asthma children – 93% reduced attacks
Low vitamin D adults: double risk of viral infections
74. 74Vitamin D and Dementia
Vitamin D may be primarily associated with cognitive
domains other than memory , such as executive cognitive
functions, depression, bipolar disorders, and schizophrenia.
Low 25(OH)D may be a risk factor for cognitive impairment
(41-60%).
Receptors for Vitamin D are present in brain cells.
Increased Vitamin D may improve cognitive function in
patients with Alzheimer's
75. Vitamin D and Obesity
Seasons
Altitude
Calcium
Link between other
diseases
Treatable
75
76. Vitamin D and Diabetes
Low serum levels at greater risk
Lack of Vitamin D interferes with insulin secretion
76
77. Vitamin D and depression
SAD (seasonal affective disorder)
130 patients
600 or 4,000 IU supplements
Re-evaluated 1 year later
77
78. 78Vitamin D Controls Genes
Gene direct or indirect control by vitamin D
Regulate cell growth and prevent malignancy
Enhance immune system (multiple mechanisms)
Improve insulin production and sensitivity
Heart contraction
Maximize bone health
80. Vitamin D and periodontal
disease
People with lower vitamin D levels had more
attachment loss than people with higher vitamin D
levels.
African-Americans had a greater risk of PD than
white Americans. African-Americans had average
vitamin D blood levels of about 16 ng/mL (40
nmol/L) compared to 26 ng/mL (65 nmol/L) for
white Americans.
Pregnant women with PD had lower vitamin D
levels and were twice as likely to have vitamin D
insufficiency.
80
81. What is the link between
vitamin D and dental caries?
Enamel is the most mineralized substance in the
human body. It is made up of mostly calcium and
phosphate.
Vitamin D is important for increasing the
absorption of calcium and phosphate
Increasing the absorption of calcium and
phosphate can improve the strength of teeth and
their ability to fight demineralization from
bacteria.
81
82. Vitamin D receptors are found on cells in immune
system and teeth. Vitamin D can bind to these
receptors and increase the amount of antimicrobial
proteins in your body which help to fight the
bacteria that cause dental caries.
In addition, the cells in the teeth that form dentin
and enamel contain vitamin D receptors, meaning
that vitamin D may play a role in their
functioning.
82
83. 83
• Mothers of children with ECC have lower vitamin D
levels during pregnancy than mothers whose children
don’t have caries.
• Children with ECC tend to have lower vitamin D levels
than healthy children.
. Children with ECC tend to have lower vitamin D
levels than healthy children
ECC AND VITAMIN D
85. Should children and adolescents be
supplemented with Vitamin D?
200 IU, 400 IU, 600 IU or 1000 IU daily?
Vitamin D2 or D3?
85
Pediatrics 122:1142, 2008
87. Group
Daily regimen
(8-12 weeks)
Weekly regimen
(8-12 weeks)
Stoss therapy (oral or IM)
Maintenance
< 1 mo old 1,000 IU 50,000 IU - 400-1,000 IU
1-12 mo old 1,000-5000 IU 50,000 IU
1 lakh -6 lakhs units over 1-5
days
400- 1,000 IU
(Preferably 3 lakh)
1-18 y old 5,000 IU 50,000 IU 3-6 lakh units over 1-5 days 600-1,000 IU
>18 y old 6,000 IU 50,000 IU 3-6 lakh units over 1-5 days 1,500-2,000 IU
Obese patients, patients 6,000-10,000 3,000-6,000 IU
with malabsorption IU/ day
syndrome, or on
medications affecting
vitamin D
* To convert (IU) to mcg of calciferol divide by 40.
87Treatment Regimens for Vitamin D Deficiency
88. What can we do?
Rule out systemic disease, endocrinopathy
bone loss
Amenorrhea in young woman be concerned!
Consider BMD measurement in at risk patients
and ones with strong family history
• Recall role of genetics in BMD determination
Encourage:
• Good nutrition, with adequate calcium and vitamin D
88
90. Deficiency (<25 nmol/l or 10 mcg/l)
Oral Therapy
1st line agent:
Fultium-D3 (Cholecalciferol) 800 iu capsules x4/d (licensed product)
- 3200 iu daily for 8-12 weeks.
2nd line:
Dekristol (Cholecalciferol) capsules 20,000 units. Prescribe 1 capsule
(20,000 units) once per week for 8-12 weeks.
Where oral therapy not appropriate (e.g. malabsorption states)
Ergocalciferol 300,000 (or 600,000) iu single dose by
intramuscular injection. The injection is gelatin free and may be
preferred for some populations.
90
91. Insufficiency (25-50 nmol/l or 10-20 mcg/l) or for long-term
maintenance following rx of deficiency
1st line therapy
Fultium-D3 800iu capsules x2/d (licensed) - 1600iu per day (a dose between
1000 – 2000 units daily is appropriate).
2nd line:
Dekristol capsules 20 000 units [unlicensed import]. Prescribe 1 capsule
(20,000 units) once per fortnight.
Alternatively where oral therapy not appropriate
Ergocalciferol 300,000 international units single dose by intramuscular injection
once or twice a YEAR.
91
92. Combined calcium & vitamin
D supplements
Calcium component usually unnecessary in
primary vitamin D deficiency
Dual replacement required where there is severe
deficiency accompanied by hypocalcaemia
leading to secondary hyperparathyroidism
Appropriate for the management of osteoporosis
and in the frail elderly.
92
93. Alfacalcidol/Calcitriol
Alfacalcidol (1 alpha- vitamin D) and Calcitriol
have no routine place in the management of
primary vitamin D deficiency
Reserved for use in renal disease, liver disease and
hypoparathyroidism.
93
94. Monitoring
1 month
Bone and renal profile
3 months
Bone and renal profile, vitamin D, and plasma
parathyroid hormone.
Once vitamin D replacement is optimised no
further measurement of vitamin D is necessary.
94
95. Nutritional Strategies to
Improve Vitamin D Status
Effective strategies in infants (current recs)
200 IU vitamin D/day
1/2 dose tri-vitamin (ADC) prep
500 ml of fortified infant formula
5 mcg calcitriol
Recent strategies (experimental)
Supplementing the pregnant mother
Supplementing the nursing mother
Single high dose therapy
95
97. Maternal Vitamin D Supplementation
During Pregnancy
IOM (2001) determines
AI as 200 IU/day
UL as 2,000 IU/day
FNB data: 50% women of reproductive age have
low vitamin D level
Infants born to Vitamin D deficient mothers have
lower vitamin D stores
97
98. Does Supplementation
During Pregnancy Work?
Supplementation of pregnant women
Improves neonatal calcium handling
Improves 9 year bone status
Improves maternal vit D levels if she was
deficient
Does not alter already sufficient maternal D
status
98
99. Who may need extra vitamin D to
prevent a deficiency?
Older age people (greater than age 50)
individuals with limited sun exposure
occupations that prevent exposure to sunlight
reduced ability to absorb dietary fat
exclusively breast-fed infants
99
100. Who is at risk to overdose on
Vitamin D?
Anyone who takes Vitamin D supplements CAN take too
much Vitamin D. But the majority of documented
overdose on vitamin D are from:
• Children whose parents accidentally give them massive
doses of vitamin D
• Elderly people who incorrectly take massive vitamin D
dosages
• Adults who take more than 10,000 IU's per day for long
periods of time.
• 'Industrial Accidents' where massive quantities of vitamin D
are put into fortified foods in error
These categories comprise nearly all people who have had
an overdose on Vitamin D.
10
0
101. What is the health risk of too much
vitamin D?
nausea
vomiting
poor appetite
constipation
weakness
weight loss
101
102. Take Home Points
Vitamin D deficiency is common
25 OH vitamin D is a predictor of bone health in terms of fracture risk
and risk of falls
25 OH vitamin D is also potentially an independent predictor of risk
of cardiovascular disease, hypertension, cancer, diabetes, all cause
mortality, and URI
At least 600 IU of vitamin D3 per day is needed to maintain vitamin
D sufficiency
Sensible sun exposure is a great way to maintain vitamin D
sufficiency
102
103. References
LEHNINGER – principles of biochemistry (3rd edition)
Biochemistry – BERG, TYMOCZK, STRYER (5TH edition)
Practical biochemistry- WILSON AND WALKER
SHAFER’S TEXTBOOK OF ORAL PATHOLOGY- (7TH edition)
NELSON’S BOOK OF PEDIATRICS
Dentistry for child and adolescents (McDONALD AND AVERY)- 8th
edition
FINN- clinical pedodontics (4th edition)
Pediatric dentistry- CASAMASSIMO,NOWAK- (5th edition)
SCULLY- oral and maxillofacial medicine (3rd edition)
TYLDESLY’S oral medicine- FIELD AND LONGMAN (5th edition)
BURKETTS ORAL MEDICINE (11th edition)
103
104. Previous questions on this
topic:
How is vitamin D formed and activated in the body? How does it regulate body
calcium levels? Write a note on hypo and hypervitaminosis D in growing child?
(April 2015)
Role of vitamins in oral health (October 2012)
Vitamin D and calcium haemostasis (April 2011)
1,25 dihydroxy cholecalciferol (1989)
Role of vitamin D (1981)
Write a short notes on vitamin D (1980)
Describe in brief about calcium metabolism (June 1977)
Describe the process of calcification in body and the role of vitamin D (June 1977)
Concept of bone resorption and calcium phosphorous blood levels in rickets
(October 1966)
104
