2. INTRODUCTION
Vitamin D is an Fat-soluble vitamin .It is present in
animals, plants and yeast & has several important
functions in the body.
Technically it should be considerd as Hormone
( Secosteroid ) because -
-It is synthesized by the body(skin) from sunlight
(UV-B ray, wave band-290-315 nm),
-It is transported by blood, activated & then acts on
specific receptors in the target tissue.
-Feedback regulation of Vit D activation occure by
plasma Ca level & by active form of Vit D.
3. HISTORYCAL BACKGROUND
In1919 it was established that Ricket was due to
deficiency of a diatery factor & lack of sunlight.
American researchers Elmer McCollum and
Marguerite Davis in 1922 discovered a substance in
cod liver oil & its struture is determined in1935.
He called it vitamin D because it was the fourth
vitamin to be named.
Sunshine
vitamin
Sunshine
vitamin
4. WHAT IS VITAMIN D
Chemistry: There are two chemical forms of vitamin D,
-Vitamin D2 (Ergocalciferol) and
-Vitamin D3 (Cholecalciferol).
The natural form of vitamin D for animals and man is
vitamin D3; it can be produced in their bodies from
cholesterol and 7-dehydrocholesterol.
An alternative vitamin D2 is commercially prepared
from ergosterol that is present in yeast.
Cholesterol in animals and man is a precursor
substance for all steroid hormones as well as vitamin D3.
The molecular structure of vitamin D is closely allied
to that of the classical steroid hormones,
6. SOURCES OF VITAMIN D
2 sources
- 90% synthesised in skin via UVB light exposure
Cholecalciferol (vitD3 = inactive)
- 10% from food – Ergocalciferol (vit D2= inactive)
Sunshine
vitamin
Sunshine
vitamin
7. DIETARY SOURCES
Fatty fish, like tuna, mackerel, and salmon.
Cod liver oil
Foods fortified with vitamin D, like some dairy
products, orange juice, soy milk, and cereals.
Beef liver.
Cheese.
Egg yolks
8 oz milk = 115 IU
8 oz juice = 100 IU
1 egg = 29 IU
3 oz smoked salmon
= 583 IU
RICHEST SOURCE - FISH LIVER OIL
CHEAPEST SOURCE - SUNLIGHT
8. DAILY REQUIRMENT
Children & adults –400IU(10µg/day)
Pregnancy and lactation – 400IU(10µg/day)
Over 70years- 800IU (20µg/day)
1microgram of vitamin D = 40 International Units
16. Mineralization of
bone at low doses
Mobilization of
calcium from bone at
high doses
Increased
reabsorption of
calcium and
phosphorus
Decreased
excretion of calcium
and phosphorus
Increases the
intestinal absorption
of calcium and
phosphate
by increased
synthesis of calcium
binding protein
(calbinding D28k)
17. PTH EFFECTS
Increases tubular reabsorption of
calcium and stimulates the kidney to
produce 1,25 OH vitamin D3.
Stimulates the activation of osteoclasts,
which dissolve mineralized collagen matrix
in the bone, causing osteopenia and
osteoporosis and increasing the risk of
fracture.
Causes phosphaturia. A low Ca-Phos
product leads to decreased mineralization
of the collagen matrix= rickets in kids and
osteomalacia in adults
19. VITAMIN D DEFICIENCY
VITAMIN D STATUS- 25(OH)D LEVEL (ng / ml)
Normal level of vitamin D - > 30
Vitamin D insufficiency -- 21-29
Vitamin D deficiency -- < 20
Severe deficiency -- <10
Exact cuts-off value for ‘deficiency’ & ‘insufficiency’ remain
controversial.
Researchers concluded that having low levels of vitamin D
(<17.8 ng/mL) was independently associated with an increase in all-
cause mortality in the general population.
20. RISK FACTORS FOR VITAMIN D
DEFICIENCY
Elderly Individuals older than 65 years
Dark skin
No sun exposure
Strict vegan diet
Obesity
Nursing home residents
Patients on medications that
induce P-450 enzyme activity.
Individuals with kidney disease (CRF)
Individuals with low bone mass or osteoporosis
Individuals with nonvertebral or hip fractures
Individuals with a history of falls
21. CAUSES OF VITAMIN D DEFICIENCY
The main reasons for low levels of vitamin D are:
Lack of vitamin D in the diet, often in
conjunction with inadequate sun exposure.
Inability to absorb vitamin D from the
intestines.
Inability to process vitamin D due to kidney
or liver disease.
22. CAUSES OF VITAMIN D DEFICIENCY. CONTD.
Inadequate sun exposure
Sunscreen with SPF 15+ blocks 99% vitamin D synthesis
Pigmented skin
Aging (older than 65 years)
Winter season
Physical agents blocking UVR exposure,clothing, season,
air pollution, cloud cover, latitude & altitude.
Decreased absorption
Bowel bypass surgery
Crohn’s disease
Celiac disease
Fat and cholesterol absorption inhibitors.
23. CAUSES OF VITAMIN D DEFICIENCY. CONTD.
Inability to process vitamin D
Impaired production of 25hydroxy vitamin D3 -
Liver disease
Impaired production of 1,25 dihydroxy vitaminD3 -
Kidney disease,
Hypoparathyroidism,
Oncogenic osteomalacia,
X-linked hypophosphatemic rickets.
24. CAUSES OF VITAMIN D DEFICIENCY. CONTD
Other Causes
Breastfeeding
Medications;
- Steroids decrease half life of vitamin D.
- Barbiturates, Phenytoin, and Rifampin can induce
hepatic p450 enzymes to accelerate the catabolism of
vitamin,
- Ketoconazole impaired 25-hydroxylation.
- Increased degradation of 25 (OH) D -Drugs such as,
Rifampicin, Isoniazid, Phenytoin, Glucocorticoids.
Target organ resistance- Vitamin D receptor
mutation.
25. VITAMIN D DEFICIENCY: INDIAN
SCENARIO
India is a country with abundant sunshine but still a
high prevalence (> 70%) of Vitamin D deficiency has
been documented.
Subclinical Vit D deficiency is very common in India in
all the age groups and both sexes across the country.
Skin complexion, poor sun exposure, vegetarian food
habits and lower intake of vitamin D fortified foods
could be attributed to the high prevalence of VDD in
India
Malabsorption is the commonest cause of Vit.D
deficiency in India
Vitamin D deficiency is likely to play an important role
in the very high prevalence of rickets, osteoporosis,
cardiovascular diseases, diabetes, cancer and infections
such as tuberculosis in India.
28. VITAMIN D DEFICIENCY RELATED
SYSTEMIC DISORDER. CONTD..
6. Musculoskeletal system
Rickets & Osteomalasia
Osteoporesis & fracture
Myopathy
Fibromyalgia
7. Malignancy-
Breaast Ca
Colon Ca
Pancreatic Ca
Ovarian Ca
Prostate Ca
30. RICKETS in Children
OSTEOMALACIA in Adults
Increase the risk of Osteoporosis .
31. Rickets and osteomalacia are disorders of the
mineralization of newly synthesized bone
matrix(osteoid).
In children, defects occur in the growth plate
and in the mineralization of cartilage, leading to
characteristic deformities; ie. Rickets.
In adults, it occurs after epiphyseal closure, &
involves only bone; ie. Osteomalasia.
32. Age incidence- 4m-2y
Clinical Feature:
Symptom-
• Irritability & restlessness
• Rocking of head in pillow & sweating
of forehead
• Delayed dentation & Delayed milestones
Sign-
• Craniotabes - Pot belly
• Frontal bossing - Harrison’s sulcus
• Rickety rosary -Pegion chest
• Bowed legs or Knocked knee
• Delayed closure of ant. frontanelle
33. Radiological changes:
Cupping widening & fraying
of lower end of radius & ulna.
Widening of wrist (soft tissue shadow)
o Biochemical changes
Increased alkaline phosphatase
Hypophosphataemia
Hypocalcimia
Decreased plasma 25(OH)D3 level
o Treatment- 6 lakhs IU of Vit-D3 oraly or im induce
rapid healing within 3-4 wks & then 400IU per day.
35. VITAMIN D RESISTANT
RICKETS
Vitamin D-resistant rickets type I
Autosomal recessive.
Failure of 1,25 vitamin D synthesis due to inactivating mutation
in renal 25(OH)D-1-alpha hydroxylase enzyme.
Clinical features are similar to those of infantile rickets .
Diagnosis is usually first suspected when the patient fails to
respond to vitamin D supplementation.
Biochemical features of type I disease are similar to vitamin D
deficiency, except that levels of 25(OH)D are normal.
Treated with the active vitamin D metabolites, 1,25 (OH)2D3
(calcitriol) with or without calcium supplements. Initial doses
are 0.25–2 μmg/day.
36. VITAMIN D RESISTANT RICKETS. CONTD..
Vitamin D-resistant rickets type II
Autosomal recessive.
Defect in the vitamin D receptor which impair its ability to
activate transcription & impaired response to 1,25(OH)2D3.
Most patients present during infancy although less severely
affected patients may not be diagnosed until adulthood.
Approximately 50–70% of children have alopecia which tends to
be associated with a more severe form of the disease.
Here 25(OH)D is normal but PTH and 1,25(OH)2D3 values
are raised.
It is extremely difficult to treat but some times responds partially
to very high doses of active vitamin D metabolites and calcium
and phosphate supplements.
37. HYPOPHOSPHATAEMIC RICKETS
(X-LINKED DOMINANT)
The disorder is inherited in an X-linked dominant manner.This
means the defective gene is located on the X chromosome.
It is associated with mutations in PHEX, FGF23 & DMPA1 gene.
Only one copy of the defective gene is sufficient to cause the
disorder when inherited from a parent who has the disorder.
Males are normally hemizygous for the X chromosome,having only
one copy. As a result, X-linked dominant disorders usually show
higher expressivity
in males than
females.
38. HYPOPHOSPHATAEMIC RICKETS. CONTD..
Defects in phosphate and pyrophosphate metabolism.
The most apparent abnormality is decreased renal
tubular reabsorption of phosphate.
The diagnosis is made on the basis of the early age
at onset and presence of hypophosphataemia with
renal phosphate wasting in the absence of vitamin D
deficiency.
Treatment is with phosphate supplements (1–4 g
daily) and active metabolites of vitamin D to promote
intestinal calcium and phosphate absorption.
39. Osteomalacia is the softening of the bones caused by
defective bone mineralization secondary to
hypocalcemia , hypophosphatemia & vitamin D
deficiency.
The causes of adult osteomalacia are varied, but
ultimately result in a vitamin D deficiency:
Even in the presence of normal calcium and phosphate
levels, chronic acidosis and drugs such as
bisphosphonates (etidronate ) & phosphate-binding
antacids can lead to osteomalacia.
Demineralization occurs mainly in spine, pelvis &
lower extremities.
40. It manifest with bone pain, severe malaise, proximal
muscle weakness & waddling gait.
Radiological feature -Pseudo fracture- or
Looser’s Zones of decalcification along the
course of major arteries.
Biochemical changes -
Decreased serum calcium or phosphorus.
Decreased serum 25-hydroxyvitamin D .
Increased Serum ALP & PTH.
Treatment - Vit D deficiency corrected by 60000 IU
once weekly for 4-6 wk. followed by once a month.
41.
42. DIAGNOSIS OF VITAMIN D
DEFICIENCY
The key diagnostic test in vitamin D deficiency is
demonstration of a decreased serum 25(OH)D3 value.
Low values of 1,25(OH)2D3 and normal levels of
25(OH)D3 suggest a defect in 1-hydroxylase that may
be genetic or acquired as a result of loss of renal function
or tumor-induced osteomalacia.
High levels of 1,25(OH)2D3 and normal levels of
25(OH)D3 are seen in patients with vitamin D
receptor defects.
43. TREATMENT: VITAMIN D
DEFICIENCY
Treatment of vitamin D deficiency should be directed at
the underlying disorder & severity of the condition.
Vitamin D should always be repleted in conjunction with
calcium supplementation since most of the consequences
of vitamin D deficiency are a result of impaired mineral
ion homeostasis.
In patients in whom 1α-hydroxylation is impaired,
metabolites that do not require this activation step are
the treatment of choice. They include 1,25(OH)2D3
[calcitriol , 0.25–0.5 g/d] and 1α-hydroxyvitamin D2 ( 2.5-
5 g/d).
44. TREATMENT: VITAMIN D DEFICIENCY.
CONTD.
If the pathway required for activation of vitamin D is
intact, severe vitamin D deficiency can be treated with
initially 50,000 IU of Vit D weekly for 3–12 weeks,
followed by maintenance therapy (800 IU daily).
Calcium supplementation should include 1.5–2 g/d of
elemental calcium. Normocalcemia is usually observed
within one week of the institution of therapy, although
increases in PTH and alkaline phosphatase levels may
persist for three to six months.
45. MONITORING OF TREATMENT
The most efficacious methods to monitor treatment of
vitamin D deficiency are serum and urinary calcium
measurements.
In patients who are vitamin D replete and are taking
adequate calcium supplementation, the 24-hour
urinary calcium excretion should be in the range of
100–250 mg/ 24 hours.
Lower levels suggest problems with adherence to the
treatment regimen or with absorption of calcium or
vitamin D supplements.
Levels >250 mg/24 hours predispose to nephrolithiasis
and should lead to a reduction in vitamin D dosage
and/or calcium supplementation.
46. TOXICITY
Side effects of vitamin D are uncommon
unless the 25(OH)D level becomes very
elevated (>100ng/ml or 250 mmol/L) and
the person is taking high dose calcium supplement.
Avoid taking multiple products that contain vitamin D
(eg, multivitamin and vitamin D).
The upper limit of intake has been set at 4000IU/day.
Toxic feature:
Anorexia, nausea , vomiting
Deposition of calcium in soft tissue like kidney, arteries
Kidney stone , Metastatic calcification
o Treatment: stop vitamin D & calcium , low calcium
diet, acidify the urine and steroids.
47. VITAMIN D PREPARATIONS
CALCIFEROL (Vit D2)
Dose- 12,000 to 500,000 IU cap daily.
CHOLECALCIFEROL (Vit. D3)
Dose- 400 to 1000 IU orally/day or 6,00000 IU orally/inj.
every 3-4 wks. Interval.
CALCITRIOL (1,25(OH)2D3).
Dose- 0.25-1ug daily / alternate day orally / inj.
ALFA CALCIDOL (1 alfa (OH)D3 )- Prodrug rapidly
hydrolysed in liver to Calcitriol /1,25(OH)2D3.
Dose-1-2ug/day orally.
DIHYDROTACHYSTEROL- A synthetic analogue of
Vit. D2. Dose- 0.25-0.5 mg/day.
48. PREVENTION OF VITAMIN D
DEFICIENCY
Sensible sun exposure- 5-30 minutes of exposure of arms
and legs between 10 am and 3 pm twice a week is often
adequate.
To prevent vitamin D deficiency, the American Academy
of Pediatrics (AAP) recommends that infants and
children receive at least 400 IU per day from diet and
supplements.
All pregnant & lactating mother should take 400IU
vitamin D supplements daily
Evidence shows that vitamin D supplementation of at
least 700 to 800 IU per day reduces fracture and fall
rates in adults.
Fortification of food with Vitamin D such as milk, butter
chapatiflour, maida, cereals etc.
49. REFFERENCE :
Harrison’s Principles Of Internal Medicine , 18th
ed, chapter 352
Williams Textbook of Endocrinology, 10th ed.
Davidson’s Principles and Practice of Medicine 21st
ed, chapter25
Medical Pharmacology 6th
edition , chapter24
Manual of practical medicine, Alagappan, 5th
ed , chapter 2
Bedside clinics in medicine part I , 6th
ed.
Evaluation, Treatment, and Prevention of Vitamin D Deficiency:-
Journal of Clinical Endocrinology & Metabolism, July 2011,
Vitamin D Status in India – Its Implications and Remedial
Measures http://www.japi.org/january_2009
http://www.uptodate.com/contents/vitamin-d-deficiency-beyond-the-basic
http://emedicine.medscape.com/article/128762-overview
http://www.medicinenet.com/vitamin_d_deficiency/related-conditions/ind
