This document discusses vitamin D, including its role, metabolism, clinical assessment, and relevance to various diseases. It covers how vitamin D is obtained from skin exposure to sunlight and diet, converted to its active form in the liver and kidneys, and acts through vitamin D receptors. Deficiency can cause bone diseases like rickets and osteomalacia or muscle weakness. Low vitamin D may also exacerbate autoimmune diseases and increase cancer and infection risks. Testing for vitamin D levels is important and supplementation can help treat deficiency. Further research is still needed on vitamin D's complex anti-inflammatory and immunoregulatory functions.
2. Objectives :
1. Role and metabolism
2. Receptor regulation
3. Clinical assessment of 25OHD and 1,25 OHD
4. Hypovitaminosis D
5. Vit D defects – Maternal status / Osteomalacia
6. Fractures
7. Relevance of – Immune system /Extra-skeletal /Cancer/DM/CKD
8. In CTD
3. Vit D is a steroid hormone ( Brincat 2015)
VitD3Cholecalciferol
Fortified diary product
Fish oil
Skin 80 %
7 dehydrocholesterol
6. • Stable to measure Vit D status - 25 OHD3 > 1,25 OH2D3
• Low Vit D and Calcium cause - High 1 alpha OH lase
• 1,25 OH2 D3 – tight regulates the system
• FGF23 -
Cause phosphate excretion ( decreased absorption in PCT )
Found in – Kidney / Parathyroid Gland /Choroid Plexus
AD Hypophosphatemic Rickets
XL Hypophosphatemic Rickets
7. • Estrogen + androgen / Estrogen +Progesterone
Stimulate 1,25 OHD3
• Estrogen by itself - Decrease 24,25 OH2D3
• 1 OH lase – Kidney / Maternal decidua / Fetal trophoblast Zehnder 2002
• 1,25 OH D3 – activates innate immunity Liu 2009
cathelecidin , antimicrobial peptide
• 1 alpha hydroxylase and 1,25 OH2D3 – Monocyte and macrophages
expresses them as well
8. Chronic kidney disease :
Decrease in 1 alpha hydroxylase
• Loss in functional renal mass Cheng 2007
• Metabolic Acidosis Lee 1977
• High phosphate level Portale 1984
• High FGF 23 ( High FGF leads to 1 alpha OH lase ) Gutierez 2005
9. Receptor Regulation
VDR – Vit. D receptor ( Cause diverse biologic reaction) Haussler 1998
Receptor -
Zinc finger also found in :
Estrogen / Androgen /Glucocorticoids/Thyroid / Retinoic Acid
N-Terminal ( Zinc finger )
C – Terminal
Unstructured region
10. Vit D is a 9 , 10 seco steroids
It exist in 2 forms
D2
28 carbon molecule
– from plant - Ergosterol
D3
27 carbon molecule
– from cholesterol
11. 25 OH D and 1 , 25 di OH D
25 OH D
CALCIFEDOL
• Half Life 21- 30 days
• Liver
• More amount is found
• Estimation level better
1,25 di OH D3
CALCITRIOL
Half Life 4 – 15 hour s
• Kidney
Less amount in found
• Eventually provides no
information with respect
to nutritional status
12. • Vitamin D deficiency cause-
Muscle weakness/Falls/Non-skeletal morbidities
• Bone effected – Osteomalacia / rickets
• Muscle function – Vitamin D fall by 20 % Bischoff- Ferrai 2004
• Vitamin D is anti-proliferative and pro differentiating effect to
stop from cancer
• Vitamin D also got immunomodulatory effect
13.
14. • Vitamin D enhance monocytic mycobacterial activity
• Vitamin D helps in decreasing cardiovascular abnormality
• Low Vitamin D – exaggerates
Connective tissue disease – Vasculitis
SLE Abou-raya 2013
Primary scleroderma Erten 2015
Inclusion myositis Azali 2013
15. • Vit D is broad immunomodulatory in innate and adaptive system
• In lupus – low Vit D related to aortic stiffness Reynolds 2012
• In lupus – low Vit D leads ti increased carotid plaque Ravenell 2012
• In lupus – low Vit D leads to increased fatigue Lima 2016
• DsDNA decreases after 4 weeks of Cholecalciferol
• In scleroderma
High VitD leads to lower –peripheral neuropathy /lymphoma
Also lowers the skin fibrosis in scleroderma
16. Difference of Osteoporosis and Osteomalacia
Osteoporosis Osteomalacia
• Decrease bone volume • Decrease bone volume
• No mineralisation defect • Excess osteoid accumulation
17.
18. Difference between Rickets and Osteomalacia
Rickets Osteomalacia
• Child and Adolescent • Child and Adult
• Impaired mineralisation of
cartilage
• Excess accumulation of
unmineralised bone matrix
21. In UK
• Face exposure /week – 2hours
• Limbs exposure /week – 30 min
• Dark skin needs more sunlight to absorb
• Birth weight is associated with Vitamin D status ( superior
neuro-cognitive outcome associated with heavier birth
weight)
22. Cause of Vitamin D deficiency
Extrinsic Intrinsic
• Low sunlight
• Sun screen use
• Dark pigmentation of
skin
MALABSORTPTION :
• Gastrectomy
• Small Bowel disease
• Gluten
• Pancreatic Insufficiency
OTHER CAUSES :
• Calcium deficiency with sec.
hyper PTH
• Primary hyper PTH
• Pagets
23. Clinical manifestation of Osteomalacia :
Osteomalcic symptoms
• Bone pain and tenderness
• Muscle weakness
• Difficulty in walking
• Skeletal pseudofractures
Biochemical classic triad :
• Low Ca
• Low PO4
• High Alk Po4
In presence of :
• Low vitamin D
• High PTH
24. Genetic
• VDDR-type 1
Vit D dependant rickets ( 1 alpha hydroxylase deficiency )
• HVDDR
VDR ( Vitamin D receptor ) is defective
25. Vitamin D ( RCT )
Reduces the risk of fall by 19 %
Reduces the risk of hip fracture by 18 %
Reduces the risk of non vertebral fracture by 20 %
Anti fall efficacy of Vit D > 60
Anti fracture efficacy of Vit D > 75
26.
27. Vitamin D
TB
innate response to TLR activation of Myc TB
Increases efficiency of macropahges
MS
Autoimmune encephalomylitis
Type I DM
Vit D protects against DM type I
Crohns
Important role in crohns
28.
29. Source :
• Vit D is the oldest homone Holic 1989
• A phytoplankton in the Sargasso sea ( Atlantic Ocean )
500 million years old – have 1 % of dry weight of Vit D2
( ergosterol)
• Cod liver oil
• Non-oily fish
• Yeast
• Mushrooms
• Fortification – milk / Orange juice
30. • Finsen received a Noble prize in 1903
Exposure to sunlight was effective in treating several skin
disorders like Lupus Vulgaris
( cause of TB infection in the skin ).
• Low level of Vit D leads to 50 % high risk of
Colorectal ,prostate, breast ,pancreatic, oesophageal cancer
Gorham 2007
• Topical 1 , 25 OH2 D3 is used in treatment of the psoriasis
Perez 1996
• High level of Vit D3 leads to low risk of MS
Munger 2006
31. Vit D helps in
• Otitis media Linday 2008
• URTI Ginde 2009
• Influenza infection Cannell 2006
• Downregulates renin productions helps in BP Li 2002
• Stimulates insulin production Mohr 2008
• Inhibit CRP and IL-10 Lee 2008
34. National Osteoporosis Society Guidelines on Vitamin D
No universal consensus in Vit D
Excluded Vit D in childhood / pregnancy / ESRD ( CKD 4-5 )
Conversion factor – 10 mu g Vit D = 400 IU Vit D
Institute of Medicine ( IOM ) vitamin D threshold
25 OH D < 30 nmol is deficient
25 OH D 30 – 50 nmol /L is inadequate
25 OH D > 50 nmol /L for almost in whole population
35. Vit D Calciferol ( D2 or D3 )
D2 Ergocalciferol
D3 Cholecalciferol
25 OHD Calcidiol / Calcifediol
1,25 di OH D Calcitriol
36. Treatment :
• 25OHD - used in measurement Prentice 2008
• 25 OH D has a inverse relationship with PTH
( but also depends on – age /calcium intake /ethnicity /renal
function/magnesium )
• Vit D3 - is the treatment of choice
Rapid treatment
- If too low
- To start bisphosphonates
No rapid treatment
- No loading dose
LOAD ING
300 000 IU for 6 weeks
-
MAINTENANCE
2000 IU daily
MAINTENANCE
800 – 2000 IU daily
37. 2 Major systematic reviews
Dietary intake of Calcium and vitamin D with relationship to
vitamin D and bone health
• Agency of healthcare research and Quality ( AHRQ) ,
University of Ottawa Chung 2009
• TUFTs evidence based practice Centre
Cranney ,2007
38. DOH guidance :
Not to test routinely in
• Pregnant /breast feeding /teenage /young woman
• > 65 years of age
• Cultural reason of non exposure to sun
• Darker skin
39. Future :
Participation of 25 (OH) D and 1,25 (OH)2 D3
in various
• anti-inflammatory
• and immunoregulatory pathway