Presented By: Lee Kian Choy

Presented by: LEE KIAN CHOY

Introduction: 1865 : Trousseau recommends cod liver oil and

sunlight as treatment for rickets. He also recognises and identifies osteomalacia as the adult form of rickets.  1919: Sir Edward Mellanby proposes that rickets is due to the absence of a fat-soluble dietary factor. 1925 McCollum and co-workers discovered vitamin D. Hess and Weinstock show that vitamin D activity is produced in the skin by ultraviolet irradiation. 1936 Windaus identifies the structure of vitamin D in cod liver oil.

Vitamin D deficiency (Ricket)

Consequences of Vit-D deficiency  In Children 1. Causes poor mineralization of the collagen matrix in

young children’s bones leading to growth retardation and bone deformities (refer to picture)  In Adults 1. Induces secondary hyperparathyroidism, which causes a loss of matrix and minerals, thus increasing the risk of osteoporosis and fractures 2. Poor mineralization can lead to painful osteomalacia 3. Causes muscle weakness

Consequences continue;  According to Holick, M.F 2005, some scientific

research showed a link between vitamin D deficiency and certain diseases; a)Diabetes b)Multiple sclerosis c) Rheumatoid arthritis d)Hypertension e)Cardiovascular disease f) Colon, breast, pancreas, prostate and ovary cancers

General facts: Vitamin D encompasses 2 molecule; ergocalciferol (D2) &

cholecalciferol (D3)

Fat soluble vitamin where it needs the presence of bile and fats in

the GUT to be absorbed by the body.

Supplements containing vitamin D3 (cholecalciferol) are obtained

from animal sources (usually as a by-product of wool fat).

Vitamin D2 (ergocalciferol) is obtained from food supplements.

Causes of Vit-D deficiency: Homebound elderly Women in veil Strict vegan Severe renal impairment (unable to convert to its active

form)

GUT problem (eg: coeliac disease, Crohn’s disease, short

bowel syndrome)

Classification of Vit-D deficiency: Mild vitamin D deficiency: Serum 25-OHD levels in the

range 25–50 nmol/L, mild deficiency leads to increased parathyroid hormone secretion and high bone turnover Moderate vitamin D deficiency: Serum 25-OHD levels of

12.5–25 nmol/L, moderate deficiency has been associated with reduced bone density, high bone turnover and increased risk of hip fracture in older people Severe vitamin D deficiency: Serum 25-OHD levels of <

12.5 nmol/L, resulting in osteomalacia may present with bone and muscle pains, weakness and pseudofractures. Cortical thinning occurs because of secondary hyperparathyroidism Note: 25-hydroxyvitamin D (25-OHD),

Indication:  Treatment of established osteoporosis Prevention of corticosteroid induced osteoporosis Treatment of hypocalcaemia in hypoparathyroidism Rickets  Renal osteodysthrophy Secondary hyperparathyroidism Psoriasis (calcipotriol)

Precaution/contraindication: Hypercalcaemia Hyperphosphatemia Hypervitaminosis D Artheriosclerosis or cardiac function impairment Renal function impairment

Note:Pregnancy and breast-feeding; No problems reported with normal intakes. There is a risk of hypercalcaemic tetany in breast fed infants whose mothers take excessive doses of vitamin D.

Production of Vit-D: •Vitamin D ingested or made

from the skin will be transported to the liver. •Metabolised to 25hydroxyvitamin D (25-OHD) which is a major circulating form in the body. •Next, hydroxylation in the kidney will form the biological active form 1,25dihydroxyvitamin D3. •UVB is resposible for the conversion of 7dehydrocholesterol into previtamin D3.

Mode of action:

Vit-D is essential for promoting the absorption and

utilisation of calcium and phosphorus and normal calcification of the skeleton

Along with parathyroid hormone and calcitonin, it

regulates serum calcium concentration by altering serum calcium and phosphate blood levels as needed, and mobilising calcium from bone

It maintains neuromuscular function and various other

cellular processes, including the immune system and insulin production

Calcipotriol: induces differentiation and suppresses

proliferation of skin cells

Dose:  1 Alpha-calcidol

Initial dosing: Adult and children >20kg needs 1µg od. <20kg needs 0.05µg/kg/day. Neonates: 0.1µg/kg/day Maintenance dosing: 0.25-2µg od Calcitriol

Post-menopausal: 0.25µg bd Renal osteodysthrophy: Initial: 0.25µg od and increase by 0.25µg over 2-4 weeks (range:0.5-1.oµg) until satisfactory serum calcium is achieved Hypoparathyroidism/rickets: 0.25µg od

Dose continues: Note : Always start on the lowest possible dose : During initial phase of the medication, serum calcium should be determined twice weekly. Subsequently, monitoring should also be undertaken at 2-4 weeks and 2-3 monthly intervals thereafter.

Side- effects: Generally well tolerated. Toxicity can occur with large dose (10,000units) for six

months.

Early signs & symptoms: Anorexia, constipation,

diarrhoea, dry mouth, fatigue, headache, nausea and vomiting, thirst and weakness

Later symptoms: calcification of soft tissues and include

bone pain, cardiac arrhythmias, hypertension, renal damage (increased urinary frequency, decreased urinary concentrating ability; nocturia, proteinuria), psychosis (rare) and weight loss.

Interactions: Anticonvulsants (phenytoin, barbiturates or primidone): may

reduce effect of vit-D by accelerating its metabolism

Calcitonin: effect of calcitonin may be antagonised by vit-D Colestyramine, colestipol: may reduce intestinal absorption

of vit-D.

Digoxin as hypercalcaemia can potentiate effect of digoxin

(arrhythmias)

Interactions continue; Liquid paraffin: reduce intestinal absorption of vit-D Sucralfate: may reduce intestinal absorption of vit-D. Thiazide diuretics: may increase risk of hypercalcaemia. Magnesium containing antacid: hypermagnesaemia

Practice points: Absorption is the best taken with fatty meals May be dropped directly into the mouth or mixed

with cereal, fruit juice, or other food Avoiding concurrent use of nonprescription

medications or dietary supplements containing calcium, phosphorus, or vitamin D, unless otherwise directed by health care professional

Untapped potential of Vitamin D: Role in infection particularly tuberculosis Autoimmune disease (eg: rheumatoid arthritis, multiple

sclerosis and inflammatory bowel diseases, including ulcerative colitis and Crohn’s disease)

Age-related macular degeneration Maternal pre-eclampsia Cardiovascular diseases (exposure to UVB decrease blood

pressure and decrease inflammatory marker eg:tumour necrosis factor which involves in artherosclerosis)

Diabetes (insufficiency predispose to type 2 diabetes)

Additional information:  Stock available: a) 1-α calcidol (0.25µg, 1.0µg) b) Calcitriol (0.25µg) c) Calcipotriol cream/ointment 50mcg/g  One International Unit of vitamin D is defined as the activity of 0.025 μg of

cholecalciferol. Thus: 1 μg vitamin D = 40 units vitamin D

 A suitable dose of vitamin D in most cases is 10 μg (400 units) daily  For prevention of fracture in older people, there is evidence that a higher

dose of 20 μg (800 units) with calcium 1200 mg daily is required

Reference:  Dietary supplements , viewed 16/06/09



 Guyton K, Kensler T, Posner G. Cancer chemoprevention using natural vitamin D and synthetic analogs.

Ann Rev Pharmacol Toxicol 2001; 41: 421–442

 Holick, M.F. The Influence of Vitamin D on Bone Health Across the Life Cycle. American Society for

Nutrition 2005; 135:2739S-2748S

 Parekh N, Chappell RJ, Millen AE, et al. Association between vitamin D and age-related macular

degeneration in the Third National Health and Nutrition Examination Survey, 1988 through 1994. Arch Ophthalmol 2007; 125: 661–669.

 Bodnar LM, Catov JM, Simhan HN, et al. Maternal vitamin D deficiency increases the risk of

preeclampsia. J Clin Endocrinol Metab 2007; 92: 3517–3522.

 Liu PT, Stenger S, Li H, et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial

response. Science 2006; 311: 1770–1773.

 Schauber J, Dorschner RA, Coda AB, et al. Injury enhances TLR2 function and antimicrobial peptide expression

through a vitamin D-dependent mechanism. J Clin Invest 2007; 117: 803–811.

Reference:  Diamond, T.H et al. Vitamin D and adult bone health in Australia and New Zealand: a position statement.

Medical Journal of Australia. 2005; 182: 281–285  Zitterman A. Vitamin D and disease prevention with special reference to cardiovascular disease. Prog

Biophys Mol Biol 2006; 92: 39–48  Pittas AG, Lau J, Hu FB, Dawson-Hughes B. The role of vitamin D and calcium in type 2 diabetes. A

systematic review and meta-analysis. J Clin Endocrinol Metab 2007; 92: 2017–2029  Gombart AF, Borregaard N, Koeffler HP. Human cathelicidin antimicrobial peptide (CAMP) gene is a

direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25dihydroxyvitamin D3. Faseb J 2005; 19: 1067–1077.  Dr Upfal, J 2007, The Australian drug guide, Black Inc Melbourne  Australian Medicine Handbook (2007)