1 dr mughals vitamin d talk

7/26/2019 1 Dr Mughals Vitamin d Talk

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Vitamin D

Zulf Mughal

Consu ltant in Paediatr ic Bo ne Disorders

Department of Paediatr ic Endo cr iolog y

Royal Manchester Chi ldren's Hospital

Manchester

M13 0JH

Bone Study Day, 28thSeptember 2012


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Overview

Sources & Metabolism of Vitamin D

Musculoskeletal consequences of Vitamin D deficiency

Non-musculoskeletal associations of Vitamin D deficien

The Criteria or Definition of Vitamin D deficiency

Prevention of Vitamin D deficiency


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Vitamin D: Sources & Metabolism


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Sources & Metabolism of Vitamin D

Solar UVB (280-310nm)

EndogenousVitamin D3

Dietary sourceVitamin D2& D3

Oily fish, eggs,

fortified foods e.g:

Infant formulas

Cereals

Liver

25-Hydroxyvitamin D(major circulating metabolite

1,25-Dihydroxyvitamin D

Kidney

1 hydroxylase

(CYP27B1)

PTH (+) P (+)

FGF23 (

(7-dehydoxycholesterol)

DBP

25-hydroxylase

(CYP2R1)

24-hydroxylase

(CYP24A1)

DBP

24,25-hydroxyvitamin D

Calcitroic acid


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Roles of 1,25-Dihydroxyvitamin D in Bone Mineral Homeosta

Stimulates GI calcium absorption

Promotes renal calcium re-absorption

Stimulates GI phosphorous absorption

Calcium homeostasis: together with PTH it mobilises calcium from

skeletal stores

Mineralisation of the growth plate & osteoid

Normal Growth Plate Rachitic Growth P

Low Calcium

or

Low Phosphorous

Radiograph showing

Rachitic Changes
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Factors which contribute to development of Vitamin D deficien

Residence in Northern or Southern Latitudes

Pigmented skin

Sun blocking creams Factor 8 Vit D synthesis by >95%

Sunshine avoidance for religious or cultural reasons

Cloud Cover & Atmospheric Pollution

Obesity

Genetic propensity

An independent protective effect of meat consumption

Low dietary Calcium & High Fibre diets


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Ethnicity

Asians

Caucasians

Maternal 25(OH)D(ng/ml)

6050403020100

Cord

25(OH)D(ng/ml)

50

40

30

20

10

0

R=0.98 (p


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Cutaneous Vitamin D Synthesis


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15 South A

109 Wh

Farrar et al Am J Clin Nutr. 2011;94(5):1219-24.

Serum 25(OH) Levels after Simulated Summer Sunlight Exposure

in Whites & South Asians


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Criteria or Definition of Vitamin D Deficiency


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Definition of vitamin D deficiency & sufficiency based on serum 25(OH)

concentrations

Vitamin D Deficiency & Insufficiency

Davies JH & Shaw NJ. Arch Dis Child. 2010 Jul 23. [Epub ahead of print]


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Low Calcium Diet & Vitamin D Deficiency


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Pune (18.340N)

N = 50

Manchester (54.40N)

N=51

Age (years) 14.7 0.7 15.3 0.4

Serum 25OHD concentrations < 12 ng/ml 70% 73%

PTH > upper end of the reference range 48% 6%

Serum calcium concentration < 2.2 mmol/l (%) 74% 0%

Non-specific aches and pains (%) 76% 26%

Genu Varum or Genu Valgum (%) 44% 0%

Dietary vitamin D intake (g/day) 0.17 1.3

% Ca intake (mg/day) - dairy products 65 (31-76) 401 (195 - 594)

Total Ca intake (mg/day) 449 (356 - 538) Data not available

Khadilkar, Das, Sayyad, Sanwalka, Bhandari, Khadilkar, Mughal. Low Calcium intake & Hypovitaminosis D in Adoles

Girls. Archives of Disease in Childhood. 2007 ;92(11):1045

Low Calcium Diet & Vitamin D Deficiency


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Low Calcium & High Fibre Diet and Vitamin D Stat

Vitamin D Dietary Ca

High fibre & phytic acid reduce dietary Ca intake

Low Ca intake leads to secondary hyperparathyroidism & raised seru

1,25(OH)2D concentration

Raised serum 1,25(OH)2D concentration degrades 25OHD to inactiv

24,25-dihydroxyvitamin D, thereby depleting body stores of vitamin Clements et al. Nature 1987;325:625


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DIETARY CALCIUM INTAKE

1 ml ~ 1mg

1 pot ~ 150 mg

~35 mg/slice

1 Bowl ~ 80

1 oz ~ 200 mg

RNI (mg/day) in the UK

Infants up to 1 yr 525

Children 1- 3 yrs 350Children 2-6 yrs 450

Children 7-10 yrs 550

Adolescent boys 11-18 yrs 1000

Adolescent girls 11-18 yrs 800


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Vitamin D Deficiency & Muscle


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DIAGNOSIS: Severe vi tam in D def ic iency & low calcium intake

Pre Rx Post Rx25(OH)D (ng/ml)


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Life threatening Cardiomyopathy in Early Infancy

Maiya S et al .Hypocalcaemia and Vitamin D deficiency: an important, but preventable cause

life threatening infant heart failure.Heart. 2007 Aug 9; [Epub]

16 infants (6 South Asian, 10 Black ethnicity) admitted to GOS with Heart Failur

Median age 5.3 months (3 weeks - 8 months);12 exclusively breast-fed

12 needed inotropic support

8 ventilated & 2 needed ECMO

2 referred for cardiac transplantation

6 suffered a cardiac arrest & 3 died!

Median (range) Reference range

Calcium (mmol/L) 1.50 (1.07

1.74) 2.17

2.44PTH (pmol/L) 34.3 (8.9 102) 0.7 5.6

25OHD (nmol/L) 18.5 (0.00 46) >50

Fractional shortening (%)10 (5-18) 28 45

Left ventricular end diastolic

dimension Z score 4.1 (3.1-7) -2 < +2


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Non-Musculoskeletal Consequences ofVitamin D Deficiency

Possible Consequences of Vitamin D Deficiency


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Holick BMJ June 2008;336:1318-1319

Possible Consequences of Vitamin D Deficiency


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Vitamin D & Innate Immunity

Adequate serum 25(OH)D

Innate immunityToll like receptors recognise pathogens

expression of VDR & CYP27B1 enz

25(OH)D 1,25(OH)2D

1,25(HO)2D leads to production of

antimicrobial proteins (AMPs)

AMPs (e.g. Cathelcidin) important role

defence against bacterial & viral infecti

Vitamin D Deficiency & Pneumonia


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Vitamin D Deficiency & Pneumonia

New RMCH July 2009

Effects of Vitamin D supplementation in children diagnos


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Proportion of children free of a repeat episode of pneumonia up to 90 days post-treatm

Rx of 1-36 month olds with 100,000 i.u.

Vitamin D3/Placebo + antibiotics

DID NOT reduce the durationof illness

(p=0.17)

DID reduce readmission to

hospital with pneumonia

(p=0.01)

Manaseki-Holland S, Qader G, Masher M I, Bruce J. Mughal M Z, Chandramohan D, Walraven G,

Effects of Vitamin D supplementation to children diagnosed with pneumonia in Kabul: A randomised controlled tr

Tropical Medicine & International Health 2010;15 (10), 11481155

Effects of Vitamin D supplementation in children diagnos

with pneumonia in Kabul: A random ised con tro l led tr ia

0.00

0.25

0.50

0.75

1.00

204 162(37) 121(35) (15)Vitamin D211 156(52) 104(45) (19)PlaceboNumber at risk (no of episodes)

0 30 60Time since recruitment (days)

Placeb

Vitami

Vitamin D Supplementation to Infants in Kabul had NO effect on th


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Proportion of Children without First or Only Episode of X-Ray Confirmed Severe

Non-Severe Pneumonia

3,406 infants randomised to

100,000 i.u. Vitamin D3 or Placebo

every 3-monthly, for 18 months

Subjects visited fortnightly to

assess their health status

Subjects with signs of pneumonia

had a chest radiograph to confirm

the diagnosis of pneumonia.

No difference in the incidence of

pneumonia between the vitamin D

and the placebo group

Vitamin D Supplementation to Infants in Kabul had NO effect on th

incidence of Pneumonia: A random ised contro l led tr ial

0.50

0.75

1.00

1477 1375(88) 1252(82) 1199(14) 1169(9) 1099(39) (13Placebo1485 1362(94) 1246(81) 1217(8) 1183(11) 1086(50) (16Vitamin D

Number at risk (no of episodes)

0 90 180 270 360 450

Time since recruitment (days)

Vitam

Placeb

Manaseki-Holland, Maroof, Bruce, Mughal, Masher, Bhutta, Walraven, Chandramohan Effect on the incidence of pneumonia of vita

supplementation by quarterly bolus dose to infants in Kabul: a randomised controlled superiority trial LANCET .2012;14;379(9824):14

Summary


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Summary

Subclinical vitamin D deficiency is very common in the UK

Severe vitamin D deficiency is associated skeletal muscle weakness &cardiomyopathy.

No clear definition of vitamin D deficiency based on serum 25(OH)D levels in childr

Pragmatic lower limit of vitamin D sufficiency 20 ng/ml or 50 nmol/l.

Adequate dietary calcium intake is important in order to prevent vitamin D breakdow

Musculoskeletal symptoms of vitamin D deficiency are less likely to occur when diecalcium intake is adequate & serum PTH is normal.

Vitamin D deficiency may be associated with increased risk of infections, autoimmudisorders, respiratory diseases & certain cancers. RCTs needed to confirm theseassociations!


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Thank You

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