04/15/23 Dr. M. S. Prasad 1

Vitamin-D DeficiencyVitamin-D Deficiency

Dr. M. S. PrasadDr. M. S. PrasadRetired Consultant & HeadDepartment of Pediatrics

VM Medical College & Safdarjung HospitalNew Delhi

04/15/23 Dr. M. S. Prasad 2

S Balasubramanian, K Dhanalakshmi and Sumanth Amperavani:

Vitamin-D Deficiency in Childhood – A Review of Current Guidelines on Diagnosis and Management.

Indian Pediatrics, Vol. 50 – July 15, 2013 pp 669 – 675.

Indian Pediatrics, Volume 51, April 15, 2014.

04/15/23 Dr. M. S. Prasad 3

IntroductionIntroduction

• Most common nutritional deficiency,

• One of the most common undiagnosed medical conditions in the world.

• Vitamin-D has evolved into a hormone.

04/15/23 Dr. M. S. Prasad 4

FunctionsFunctions

• Regulates calcium and bone metabolism,

• Reduce the risk of chronic diseases:– Auto-immune diseases,– Malignancies,– Cardiovascular, and– Infectious diseases.

04/15/23 Dr. M. S. Prasad 5

Facts!!Facts!!• It has been estimated that 1 billion people

worldwide have vitamin-D deficiency or insufficiency.

• Though majority of population in India lives in areas with ample sunlight throughout the year, vitamin-D deficiency is very common in all the age groups and both the sexes across the country.

04/15/23 Dr. M. S. Prasad 6

Facts!!!Facts!!!

• Nutritional Rickets has recently re-emerged as a problem in many countries where it was thought to have been eradicated.

• Hospitalization rates for rickets in England are now the highest in 5 decades.

04/15/23 Dr. M. S. Prasad 7

EtiologyEtiology

• Prevalence: 50-90% in India,

• Low dietary intake of calcium, skin color and changing life-style.

• Deficiency of dietary calcium is more responsible for rickets than deficiency of vitamin-D.

04/15/23 Dr. M. S. Prasad 8

EtiologyEtiology (continued)

• Vitamin-D insufficiency + decreased calcium intake or high phytate intake combine to induce rickets.

• Common in infancy:– Decreased dietary intake,– Decreased cutaneous synthesis,– Increased rate of exclusive breastfeeding, and – Low maternal vitamin-D.

04/15/23 Dr. M. S. Prasad 9

EtiologyEtiology (continued)

• Decreased vitamin-D synthesis,

• Decreased nutritional intake of vitamin-D,

• Age & Physiology related,

• Decreased maternal vitamin-D stores,

04/15/23 Dr. M. S. Prasad 10

Etiology Etiology (continued)

• Malabsorption,

• Decreased metabolic conversion to active form,

• Increased degradation of 25(OH)D.

04/15/23 Dr. M. S. Prasad 11

Decreased vitamin-D synthesisDecreased vitamin-D synthesis

• Skin pigmentation,

• Physical agents blocking UVR exposure,

• Clothing,

• Latitude,

• Season,

• Air-pollution,

• Cloud cover,

• Altitude.

04/15/23 Dr. M. S. Prasad 12

MalabsorptionMalabsorption

• Celiac disease,

• Pancreatic insufficiency (cystic fibrosis),

• Biliary obstruction (Biliary Atresia)

04/15/23 Dr. M. S. Prasad 13

Decreased metabolic conversionDecreased metabolic conversion

• Chronic Liver Disease,

• Chronic Renal Failure.

04/15/23 Dr. M. S. Prasad 14

Increased degradation of 25(OH)DIncreased degradation of 25(OH)D

• Drugs such as:– Rifampicin,

– Isoniazid,

– Anticonvulsants,

– Glucocorticocoids.

04/15/23 Dr. M. S. Prasad 15

OthersOthers• Decreased nutritional intake:

– Strict Vegan Diet.

• Age & Physiology related:– Elderly,– Obese,– Institutionalized.

• Decreased maternal vitamin-D stores:– Exclusive Breastfeeding.

04/15/23 Dr. M. S. Prasad 16

Definition of vitamin-D statusDefinition of vitamin-D status

• Debated by clinicians and researchers,

• Defined as serum level of 25(OH)D less than 20 ng/dL.

• Less than 15 ng/dl: Definite Deficiency.

• Less than 5 ng/dL: Severe Deficiency.

04/15/23 Dr. M. S. Prasad 17

Serum vitamin-D levelsSerum vitamin-D levels

• Sufficient data are not available to define the upper level of normal or dose levels above which toxicity occurs.

• Previous thought: intoxication does not occur until serum levels of 25(OH)D reach 100 to 200 ng/dL.

• Recently, risks identified at higher levels above 50 ng/dL.

04/15/23 Dr. M. S. Prasad 18

Vitamin-D levels Vitamin-D levels (continued)

• 25(OH)D:– Major circulating vitamin-D,– Half-life 2-3 weeks,– Best available indicators of vitamin-D status.

• 1,25(OH)2D (calcitriol):– Active form,– Half-life only 4 hours.

04/15/23 Dr. M. S. Prasad 19

When to treat?When to treat?

• Symptomatic:– Signs & symptoms of

hypocalcaemia,– Signs & symptoms of Rickets.

• Asymptomatic:– When vitamin-D levels are in the

deficient range even if asymptomatic.

04/15/23 Dr. M. S. Prasad 20

Treatment RegimenTreatment Regimen

• D3: 2000 IU daily or D2: 50000 IU weekly.

• Stoss Therapy: 6 lakh units once, or

• D3: 1000 – 5000 IU/day for weeks, or

• D2: 50000 units/wk for 8 weeks.

04/15/23 Dr. M. S. Prasad 21

TreatmentTreatment

GroupDaily regimen(8-12 weeks)

Weekly regimen

(8-12 weeks)

Stoss Therapy (Oral or IM)

Maintenance

<1 mo old 1000 IU 50000 IU 400-1000 IU

1-12 mo 1000-5000 IU 50000 IU1 – 6 lakh units over 1-5 days

400-1000 IU

1-18 y old 5000 IU 50000 IU3-6 lakh units over 1-5 days

600-1000 IU

>18 y old 6000 IU 50000 IU3-6 lakh units over 1-5 days

1500-2000 IU

Obese, Malabsorption 6000-10000 IU 3000-6000 IU

04/15/23 Dr. M. S. Prasad 22

Treatment Treatment (continued)

• A single dose of 300, 000 IU is not inferior to double of this dose (600, 000 IU).

• The dose is effective orally.

• Intramuscular dose is painful and unnecessary.

• I. M. reserved for cases with malabsorption only.

04/15/23 Dr. M. S. Prasad 23

DiscussionDiscussion• Lack of compliance lack of response.

• Solution: Administer high dose of 100000 to 600000 IU over 1-5 days (Stoss Therapy).

• Advantage of Stoss therapy: Vitamin-D is efficiently stored in adipose tissue and muscle and is continuously converted into active form.

• Shah and Finberg successfully administered 1 lakh IU every 12 hours over 12 hour period.

04/15/23 Dr. M. S. Prasad 24

MaintenanceMaintenance

• After completion of treatment, continue vitamin-D at 800-1000 IU/day till serum alkaline phosphatase returns to normal.

• D3 is 3 times more potent than D2.

• Provide Calcium supplement throughout treatment and maintenance. (elemental calcium 30-75 mg/kg/day in 3 divided doses).

04/15/23 Dr. M. S. Prasad 25

Indian Pediatrics: Volume 51, April 15, 2014Indian Pediatrics: Volume 51, April 15, 2014

• Both 3 lakh and 6 lakh IU vitamin D3 as single day doses are equally effective in treating children between 6 months and 5 years of age with vitamin D deficiency rickets.

• Neither dose is able to normalize the vitamin D status of the children 3 months after the administered dose.

04/15/23 Dr. M. S. Prasad 26

How to screen?

SAP

Normal ElevatedElevated

1. 25(OH)D2. Calcium3. Phosphorus4. PTH and5. Radiology.SAP =Serum Alkaline Phosphatase

04/15/23 Dr. M. S. Prasad 27

Whom to screen?Whom to screen?• Dark skinned infants who live at higher

altitude and infants born to vitamin-D deficient mothers.

• In the presence of non-specific symptoms like poor growth, gross motor developmental delay and unusual irritability.

04/15/23 Dr. M. S. Prasad 28

Whom to screen?

• Children with suspected rickets, those with osteopenia.

• Chronic Kidney Disease.

• Hepatic Failure.

• Hyperparathyroidism.

04/15/23 Dr. M. S. Prasad 29

Whom to screen?

• Malabsorption syndrome:– Cystic Fibrosis,– IBD (Inflammatory Bowel Disease),– Crohn’s Disease

• Medications:– Anticonvulsants,– Glucocorticosteroids,– AIDS medication,– Antifungal (ketoconazole).

04/15/23 Dr. M. S. Prasad 30

Whom to screen?

• Obese children and adults (BMI>30 kg/M2)

• Granuloma forming disorders:– Sarcoidosis,– Tuberculosis,– Histoplasmosis.

04/15/23 Dr. M. S. Prasad 31

PreventionPrevention

• Improve maternal vitamin-D status,

• Administration of high dose of vitamin-D (400-6400 IU) daily to breastfeeding mothers increases anti-rachitic activity of breastmilk without causing hypervitaminosis in the mother.

• Vitamin-D supplementation to preterm babies since birth (400-800 IU/day)

04/15/23 Dr. M. S. Prasad 32

Sources of vitamin-DSources of vitamin-D

• Sunlight,

• Diet:– Oily fish (salmon, mackerel and sardine),– Cod liver oil,– Liver and organ meat.

04/15/23 Dr. M. S. Prasad 33

04/15/23 Dr. M. S. Prasad 34

04/15/23 Dr. M. S. Prasad 35