Vitamin D Deficiency Rickets

Fan Yang Associated Professor Pediatric Department

Vitamin D
Vitamin D comprises a group of sterols Vitamin D2 = ergocalciferol
Completely synthetic form produced by the irradiation of the plant steroid ergosterol

Vitamin D3 = cholecalciferol
Produced photochemically by the action of sunlight or ultraviolet light from the precursor sterol 7-dehydrocholesterol

Vitamin D = calciferol

VITAMIN D
Humans & animal utilize only vitamin D3 & they can produce it inside their bodies from cholesterol.
Cholesterol is converted to 7-dehydrocholesterol (7DC), which is a precursor of vitamin D3.

VITAMIN D
Exposure to the ultraviolet rays in the

sunlight convert 7DC to cholecalciferol.

Vitamin D3 is metabolically inactive until it is hydroxylated in the kidney & the liver to the active form 1,25 Dihydroxycholecalciferol. 1,25 DHC acts as a hormone rather than a vitamin, endocrine & paracrine properties.

Vitamin D: The Sunshine Vitamin

Not always essential
Body can make it if exposed to enough sunlight Made from cholesterol in the skin

Formation of Vitamin D
Skin (UV light) 7-dehydro cholesterol Vitamin D3 Ergosterol Vitamin D2 Liver OH-group added 25-Hydroxy vitamin D3 Storage form of vitamin (~3 months storage in liver) Kidney OH-group added by 1-hydroxylase 1,25-dihydroxy vitamin D3 Active form of vitamin D, a steroid hormone OH-group added by 24-hydroxylase 24,25-dihydroxy vitamin D3 Inactive form of vitamin D, ready for excretion

FUNCTIONS
Calcium metabolism: vitamin D enhances ca absorption in the gut & renal tubules.

Cell differentiation: particularly of collagen & skin epithelium

Immunity: important for Cell Mediated Immunity & coordination of the immune response.

Vitamin D - Functions
Bone development Calcium absorption (small intestine) Calcium resorption (bone and kidney) Maintain blood calcium levels Phosphorus absorption (small intestine) Hormone Regulation of gene expression Cell growth

Vitamin D Functions

Vitamin D Affects Absorption of Dietary Ca

1,25-(OH)2 D binds to vitamin D receptor (VDR) in nucleus Increase in calbindin (Ca-binding protein)
Groff & Gropper, 2000

Vitamin D Affects Absorption of Dietary Phosphorus

1,25-(OH)2 D3 increases activity of alkaline phosphatase
Hydrolyses phosphate ester bonds
Releases phosphorus

Increase in phosphate carriers

Vitamin D deficiency

Etiology
1. Lack of sunshine due to: 1) Lack of outdoor activities 2) Lack of ultraviolet light in fall and winter 3) Too much cloud, dust vapour and smoke

Etiology
2. Improper feeding: 1) Inadequate intake of Vitamin D Breast milk 0-10IU/100ml Cows milk 0.3-4IU/100ml Egg yolk 25IU/average yolk Herring 1500IU/100g 2) Improper Ca and P ratio

Etiology
3. Fast growth, increased requirement Relative deficiency 4. Diseases and drug: Liver diseases, renal diseases Gastrointestinal diseases Antiepileptic Glucocorticosteroid

GROUPS AT RISK
Infants Elderly Dark skinned Covered women Kidney failure patients Patients with chronic liver disease Fat malabsorption disorders Genetic types of rickets Patients on anticonvulsant drugs

Vitamin D deficiency
Deficiency of vitamin D leads to:
Rickets in small children.
Osteomalacia

Osteoporosis

Parathyroid Hormone (PTH)

Calcium-sensor protein in the thyroid gland
Detects low plasma calcium concentrations

Effects of parathyroid hormone

Urine / kidneys
Increases calcium reabsorption Increases phosphorus excretion

Stimulates 1-hydroxylase activity in the kidneys

PTH required for resorption of Ca from bone

Activates a calcium pump on the osteocytic membrane Activates osteoclasts

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

Pathogenesis
Vitamin D deficiency Absorption of Ca, P Serum Ca Function of Parathyroid

Pathogenesis

PTH
High secretion P in urine P in blood Decalcification of old bone Ca in blood normal or low slightly

Ca, P product Rickets

Pathogenesis

Low secretion of PTH Failure of decalcification of bone Low serum Ca level Rachitic tetany

Clinical manifestation
Rickets is a systematic disease with skeletons involved most, but the nervous system, muscular system and other system are also involved.

Clinical manifestation
Early stage Usually begin at 3 months old Symptoms: mental psychiatric symptoms Irritability, sleepless, hidrosis Signs: occipital bald Laboratory findings: Serum Ca, P normal or decreased slightly, AKP normal or elevated slightly,25(OH)D3 decreased Roentgenographic changes: normal or change slightly

Clinical manifestation
Advanced stage On the base of early rickets, osseous changes
become marked and motor development becomes delayed. 1. Osseous changes: 1) Head: craniotables, frontal bossing, boxlike appearance of skull, delayed closure of anterior fontanelle 2) Teeth: delayed eruption, with abnormal order, defects 3) Chest: rachitic rosary, Harrisons groove, pigeon chest, funnel-shaped chest, flaring of ribs

Clinical manifestation
4) Spinal column: scoliosis,kyphosis, and lordosis 5) Extremities: bowlegs,or knock knee, greenstick fracture 6) Rachitic dwarfism 2. Muscular system: potbelly, late in standing and walking 3. Motor development: delayed 4. Other nervous and mental symptoms

Clinical manifestation
Laboratory findings: Serum Ca and P decreased Ca and P product decreased AKP elevated Roentgenographic changes: Wrist is the best site for watching the changes. Late appearance of ossification center Widening of the epiphyseal cartilage Blurring of the preparatory calcification line metaphyses like a cup rarefaction of the bone thinned cortex of the shaft of long bone

Clinical manifestation
Healing stage: Symptoms and signs of Rickets alleviate or
disappear by use of appropriate treatment. The blood chemistries become normal, except AKP may be slightly elevated.

Sequelae stage:
All the clinical symptoms and signs disappear. Blood Chemistries and X-ray changes are recovered, but osseous deformities may be left. Usually seen in Children after 3 years old.

Rachitic vs. normal chick Rickets due to deficiency of vitamin D, Ca, or P

Vitamin D Deficiency - Rickets

Rickets in wrist - uncalcified lower ends of bones are porous, ragged, and saucer-shaped

(A) Rickets in 3 month old infant

A
(B) Healing after 28
days of treatment

(C) After 41 days

of treatment

Diagnosis
Assessed according to the followings: 1. History 2. Physical examination 3. Laboratory findings 4. Roentgenographic changes

Differential diagnosis
1. Hypophosphatemic Vitamin D resistant rickets 2. Rickets of Vitamin D dependency 3. Distal renal tubular acidosis 4. Cretinism 5. Chondrodystrophy

Treatment
1. Food and nursing care

2. Prevention of complications 3. Special therapy 1) Vitamin D therapy A. General method

Vitamin D 2000-4000IU/day for 2-4 weeks, then change to preventive dosage (400IU). B. A single large dose: For severe case, or Rickets with complication, or those who cant bear oral therapy. Vitamin D3 200000-300000IU, im, preventive dosage will be used after 2-3 months.

Treatment
2) Calcium supplementation: only used for special cases, such as baby fed mainly with cereal, or infants under 3 months of age, and those who have already developed tetany. Dosage:1-3 g/day. 3) Plastic therapy: In children with bone deformities after 4 years old plastic surgery may be useful.

Prevention
1. Pay much attention to the health care of pregnant and lactating women, instruct them to take adequate amount of vitamin D. 2. Advocate sunbathing 3.Advocate breast feeding, give supplementary food on time

Prevention
4. Vitamin D supplementation: In prematures, twins and weak babies, give Vitamin D 800IU per day, For term babies and infants the demand of Vitamin D is 400IU per day, For those babies who cant maintain a daily supplementation, inject muscularly Vitamin D3 10000-200000 IU.

Prevention
5. Calcium supplementation: 0.5-1gm/day, for premature, weak babies and babies fed mainly with cereal

Sources of Vitamin D
Sunlight is the most important source Fish liver oil Fish & sea food (herring & salmon) Eggs Plants do not contain vitamin D3

Vitamin D - Sources
Not found naturally in many foods Synthesized in body Plants (ergosterol)
Sun-cured forages

Fluid milk products are fortified with vitamin D Oily fish Egg yolk Butter Liver Difficult for vegetarians

TOXICITY
Hypervitaminosis D
causes hypercalcemia, which manifest as:
Nausea & vomiting

Excessive thirst & polyuria

Severe itching Joint & muscle pains Disorientation & coma.

Vitamin D Toxicity
Calcification of soft tissue
Lungs, heart, blood vessels Hardening of arteries (calcification)

Hypercalcemia
Normal is ~ 10 mg/dl Excess blood calcium leads to stone formation in kidneys

Lack of appetite Excessive thirst and urination Infants: