Vitamin D

Introduction

Vitamin D Metabolism

• Synthesis: Vitamin D is synthesized in the skin (cholecalciferol, Vitamin D3) from 7-dehydrocholesterol upon exposure to UVB radiation.
• Hydroxylation:
  • First hydroxylation occurs in the liver, converting Vitamin D3 to 25-hydroxyvitamin D [25(OH)D], the major circulating form.
  • Second hydroxylation occurs in the kidney, converting 25(OH)D to its active form, 1,25-dihydroxyvitamin D [1,25(OH)2D], or calcitriol.
• Function:
  
  1. Increases calcium and phosphate absorption from the gut
  2. Increases calcium and phosphate reabsorption in the distal convoluted tubules of the kidney
  3. Modulates bone mineralization.
• Regulation: If the Ca+2 level is low, active vitamin D increases bone resorption of calcium (moving calcium from bone and into the circulation).

Vitamin D Daily Supplementation

• Vitamin D levels are very low in breast milk, so exclusively breastfed infants need supplementation.
• For older children with adequate exposure to sunlight, vitamin D supplementation is usually not necessary.
• The recommended dose of vitamin D for children is 400 IU per day.
• This recommended dosage begins within the first few days after birth and continues throughout adolescence

Vitamin D Deficiency

Introduction

• Rickets: A pediatric bone disorder caused by defective mineralization of the growth plate and newly formed bone, leading to soft and weakened bones.
• Primary Rickets: Occurs due to deficiencies in vitamin D, calcium, or phosphate, which impair osteoid mineralization.
• Secondary Rickets: Caused by genetic mutations affecting vitamin D metabolism or phosphate regulation, chronic kidney disease, or liver disorders.
• In adults, the equivalent condition is called osteomalacia, where mature bone mineralization is impaired.
• It’s a worldwide problem, affecting 30-60% of the population in all tested countries.

Causes of Vitamin D Deficiency

• Inadequate sun exposure: Limited UVB exposure, use of sunscreen, living in higher latitudes.
• Dietary insufficiency: Low intake of vitamin D-rich foods such as fish and fortified milk.
• Chronic intestinal inflammation: Seen in conditions like untreated celiac disease and Crohn's disease.
• Renal or hepatic dysfunction: These impair the conversion of vitamin D into its active forms.
• Obesity: Vitamin D gets sequestered in adipose (fat) tissue.
• Medications: Certain drugs like glucocorticoids and anticonvulsants can reduce vitamin D levels.

Types of Rickets

1. Nutritional Rickets: Caused by deficiencies in vitamin D, calcium, or phosphate.
2. Vitamin D-Dependent Rickets:
   • Type 1: Autosomal recessive disorder caused by 1-alpha-hydroxylase deficiency, leading to impaired conversion of 25(OH)D to 1,25(OH)D (calcitriol). Patients require vitamin D supplementation.
   • Type 2: Caused by mutations in the vitamin D receptor (VDR), leading to tissue insensitivity to calcitriol.
3. Hypophosphatemic Rickets: An X-linked disorder marked by impaired renal phosphate retention, resulting in low serum phosphate and impaired bone mineralization.

Clinical Manifestations

• The most common presentation in infants and children with rickets is asymptomatic, meaning many cases are detected incidentally.
• Diagnosis is often made during physical examination or routine lab screening.
• Other common manifestations of rickets include:
  • Bone-related symptoms
    • Bone pain or tenderness (arms, legs, spine, pelvis).
  • Skeletal deformities
    • Bowlegs (genu varus).
    • Pigeon chest (forward projection of the breastbone).
    • Rachitic rosary (enlargement of the costochondral joints of the ribs).
    • Craniotabes (soft skull bones with a "pingpong ball" feel).
    • Asymmetrical or oddly shaped skull.
    • Harrison’s sulci (horizontal grooves at the lower ribs).
    • Spine deformities such as scoliosis and kyphosis.
    • Pelvic deformities.
  • Other manifestations
    • Increased risk of bone fractures.
    • Dental abnormalities:
      • Delayed eruption of teeth.
      • Defective enamel with pits or holes.
      • Increased dental cavities.
    • Muscle issues: Cramps and muscle weakness.
    • Growth delays and short stature.

  

Diagnosis

• Rickets is usually diagnosed through radiographic (X-ray) examination of the long bones.
• Findings may include:
  • Osteopenic bone shafts (low bone density).
  • Widened growth plates.
  • Frayed and cupped metaphyseal ends (irregular and blurred bone ends).
• After starting vitamin D therapy, the long bone ends often appear brighter on X-ray, indicating healing.
   

 

 

Treatment of Vitamin D Deficiency and Rickets

• Vitamin D Supplementation:
  • Mild deficiency: 600–2,000 IU/day of vitamin D.
  • Severe deficiency: 50,000 IU/week for 6–8 weeks followed by maintenance dosing.
  • For rickets: High-dose oral vitamin D (up to 2,000–6,000 IU/day) or calcitriol for genetic forms.
  • Calcium supplementation: Often required in cases of severe deficiency or rickets.
• Treatment of Vitamin D-Dependent Rickets:
  • Type 1: Calcitriol supplementation.
  • Type 2: High-dose calcitriol and calcium, with close monitoring of biochemical response.