How is Vitamin D (Vitamin D) dependent rickets managed?

Management of Vitamin D Dependent Rickets

Vitamin D dependent rickets should be treated with a combination of oral phosphate supplements and active vitamin D (calcitriol or alfacalcidol), with dosing tailored to the specific type of rickets and disease severity. 1

Types of Vitamin D Dependent Rickets

Vitamin D dependent rickets can be classified into two main types:

1. Type I (VDDR-I): Caused by defective renal tubular 25-hydroxyvitamin D 1-α hydroxylase 2

   • Results in inability to convert 25-hydroxyvitamin D to active 1,25-dihydroxyvitamin D
   • Characterized by normal 25-hydroxyvitamin D but low 1,25-dihydroxyvitamin D levels

2. Type II (VDDR-II): Caused by end-organ resistance to active vitamin D 2, 3

   • Results from defects in vitamin D receptor function
   • Characterized by normal or elevated 1,25-dihydroxyvitamin D levels
   • May present with alopecia in severe cases

Diagnostic Evaluation

Before initiating treatment, confirm diagnosis with:

• Serum calcium (typically low or low-normal)
• Serum phosphate (typically low)
• Alkaline phosphatase (markedly elevated)
• Parathyroid hormone (elevated)
• 25-hydroxyvitamin D levels
• 1,25-dihydroxyvitamin D levels (low in Type I, high in Type II)
• Radiographic evidence of rickets

Treatment Protocol

For Type I VDDR:

1. Active Vitamin D supplementation:

   • Calcitriol: 0.25-1.0 μg daily 1
   • OR Alfacalcidol: 1-3 μg daily (1.5-2.0 times the calcitriol dose due to differences in bioavailability) 1
   • Initial pediatric dose: 20-30 ng/kg body weight daily for calcitriol or 30-50 ng/kg for alfacalcidol 4

2. Oral phosphate supplements:

   • Starting dose: 20-60 mg/kg/day of elemental phosphorus 1
   • Divide into 4-6 doses daily in young patients with high ALP levels 1
   • Less frequent dosing (2-3 times daily) may improve adherence in adolescents 1

3. Monitoring:

   • Follow serum calcium, phosphate, ALP, and PTH levels regularly
   • Adjust dosage based on biochemical response and healing of rickets

For Type II VDDR:

1. High-dose active Vitamin D therapy:

   • Requires significantly higher doses than Type I to overcome receptor resistance 3
   • May need 5-20 times the standard doses of calcitriol 3
   • Start with higher doses and monitor response

2. Oral phosphate supplements:

   • Similar dosing as Type I, adjusted based on serum levels

3. Calcium supplementation:

   • May require calcium supplements (1-3 g elemental calcium daily) 4
   • Divide into 2-3 doses, taken with meals 4

Treatment Goals and Monitoring

1. Primary treatment goals:

   • Normalize serum calcium
   • Heal rickets (evidenced by normalization of ALP)
   • Promote growth and development
   • Reduce bone pain
   • Correct leg deformities
   • Improve dental health 1

2. Monitoring parameters:

   • Serum calcium and phosphate: Initially weekly, then monthly once stable
   • Alkaline phosphatase: Every 3 months to assess rickets healing
   • PTH levels: Every 3-6 months
   • Urinary calcium: To monitor for hypercalciuria
   • Renal ultrasound: Annually to check for nephrocalcinosis
   • Growth velocity and height
   • Radiographs: To assess healing of rickets

Important Considerations and Precautions

1. Avoid hypercalciuria and nephrocalcinosis:

   • Monitor urinary calcium excretion
   • Nephrocalcinosis has been reported in 30-70% of patients on treatment 1
   • Higher risk with higher doses of phosphate supplements

2. Medication timing:

   • Do not give phosphate supplements together with calcium supplements or high-calcium foods (e.g., milk) as this reduces absorption 1
   • Consider evening dosing of active vitamin D to prevent excessive calcium absorption after food intake 1

3. Secondary hyperparathyroidism:

   • Monitor for development of secondary hyperparathyroidism
   • May result from long-term stimulation of parathyroid cells by phosphate supplements 1

4. Nutritional considerations:

   • Maintain normal calcium intake for age
   • Calcium supplements are generally not recommended unless specifically indicated 1

5. Special populations:

   • Pregnant women may require adjusted dosing of active vitamin D 4
   • Infants diagnosed before bone changes develop should receive treatment to prevent rickets 1

By following this management approach, most patients with vitamin D dependent rickets can achieve significant clinical improvement, with normalization of biochemical parameters and healing of skeletal deformities.