Rickets
DR ABHISHEK SHETTY
Overview
 What is Rickets?
 Vitamin D Deficiency Rickets
 Calcium Deficiency Rickets
 Vitamin D Dependent Rickets type I & type II
 X-Linked Hypophosphataemic Rickets
What is Rickets ?
Rickets – Historical Perspective
 19th CENTURY - Rickets rampant
among the poor children living in the
industrialised & polluted northern cities
 “Disappearance of Rickets” in early 20th
Century:



Cod-liver oil supplements in 1930s
Improvement in nutrition
Pollution control measures
 Recent resurgence of Rickets
Francis Glisson - "De Rachitide” 1650
What is Rickets ?



Disease of the growing child
Impaired mineralisation of the growth plate & osteoid
Low serum phosphate is fundamental to pathogenesis of rickets
Rachitic Growth Plate
Normal Growth Plate
Apoptosis of
Hypertrophic
Chondrocytes
caused by
PHOSPHATE ions
HYPOPHOSPHATEMIA
No Apoptosis of
Hypertrophic
Chondrocytes
What is Rickets ?
Impaired Apoptosis of Terminally Differentiated Chondrocytes in the Growth Plate
Responsible for Clinical & Radiological Signs of Rickets
What is Rickets ?
Calcipaenic Rickets
Phosphopaenic Rickets
Hypophosphataemic Rickets
- X-linked Dominant (PHEX gene mutation)
Vitamin D Related Rickets
- Vitamin D Deficiency
- Impaired Hepatic 25-hydroxylation
- Impaired Renal 1α-hydroxylation of 25(OH)D
- End organ resistance to 1,25(OH)2D
Rickets due to Dietary Calcium Deficiency
Raised PTH
- Autosomal Dominant (FGF23 mutation)
- Autosomal Recessive Type 1 (DMP1mutation)
- Autosomal Recessive Type 2 (ENPP1mutation)
- With Hypercalciuria (SLC34A3 gene mutation)
- Associated with:
(a) McCune-Albright syndrome
(b) Tumour induced osteomalacia
(c) Linear nevus sebaceous syndrome
-
Renal Phosphate Wastage
Hypophosphatemia
Impaired Apoptosis of Terminally Differentiated Chondrocytes in the Growth Plate
Calcipaenic Rickets
Vitamin D Related Rickets

Vitamin D Deficiency Rickets

Impaired Hepatic 25-hydroxylation

Vitamin D Dependent Rickets Type I (Impaired Renal
1α-hydroxylation of 25(OH)D)

Vitamin D Dependent Rickets Type II (End organ resistance to
1,25(OH)2D)
Rickets due to Dietary Calcium Deficiency
Vitamin D Deficiency Rickets
Vitamin D Deficiency in Adolescents
 Tetany & Convulsions
 Limb pains
 Lower limb & pelvic deformities
 Proximal myopathy
Biochemical Changes in Vitamin D Deficiency
Early vitamin D deficiency:
25(OH)D
↓
PTH
↑
1,25(OH)2D ↑
Ca
P
ALP
Normal
↓
↑
Severe vitamin D deficiency:
25(OH)D
↓↓
PTH
↑↑
1,25-(OH)2D ↓
Ca
↓
P
↓↓
Archives
of Disease
ALP
↑ in↑ Childhood. 2009; 94:932-937
Occasionally PTH resistance: Ca ↓, P ↑, 25(OH)D ↓↓,
PTH ↑↑ & 1,25-(OH)2D ↓↓
Radiological Changes
Rx
Vitamin D3
+
Calcium
Treatment of Vitamin D Deficiency Rickets
 Oral vitamin D2 or D3, 3000 - 6000 i.u./day for 6 to 8 weeks
 Oral calcium supplements if necessary
 Monitoring:
 Improvement in symptoms (~ 2weeks)
 ↓ in serum PTH & alkaline phosphatase
 ↑ in serum phosphate, calcium & 25(OH)vitamin D
 Radiological healing (~ 3 months)
 Improvement of bow legs or knock-knees (~ 2 years)
 Provide vitamin D supplements (~ 400 iu/day) after the rickets
has healed
Vitamin D3 or Vitamin D2 ?
Time course of the rise in serum 25OHD after a single oral dose of 50,000 IU of either cholecalciferol
(vitamin D3) or ergocalciferol (vitamin D2) to two groups of 10 normal men each
Armas, L. A. G. et al. J Clin Endocrinol Metab 2004;89:5387-5391
Prevention of Vitamin D Deficiency
Vitamin D supplementation During Pregnancy,
Lactation & Infancy
DOH
 All 0 to 6 months – 340 i.u/day or 8.5 mcg/day
(Not necessary for formula fed infants unless volume
< 500 mls/day)
 All 7 months to 5 years – 280 i.u/day or 7 mcg/day
 Adolescents at risk of vitamin D deficiency - 400 i.u/day
or 10 mcg/day
 All pregnant & lactating mothers - 400 i.u/day or 10 mcg/day
Children’s Healthy Start Vitamin drops
contain (5 drops daily):
• 233 micrograms of vitamin A
• 20 milligrams of vitamin C
• 7.5 micrograms of vitamin D3
(www.healthystart.nhs.uk)
Calcium Deficiency Rickets
Rickets Due to Calcium Deficiency
Wind-swept Abnormality due to Calcium
Deficiency Rickets – taken from a
review by Dr John Pettifor
Oginni et al Archives of Disease in Childhood. 2003;88:812-817
• Male infant born to Somali parents
• Breast fed from birth
Severe Calcium Deficiency Rickets
• Allergic to dairy, eggs & fish
• Weaned mainly on pasta, rice,
potatoes & small amount of meat
• Dalivit 0.6 mls daily
• Calcium supplements prescribed
• Presented with delayed walking
Age
19 months
20 12 2011
23 months
04 04 2012
Ca mmol/l
2.36
2.39
ALP iu/l
1023
1301
P mmol/l
1.01
0.79
PTH pg/ml (11-35) 192
25OHD2nmol/l
25OHD3nmol/l
70.6
<15
465
16th March 2012
Severe Calcium Deficiency Rickets
16th March 2012
11th June 2012
 Ca 2.35 mmol/l (2.2 – 2.7)
 P 0.98 mmol/l (1.05-1.95)
 ALP 538 IU/l (60 -300)
Rx
Calcium
Sandoz
 PTH 35 pg/ml (10 - 60)
 25(OH)D2 46 nmol/ml
 25(OH)D3 6.9 nmol/ml
 Total 25(OH)D 52.9 nmol/ml
Vitamin D Dependent Rickets (VDDR)
Type I & Type II
VDDR Type I
 Corr Ca 2.02 mmol/l
 P 0.59 mmol/l (1.1 – 2.0)
 ALP 3636 IU/l (100 - 733)
 PTH 1087 pg/ml (10 - 60)
 25(OH)D 31 ng/ml
 1,25(OH)2D < 10 pg/ml (20 - 50)
Known inactivating
mutations in
the CYP27B1 gene
September 2005 - 16 month old child with severe Rickets
Vitamin D Dependent Rickets Type I & Type II
VDDR Type I
 Physiological doses of calcitriol (1,25(OH)2D) or alphacalcidiol
VDDR Type II
 Pharmacological doses of calcitriol or alphacalcidiol
(e.g. 3-6 mcg/day)
+
Oral calcium – 2 to 3 grams/day
 Long-term treatment calcium infusions (especially patients
with alopecia )
Thank You