2. Do you remember?
1. Which part of a long bone contains the growth plate?
2. Is there a difference between rickets and osteomalacia?
3. Can you name the 3 hormones responsible for calcium homeostasis?
4. Which body part has the highest concentration of phosphate?
5. What is the active form of vitamin D called?
2
5. Regulation of Vitamin D Synthesis
5
Source: Ganong’s review of medical physiology, 24th edition
6. Vitamin D Effects
6
Net actions of activated vitamin D:
1. Increase in intestinal calcium
absorption
2. Increase renal calcium
reabsorption
3. Stimulation of osteoblastic
activity
Vitamin D action on intestinal cells
7. Regulation of Vitamin D Synthesis
7
Source: Etiology and treatment of calcipenic rickets in children- UpToDate
1. When plasma calcium level is high, little 1,25
dihydroxycholecalciferol is produced as the kidneys
instead make the relatively inactive 24,25
dihydroxycholecalciferol
2. PTH strongly stimulates the action of 1,25
dihydroxycholecalciferol
3. 1, 25 dihydroxycholecalciferol also increases when the PO4
is low & vice versa
9. PTH Effects
9
1. Acts directly on the bone to increase bone
resorption and mobilize calcium
2. Increase renal calcium absorption via distal
tubules
3. Stimulates 1,25 dihydroxy vitamin D formation
and increases calcium absorption from intestine
4. Causes phosphate excretion in the urine thereby
decreasing phosphate levels in blood
10. PTH Regulation
1. Circulating calcium acts directly on the parathyroid glands in a negative feedback fashion:
• High Ca PTH inhibited calcium deposited in bones
• Low Ca PTH stimulated calcium mobilized from bones
2. 1, 25 dihyroxycholecalciferol acts directly on parathyroid gland to decrease PTH synthesis
3. High serum phosphate will increase PTH secretion by lowering plasma level of free calcium and
inhibiting formation of 1, 25 dihyroxycholecalciferol
4. Magnesium is required to maintain normal parathyroid secretory responses
10
12. Importance of Magnesium
12
• Magnesium is required to maintain
normal parathyroid secretory
responses
• Hypomagnesemia impaired PTH
release and diminished target organ
responses to PTH
14. Calcitonin
14
• Produced by the para- follicular cells of the
thyroid gland
• Released in response to high calcium in blood
• Receptors are present in bones and kidneys
• Directly inhibits bone resorption of calcium and
increases excretion of calcium in urine
15. Rickets & Osteomalacia
Rickets represents deficient
mineralization & architectural
disruption of the growth plate
It is a disease of the growing
bones!
Osteomalacia represents
impaired mineralization of the
bone matrix
It usually occurs with rickets in
children as long as the growth
plates are open!
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19. Pathogenesis
Deficiency of calcium or phosphate at the growth plate
Delayed vascular invasion of growth plate for conversion into
primary bony spongiosa
Growth plate cartilage accumulates and thickens
Metaphysis also has a mineralization defect & osteoid
accumulation
Chondrocytes of growth plate become disorganized, losing their
columnar orientation & have expansion of the hypertrophic zone
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20. Pathogenesis
• As a result:
• The overall geometry of skeletal sites is affected
• Growth plate and metaphysis diameter is increased
• Bone size increases to compensate for the decreased bone
strength
• Eventually bone stability is compromised and bone
deformities occur
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21. Clinical Presentation
Delayed closure of
fontanelles
Parietal and frontal
bossing
Craniotabes Rachitic rosary
Harrison sulcus or
groove
Widening of wrist
Bowing of distal
radius and ulna
Progressive lateral
bowing of femur
and tibia
Spine deformities
Delayed dentition,
dental caries
Proximal muscle
weakness,
protruding
abdomen
Failure to thrive Listlessness
Respiratory
infections,
atelectasis
Hypocalcemic
seizures, tetany,
laryngeal spasms
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22. Skeletal Features
• Sites of rapid bone growth are most affected:
• Distal forearm
• Knee
• Costochondral junctions
• The exact bone deformity depends on child’s age and
weight- bearing pattern in the limbs
22
23. Skeletal Features
Infants
Deformity of the
forearm and
posterior bowing
of the distal tibia
Toddlers
Genu varum due
to exaggeration
of physiologic
bowing of legs
Children
Valgus or
windswept
deformity
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24. Lower Limb Deformities
24
Type of deformity depends on the biomechanical
forces acting on the bone at the time when structural
weakness develops
Genu Varum Genu Varum Wind-swept deformity Genu Valgus
26. Rachitic Rosary
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Rachitic rosary is enlargement of costochondral junctions visible as
beading along the antero- lateral aspect of the chest
27. Others
27
Harrison Sulcus Craniotabes Frontal Bossing
Harrison sulcus/ groove occurs at the lower margin of the thorax caused by inwards pull of diaphragmatic
attachments of the softened lower ribs
28. Radiographic Features
Pathologic fractures & looser zones (Milkman Pseudofractures)
Long bone shaft deformity
Reduced and coarse trabecular pattern
Osteopenic long bone shaft with thin cortices
Small osteopenic ill- defined epiphyseal bone centers
Disorganization of growth plate: cupping, splaying, cortical spurs and stippling
Widening of epiphyseal plate, loss of definition of provisional calcification at epiphysis- metaphysis interface
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Best observed at areas of rapidly growing bone (distal
ulna in upper limb & knee metaphysis in lower limb)
29. Milkman Pseudofractures
• Characteristic radiologic finding of osteomalacia
• Narrow radiolucent lines around 2- 5 mm with wide sclerotic borders
• Found bilateral and symmetrically perpendicular to cortical margins of bone
• Usually present at femoral neck of medial part of femoral shaft immediately under lesser trochanter
• May also occur in ulna, scapula, clavicle, rib or metatarsal bone
• Pseudofractures are seen as hot spots on bone scans
29
34. Lab Tests
Calcium,
phosphate and
magnesium
25- hydroxy
vitamin D & 1,
25 hydroxy-
vitamin D
Alkaline
phosphatase
Parathyroid
hormone (PTH)
Urine levels of
calcium and
phosphate
Liver and kidney
function
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38. Treatment of nutritional rickets
Vitamin D deficiency nutritional rickets Calcium deficiency nutritional rickets
< 1 m : 1000 IU OD 3 months 400 IU OD
1- 12 m : 1000- 2000 IU OD 3 months 400 IU OD
1- 12 y : 2000- 6000 IU OD 3 months 600 IU OD
Over 12 y : 6000 IU OD 3 months 600 IU OD
Stoss therapy for > 3 m old can be tried if compliance
is a concern
Plus calcium supplementation 30- 50 mg/kg/day of
elemental calcium to avoid hungry bone syndrome
(worsening hypocalcemia after starting vitamin D
therapy)
Plus dietary advice
1000 mg elemental calcium plus maintenance dose of
vitamin D
Maintenance doses of vitamin D: *
< 1 year : 400 IU OD
Over 1 year : 600 IU OD
*Higher doses for those at high risk for deficiency –
anti- epileptic medications, malabsorption syndromes
Plus dietary advice
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39. Treatment of vitamin D metabolic defects
25- hydroxylase deficiency 1- alpha hydroxylase deficiency
Hereditary resistance to
vitamin D
High dose vitamin D3 plus calcium
supplementation
Calcitriol (activated 1,25 (OH)3 D at
1 mcg OD till bones heal 0.2- 2
mcg/ day
Or Alpha- calcidiol 1- 3 mcg/ day
Note: Side effects of Calcitriol
include hypercalcemia,
hypercalciuria, nephrocalcinosis,
intra- ocular calcifications hence
close follow- up required
Very high doses of Calcitriol 2 mcg/
day (up to 30- 60 mcg/ day) plus
calcium 1000 mg/day (up to 3
grams/ day)
May need central line for calcium
infusion
Treatment is continued for 3- 5
months, & considered failed if
there is no response by then
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43. Treatment of phosphopenic rickets
Renal Fanconi
Syndrome
X- linked
hypophosphatemic
rickets
Hereditary
hypophosphatemia
with hypercalciuria
Tumour induced
osteomalacia
Bicarbonate
supplementation to
correct the metabolic
acidosis, which in turn will
reduce urinary calcium,
potassium & electrolyte
losses
Burosumab as first line
(monoclonal antibody to
FGF 23)
If Burosumab cannot be
given, then for calcitriol &
phosphate therapy
Phosphate alone Complete tumour
resection or Burosumab if
not possible
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44. References
• Overview of rickets in children- UpToDate
• Etiology and treatment of calcipenic rickets in children- UpToDate
• Hereditary hypophosphatemic rickets and tumor-induced osteomalacia- UpToDate
• Treatment of distal (type 1) and proximal (type 2) renal tubular acidosis- UpToDate
• Rickets- Osmosis.org & Radiopedia.org
• Ganong’s review of medical physiology, 24th edition
• www.basicmedicalkey.com
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