1. RICKETS & OSTEOMALACIA

2. Objectives Define osteomalacia & rickets & list the causes
Explain the metabolic defects that cause Rickets and Osteomalacia
Understand why a lack of vitamin D presents with deformity of the skeleton in a child (rickets), but not in an adult (osteomalacia).
Compare the clinicopathologic features of Rickets & Osteomalacia and differentiate them from those of Osteoporosis.

3. Osteomalacia & Rickets
Osteomalacia (soft bones): Decreased mineralization of newly formed bone matrix → pathologic fractures (Osteopaenia on X rays)
Rickets : Similar condition but in children = growth plates (physes) are open → defective mineralization of :
Bone matrix & of the cartilaginous matrix of the growth plate → microfractures and bone deformities

5. Causes of Rickets and Osteomalacia
1. ↓ed Synthesis or ↓ed Dietary vit D
Inadequate exposure to sunlight
Limited dietary intake of fortified foods
2. ↓ed Absorption of fat-soluble vitamin D in the intestine (Malabsorption syndromes)

6. 3. Defective Vit D Metabolism
↑ed degradation (enzyme induction)
Defective synthesis of 25(OH)D (liver disease)
Defective synthesis of 1,25(OH)2 D (Advanced renal disease & Inherited deficiency of renal α1-hydroxylase)
End-organ resistance to 1,25(OH)2 D (defective receptors for metabolites of vit D)

7. 4. Phosphate depletion
Poor absorption of Phosphate due to chronic use of antacids
Excess renal tubular excretion of Phosphate (X-linked hypophospatemic rickets)

8. Fundamental rule
Calcium is deposited in bone matrix in the form of Calcium phosphate
Even if serum calcium is normal, mineralization cannot occur unless serum phosphate levels are also adequate

9. ↓ed serum PO4 levels mean that although serum Ca level may be brought to normal by PTH but mineralization of bone defective
Bone trabeculae normal thickness but have more osteoid than normal (osteopenia)

10. Deficiency of vitamin D↓
Tendency for Hypocalcemia
↑ed PTH production

11. ↑ed PTH production ↑ed Absorption of Vit D & Ca↓
↑ed Absorption of Vit D & Ca
↑ed Mobilization of calcium from bone
↓ed Renal calcium excretion
But ↑ed Renal excretion of phosphate
Serum Ca++ normal but Hypophosphatemia persists, and so mineralization of bone is impaired.

12. Morphology of Rickets
The basic derangement in both rickets and Osteomalacia is an excess of unmineralized matrix (excess osteoid)
Total bone mass is normal, but bone is weak = low calcium ( Osteopenia on X ray)
In Rickets there is defective mineralization of bone and of the cartilage of the endochondral ossification at the growth plate

13. Morphology of Rickets
Failure of mineralization in growing bones & cartilage of children
Inadequate provisional calcification of epiphyseal cartilage →
Recurrent microfractures of bone and of growth plate cartilage
Defective endochondral bone growth
Deformities of skeleton

15. Rachitic growth plate

16. Sequence of changes in Rickets
↓ed calcification of growth plate cartilage
Failure of the growth plate cartilage cells to mature and disintegrate
Overgrowth of epiphyseal cartilage
Persistence of distorted, irregular masses of cartilage projecting into medullary cavity

17. Excess osteoid matrix on inadequately calcified cartilaginous remnants
Replacement of cartilage by osteoid matrix, with enlargement and lateral expansion of the costochondral junction→Rickety rosary

18. Microfractures of inadequately
mineralized, weak, poorly formed bone
Deformaties due to loss of structural rigidity of the developing bones
Total bone mass normal but excess osteoid→ Osteopenia on X’ ray

19. Gross, Clinical & Radiologic skeletal changes
According to:
Severity of the rachitic process
Duration of the condition
Stresses to which individual bones are subjected (whether child is crawling, walking, running)

20. Nonambulatory stage of infancy
Head and chest affected most
Softened occipital bones
Excess osteoid → Frontal bossing + squared appearance of the head
Excess cartilage or osteoid at the costochondral junction → "rachitic rosary."
Deformation of the chest.

21. The weakened metaphyseal areas of the ribs are subject to the pull of the respiratory muscles and bend inward → Anterior protrusion of sternum (pigeon chest deformity)
Inward pull at the margin of the diaphragm creates the Harrison groove, girdling the thoracic cavity at the lower margin of the thoracic cage
Possible pelvic deformity

25. In the ambulating child
Deformities are likely to affect the spine, pelvis, and long bones (e.g., tibia), causing lumbar lordosis and bowing of the legs

27. In adults= Osteomalacia
↓ed vitamin D→ Defective bone remodeling
Osteoid matrix inadequately mineralized
Large osteoid seams (Osteopenia)
Bone is weak → gross fractures or microfractures (vertebral bodies and femoral necks)

28. Total bone mass is normal but the bone is weak and vulnerable to gross fractures or microfractures, which are most likely to affect vertebral bodies and femoral necks.

29. Microscopically
Excess osteoid matrix (which stains pink in H&E preparations) around the more basophilic, normally mineralized trabeculae.
X ray = osteopenia→ difficult to differentiate osteomalacia from other osteopenias such as osteoporosis
Loosers’ zones = incomplete fractures

33. Rickets
Osteomalacia
Osteoporosis
Children
Old age
Skeletal deformities
Deformities not common and affect vertebrae
Deformities not common & affect vertebrae
Microfractures usual
Pathologic fractures
Serum calcium or phospate is low
Serum calcium is low
No biochemical
changes in blood

34. Rickets
Osteomalacia
Osteoporosis
Serum calcium or phospate is low
Serum calcium is low
No biochemical
changes in blood
Males& females equally affected unless it is X linked
Females more often
Females more often=postmenopause & senility
↓ed mineralizat. of Bone & cartilage at growth plate
Decreased mineralization of bone
No defect in mineralization

35. Total bone mass is normal but inadequate calcification
Total bone mass is reduced
Trabeculae of normal thickness, but bone and cartlage may be distorted & with microfractures
Increased osteoid seams
Trabeculae of bone are of normal thickness, but may be distorted & with microfractures
Thin, interrupted trabeculae with adequate calcium
No increase in Osteoid