RICKETS & OSTEOMALACIA

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.

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

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)

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)

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

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

↓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)

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

↑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.

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

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

Rachitic growth plate

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

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

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

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)

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.

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

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

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)

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.

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

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

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

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