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Rickets & Osteomalacia - Pathology Study Guide (First Year MBBS)

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1. Basic Concept - What Are They?

The fundamental defect in both = failure of osteoid (unmineralized bone matrix) to calcify, leading to accumulation of unmineralized osteoid.

• Robbins & Kumar Basic Pathology, p. 3648

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2. Etiology / Causes

1. Adequate calcium and phosphate ions
2. Appropriate pH (~7.6)
3. Normal bone matrix composition
4. Control of inhibitors of mineralization

A. Vitamin D Deficiency (Most Common)

• Inadequate dietary intake (rare in developed countries due to food fortification)
• Lack of sunlight exposure (UV light converts 7-dehydrocholesterol → vitamin D3 in skin)
• Fat malabsorption - vitamin D is fat-soluble, so celiac disease, biliary/pancreatic disease, steatorrhea impair absorption
• Chronic liver disease - impairs 25-hydroxylation
• Chronic renal disease - impairs 1α-hydroxylation → cannot produce active 1,25(OH)2D3

Vitamin D Metabolism Pathway (Exam Favorite!)

7-dehydrocholesterol (skin)
         ↓ UV light
    Vitamin D3
         ↓ 25-hydroxylase (LIVER)
    25(OH)D3 (storage form, measured for screening)
         ↓ 1α-hydroxylase (KIDNEY)
    1,25(OH)2D3 = CALCITRIOL (ACTIVE FORM)
         ↓
    ↑ Calcium absorption from gut
    ↑ Calcium resorption from bone (via RANKL on osteoblasts)
    ↑ Calcium reabsorption from kidney

• Grainger & Allison's Diagnostic Radiology, p. 1103

B. Phosphate Depletion

• X-linked hypophosphatemia (vitamin D-resistant rickets) - defect in phosphate-regulating endopeptidase
• Renal phosphate wasting

C. Systemic Acidosis

• Disrupts mineralization pH

D. Other Rare Causes

• Vitamin D-dependent rickets Type I - defect in renal 1α-hydroxylase (autosomal recessive)
• Vitamin D-dependent rickets Type II - mutations in vitamin D receptor (end-organ resistance)
• Tumor-induced osteomalacia (TIO) - rare paraneoplastic syndrome; mesenchymal tumors secrete excess FGF-23, which inhibits renal phosphate reabsorption and 1α-hydroxylase

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3. Pathogenesis

1. Low vitamin D → decreased gut calcium absorption → hypocalcemia
2. Hypocalcemia stimulates parathyroid glands → secondary hyperparathyroidism (elevated PTH)
3. PTH increases osteoclast activity → bone resorption (RANKL pathway)
4. Osteoblasts continue laying down osteoid, but it fails to mineralize (no adequate Ca²⁺/PO₄³⁻)
5. Unmineralized osteoid accumulates → soft, weak bone

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4. Morphology / Histopathology

Rickets (Children) - Growth Plate Changes

1. Resting zone
2. Proliferating zone
3. Zone of hypertrophy (enlarged and distorted in rickets)
4. Zone of provisional calcification (absent/poorly defined in rickets)

• Widened, irregular, disorganized growth plate
• Enlarged and distorted zone of hypertrophy - cartilage cells fail to die/resorb
• Poorly defined zone of provisional calcification - calcification fails
• Widened osteoid seams ("Swiss cheese trabeculae") - bone trabeculae surrounded by thick rims of unmineralized osteoid
• Compensatory overgrowth of epiphyseal cartilage
• Secondary hyperparathyroidism causes osteoclastic bone resorption histologically
• Miller's Review of Orthopaedics, p. 322

Osteomalacia (Adults) - Bone Biopsy

• Widened osteoid seams (osteoid covers >20% of trabecular surface; normally <5%)
• Reduced mineral-to-osteoid ratio
• Increased unmineralized matrix throughout skeleton
• Looser zones (pseudofractures) - deposits of unmineralized osteoid at stress points or along nutrient vessels; appear as bilateral, symmetric transverse lucent bands on X-ray (pathognomonic!)
• Henry's Clinical Diagnosis & Management by Lab Methods

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5. Clinical Features

Rickets (Children)

• Fitzpatrick's Dermatology (Table 123-9) | Grainger & Allison's

Osteomalacia (Adults)

• Bone pain and tenderness (diffuse, especially pelvis, spine, legs)
• Muscle weakness (proximal myopathy)
• Skeletal deformities - triradiate pelvis (causes obstetric problems), protrusio acetabuli
• Pathological fractures (especially vertebral, femoral neck)
• Looser zones (pseudofractures) on X-ray - pathognomonic

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6. Radiology

Rickets (X-ray findings):

• Widening and irregularity of the growth plate (earliest sign)
• Cupping, fraying, and splaying of metaphyses (classic appearance)
• Blurring of epiphyseal-metaphyseal junction
• Generalized osteopenia (less radiodense bones)
• Cortical thinning
• Bowing of long bones (tibia, fibula, femur)
• Coxa vara or coxa valga (hip deformity)
• Changes most prominent at rapidly growing areas: knee (distal femur/proximal tibia), wrist (distal ulna), proximal femur, anterior rib ends
• Grainger & Allison's Diagnostic Radiology

Osteomalacia (X-ray findings):

• Looser zones / Milkman fractures (pseudofractures) - transverse lucent bands, bilateral and symmetric, typically at medial femoral neck, pubic rami, ribs, scapulae - pathognomonic
• Generalized decreased bone density (cannot distinguish from osteoporosis on X-ray alone)
• Triradiate pelvis (in severe long-standing cases)

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7. Lab Findings (Biochemistry)

• Henry's Clinical Diagnosis & Management

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8. Differences: Rickets vs. Osteoporosis vs. Osteomalacia (Exam Trap!)

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9. Types of Rickets - Summary Table

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10. Key Points for Your Exam

1. Fundamental defect = accumulation of unmineralized osteoid (failure of mineralization)
2. Rickets = growing skeleton (children); Osteomalacia = mature skeleton (adults) - same process
3. Vitamin D metabolism: skin → liver (25-OH) → kidney (1α-OH) → active calcitriol
4. Secondary hyperparathyroidism is always present in vitamin D deficiency
5. Rachitic rosary = swelling at costochondral junctions (most classic sign of rickets)
6. Looser zones = pathognomonic of osteomalacia
7. ALP is always elevated (key lab clue)
8. Histology: widened osteoid seams, enlarged zone of hypertrophy in growth plate, "Swiss cheese" trabeculae
9. Gold standard diagnosis = undecalcified bone biopsy
10. X-linked hypophosphatemia = most common hereditary form; phosphate wasting; FGF-23 elevated

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