Acquired diseases of bone development (osteoporosis, rickets, osteomalacia)

1. Overview

Nutritional deficiencies causing bone disease:

• Vitamin C → collagen cross-linking → scurvy.
• Vitamin D → Ca²⁺ uptake → rickets + osteomalacia.

2. Osteoporosis

Definition

• Skeletal disease of reduced bone mass → ↑ porosity of skeleton → ↑ bone fragility → ↑ fracture susceptibility.
• Histologically normal bone, just less of it.

Classification

A) Primary Osteoporosis

• Senile osteoporosis: age-related; affects everyone eventually.
• Postmenopausal osteoporosis: ↑ rate after menopause from ↓ estrogen.

B) Secondary Osteoporosis

• Endocrine: hyperparathyroidism, Addison disease, hyperthyroidism, Cushing, hypogonadism.
• GI: vit C/D deficiency, malabsorption, malnutrition.
• Drugs: corticosteroids (#1 secondary cause), anticoagulants (heparin), antiseizure.
• Other: osteogenesis imperfecta, chronic pulmonary disease, immobilization.

Pathogenesis

• Dynamic equilibrium between:
  • Osteoblasts (formation)
  • Osteocytes (maintenance)
  • Osteoclasts (resorption)
• Osteoporosis = balance tilts toward resorption.

Contributing factors

• Age: osteoblast activity ↓ but osteoclast activity unchanged.
• Hormones: estrogen decline (menopause) → ↑ RANKL signaling → ↑ osteoclast activity.
• Physical activity: mechanical loading stimulates remodeling; immobility → bone loss.
• Genetic: vitamin D receptor polymorphisms.
• Ca²⁺ nutrition: low intake → earlier osteoporosis.
• Secondary causes: glucocorticoids ↑ resorption + ↓ formation.

Morphology

• Thinned cortices.
• Attenuated trabeculae (especially vertical loading-bearing).
• Normal mineralization.

Clinical Course

• Thoracic + lumbar vertebral fractures → loss of height, kyphosis (dowager’s hump), compromised respiration.
• Femoral neck, pelvis, spine fractures → risk of PE + pneumonia (immobility).
• Distal radius (Colles fracture).

Diagnosis

• DEXA scan → T-score ≤ –2.5 = osteoporosis.
• Labs: Ca²⁺, PO₄, ALP, PTH normal.

Treatment

• Ca²⁺ + vitamin D supplementation.
• Regular weight-bearing exercise.
• Bisphosphonates (alendronate) — ↓ resorption.
• Others: denosumab (anti-RANKL), teriparatide (PTH analog), SERMs (raloxifene), estrogen.

3. Rickets + Osteomalacia

Definition

• Both = vitamin D deficiency / abnormal metabolism.
• → Formation of abundant non-mineralized osteoid.
• Rickets = childhood; deranged bone growth + skeletal deformities (before epiphyseal closure).
• Osteomalacia = adult equivalent; low mineral density (osteopenia) → ↑ fractures.

Pathogenesis

• Diet deficient in Ca²⁺ + vitamin D.
• Occurs in limited sunlight exposure (northern climates, heavily veiled women, dark-skinned populations).
• Vit D deficiency → ↓ intestinal Ca²⁺ absorption → hypocalcemia → ↑ PTH (secondary hyperparathyroidism):
  • Mobilizes Ca²⁺ from bone.
  • ↓ Renal Ca²⁺ excretion.
  • ↑ Renal PO₄³⁻ excretion (→ hypophosphatemia).

Clinical Features of Rickets

• Pigeon-breast deformity (sternum protrusion).
• Frontal bossing (forehead prominence).
• Bowing of legs (genu varum).
• Rachitic rosary (costochondral junction beading).
• Craniotabes (soft skull), delayed fontanelle closure.
• Delayed dentition.

Clinical Features of Osteomalacia

• Weak bones → ↑ fracture risk (unmineralized bone).
• ↓ Ca²⁺ + ↓ PO₄³⁻ + ↑ PTH + ↑ ALP.
• Bone pain, proximal muscle weakness.
• Looser zones (pseudofractures) on X-ray.

4. Comparison Table

Feature	Osteoporosis	Osteomalacia / Rickets
Defect	↓ Bone mass (normal mineralization)	↓ Mineralization (excess unmineralized osteoid)
Cause	Aging, menopause, steroids, secondary	Vitamin D deficiency
Ca²⁺	Normal	↓
PO₄³⁻	Normal	↓
PTH	Normal	↑ (secondary HPT)
ALP	Normal	↑
Fractures	Vertebrae, hip, distal radius	Looser zones; bowed legs (rickets)

💡 High-yield: Osteoporosis = ↓ bone mass with normal mineralization; postmenopausal (estrogen ↓) + senile + steroids (#1 secondary); Ca/PO₄/PTH/ALP normal; DEXA T ≤ –2.5; vertebral compression fractures + hip fractures + PE/pneumonia; Tx = bisphosphonates + Ca + vit D + exercise. Rickets (kids) + Osteomalacia (adults) = vitamin D deficiency → ↓ mineralization + abundant unmineralized osteoid; ↓ Ca + ↓ PO₄ + ↑ PTH + ↑ ALP; rickets = bowed legs + frontal bossing + rachitic rosary + pigeon chest + craniotabes; osteomalacia = bone pain + Looser zones + fractures.