Bone Remodeling: Coupled Resorption and Formation Throughout Life

Bone remodeling is the lifelong cycle of osteoclast-mediated resorption followed by osteoblast-mediated formation, occurring in basic multicellular units (BMUs) on trabecular and endocortical surfaces.

Resorption (Osteoclasts)

• Acidify lacuna (H⁺-ATPase) → dissolve mineral.
• Secrete cathepsin K, MMPs → degrade collagen.
• Release Ca²⁺, PO₄³⁻, growth factors (TGF-β, IGF-1) into circulation.

Formation (Osteoblasts)

• Differentiate from mesenchymal precursors (Runx2, Osterix).
• Deposit osteoid (type I collagen + non-collagenous proteins).
• Mineralize with hydroxyapatite [Ca₁₀(PO₄)₆(OH)₂].

Regulation

• Hormonal: PTH (intermittent → anabolic; continuous → catabolic), calcitonin (inhibits resorption), estrogen (↓ osteoclastogenesis), vitamin D (↑ Ca absorption, osteoblast function), GH/IGF-1.
• Mechanical: Strain → Wnt/β-catenin → osteoblast activity; disuse → sclerostin ↑ → resorption.
• Nutritional: Ca, vit D, protein, Mg, K, vit K₂.

Clinical Imbalance

Osteoporosis = resorption > formation. Anabolic agents (teriparatide, romosozumab) stimulate formation; antiresorptives (bisphosphonates, denosumab) inhibit resorption.