🦴 Bone Physiology
Bone cells, cortical vs cancellous architecture, Wolff’s Law, blood supply of long bones, primary vs secondary fracture healing, and bone graft types — fully mapped to MRCS Applied Basic Sciences.
The Four Bone Cells
Bone is a dynamic connective tissue composed of a protein matrix (predominantly type I collagen — 90% of the organic matrix) and an inorganic mineral phase (calcium hydroxyapatite). Understanding the four cell types and their roles is a high-yield MRCS topic.
Osteoprogenitor Cells
- Pluripotential mesenchymal stem cells — the earliest committed precursor
- Located on all bony surfaces (periosteum, endosteum, Haversian canals)
- Divide mitotically to produce osteoblasts in response to bone injury or growth signals
- Respond to PTH, Wnt signalling, and mechanical load
Osteoblasts
- “Bone builders” — mononuclear, derived from osteoprogenitor cells
- Synthesize, transport and arrange the organic matrix (osteoid) — type I collagen + proteoglycans
- Initiate mineralisation by releasing matrix vesicles containing calcium and phosphate
- Express RANKL — the signal that activates osteoclasts (the coupling mechanism)
- Fate: become osteocytes (trapped), bone-lining cells, or undergo apoptosis
Osteocytes
- Mature bone cells formed when osteoblasts become trapped within mineralised matrix
- The most numerous bone cell (~95% of all cells)
- Communicate via long cytoplasmic processes through canaliculi — a network linking all osteocytes
- Mechanosensors — translate mechanical strain into biochemical signalling (mechanotransduction)
- Produce sclerostin (inhibits Wnt/osteoblast activity) and FGF-23 (regulates phosphate)
Osteoclasts
- Derived from monocyte/macrophage lineage (haematopoietic, not mesenchymal)
- Multinucleated giant cells (5–50 nuclei)
- Attach to bone surface via integrin receptors, creating a sealed “ruffled border” resorption pit (Howship’s lacuna)
- Secrete hydrochloric acid (via H⁺/K⁺-ATPase) → dissolves hydroxyapatite
- Secrete cathepsin K and MMPs → degrade the collagen matrix
- Activated by RANKL (from osteoblasts); inhibited by osteoprotegerin (OPG)
This signalling triad governs the balance between bone formation and resorption and is a key MRCS exam concept:
| Molecule | Produced by | Action | Clinical Relevance |
|---|---|---|---|
| RANKL (Receptor Activator of NF-κB Ligand) | Osteoblasts, T-cells, stromal cells | Binds RANK on osteoclast precursors → osteoclast activation and survival → increased resorption | Elevated in osteoporosis, rheumatoid arthritis, bone metastases; target of denosumab |
| RANK (Receptor Activator of NF-κB) | Osteoclast precursors | Transmembrane receptor that, when bound by RANKL, activates osteoclastogenesis | Mutations cause familial expansile osteolysis |
| OPG (Osteoprotegerin) | Osteoblasts, stromal cells | Decoy receptor — binds RANKL to prevent it activating RANK → inhibits osteoclast formation | OPG/RANKL ratio determines net bone balance; oestrogen upregulates OPG (explains post-menopausal osteoporosis) |
Why Cell Lineage Matters Surgically
Osteoblasts and osteoclasts have completely different lineages — a common MCQ trap. Osteoblasts are mesenchymal (same family as fibroblasts, chondrocytes, adipocytes). Osteoclasts are haematopoietic (monocyte/macrophage line). This means in Paget’s disease, the primary defect is in osteoclasts, not osteoblasts. In fibrous dysplasia, it is the mesenchymal lineage that is abnormal.
Tightly linked to bone cell activity — frequently tested in MRCS alongside bone physiology:
| Hormone | Source | Effect on Bone | Effect on Ca²⁺ | Surgical Relevance |
|---|---|---|---|---|
| PTH | Chief cells of parathyroid | ↑ osteoclast activity (via RANKL upregulation on osteoblasts) → ↑ resorption | ↑ serum Ca²⁺ | Primary hyperparathyroidism → osteitis fibrosa cystica; “brown tumours” |
| Vitamin D (1,25-OH) | Kidney (1α-hydroxylase) | ↑ osteoblast activity at physiological levels; also supports osteoclast activation | ↑ serum Ca²⁺ (↑ gut absorption) | Deficiency → rickets (children), osteomalacia (adults) — weak unmineralised osteoid |
| Calcitonin | Parafollicular C-cells of thyroid | ↓ osteoclast activity → ↓ resorption | ↓ serum Ca²⁺ | Marker for medullary thyroid carcinoma (MEN2) |
| Oestrogen | Ovaries (and peripheral aromatisation) | ↑ OPG → ↓ osteoclast activity; protective | Mild ↑ (promotes gut absorption) | Post-menopausal ↓ oestrogen → ↑ bone resorption → osteoporosis |
| Glucocorticoids | Adrenal cortex / exogenous | ↓ osteoblast activity + ↑ osteoclast activity → net bone loss | ↓ (↓ gut absorption) | Long-term steroids → avascular necrosis (femoral head), osteoporosis |