Makindo Medical Notes

Related Subjects: |Cardiac Physiology |Renal Physiology |Pulmonary Physiology |Pancreas Physiology |Spleen Physiology |Gastrointestinal tract Physiology |Brainstem Physiology |Bone Physiology

🦴 Bone physiology examines the structure, function, and dynamic remodeling of the skeletal system — a living tissue that constantly adapts to mechanical, metabolic, and hormonal signals. Bones provide the rigid framework for movement, protect vital organs, serve as a mineral reservoir for calcium and phosphate, and house the bone marrow responsible for haematopoiesis. Although seemingly inert, bone is in a continuous cycle of formation and resorption that maintains both skeletal strength and mineral homeostasis.

🏗️ Structure and Composition of Bone

• Bone Types:
  • Cortical (Compact) Bone:
    • Dense and forms ~80% of skeletal mass, predominantly in the shafts (diaphyses) of long bones.
    • Organised into osteons (Haversian systems) — concentric lamellae around a central canal containing blood vessels and nerves.
    • Provides mechanical strength and resistance to bending and torsion.
  • Trabecular (Cancellous/Spongy) Bone:
    • Porous network of trabeculae at the epiphyses and vertebral bodies.
    • Contains red or yellow bone marrow and contributes to metabolic exchange (calcium mobilisation).
    • High turnover rate → early site of osteoporosis.
• Bone Matrix:
  • Organic component (≈30%): Predominantly type I collagen, providing tensile strength and flexibility.
  • Inorganic component (≈70%): Crystals of hydroxyapatite [Ca₁₀(PO₄)₆(OH)₂], conferring hardness and compressive strength.
  • Also contains small quantities of non-collagenous proteins (osteocalcin, osteonectin) and proteoglycans that regulate mineralisation.
• Bone Cells:
  • Osteoblasts:
    • Derived from mesenchymal stem cells; responsible for bone formation and mineralisation.
    • Secrete collagen, alkaline phosphatase, and osteocalcin.
    • Some become trapped in the matrix and differentiate into osteocytes.
  • Osteocytes:
    • Mature cells within lacunae; maintain bone tissue and sense mechanical stress.
    • Connected via canaliculi to form a cellular network for ion and nutrient exchange.
    • Secrete sclerostin, which inhibits bone formation (Wnt pathway regulation).
  • Osteoclasts:
    • Multinucleated, macrophage-derived cells that resorb bone.
    • Form resorption lacunae (Howship’s lacunae) by secreting acid and proteolytic enzymes.
    • Activity regulated by RANK–RANKL–OPG system:
      • RANKL (from osteoblasts) binds to RANK on osteoclast precursors to promote differentiation.
      • Osteoprotegerin (OPG) acts as a decoy receptor, inhibiting osteoclast activation.

🧬 Bone Development and Growth

• Ossification (Osteogenesis):
  • Intramembranous Ossification: Direct bone formation from mesenchyme — occurs in flat bones (skull, mandible, clavicle). Osteoblasts form ossification centres that secrete osteoid and mineralise rapidly.
  • Endochondral Ossification: Bone forms on a cartilage model. Cartilage is replaced by bone via chondrocyte hypertrophy, calcification, and invasion of osteogenic cells. Responsible for long bone elongation at the epiphyseal growth plates.
• Bone Growth:
  • Longitudinal Growth: Occurs at growth plates — chondrocytes proliferate, enlarge, and ossify, adding length until closure at puberty.
  • Appositional Growth: Osteoblasts beneath the periosteum deposit new lamellae → increased diameter and strength.

♻️ Bone Remodeling and Turnover

• Bone remodeling is a lifelong process maintaining both structural integrity and calcium homeostasis:
  • Basic Multicellular Units (BMUs): Clusters of osteoclasts and osteoblasts that resorb and rebuild bone.
  • Cycle duration: ~3–6 months; about 5–10% of adult skeleton renewed annually.
  • Wolff’s Law: Bone remodels in response to mechanical stress — load-bearing stimulates deposition, disuse causes resorption.
  • Remodeling also repairs microdamage and prevents fatigue fractures.

🔬 Regulation of Bone Physiology

• Hormonal Regulation:
  • Parathyroid Hormone (PTH):
    • Released in response to low plasma Ca²⁺.
    • Stimulates osteoblasts to express RANKL → osteoclast activation → bone resorption.
    • Enhances renal Ca²⁺ reabsorption and 1,25(OH)₂D synthesis.
  • Calcitonin: Secreted by thyroid C cells; inhibits osteoclasts to reduce serum calcium — clinically used in hypercalcaemia.
  • Vitamin D (Calcitriol): Enhances intestinal Ca²⁺ and phosphate absorption; promotes mineralisation; deficiency causes osteomalacia/rickets.
  • Growth Hormone and IGF-1: Stimulate chondrocyte proliferation and osteoblast activity — deficiency causes short stature, excess causes gigantism/acromegaly.
  • Sex Hormones (Oestrogen/Testosterone): Promote bone formation, inhibit resorption; loss of oestrogen after menopause accelerates bone loss.
  • Glucocorticoids: Inhibit osteoblasts and enhance resorption — chronic use causes secondary osteoporosis.
• Mechanical Regulation:
  • Physical stress generates electrical potentials that stimulate osteoblastic activity (piezoelectric effect).
  • Weight-bearing exercise increases bone density, particularly in trabecular-rich regions (femoral neck, vertebrae).
  • Disuse (e.g. immobilisation, spaceflight) causes rapid bone loss through increased resorption and decreased formation.

🩹 Bone Healing and Repair

• Fracture healing occurs in three overlapping phases:
  • Inflammatory Phase (Days 1–7): Haematoma forms; inflammatory cells release cytokines (IL-1, TNF, TGF-β) to recruit osteoprogenitors.
  • Reparative Phase (Weeks 1–6): Formation of soft (fibrocartilaginous) callus → replaced by hard callus through endochondral ossification.
  • Remodelling Phase (Months–Years): Woven bone replaced by lamellar bone along lines of stress.
• Effective healing requires vascular supply, stability, adequate calcium, vitamin D, and avoidance of infection.

⚕️ Clinical Correlations

• Osteoporosis:
  • Reduced bone mass and microarchitectural deterioration → fragility fractures (spine, hip, wrist).
  • Risk factors: age, postmenopausal oestrogen loss, glucocorticoid use, inactivity.
  • Treatments: Bisphosphonates (inhibit osteoclasts), Denosumab (anti-RANKL), Teriparatide (intermittent PTH analogue to stimulate osteoblasts).
• Osteomalacia / Rickets:
  • Defective mineralisation due to vitamin D deficiency or phosphate loss.
  • Children: bowing of legs and rachitic rosary; adults: bone pain, pseudofractures.
• Paget’s Disease of Bone (Osteitis Deformans):
  • Localised excessive bone turnover: chaotic resorption and formation → enlarged, deformed bones.
  • Causes pain, fractures, and elevated ALP; treated with bisphosphonates.
• Osteogenesis Imperfecta:
  • Genetic collagen type I defect → brittle bones, blue sclerae, hearing loss.
• Renal Osteodystrophy:
  • Chronic kidney disease → phosphate retention, ↓ vitamin D activation, secondary hyperparathyroidism → bone demineralisation.
• Fracture Malunion/Non-Union:
  • Results from poor immobilisation, infection, or impaired blood supply (e.g. scaphoid, femoral neck).

📊 Quantitative Bone Facts

• Total body calcium: ~1 kg, 99% in bone as hydroxyapatite.
• Adult skeleton mass: ~10–12 kg; renewed every 10 years.
• Peak bone mass achieved around age 30; declines ~0.5–1% per year thereafter (accelerated post-menopause).
• Serum Ca²⁺ tightly regulated at 2.2–2.6 mmol/L; small deviations affect neuromuscular excitability.

🧠 Summary and Integration

Bone is a living organ integrating mechanical, hormonal, and metabolic functions. It constantly remodels to adapt to physical stress and maintain calcium homeostasis. The interplay between osteoblasts, osteoclasts, and osteocytes — governed by the RANK–RANKL–OPG and Wnt–sclerostin pathways — underpins skeletal health. Disruption of these systems leads to diseases such as osteoporosis, rickets, and Paget’s disease. Understanding bone physiology is crucial for effective prevention and management of musculoskeletal disorders across the lifespan.

💡 Teaching Tip: Think of bone as a “biological bank”: Osteoblasts are the deposit clerks, adding mineral; osteoclasts are the withdrawal officers; and osteocytes are the accountants ensuring balance. In osteoporosis, withdrawals exceed deposits; in Paget’s disease, the transactions are chaotic — the secret is maintaining a healthy ledger through load, hormones, and nutrition.