Bone & Joint Pathology: Basic Structure, Cells, and Fract...

Got it. Here are the notes: --- BONE & JOINT PATHOLOGY — Condensed Study Notes Dr Lilian Bosire MKU Pathology --- PART 1: BASIC STRUCTURE AND FUNCTION OF BONE Composition The adult skeleton has 206 bones (~12% body weight). Functions include mechanical support, organ protection, mineral homeostasis, and hematopoiesis. Matrix (extracellular component): Osteoid (35%) — type I collagen + glycosaminoglycans + osteopontin (osteocalcin) Minerals (65%) — primarily hydroxyapatite [Ca10(PO4)6(OH)2]; stores 99% of body calcium and 85% of phosphorus Serum osteopontin = marker of osteoblast activity Matrix types: Woven bone — rapidly produced, haphazard collagen arrangement, structurally weak. Always abnormal in adults Lamellar bone — parallel collagen fibers, strong, normal mature bone --- Bone Cells Cell Origin Function ------ --------- ---------- Osteoblast Mesenchymal Synthesizes and assembles osteoid; regulates mineralization Osteocyte Embedded osteoblast Detects mechanical forces (mechanotransduction); regulates Ca/PO4 Osteoclast Circulating monocytes Resorbs bone via acid + MMPs in a sealed resorption pit --- Development Most bones form via endochondral ossification — cartilage mold (anlage) replaced by bone: Primary ossification center — diaphysis Secondary ossification centers — epiphyses Growth plates (physes) — chondrocytes proliferate, hypertrophy, then undergo apoptosis; matrix mineralizes and is replaced by bone Flat bones (e.g., cranium) form via intramembranous ossification — mesenchyme ossified directly, no cartilage intermediate. Key regulators of bone development: Factor Source Effect -------- -------- -------- Growth hormone Anterior pituitary Chondrocyte proliferation Thyroid hormone Thyroid Chondrocyte hypertrophy PTHrP Perichondrium Maintains chondrocyte proliferation Indian hedgehog (Ihh) Prehypertrophic chondrocytes Coordinates chondrocyte/osteoblast proliferation FGF-3 Mesenchymal cells Inhibits chondrocyte proliferation SOX9 Proliferating chondrocytes Chondrocyte differentiation RUNX2 Hypertrophic chondrocytes Osteoblast and terminal chondrocyte differentiation BMPs (TGF-β family) Various Diverse effects on chondrocyte proliferation/hypertrophy Wnt/β-catenin Growth plate Chondrocyte proliferation and maturation --- Remodeling and Homeostasis Approximately 10% of skeleton remodeled per year within the Basic Multicellular Unit (BMU) — coupled osteoclast and osteoblast activity. RANK/RANKL/OPG pathway: RANK — receptor on osteoclast precursors RANKL — expressed on osteoblasts/stromal cells; binds RANK → activates NF-κB → osteoclast generation and survival OPG — decoy receptor secreted by osteoblasts; binds RANKL, blocking RANK activation → inhibits bone resorption M-CSF — produced by osteoblasts; also essential for osteoclast generation Sclerostin — produced by osteocytes; inhibits WNT/β-catenin → reduces bone formation Systemic modulators: Factor Effect on Bone -------- ---------------- PTH, IL-1, glucocorticoids Promote osteoclast differentiation → bone resorption Sex hormones, BMPs Promote OPG expression → bone deposition Estrogen, testosterone Block osteoclast activity --- PART 2: FRACTURES Types Type Description ------ ------------- Simple Skin intact Compound Bone communicates with skin surface Comminuted Bone fragmented Displaced Bone ends not aligned Stress Slowly developing; repetitive loading Greenstick Incomplete; common in infants Pathologic Through bone weakened by disease --- Fracture Healing — Stages 0–1 day: Hematoma formation — fibrin mesh seals site; platelets release PDGF, TGF-β, FGF → activate osteoprogenitor cells 0–2 weeks (Soft callus): Osteoprogenitor cells proliferate; woven bone trabeculae deposited subperiosteally; fibrocartilage and hyaline cartilage formed by chondrocytes 2–3 weeks (Bony callus): Endochondral ossification converts cartilage to bone; fracture ends bridged; callus stiffens; weight bearing possible 3 weeks–months: Remodeling — woven bone replaced by lamellar bone; medullary cavity restored; excess callus resorbed Near-perfect union is the norm in children. In older adults, surgical immobilization often required. Complications of poor healing: Inadequate immobilization → delayed union or nonunion Nonunion → pseudoarthrosis (false joint with synovial-like lining) Open fractures → infection Malnutrition, skeletal dysplasia --- PART 3: OSTEONECROSIS (AVASCULAR NECROSIS) Infarction of bone and marrow. Can be medullary or subchondral. Common causes: Fractures, corticosteroid use, alcohol abuse, sickle cell crisis, bisphosphonate therapy, radiation, Gaucher disease, dysbarism Morphology: Medullary infarcts — geographic; trabecular bone + marrow necrosis; collateral flow limits cortical involvement Subchondral infarcts — wedge/triangular shape; overlying cartilage survives (nourished by synovial fluid); dead bone shows empty lacunae + necrotic adipocytes; calcium soaps form from released fatty acids Outcome: Subchondral infarcts collapse → secondary osteoarthrit