Bone Tissue PDF

# Bone Tissue ## Bone Cells - **Osteoblast**: form bone cells - **Osteocytes**: mature bone cells - **Osteoclasts**: break down bone matrix - **Osteogenic cells**: stem cells in periosteum & endosteum give rise to osteoblasts ## Bone Types - **Compact**: also known as cortical - **Spongy**: als...

# Bone Tissue ## Bone Cells - **Osteoblast**: form bone cells - **Osteocytes**: mature bone cells - **Osteoclasts**: break down bone matrix - **Osteogenic cells**: stem cells in periosteum & endosteum give rise to osteoblasts ## Bone Types - **Compact**: also known as cortical - **Spongy**: also known as trabecular - **Woven bone**: produced rapidly in fetal development, fracture repair. - Naphtazard arrangement of collagen fibers - Less structural integrity, bone producing tumors are woven - Presence always abnormal but non-specific - **Lamellar bone**: mature bone found in adult skeleton - Cortical and trabecular bone are lamellar - Slow formation, durable, mineralized - Hypocellular but more mineralized - Parallel collagen fibers ## Ossification - **Endochondral ossification**: development of long bones - **Intramembranous ossification**: development of flat bones ## Osteoclast Regulation - **Paracrine metabolism of Osteoclast Regulation** - RANKL (on osteoblast & marrow stromal cells) bind RANK (on surface of osteoclast precursors) - Osteoprotegerin/OPG (produced by osteoblasts) block RANKL-RANK interaction - Bone resorbtion/formation ratio = RANK-OPG ratio. - PTH, 1,25-dihydroxyvitamin D, glucocorticoids promote osteoclasts & bone turnover. - BMP, sex hormones block osteoclast, favor OPG expression ## Achondroplasia - Autosomal dominant - Most common dwarfism - Affects endochondral ossification - Point mutation in FGFR3 (inhibit chondrocyte proliferation on growth plate - Short proximal extremities, normal trunk, enlarged head, bulging forehead, nose root depression - No change in longevity, intelligence, reproductive status ## Osteogenesis Imperfecta - Brittle bone disease (cam kemik) - Defective synthesis of type I collagen - Numerous extraskeletal manifestations due to defective synthesis of type I collagen - Premature degradation of type I collagen - Too little bone → Extreme skeletal fragility - Type I: normal lifespan, tendency for fractures during childhood - Type II: uniformly lethal in utero/postpartum → multiple fractures - Result in bone deformities - Blue sclerae (scleral collagen) - Hearing loss (conduction defect in ear bones) - Small misshapen teeth (dentin deficiency) ## Osteopetrosis - Defective osteoclast mediated bone resorption - Stone/marble bone disorder - CA2, TCIRGI mut. - Turnover → "piece of chalk" - Severe osteopenia → ↑ risk of fracture - Bone mass, bone fragility, susceptibility to fractures - High turnover - Senile (with aging) → ↑ RANKL, ↓ OPG - Primary Osteoporosis - Histologically normal bone decreased in quantity - Vertebral fractures (kyphoscoliosis) compromise respiratory function - Fractures of femoral neck, pelvis, spine → Pulmonary embolus, pneumonia → death - Asymptomatic until fracture - DEXA ≤ 2.5 → LRP5 mut. ## Hyperparathyroidism - ↑ PTH → ↑ osteoclastic activity → bone resorption → osteopenia - Entire skeleton is affected, but some bones (phalanges) are more conspicuous in radiography - PTH central role in calcium homeostasis - Osteoclastic activation (↑ RANKL) - Resorption of calcium by renal tubules - ↑ urinary excretion of phosphates - Synthesis of active Vitamin D from kidneys → Ca absorption from gut - PTH → ↑ serum calcium ## Secondary Hyperparathyroidism - Chronic renal failure → ↓ active form of Vitamin D - Inadequate 1.25(OH)2-D synthesis → Affect GI Ca absorption - Due to ↓ serum Ca → ↑ PTH occurs. - Reversible by reduction of PTH levels. ## Brown Tumor - Osteitis fibrosa cystica - Manifestation of symptomatic, untreated hyperparathyroidism - Generalized osteoporosis most severe in phalanges, vertebrae, femur - Bone loss, micro fractures & secondary hemorrhages that elicit influx of macrophages and ingrowth - Reparative fibrous tissue, creating mass of reactive tissue → Brown Tumor - Brown color result of vascularity, hemorrhage, hemosiderin ## Paget Disease - Osteitis deformans - Increased but disordered, structurally unsound bone - Phases: - Osteolytic - Osteoclastic-osteoblastic: by unusually prominent cement lines - Osteosclerotic: hallmark: mosaic pattern lamellar bone - Present mid-late adulthood ## Factors Affecting Paget Disease - Both genetic & environmental - 50% familial, 10% sporadic - Mutations in SQSTM1 (PRANK, ↓ osteoclastic activity) - Activating mut. in RANK & inactivating mut. in OPG account - Some cases of juvenile Paget disease - 15% monostotic (involve one bone) - 35% polyostotic → Axial skeleton/proximal femur 80% of cases - ↑ serum alkaline phosphatase & ↑ urinary excretion of hydroxyproline - Reflect increased bone turnover - In some patients, early hypervascular bone lesions cause warmth of overlying skin. - With extensive polyostotic hypervascularity → High-output congestive heart failure - Involving skull → Headache, visual/auditory disturbance - Brittle long bones subject to chalk-stick fractures. - 1-1. Sarcoma development (osteosarcoma) - Treatment: biphosphonates, interfere with bone resorption ## Factors Disturbing the Healing of Fracture - Displaced & comminuated (para-axial) fractures - Delay healing, enlarges callus, long remodelling - Inadequate immobilisation - Normal constituents of callus do not form. - Unstable tissue → Delayed union & non-union - pseudoarthrosis - Central portion of callus cystic degeneration, false joint - Infection - Malnutrition & skeletal dysplasia ## Pyogenic Osteomyelitis - Inflammation of bone & marrow due to infection - Hematogenous dissemination - Most frequent causative → Staphylococcus aureus ## Osteomyelitis Complications - Suppurative & ischemic injury → Segmental bone necrosis - Rupture of periosteum → Subperiosteal abscess → Draining sinus - Epiphyseal infection spread → Suppurative arthritis - Extensive destruction of articular cartilage → Permanent disability - **Sequestrum**: necrotic bone embedded in infected granulation tissue - **Involucrum**: new bone by periosteum that surrounds sequestra. ## Tuberculous Osteomyelitis - Mycobacterium tuberculosis - 1-3% of pulmonary tuberculosis → Tuberculosis osteomyelitis - Hematogenous spread - Long bones & vertebrae favored sites - Often solitary, multifocal in immunocompromised - Synovium of Oz pressures, common site for initial infection - Infection spreads to adj. epiphysis → Granulomatous inflammation, with caseous necrosis. - Extensive bone destruction - Infection at vertebra → Pott disease → Neurologic deficits - Infection to adjacent soft tissues → Psoas muscle abscess common ## Bone Tumors - Metastatic tumors are the most common tumors of bone. ## Osteoma - Mostly head & neck → Paranasal sinuses - Slow growth - Middle age - Looks like mature cortical bone - Multiple osteomas → Gardner Syndrome - Benign/locally aggressive - No malignant transformation ## Osteoid Osteoma & Osteoblastoma - Similar morphology, ages 10-20, in men - Differentiated by clinical size - < 2cm → Osteoid osteoma - > 2cm → Osteoblastoma - No malignant transformation unless irradiation treatment - **Osteoid osteoma:** proximal femur, fibula, spinal elements, localized bone pain worsen at night, respond to Aspirin (< 2cm) - **Osteoblastoma:** vertebral column, painful not localized, do not respond to aspirin. ## Osteosarcoma - Most common primary malignant bone tumor other than myeloma and lymphoma - < 20yr → Primary osteosarcoma - > 40yr → Usually on basis of Paget's disease, bone infarcts, radiotherapy - RB gene mut. → Sporadic tumors - Mostly in knee, metaphysis of long bones - Immature bone tissue, osteoid made by malignant cells - Painful mass typically grows rapidly. - First symptom → Pathological fracture - Pierce cortex, lift periosteum → Cause reactive bone formation - Radiologically → Codman triangle: lifted periosteum - Typically hematogenous spread → Lung metastasis ## Osteochondroma - Benign lesion connected with bone stalk & have cartilage cap - Usually solitary in sporadic → Men early adulthood - Autosomal dominant multiple osteochondromas → Children - Only in bones of endochondral origin → Metaphysis of long tubular bones, adj. to growth plates → Around knee - Growth stops when normal skeletal growth stops - When stem is broken → Nerve compression → Painful - Grow slowly - Develop from medulla ## Chondroma/Enchondroma - Benign tumor from hyaline cartilage → Composed of chondrocytes - 20-50yr, usually solitary → Small tubular bones of hand & feet - Multiple chondromas accompany Soillier & Maffucci syndromes → IDH-1 mut. - ≥ 5cm, macroscopically gray-blue, transparent - Detected incidentally ## Chondrosarcoma - Malignant connective tissue tumor → Cells produce neoplastic cartilage matrix, shiny mass forms within medullary cavity of bone → Expands, erodes cortex. - ≥ 20yr, men - Pelvic, shoulder, ribs → Rarely involve distal extremities - Unlike enchondroma → Painful, slow growing - Locum more aggressive - Hematogenous metastasis to lung & skeleton. ## Fibrous Cortical Defect & Non-Ossifying Fibroma - Developmental disorder - < 5mm - 50% bilateral & multiple - Lesions w/ diameter of 5-6cm → Non-ossifying fibroma - Osteoclast type giant cells - Detected incidentally - Distal femur & proximal tibia ## Fibrous Dysplasia - Benign! - Not precancerous tissue - GNAS mut. - McCune Albright Syndrome: polyostatic fibrous dysplasia, cafe-au-lait pigmentations, endocrine abnormalities ## Chordoma - Malignant - Develop from notochord residues in intervertebral discs - Sacrococygeal vertebra region - Diagnostic marker: BRACHURY ## Ewing Sarcoma/PNET - Round cell malignant tumor of bone & soft tissue - Blastic, undifferentiated → < 20yr - Rearrangement of EWS gene + (11;22) or + (21;22) - Originate from medulla, infiltrate cortex & periosteum - Homer-Wright rosettes → Femur - Onion peel-laminated reaction - Diaphysis of long bones - More than 75% of bone metastases in adults originate from: prostate, breast, kidney & lung cancers ## Osteoarthritis - Degeneration of articular cartilage → Most common joint disease - > 50yr → Primary osteoarthritis - Young age & predisposing factors → Secondary osteoarthritis - Hand, knee & spine joints - In women → Osteophyte protrusions on fingers: Heberden nodes & Bouchard nodes: characteristic - Painful movement, morning stiffness, crepitation. - Degeneration occurs in cartilage & subchondral bone - Unlike rheumatoid arthritis, fusion does not develop on joint. - Joint mouse, eburnation, osteophyte, cysts ## Rheumatoid Arthritis - Systemic autoimmune disease affecting joints & other tissues - Characterized by chronic progressive inflammation - Non-suppurative proliferative synovitis & arthritis that progresses to disability with fusion in the joints. - Female, 20-40, symmetrical involvement, polyarticular - Small joints: hand, foot, wrist, ankle, knee, elbow, shoulder joint. - Unlike osteoarthritis, hip joint involvement rare. - Morning pain, joint stiffness, limited movement, systemic symptoms: mild fever, weakness due to inflam. cytokines - Radial deviation of wrist → Ulnar deviation of fingers - Boutonniere deformity, swan neck - Juvenile RA: < 16yr, last > 6 weeks, systemic form: Still's disease - Diagnostic: + anti-CCP antibodies in serum & demonstration of rheumatoid factor (RF) positivity. - HLA class II locus assc. w/ ACPA-positive RA - PTPN22 - Metacarpophalangeal & interphalangeal → swollen, warm, painful ## Seronegative Spondyloarthropathies - Unlike other arthritis pathological charges start from ligaments of bone, not from synovium. - Associated with HLA-B27 - Rheumatoid Factor (-): SERONEGATIVE - Ankylosing spondylitis - Reiter's syndrome: post inflammatory, reactive arthritis - Psoriatic arthritis ## Gout Disease - When uric acid accumulates in tissue & body fluids causing monosodium urate crystals, triggering inflammatory response. - Hyperuricemia - Common in men. - Begins as acute arthritis in the big toe - Risk factors: obesity, diabetes, excessive alcohol, purine-rich diet, kidney failure. - Primary gout: uric acid → basis unknown, partial deficiency of HGPRT - Secondary gout: complete absence of HGPRT, neurological manifestation → Lesch-Nyhan Syndrome - Acute arthritis, chronic tophus arthritis (ankylosis in bone), tophus diagnostic, gout nephropathy ## Pseudogout - Chondrocalcinosis - Wrist, elbow, shoulder, ankles - Calcium pyrophosphate accumulation.