PPT 4: Osteitis Deformans (Paget Disease) PDF

PPT 4 Ostei&s Deformans (PAGET Disease) • condi'on of increased but disordered and structurally unsound bone • most common in WHITES, 40+ • 3 phases: 1. Ini'al OSTEOLYTIC stage 2. Mixed OSTEOCLASTIC-OSTEOBLASTIC stage ending with a predominance of osteoblas'c ac'vity evolving into 3. “burned-out” OS...

PPT 4 Ostei&s Deformans (PAGET Disease) • condi'on of increased but disordered and structurally unsound bone • most common in WHITES, 40+ • 3 phases: 1. Ini'al OSTEOLYTIC stage 2. Mixed OSTEOCLASTIC-OSTEOBLASTIC stage ending with a predominance of osteoblas'c ac'vity evolving into 3. “burned-out” OSTEOSCLEROTIC stage • Gene'c and environmental e'ology (can result from monocytes infected w/ measles/RNA/other viruses) • Gene muta'on alters the protein à signals INCR osteoclas&c ac'vity • HALLMARK is prominent cement lines in sclero'c phase = mosaic lamellar bone w/ jig-saw puzzle appearance • 15% MONOSTOTIC (one bone affected) • 80% POLYOSTOTIC (mul'ple bones affected) • 80% of 'me axial skeleton or proximal femur • Symptoms: o Localized pain because of microfractures o leon&asis ossea (lion face): enlargement of the facial skeleton o invagina&on of the cranial base (platybasia) and compression of the posterior cranial fossa o anterior bowing of the femora and 'biae and distor'on of the femoral heads à severe “secondary” osteoarthri's o Compression fractures of the vertebrae results in spinal cord injury and kyphosis • Various tumor condi'ons: secondary OSTEOSARCOMA rare but more common in polyosto'c disease • Tx: usually mild symptoms suppressed w/ calcitonin and bisphosphonates Fractures • Loss of bone integrity resul'ng from a mechanical injury or failure with diminished bone strength • Most common pathological condi'on affec'ng skeletal system • Classified by type of disturbance: o Simple: the overlying skin is intact o Compound: the bone communicates with the skin surface o Comminuted: fragmenta'on of bone o Displaced: the ends of the bone at the fracture site are not aligned o Stress: a slow developing fracture that follows a period of increased physical ac'vity in which the bone is subjected to repe''ve loads. o Greens&ck: extending only par&ally transversely through the bone, common in infants when bones are “soJer.” o Pathologic: involving bone weakened by an underlying disease process, such as a tumor or systemic • Fracture repair involves mul'ple genes expression in stages w/ molecular, biochemical, histological, and biomechanical features • Immediately aeer/during a break, rupture of blood vessels results in HEMATOMA o Fills the fracture gap and surrounds bone injury o Clofed blood provides FIBRIN mesh that seals fracture site and forms scaffold for incoming inflammatory cells, fibroblasts, new capillaries • Simultaneously, degranulated platelets and migra'ng inflammatory cells release PDGF, TCF-B, FGF to jumpstart/ac'vate OSTEOPROGENITOR cells in periosteum, medullary cavity, soe 'ssues and s'mulate osteoclast/blast ac'vity • 1 Week: soJ callus (uncalcified 'ssue) between the fractured ends • 2 Weeks: bony callous: o WOVEN BONE deposited by blasts o chondroblasts produce fibrocar'lage and hyaline car'lage on joint surface à endochondral ossifica'on • Callus remodeled into LAMELLAR BONE • • • • • • Healing completed when MEDULLARY CAVITY restored Fracture healing impeded or blocked à non-union à malformed callus undergoes cys&c degenera&on à luminal surface lined with synovial-like cells crea'ng a PSEUDOARTHROSIS (false joint) Healing hindered by infec'on, malnutri'on, skeletal dysplasia Osteonecrosis (avascular necrosis) • loss of blood to bone or bone marrow cells • INFARCTION – a blockage in a blood vessel resul'ng in death to the receiving 'ssue • Necrosis – death of cells due to lack of blood • Risk factors: o bone ischemia (vascular injury) o drugs (cor'costeroids) o systemic disease (sickle cell crisis) o radia&on • 3 Causes: o mechanical disrup'on of vessels o thrombo&c occlusion o extravascular compression • 10% hip replacements b/c lack of blood to femur head • Medullary infarc'on: localized, in trabecular bone and marrow • Subchondral infarc'on: necrosis of subchondral bone plate (triangle or wedge-shaped) o Creeping subs'tu'on too slow leading to collapse of the necro'c gone field and distor'on, fracture, and even sloughing of the ar'cular car'lage o Pain w/ ac'vity gradually becomes constant • Creeping subs'tu'on: remaining trabeculae are scaffolding for new bone deposi'on • Tx: limited weight bearing, immobiliza'on, surgery Osteomyeli&s (osteo: bone and marrow) • Bone inflamma'on – almost always secondary to infec&on • Causes: PYOGENIC BACTERIA and MYCOBACTERIA • Pyogenic Osteomyeli&s o 80-90% caused by Staphylococcus aureus in which cell wall proteins bind to bone collagen o Osseous vascular circula&on determine loca&on of infec'on • Organisms reach the bone by: o Hematogenous spread (most common in children in their long bones, avascular growth plate can interrup infec'on) o Extension from a con&guous/neighboring site (in adults) o Direct implanta&on aeer compound fractures or orthopedic procedures (adults) • GI /IV users: E. coli, Pseudomonas, and Klebsiella • Fractures/surgery: mixed bacterial infec'on • Neonates: Haemophilus influenze and B streptococci Mycobacterial Osteomyeli&s • Common in developing countries, immunocompromised, TB pt • More destruc've that Pyogenic • Bloodborne organism gets into rib or vertebrae – may persist yrs before found • Histo: caseous necrosis and granulomas • 40% have Tuberculous spondyli&s (PoU’s disease) - a destruc&on of the vertebrae leads to scoliosis or kyphosis and neurological deficits secondary to spinal cord and nerve compression Smooth muscle tumors • Leiomyoma (Benign, common) o Most common in uterus aka “uterine fibroid” o Symptoms: infer'lity and menorrhagia (prolonged menstrual cycle with much blood loss) o Surgical removal if needed • Leiomyosarcoma (mito&c, necrosis, involu&on) o Adult women o develop in: § Extremi&es deep soe 'ssue § Retroperitoneum § Great vessels o Retroperitoneum space contains: § Kidneys § adrenal glands § pancreas § lymph nodes § nerve roots § abdominal aorta § inferior vena cava o Retroperitoneum leiomyosarcoma metastasize to LUNGS Skeletal muscle tumors = ALL MALIGNANT • Rhabdomyosarcoma (malignant; mesynchymal origin) o skeletal muscle differen'a'on with three main subgroups o ALVEOLAR – 20% in reference to lung alveoli, not dental (child) § network of fibrous septae divide the cells into clusters of aggregates that resemble pulmonary alveoli o EMBRYONAL – 60% (child) § soe gray, infiltra've mass; mimic skeletal muscle at various stages of differen'a'on and consist of sheet of odd cells § Sarcoma Botryoides: variant of embryonal that develops in the walls of hollow viscera like the urinary bladder or vagina o PLEOMORPHIC – 20% (adult) § Most of the pleomorphic subtypes are fatal o Pediatric forms appear in sinuses, head/neck, GI o Tx: Aggressive will need surgery and chemo