2. * Bone modeling, remodeling, and peak bone mass * Osteoprogenitor cells * Osteoblasts and lining cells * Osteocytes - mechanotransduction * Osteoclasts * Proteins of bone matrix – Table 26-1 * Lamellar bone gradually replaces woven bone during growth and is deposited much more slowly and is stronger than woven bone

3. * Bone Growth and Development * Homeobox genes * Primary center of ossification * Secondary center of ossification * Growth plate (physis) * Intramembranous formation * Appositional growth

4. * Developmental Abnormalities in Bone Cells, Matrix, and Structure * Malformations and disease caused by defects in nuclear proteins and transcription factors * Diseases caused by defects in hormones and signal transduction mechanisms * Diseases associated with defects in extracellular structural proteins * Diseases associated with defects in folding and degradation of macromolecules * Diseases associated with defects in metabolic pathways ((enzymes, Ion channels, and transporters) * Diseases associated with decreased bone mass * Diseases caused by osteoclast dysfunction * Diseases associated with abnormal mineral homeostasis

5. * Osteogenesis Imperfecta * Brittle bone disease * Deficiency in the synthesis of type 1 collagen * Childhood fractures, blue sclera, hearing loss, dental abnormalities

6. * Mucopolysaccharidoses * Abnormalities in hyaline cartilage * Short stature, chest wall abnormalities, malformed bones

7. * Osteopetrosis * Marble bone disease ( Albers-Schonberg disease) * Reduced bone resorption and diffuse symmetric skeletal sclerosis * Impaired formation or function of osterclasts * Fractures, anemia, hydrocephaly * Cranial nerve defects * Infections

8. * Osteoporosis * Porous bones and reduced bone mass * Categories of generalized osteoporosis * Table 26-4 * Pathophysiology of postmenopausal and senile osteoporosis – Figure 26-9 * Pathogenesis * Age-related changes * Reduced physical activity * Genetic factors * Calcium nutritional status * Hormonal influences * Clinical – vertebral fractures, bone density tests

9. * Paget disease (osteitis deformans) * Three phases * Initial osteolytic stage * Mixed osteoclastic-osteoblastic stage * Burnt-out quiescent osteosclerotic stage * Pathogenesis * Mosaic pattern of lamellar bone * Uncertain cause * Clinical * Elderly, often incidental finding, axial or proximal femur – 80%, pain heavy cranium, severe secondary osteoarthritis. tumors, fractures

10. * Rickets in children = osteomalacia in adults * Hyperparathyroidism * Osteitis fibrosa cystica = severe * Increased bone cell activity, peritrabecular fibrosis, cystic brown tumors

11. * Renal Osteodystrophy * Increased osteoclastic bone resorption * Delayed matrix mineralization * Osteosclerosis * Growth retardation * Osteoporosis * Pathogenesis * CRF -> phosphate retention -> secondary hyperparathyroidism * Hypocalcemia develops because of decreased levels of 1,25 dihydroxy D3 * Increased osteoclast activity * Metabolic acidosis * Amyloid in bone from dialysis

12. * Fractures * Complete or incomplete * Closed (simple) * Compound * Comminuted * Displaced * Pathologic * Stress * Repair * Hematoma surrounds fracture-> creates framework-> soft-tissue callus -> bony callus -> reduced in size and shape until original outline is reestablished and medullary cavity is restored

13. * Osteonecrosis ( Avascular necrosis) * Conditions associated with osteonecrosis * Table 26-5 * Trauma and corticosteroid use most common * Creeping substitution * Chronic pain, secondary arthritis

14. * Infections – osteomyelitis * Pyogenic * Hematogeneous spread * Extension from a contiguous site * Direct implantaiton * Organisms * S.aureus 80-90% * Gram negatives * H.flu and GroupB strep in neonates * Salmonella in sickle cell anemia * TB – Pott disease – TB of the spine * Skeletal syphilis – nose, palate, skull, and extremities, “saber skin”

15. * Bone tumor and tumor-like Lesions * Bone-forming tumors * Cartilage-forming tumors * Fibrous and fibro-osseous tumors * http://www.pediatricsconsultant360.com/Bone- Tumors-Childhood

16. * Classification of Major Primary Tumors involving bones – Table 26-6 * Bone forming * Osteoma - sessile tumors, Gardner syndrome * Osteoid osteoma - < 2cm, nocturnal pain relieved by aspirin, teens and 20’s * Osteoblastoma - > 2 cm, pain not responsive to aspirin * Osteosarcoma – Malignant mesenchymal tumor, cancerous cells produce bone matrix, RB and p53,

17. * Osteosarcoma * Most common primary malignant tumor of bone, exclusive of myeloma and lymphoma * Bimodal age distribution – 75% < 20 years of age, rest elderly with Paget, bone infarcts, proior irradiation * Figure 26-21 Major sites of origin * Subtypes * Site of origin * Degree of differentiation * Multicentricity * Primary or secondary * Histologic features * Clinical – Codman triangle, Painful, enlarging mass or pathologic fracture

18. * Cartilage-forming tumors * Osteochondroma – exostosis, most common benign bone tumor, multiple hereditary exostosis syndrome, bones of endochondral origin, metaphysis near growth plate * Chondromas – endrochondromas, subperiosteal or juxtacortical, Ollier disease, Maffuci syndrome, most are incidental findings * Chondroblastoma – epiphysis or apophyses, painful, joint findings * Chondromyoxoid fibroma * Chondrosarcoma – intramedullary or juxtacortical (surface), conventional,clear cell, dedifferentiated, mesenchymal, central portion of the skeleton

19. * Fibrous and fibro-osseous tumors * Fibrous cortical defect and non-ossifying fibroma * Fibrous dysplasia – monostotic or polyostotic without endocrine dysfuntion, poyostotic with café-au-lait spots and endocrinopathies ( McCune-Albright syndrome) * Fibrosarcoma variants

20. * Miscellaneous Tumors * Ewing sarcoma/primitive neuroectodermal tumor – (11;22) (q24;q12) translocation, Homer-Wright rosettes * Giant-cell tumor – osteoclastoma * Aneurysmal bone cyst – multiloculated blood- filled cystic spaces * Metastatic disease – most common form of skeletal malignancy

21. * Arthritis * Osteoarthritis * Rheumatoid arthritis * Juvenile idiopathic arthritis * Seronegative spondyloarthropathies * Infectious arthritis * Crystal-induced arthritis

22. * Osteoarthritis * Degenerative joint disease * Progressive erosion of articular cartilage * Primary or secondary * Chondroytes, joint mice, bone eburnation * Deep,achy pain that worsens with use, morning stiffness, crepitus, limitation of ROM, hips, knees, lowerlumbar, cervical vertebrae, PIP And DIPs first carbometacarpal and first tarsometatarsal, Heberden nodes at DIP

23. * Rheumatoid Arthritis * Chronic systemic inflammatory disorder that may affect many tissues and organs, - skin, blood vessels, heart, lungs, and muscle – but principally the joints, producing a nonsuppurative proliferative and inflammatory synovitis that often progresses to destruction of the articular cartilage and ankylosis of the joints * Pannus, fibrous ankylosis, rheumatoid nodules * HLA-DRB1 * Immunopathogenesis – Figure 26-44 * Symmetrical, small joints before large, warm,painful, stiff, joint effusions, juxtaarticular osteopenia, erosions and narrowing of joint space on x-ray, RF

24. * Juvenile idiopathic arthritis * Classification * Systemic arthritis – fevers, fleeting ras, hepatosplenomegaly, serositis * Oligoarthritis – ANA+, iridoylitis * RF-positive polyarthritis * RF-negative polyarthritis * Enthesitis-assocaited arthritis – HLA-B27 * Psoriatic arthritis * Undifferentiated arthritis * Differs from adult RA * Oligoarthritis is more common * Systemic is more frequent * Large joints> small joints * RF and nodules absent * ANA+

25. * Seronegative spondyloarthropathies * Ankylosing spondyloarthritis – HLA-B27 * Reiter syndrome – with nongonococcal urethritis or cervitis and conjunctivits, HLA-B27, HIV * Enteritis-associated arthritis – GI infections * Psoriatic arthritis – HLA-B27 and HLA-Cw6

27. * Infectious Arthritis * Bacterial * TB * Lyme * Viral

28. * Crystal-Induced Arthritis * Gout and Gouty arthritis * Classification – Table 26-7 * Precipitation of monosodium urate crystals in the joints * Acute arthritis, chronic tophaceous arthritis, gouty nephropathy * Calcium pyrophosphate crystal deposition disease (pseudo-gout)

29. * Tumors and Tumor-like lesions * Ganglion and synovial cyst * Tenosynovial Giant-cell tumor (localized and diffuse)

30. * Pathogenesis and general features – Table 26-8 * Fatty tumors * Fibrous tumors and tumor0like lesions * Fibrohistiocytic tumors * Tumors of skeletal muscle * Tumors of smooth muscle * Synovial sarcoma