Bone PathologyBone Pathology

Normal anatomyNormal anatomy

• Parts of a long bones:Parts of a long bones: diaphysisdiaphysis (shaft), (shaft), physisphysis (growth plate), (growth plate), epiphysisepiphysis (ends of (ends of bone, partially covered by articular bone, partially covered by articular cartilage),cartilage), metaphysis metaphysis (junction of diaphysis (junction of diaphysis and epiphysis, most common site of primary and epiphysis, most common site of primary bone tumors)bone tumors)

• Cross section:Cross section: periosteum, cortex periosteum, cortex (composed of cortical bone or compact (composed of cortical bone or compact bone), medullary space (composed of bone), medullary space (composed of cancellous or spongy bone)cancellous or spongy bone)

Normal histologyNormal histology

• Bone: Bone: mineralized osteoid; either mineralized osteoid; either lamellar bone or woven bone.lamellar bone or woven bone.

• Lamellar bone:Lamellar bone: layered bone with layered bone with concentric parallel lamellae; concentric parallel lamellae; gradually replaces woven bone; gradually replaces woven bone; normal type of bone found in adult normal type of bone found in adult skeleton; stronger than woven boneskeleton; stronger than woven bone

• Osteoblasts:Osteoblasts: arise from marrow arise from marrow mesenchymal cells; when active, are mesenchymal cells; when active, are plump and present on bone surface; plump and present on bone surface; eventually are encased within the eventually are encased within the collagen they produce.collagen they produce.

• Osteoblasts control osteoclast Osteoblasts control osteoclast activity via parathyroid hormone.activity via parathyroid hormone.

HISTOLOGYHISTOLOGY

• INFECTIONSINFECTIONS

• BONE TUMORSBONE TUMORS

OSTEOMYELITIS:OSTEOMYELITIS: Denotes inflammation of bones and Denotes inflammation of bones and

marrow and the common use of the term marrow and the common use of the term virtually always implies infection.virtually always implies infection.

• May be a May be a complicationcomplication of any of any systemic systemic infection but frequently manifests as a infection but frequently manifests as a primaryprimary solitary focus of disease. solitary focus of disease.

• All types of organisms ,including viruses, All types of organisms ,including viruses, parasites, fungi and bacteria can parasites, fungi and bacteria can produce osteomyelitis, but infections produce osteomyelitis, but infections caused by certain pyogenic bacteria and caused by certain pyogenic bacteria and mycobacteria are the most common.mycobacteria are the most common.

• Pyogenic Osteomyelitis.Pyogenic Osteomyelitis.

• Tuberculous osteomyelitisTuberculous osteomyelitis

• PYOGENIC OSTEOMYELITIS:PYOGENIC OSTEOMYELITIS:

is almost always caused by bacteria.is almost always caused by bacteria.

1.1. Hematogenous spread.Hematogenous spread.

2.2. Extension from a contiguous site.Extension from a contiguous site.

3.3. Direct implantation.Direct implantation.

• E.coli, Klebsiella and Pseudomonas E.coli, Klebsiella and Pseudomonas are more frequently isolated from are more frequently isolated from patients with genitourinary tract patients with genitourinary tract infections or with intravenous drug infections or with intravenous drug abusers.abusers.

• Mixed bacterial infections can be Mixed bacterial infections can be seen in the setting of direct spread seen in the setting of direct spread during surgery or open fractures.during surgery or open fractures.

• Salmonella infections for unknown Salmonella infections for unknown reasons common in sickle cell reasons common in sickle cell patients.patients.

• In 50% of the cases no organisms In 50% of the cases no organisms can be isolated.can be isolated.

Sites of involvement:Sites of involvement:

• Influenced by the vascular Influenced by the vascular circulation, which varies with age.circulation, which varies with age.

• NeonatesNeonates: the metaphyseal vessels : the metaphyseal vessels penetrate the growth plate, resulting penetrate the growth plate, resulting in frequent infection of the in frequent infection of the metaphysis, epiphysis or both.metaphysis, epiphysis or both.

• In In children:children: metaphyseal. metaphyseal.

• Adults:Adults: epiphyses and subchondral epiphyses and subchondral regions.regions.

Stages :Stages : DDesignated as,esignated as,• AcuteAcute• Sub acuteSub acute• Chronic , On clinical duration of Chronic , On clinical duration of

diseasedisease SEQUENCE OF INFECTION:SEQUENCE OF INFECTION: Once localized in bone, the bacteria Once localized in bone, the bacteria

proliferate and induce an acute proliferate and induce an acute inflammatory reaction and cause cell inflammatory reaction and cause cell death.death.

• Necrosis of the bone within first 48hrs.Necrosis of the bone within first 48hrs.

• Spread of bacteria and inflammation Spread of bacteria and inflammation within the shaft of the bone and may within the shaft of the bone and may percolate through the haversian percolate through the haversian systems to reach the periosteum.systems to reach the periosteum.

• In children ,the periosteum is loosely In children ,the periosteum is loosely attached to the cortex; therefore attached to the cortex; therefore sizable subperiosteal abscess sizable subperiosteal abscess formation occurs.formation occurs.

• Further ischemia and bone necrosis Further ischemia and bone necrosis occurs.occurs.

• Dead pieces of bone are known as the Dead pieces of bone are known as the sequestrum.sequestrum.

• Rupture of the periosteumRupture of the periosteum→soft tissue →soft tissue abscess formation→draining sinuses.abscess formation→draining sinuses.

• In infants epiphyseal infection may In infants epiphyseal infection may spread to the adjacent joint and causes spread to the adjacent joint and causes septic or suppurative arthritis.; may septic or suppurative arthritis.; may lead to permanent disability.lead to permanent disability.

• After the first week chronic After the first week chronic inflammatory cells become more inflammatory cells become more numerous with the release of numerous with the release of cytokines and deposition of new cytokines and deposition of new bone formation at the periphery.bone formation at the periphery.

• New bone may be deposited as a New bone may be deposited as a sleeve of living tissue known as the sleeve of living tissue known as the Involucrum.Involucrum.

• Brodies abscess:Brodies abscess:

is a small intraosseus abscess that is a small intraosseus abscess that frequently involves the cortex and is frequently involves the cortex and is walled off reactive bone.walled off reactive bone.

• Sclerosing osteomyelitis of Garre Sclerosing osteomyelitis of Garre typicallytypically

develops in the jaw.develops in the jaw.

• Clinical Course:Clinical Course:

• Fever ,chills, malaise, marked to Fever ,chills, malaise, marked to intense throbbing pain over the intense throbbing pain over the affected region.affected region.

Diagnosis;Diagnosis;

• Sign/symptoms.Sign/symptoms.

• X-rayX-ray

• Blood culturesBlood cultures

• biopsybiopsy

Rx :Rx :

combination of antibiotics and combination of antibiotics and surgical drainage is usually curative.surgical drainage is usually curative.

ComplicationsComplications::

• Pathologic fracture.Pathologic fracture.

• Secondary amyloidosisSecondary amyloidosis

• EndocarditisEndocarditis

• SepsisSepsis

• Squamous cell carcinoma.Squamous cell carcinoma.

• Rarely sarcoma in the affected boneRarely sarcoma in the affected bone

Tuberculous osteomyelitisTuberculous osteomyelitis::

Routes of entry;Routes of entry;

• Usually blood borne and originate Usually blood borne and originate from a focus of active visceral from a focus of active visceral disease.disease.

• Direct extension (e.g. from a Direct extension (e.g. from a pulmonary focus into a rib or from pulmonary focus into a rib or from tracheobronchial nodes into adjacent tracheobronchial nodes into adjacent vertebrae) or spread via draining vertebrae) or spread via draining lymphatics.lymphatics.

• In patients with AIDS frequently In patients with AIDS frequently multifocal.multifocal.

• Pott disease is the involvement of spine.Pott disease is the involvement of spine.

• Thoracic and lumber vertebrae followed Thoracic and lumber vertebrae followed by the knees and hips are the most by the knees and hips are the most common sites of skeletal involvement.common sites of skeletal involvement.

• The infection breaks through the The infection breaks through the invertebral discs and extends into the invertebral discs and extends into the soft tissues forming abscesses.soft tissues forming abscesses.

Clinical features and complications:Clinical features and complications:

• PainPain

• Fever weight lossFever weight loss

• May form an inguinal mass ‘which May form an inguinal mass ‘which represents a cold fluctuant psoas represents a cold fluctuant psoas abscess.abscess.

• Bone destruction.Bone destruction.

• Tuberculous arthritis. Tuberculous arthritis.

• sinus tract formationsinus tract formation

• amyloidosisamyloidosis

Bone tumorsBone tumors

Although the cause of most bone tumors is unknown.Although the cause of most bone tumors is unknown.

Genetic alterations e.g. bone sarcomas in the Li-Fraumeni Genetic alterations e.g. bone sarcomas in the Li-Fraumeni and hereditary retinoblastoma which are linked to and hereditary retinoblastoma which are linked to mutations in p53 and Rb genes. mutations in p53 and Rb genes.

Bone infarctsBone infarcts chronic osteomyelitischronic osteomyelitis pagets diseasepagets disease radiation and radiation and metal prostheses are also associated with increased metal prostheses are also associated with increased

incidence of bone neoplasia.incidence of bone neoplasia.

Classification of primary tumors Classification of primary tumors involving bones:involving bones:

• Bone Forming tumors.Bone Forming tumors.

• Cartilage forming tumors.Cartilage forming tumors.

• Fibrous and fibro-osseous tumors.Fibrous and fibro-osseous tumors.

• Miscellaneous tumors.Miscellaneous tumors.

Bone Forming Tumors:Bone Forming Tumors:

Production of bone by the neoplastic Production of bone by the neoplastic cells.cells.

1.1. OsteomaOsteoma

2.2. Osteoid osteomaOsteoid osteoma

3.3. Osteoblastoma.Osteoblastoma.

4.4. OsteosarcomaOsteosarcoma

OsteomaOsteoma

• Small bosselated benign tumorsSmall bosselated benign tumors

• Usually solitary and detected in the Usually solitary and detected in the middle agemiddle age

• Multiple in the setting of Gardner Multiple in the setting of Gardner syndrome.syndrome.

• Do not transform into osteosarcoma.Do not transform into osteosarcoma.

Osteoid Osteoma & Osteoid Osteoma & OsteoblastomaOsteoblastoma

• Benign bone tumors .Benign bone tumors .• Osteoid Osteoma are by definition Osteoid Osteoma are by definition

<2cm,usually occurs in teens and <2cm,usually occurs in teens and twenties.twenties.

• Male to female 2:1Male to female 2:1• Osteoid osteomas 50% involve femur Osteoid osteomas 50% involve femur

and tibia.and tibia.• Osteoid osteoma are painful lesions, Osteoid osteoma are painful lesions,

occurs at night and relieved by aspirin.occurs at night and relieved by aspirin.

Osteoid osteomaOsteoid osteoma

OsteoblastomasOsteoblastomas

• Osteoblastomas involve spine more Osteoblastomas involve spine more commonly.commonly.

• Dull pain Dull pain

• Not responsive to aspirinNot responsive to aspirin

• Both can be treated by conservative Both can be treated by conservative surgerysurgery

• Recurs if not excised entirely.Recurs if not excised entirely.

OSTEOCHONDROMAOSTEOCHONDROMA

• Also called exostosisAlso called exostosis• Most common benign bone tumorMost common benign bone tumor• 50-75% males, mean age 10 years, usually age 50-75% males, mean age 10 years, usually age

20 years or less20 years or less• Common; solitary or multiple Common; solitary or multiple • Slow growing, painful if impinges on nerve or Slow growing, painful if impinges on nerve or

stalk is broken; usually stops growing and ossifies stalk is broken; usually stops growing and ossifies at pubertyat puberty

• Benign, but 1-2% of solitary tumors and 5-25% of Benign, but 1-2% of solitary tumors and 5-25% of multiple tumors undergo malignant multiple tumors undergo malignant transformation to chondrosarcoma.transformation to chondrosarcoma.

OSTEOCHONDROMAOSTEOCHONDROMA

• Multiple hereditary exostosis:Multiple hereditary exostosis: also called also called osteochondromatosis; autosomal dominant osteochondromatosis; autosomal dominant disorder.disorder.

• Sites:Sites: metaphysis, not medullary cavity; metaphysis, not medullary cavity; usually distal femur, proximal tibia, proximal usually distal femur, proximal tibia, proximal humerus; occasionally pelvis, scapula, ribs; humerus; occasionally pelvis, scapula, ribs; rarely digits; not in intramembranous bonesrarely digits; not in intramembranous bones

• Xray: Xray: metaphyseal lesions grow in direction metaphyseal lesions grow in direction opposite to adjacent joint; cortex and opposite to adjacent joint; cortex and medulla are continuous with underlying medulla are continuous with underlying bone.bone.

OSTEOCHONDROMAOSTEOCHONDROMA

• Gross:Gross: cartilage-capped bony cartilage-capped bony outgrowth up to 10 cm (mean 4 cm), outgrowth up to 10 cm (mean 4 cm), attached to skeleton by bony stalk, attached to skeleton by bony stalk, not in medullary cavity; may have not in medullary cavity; may have bursa around its head; cartilage cap bursa around its head; cartilage cap usually regular and thin.usually regular and thin.

OSTEOCHONDROMAOSTEOCHONDROMA

• Secondary chondrosarcoma:Secondary chondrosarcoma: if the if the tumor grows during adolescence, > 8 tumor grows during adolescence, > 8 cm, irregular cartilaginous cap > 3 cm, irregular cartilaginous cap > 3 cm or lucent zones within lesion, cm or lucent zones within lesion, invasion of surrounding tissueinvasion of surrounding tissue

OSTEOCHONDROMAOSTEOCHONDROMA

• Cartilagenous cap overlying bony Cartilagenous cap overlying bony trabeculae.trabeculae.

Chondroma Chondroma

• Benign cartilaginous tumorBenign cartilaginous tumor

• Either enchondroma (arise from diaphyseal Either enchondroma (arise from diaphyseal medullary cavity), subperiosteal/juxtacortical medullary cavity), subperiosteal/juxtacortical chondroma or soft tissue chondromachondroma or soft tissue chondroma

• One study claims cytofluorometric DNA One study claims cytofluorometric DNA ploidy analysis is more reliable than clinical ploidy analysis is more reliable than clinical and histologic features in distinguishing and histologic features in distinguishing these tumors from chondrosarcomasthese tumors from chondrosarcomas

Osteogenic SarcomaOsteogenic Sarcoma

• It is a malignant mesenchymal tumor in It is a malignant mesenchymal tumor in which the cancerous cells produce bone which the cancerous cells produce bone matrix.matrix.

• It is the most common primary malignant It is the most common primary malignant bone tumor.bone tumor.

• Bimodal age distribution 75% in patients Bimodal age distribution 75% in patients less than 20Years of age.less than 20Years of age.

• Smaller second group in elderly; Smaller second group in elderly; frequentlyfrequently

Osteogenic SarcomaOsteogenic Sarcoma

Predisposing conditionsPredisposing conditions including: including: Paget disease, bone infarcts and prior Paget disease, bone infarcts and prior radiation.radiation.

• Male to female ratio 1.6:1Male to female ratio 1.6:1

• Usually arise in the metaphyseal region of Usually arise in the metaphyseal region of the long bones.the long bones.

• 50% occur about the knee.50% occur about the knee.

• After the age of 25,the incidence in flat After the age of 25,the incidence in flat bones and long bones is almost equal.bones and long bones is almost equal.

Osteogenic sarcomaOsteogenic sarcoma

• Pathogenesis;Pathogenesis;

• Mutations in retinoblastoma genes Mutations in retinoblastoma genes patients with hereditary patients with hereditary retinoblastomas have several hundred- retinoblastomas have several hundred- fold greater risk of subsequently fold greater risk of subsequently developing osteosarcoma.developing osteosarcoma.

• Mutations in p53 gene.Mutations in p53 gene.

• Overexpression of MDM2 genes.Overexpression of MDM2 genes.

Osteogenic SarcomaOsteogenic Sarcoma

• Most commonly involves metaphysis of long Most commonly involves metaphysis of long bones.bones.

• Gross featuresGross features: big bulky tumors, grey white : big bulky tumors, grey white often containing areas of hemorrhage and often containing areas of hemorrhage and cystic degeneration.cystic degeneration.

• MicroMicro:pleomorphic tumor cells with large :pleomorphic tumor cells with large hyper chromatic nuclei ,mitotic figures. hyper chromatic nuclei ,mitotic figures. Formation of pink homogenous bone Formation of pink homogenous bone formation is the most characteristic feature of formation is the most characteristic feature of osteogenic sarcomaosteogenic sarcoma

Osteogenic sarcoma Osteogenic sarcoma HistologyHistology

Osteogenic sarcomaOsteogenic sarcoma

ChondrosarcomaChondrosarcoma

• Malignant cartilage forming tumor Malignant cartilage forming tumor that does not produce osteoidthat does not produce osteoid

• May arise from osteochondromaMay arise from osteochondroma

• Third most common bone Third most common bone malignancy after myeloma and malignancy after myeloma and osteosarcomaosteosarcoma

• Divided into conventional (central, Divided into conventional (central, peripheral, juxtacortical/periosteal) peripheral, juxtacortical/periosteal) and variants (clear cell, and variants (clear cell, dedifferentiation, mesenchymal, dedifferentiation, mesenchymal, myxoid)myxoid)

• Conventional tumors are divided by Conventional tumors are divided by location into central, peripheral and location into central, peripheral and juxtacortical/periosteal formsjuxtacortical/periosteal forms

• Sites:Sites: large boneslarge bones - pelvis, ribs, femur, - pelvis, ribs, femur, humerus, vertebrae; unusual in hands, humerus, vertebrae; unusual in hands, feet, jaw, skullfeet, jaw, skull

• Xray correlation:Xray correlation: presume malignant if presume malignant if large tumor of long bones or grows rapidly large tumor of long bones or grows rapidly during adolescence to 8 cm or more; have during adolescence to 8 cm or more; have fluffy calcification, poorly defined margins, fluffy calcification, poorly defined margins, erosion or thickening of cortex; usually no erosion or thickening of cortex; usually no periosteal new bone formationperiosteal new bone formation

• Treatment:Treatment: since often implants in since often implants in soft tissue after biopsy, wide en bloc soft tissue after biopsy, wide en bloc excision advocated except for well excision advocated except for well differentiated tumors, which are differentiated tumors, which are amenable to conservative therapy; amenable to conservative therapy; patients may have local recurrence patients may have local recurrence or metastases up to 20 years lateror metastases up to 20 years later

• Micro:Micro: tumor cells produce cartilaginous tumor cells produce cartilaginous matrix; either well, moderate or poorly matrix; either well, moderate or poorly differentiated; may have only minor or focal differentiated; may have only minor or focal atypia, but consider malignant if malignant atypia, but consider malignant if malignant radiologic features (see above); no direct radiologic features (see above); no direct osteoid or bone formation by tumor cells (if osteoid or bone formation by tumor cells (if present, classify as osteosarcoma, although present, classify as osteosarcoma, although may be non-neoplastic bone); may be non-neoplastic bone); intracytoplasmic hyaline globules common in intracytoplasmic hyaline globules common in low grade tumorslow grade tumors

• Grading:Grading: based on cellularity and based on cellularity and nuclear changes in chondrocytes; nuclear changes in chondrocytes; well, moderate or poorly well, moderate or poorly differentiated correspond to grades differentiated correspond to grades 1-3;1-3;

GIANT CELL TUMORGIANT CELL TUMOR

• Also called osteoclastomaAlso called osteoclastoma

• Benign but locally aggressive neoplasm Benign but locally aggressive neoplasm with large numbers of osteoclast-like with large numbers of osteoclast-like giant cells in background of epithelioid giant cells in background of epithelioid to spindle shaped mononuclear cellsto spindle shaped mononuclear cells

• Ages 20-40 years; 55% women, Ages 20-40 years; 55% women,

• Associated with Paget’s disease of boneAssociated with Paget’s disease of bone

Components of giant cell Components of giant cell tumortumor

• Giant cells Giant cells

appear to be due to fusion of appear to be due to fusion of circulating monocytes;circulating monocytes;

stromal cells stromal cells appear to be neoplastic appear to be neoplastic and may originate from and may originate from mesenchymal stem cells that reside mesenchymal stem cells that reside in bone marrow in bone marrow

SITES INVOLVED:SITES INVOLVED:

• knee is common site (distal femur, knee is common site (distal femur, proximal tibia), distal radius, sacrum but proximal tibia), distal radius, sacrum but can affect any bone, usually at epiphysis, can affect any bone, usually at epiphysis, may spread into metaphysis.may spread into metaphysis.

• Xray:Xray: lytic, expansile lesion of epiphysis lytic, expansile lesion of epiphysis extending to articular cartilage, usually extending to articular cartilage, usually without peripheral bone sclerosis, without peripheral bone sclerosis, periosteal reaction or mineralization periosteal reaction or mineralization within the lesion; within the lesion;

• within soft tissues usually produces within soft tissues usually produces eggshell ossification at periphery.eggshell ossification at periphery.

JOINTS/TYPESJOINTS/TYPES

Synovial or nonsynovialSynovial or nonsynovial

• Synovial joints:Synovial joints: also called diarthroses; also called diarthroses; contain joint space between ends of bones, contain joint space between ends of bones, joints covered by hyaline cartilage, joints covered by hyaline cartilage, strengthened by dense fibrous capsule strengthened by dense fibrous capsule continuous with periosteum of bones and an continuous with periosteum of bones and an inner synovial membrane; joint is reinforced inner synovial membrane; joint is reinforced by ligaments and muscles; presence of joint by ligaments and muscles; presence of joint space allows wide range of motion.space allows wide range of motion.

JOINTS/TYPESJOINTS/TYPES

• Nonsynovial joints:Nonsynovial joints: also called also called solid joint or synarthrosis; no joint solid joint or synarthrosis; no joint space present; provides structural space present; provides structural integrity and minimal movementintegrity and minimal movement

ArthritisArthritis

• SUPPURATIVE ARTHRITISSUPPURATIVE ARTHRITIS

• TUBERCULOUS ARTHRITISTUBERCULOUS ARTHRITIS

• OSTEOARTHRITISOSTEOARTHRITIS

• RHEUMATOID ARTHRITISRHEUMATOID ARTHRITIS

ARTHRITISARTHRITIS

• Suppurative arthritis:Suppurative arthritis:

• Due to seeding of joint during bacteremia, most Due to seeding of joint during bacteremia, most commonly due to commonly due to StaphylococcusStaphylococcus, , StreptococcusStreptococcus, , gram negative rods; rarely syphilisgram negative rods; rarely syphilis

• Also due to postsurgical infectionAlso due to postsurgical infection• Neonates:Neonates: often due to osteomyelitis often due to osteomyelitis• Young women:Young women: most commonly due to most commonly due to

gonorrhea (gram negative intracellular diplococci, gonorrhea (gram negative intracellular diplococci, which is associated with multiple joint which is associated with multiple joint involvement, including the knee)involvement, including the knee)

• Sickle cell disease:Sickle cell disease: Salmonella Salmonella

• Risk factors:Risk factors: immune deficiencies, severe immune deficiencies, severe illness, joint trauma, chronic arthritis, illness, joint trauma, chronic arthritis, intravenous drug abuseintravenous drug abuse

• Symptoms:Symptoms: sudden development of acutely sudden development of acutely painful and swollen joint with restricted range painful and swollen joint with restricted range of motion, systemic findingsof motion, systemic findings

• Sites:Sites: usually single joint (knee, hip, shoulder) usually single joint (knee, hip, shoulder)• Micro:Micro: neutrophils infiltration (also Bechet’s neutrophils infiltration (also Bechet’s

disease, familial Mediterranean fever)disease, familial Mediterranean fever)

ARTHRITISARTHRITIS

• Tuberculous arthritis:Tuberculous arthritis:

• Insidious onset ofInsidious onset of chronic progressive arthritis, chronic progressive arthritis, usually monoarticular in knee and hip; usually after usually monoarticular in knee and hip; usually after osteomyelitisosteomyelitis

• Leads to fibrous ankylosis of joint with obliteration Leads to fibrous ankylosis of joint with obliteration of joint spaceof joint space

• Can detect from culture and examination of Can detect from culture and examination of synovial fluid.synovial fluid.

• PCR is sensitive; apparent false positives in PCR is sensitive; apparent false positives in clinically negative patients may represent early clinically negative patients may represent early disease. disease.

• Micro:Micro: granulomas with caseous granulomas with caseous necrosis; AIDS patients often have necrosis; AIDS patients often have histiocytes with numerous acid-fast histiocytes with numerous acid-fast organisms but no granulomas.organisms but no granulomas.

ARTHRITISARTHRITIS

Degenerative joint disease:Degenerative joint disease:

• Also called osteoarthritis. Also called osteoarthritis. • Nonneoplastic disorder of progressive erosion of Nonneoplastic disorder of progressive erosion of

articular cartilage associated with aging, trauma, articular cartilage associated with aging, trauma, occupational injury.occupational injury.

• Usually age 50+ years (present in 80% at age 65 Usually age 50+ years (present in 80% at age 65 years)years)

• Cartilage degradation may be mediated by IL-1.Cartilage degradation may be mediated by IL-1.• Sites:Sites: men-hips, women-knees and hands; also men-hips, women-knees and hands; also

first metatarsophalangeal joint, lumbar spine; first metatarsophalangeal joint, lumbar spine; usually one joint or same joint bilaterally, at least usually one joint or same joint bilaterally, at least initiallyinitially

OsteoarthritisOsteoarthritis

• Symptoms:Symptoms: pain worse with use of joint, pain worse with use of joint, crepitus, limited range of motion, nerve root crepitus, limited range of motion, nerve root compression; Heberden nodes in fingers of compression; Heberden nodes in fingers of women only (osteophytes at DIP joints)women only (osteophytes at DIP joints)

• Secondary degenerative joint disease:Secondary degenerative joint disease: younger patients with predisposing younger patients with predisposing condition (trauma, congenital, diabetes, condition (trauma, congenital, diabetes, obesity, ochronosis, hemochromatosis), obesity, ochronosis, hemochromatosis), such as knees of basketball playerssuch as knees of basketball players

OsteoarthritisOsteoarthritis

• GrossGross:: early changes are even degeneration of early changes are even degeneration of hyaline cartilage of articular surface, with hyaline cartilage of articular surface, with fibrillation of cartilaginous matrix and possible fibrillation of cartilaginous matrix and possible cartilage fragmentationcartilage fragmentation

• later thinninglater thinning of cartilage and overgrowth of of cartilage and overgrowth of apposing joint surface; articular surface is often apposing joint surface; articular surface is often soft and granular with altered shape, sloughing of soft and granular with altered shape, sloughing of cartilage .cartilage .

cysts:cysts: (synovial fluid forced into fractures via (synovial fluid forced into fractures via ball valve-like mechanism),ball valve-like mechanism),

osteophytes:osteophytes: (bony outgrowths at margins of (bony outgrowths at margins of articular surface) articular surface)

OsteoarthritisOsteoarthritis

• Loose bodies:Loose bodies: may form if portion may form if portion of articular cartilage breaks off; of articular cartilage breaks off; normally loose body is nourished by normally loose body is nourished by synovium and continues to grow.synovium and continues to grow.

   

OsteoarthritisOsteoarthritis

• MicroMicro:: ghost chondrocytes (no nuclei) or ghost chondrocytes (no nuclei) or necrotic chondrocytes,necrotic chondrocytes,

• marked irregularity, thinning,marked irregularity, thinning,• fragmentation and fibrillation of thinned fragmentation and fibrillation of thinned

cartilage; cartilage; • subchondral cysts with mucoid fluid subchondral cysts with mucoid fluid

surrounded by sclerotic bone; usually no surrounded by sclerotic bone; usually no significant inflammatory component significant inflammatory component although advanced cases have synovial although advanced cases have synovial hyperplasia with lymphoid follicles.hyperplasia with lymphoid follicles.

Cracking and fibrillation of Cracking and fibrillation of cartilagecartilage

GOUTGOUT• Gout and gouty arthritisGout and gouty arthritis

• Transient attacks of acute arthritis Transient attacks of acute arthritis initiated by crystallization of urates and initiated by crystallization of urates and neutrophils, followed by chronic gouty neutrophils, followed by chronic gouty arthritis with tophi in joints and urate arthritis with tophi in joints and urate nephropathy nephropathy

• Causes 2-5% of chronic joint diseaseCauses 2-5% of chronic joint disease• Sites:Sites: 50% have initial attack in first 50% have initial attack in first

metatarsophalangeal joint; also ankles, metatarsophalangeal joint; also ankles, heels, knees, wrists, fingers, elbowsheels, knees, wrists, fingers, elbows

GOUTGOUT

• Primary gout (90%):Primary gout (90%): idiopathic (85%) idiopathic (85%) with overproduction of uric acid or known with overproduction of uric acid or known enzyme defects (partial hypoxanthine-enzyme defects (partial hypoxanthine-guanine phosphoribosyl transferase guanine phosphoribosyl transferase deficiency [HGPRT])deficiency [HGPRT])

• Secondary gout (10%):Secondary gout (10%): increased increased nucleic acid turnover due to nucleic acid turnover due to leukemia/lymphoma, chronic renal leukemia/lymphoma, chronic renal disease, HGPRT deficiencydisease, HGPRT deficiency

GOUTGOUT

• Pathophysiology:Pathophysiology: there are two there are two pathways for purine synthesis: de pathways for purine synthesis: de novo (creates purines) and salvage novo (creates purines) and salvage pathway (HGPRT)pathway (HGPRT)

• HGPRT deficiency causes increased HGPRT deficiency causes increased synthesis via de novo pathway, synthesis via de novo pathway, leading to hyperuricemialeading to hyperuricemia

GOUTGOUT

• Gout is due to hyperuricemia (present in 10% Gout is due to hyperuricemia (present in 10% of population, although only half develop gout) of population, although only half develop gout) and deposition of monosodium urate crystals and deposition of monosodium urate crystals in joints and viscera and uric acid kidney stone in joints and viscera and uric acid kidney stone formation.formation.

• Need serum urate > 7 mg/dl for deposition Need serum urate > 7 mg/dl for deposition (saturation threshold for urate at 98.6 F)(saturation threshold for urate at 98.6 F)

• Risk factors for gout with hyperuricemia are Risk factors for gout with hyperuricemia are age > 30 years, familial history of gout, age > 30 years, familial history of gout, alcohol use, obesity, thiazide administration, alcohol use, obesity, thiazide administration, lead etc.lead etc.

GOUTGOUT

• Arthritis:Arthritis: synovial fluid is poorer solvent for synovial fluid is poorer solvent for sodium urate than plasma, so with hyperuricemiasodium urate than plasma, so with hyperuricemia

• urates in joint fluid crystallize, particularly in ankle urates in joint fluid crystallize, particularly in ankle due to lower temperature; crystals develop in due to lower temperature; crystals develop in synovial lining cells, stimulate formation of synovial lining cells, stimulate formation of antibodies,antibodies,

• which accelerates formation of new crystals; which accelerates formation of new crystals; release of crystals attracts neutrophils and release of crystals attracts neutrophils and complement, generates C3a, C5a, attracts more complement, generates C3a, C5a, attracts more neutrophils, neutrophils,

• releases free radicals, releases lysosomal enzymes releases free radicals, releases lysosomal enzymes which eventually causes acute arthritis that last which eventually causes acute arthritis that last days to weeks without treatment; repeated attacks days to weeks without treatment; repeated attacks of acute arthritis cause of acute arthritis cause

GOUTGOUT

chronic arthritis and formation of tophi chronic arthritis and formation of tophi in synovial membranes and in synovial membranes and periarticular tissue, which eventually periarticular tissue, which eventually damages jointsdamages joints

• Aspirate:Aspirate: grossly white-gray and grossly white-gray and granular; strongly negative birefringent granular; strongly negative birefringent needle-shaped crystals under polarized needle-shaped crystals under polarized light; foreign body giant cellslight; foreign body giant cells

GOUTGOUT

• Gross:Gross: chalky white appearance of gouty chalky white appearance of gouty depositsdeposits

• Micro:Micro: earlyearly - edematous synovium with acute - edematous synovium with acute and chronic inflammatory infiltrateand chronic inflammatory infiltrate

• latelate - tophi (large aggregates of urate crystals, - tophi (large aggregates of urate crystals, granulomatous inflammation, hyperplastic fibrotic granulomatous inflammation, hyperplastic fibrotic synovium); synovium);

• gout crystals are long, slender, needle shaped, gout crystals are long, slender, needle shaped, but difficult to visualize with routine staining but difficult to visualize with routine staining because they are dissolved during formalin because they are dissolved during formalin processing (crystals are water soluble); easier to processing (crystals are water soluble); easier to identify on scrape or with alcohol fixationidentify on scrape or with alcohol fixation

GOUTGOUT

• With chronic disease, urate deposits With chronic disease, urate deposits may be present in soft tissue, may be present in soft tissue, ligaments, skinligaments, skin

• Gouty deposits may be surrounded Gouty deposits may be surrounded by fibrous tissue and be rimmed by by fibrous tissue and be rimmed by histiocytes and giant cellshistiocytes and giant cells

     

GOUTGOUT

Rheumatoid arthritisRheumatoid arthritis

Rheumatoid arthritisRheumatoid arthritis

• Chronic systemic inflammatory disorder affecting Chronic systemic inflammatory disorder affecting synovial lining of joints, bursae and tendon synovial lining of joints, bursae and tendon sheaths; also skin, blood vessels, heart, lungs, sheaths; also skin, blood vessels, heart, lungs, musclesmuscles

• Produces nonsuppurative proliferative synovitis, Produces nonsuppurative proliferative synovitis, may progress to destruction of articular cartilage may progress to destruction of articular cartilage and joint ankylosisand joint ankylosis

• 1% of adults, 75% are women, peaks at ages 10-1% of adults, 75% are women, peaks at ages 10-29 years; also menopausal women29 years; also menopausal women

• Sites:Sites: small bones of hand affected first (MCP, small bones of hand affected first (MCP, PIP joints of hands and feet), then wrist, elbow, PIP joints of hands and feet), then wrist, elbow, kneeknee

Rheumatoid arthritisRheumatoid arthritis

• Pathophysiology:Pathophysiology: triggered by exposure triggered by exposure of immunogenetically susceptible host to of immunogenetically susceptible host to arthitogenic microbial antigen; autoimmune arthitogenic microbial antigen; autoimmune reaction then occurs with T helper activation reaction then occurs with T helper activation and release of inflammatory mediators and and release of inflammatory mediators and cytokines that destroys joints; circulating cytokines that destroys joints; circulating immune complexes deposit in cartilage, immune complexes deposit in cartilage, activate complement, cause cartilage activate complement, cause cartilage damagedamage

• Parvovirus B19 may be important in Parvovirus B19 may be important in pathogenesis.pathogenesis.

Rheumatoid arthritisRheumatoid arthritis

• Genetics:Genetics: HLA-DR4, DR1 (65%); HLA-DR4, DR1 (65%); • Laboratory:Laboratory: 80% have IgM autoantibodies 80% have IgM autoantibodies

to Fc portion of IgG (rheumatoid factor), to Fc portion of IgG (rheumatoid factor), which is not sensitive or specific; synovial which is not sensitive or specific; synovial fluid has increased neutrophils (particularly fluid has increased neutrophils (particularly in acute stage), protein, low mucinin acute stage), protein, low mucin

• Other antibodies include antikeratin Other antibodies include antikeratin antibody (specific, not sensitive), antibody (specific, not sensitive), antiperinuclear factor, anti-rheumatoid antiperinuclear factor, anti-rheumatoid arthritis associated nuclear antigen (RANA) arthritis associated nuclear antigen (RANA)

Rheumatoid arthritisRheumatoid arthritis

• Clinical course:Clinical course: variable; malaise, fatigue, variable; malaise, fatigue, musculoskeletal pain, then joint involvement;musculoskeletal pain, then joint involvement;

• joints are warm, swollen, painful, stiff in joints are warm, swollen, painful, stiff in morning; 10% have acute onset of severe morning; 10% have acute onset of severe symptoms, but usually joint involvement symptoms, but usually joint involvement occurs over months to years; 50% have occurs over months to years; 50% have spinal involvementspinal involvement

• Reduces life expectancy by 3-7 years, death Reduces life expectancy by 3-7 years, death due to amyloidosis, vasculitis, GI bleeds from due to amyloidosis, vasculitis, GI bleeds from NSAIDs, infections from steroids.NSAIDs, infections from steroids.

Rheumatoid arthritisRheumatoid arthritis

• Xray:Xray: joint effusions, juxta-articular joint effusions, juxta-articular osteopenia, erosions osteopenia, erosions

• narrowing of joint space; destruction narrowing of joint space; destruction of tendons, ligaments and joint of tendons, ligaments and joint capsules produce radial deviation of capsules produce radial deviation of wrist, ulnar deviation of digits, swan wrist, ulnar deviation of digits, swan neck finger abnormalitiesneck finger abnormalities

Rheumatoid arthritisRheumatoid arthritis

• Diagnosis:Diagnosis: morning stiffness, morning stiffness, arthritis in 3+ joint areasarthritis in 3+ joint areas

• arthritis in hand joints,arthritis in hand joints,

• symmetric arthritis,symmetric arthritis,

• rheumatoid nodules, rheumatoid rheumatoid nodules, rheumatoid factor, typical radiographic changesfactor, typical radiographic changes

Rheumatoid arthritisRheumatoid arthritis

• Gross:Gross: joints have edematous, thick, joints have edematous, thick, hyperplastic synovium, covered by hyperplastic synovium, covered by delicate and bulbous fronds. delicate and bulbous fronds.

Rheumatoid arthritisRheumatoid arthritis

NORMAL SYNOVIUMNORMAL SYNOVIUM

Rheumatoid arthritisRheumatoid arthritis

• Micro:Micro: dense perivascular inflammatory infiltrate of dense perivascular inflammatory infiltrate of T lymphocytes, plasma cells (often with eosinophilic T lymphocytes, plasma cells (often with eosinophilic cytoplasmic inclusions called Russell bodies) cytoplasmic inclusions called Russell bodies)

• inflammation extends to subchondral bone inflammation extends to subchondral bone (relatively specific for rheumatoid arthritis); (relatively specific for rheumatoid arthritis); proliferative synovitis with synovial cell hyperplasia proliferative synovitis with synovial cell hyperplasia and hypertrophy, lymphoplasmacytic infiltrate with and hypertrophy, lymphoplasmacytic infiltrate with variable germinal centers, necrobiotic nodules and variable germinal centers, necrobiotic nodules and fibrosis;fibrosis;

• increased vascularity with hemosiderin deposition; increased vascularity with hemosiderin deposition; organizing fibrin floating in joint space as rice organizing fibrin floating in joint space as rice bodies; neutrophils present on synovial surface; bodies; neutrophils present on synovial surface;

METABOLIC BONE DISESES

OSTEOPOROSISOSTEOPOROSIS

• Many diseases and disorders have been Many diseases and disorders have been associated with osteoporosis associated with osteoporosis

• In general, immobilization causes bone In general, immobilization causes bone loss (following the 'use it or lose it' rule). loss (following the 'use it or lose it' rule).

• Hypogonadal states can cause secondary Hypogonadal states can cause secondary osteoporosis osteoporosis

• These include Turner syndrome, Klinefelter These include Turner syndrome, Klinefelter syndrome, Kallmann syndrome, anorexia syndrome, Kallmann syndrome, anorexia nervosa, hypothalamic amenorrhea nervosa, hypothalamic amenorrhea

OSTEOPOROSISOSTEOPOROSIS

• A bilateral oophorectomy (surgical A bilateral oophorectomy (surgical removal of the ovaries) or a premature removal of the ovaries) or a premature ovarian failure ovarian failure

• Endocrine disorders that can induce Endocrine disorders that can induce bone loss include Endocrine disorders bone loss include Endocrine disorders that can induce bone loss include that can induce bone loss include Cushing's syndrome, Cushing's syndrome, hyperparathyroidism, thyrotoxicosis, hyperparathyroidism, thyrotoxicosis, hypothyroidism, diabetes mellitus type 1 hypothyroidism, diabetes mellitus type 1 andand

OSTEOPOROSISOSTEOPOROSIS

Is a term that denotes increased Is a term that denotes increased porosity of the skeleton resulting from porosity of the skeleton resulting from reduction in the bone mass.reduction in the bone mass.

It may be localized It may be localized →disuse →disuse osteoporosis of a limb. osteoporosis of a limb.

or or

may involve the entire skeleton, as a may involve the entire skeleton, as a metabolic bone disease. metabolic bone disease.

OSTEOPOROSISOSTEOPOROSIS

• Primary Primary

• SecondarySecondary

PRIMARY: post menopausalPRIMARY: post menopausal

SenileSenile

OSTEOPOROSISOSTEOPOROSIS

• Secondary:Secondary:

• Endocrine DisordersEndocrine Disorders

OSTEOPOROSIS

OSTEOPOROSIS

Vertebral bone with Vertebral bone with osteoporosis demonstrates a osteoporosis demonstrates a compressed compressed

OSTEOPOROSISOSTEOPOROSIS

Pathophysiology:Pathophysiology:

• AGINGAGING

• ↓ ↓ replicative activity of the replicative activity of the osteoprogenitorcellsosteoprogenitorcells

• ↓ ↓ synthetic activity of the osteoblasts.synthetic activity of the osteoblasts.

• ↓ ↓ activity of the matrix bound growth activity of the matrix bound growth factors.factors.

OSTEOPOROSISOSTEOPOROSIS

• Menopause:Menopause:

• ↓ ↓ serum estrogenserum estrogen

• ↑ ↑ IL-1,IL-6 levelsIL-1,IL-6 levels

• ↑ ↑ osteoclast activityosteoclast activity

Genetic factorsGenetic factors

Nutritional effectsNutritional effects

OSTEOPOROSISOSTEOPOROSIS

• The two main biochemical markers The two main biochemical markers for bone formation are for bone formation are

• serum serum alkaline phosphatasealkaline phosphatase and and serum serum osteocalcinosteocalcin. .

• Markers for bone resorbtion include Markers for bone resorbtion include urinary calcium and urinary urinary calcium and urinary hydroxyproline hydroxyproline

OSTEOPOROSISOSTEOPOROSIS

Prevention StrategiesPrevention Strategies• The best long-term approach to osteoporosis The best long-term approach to osteoporosis

is prevention. is prevention. • children and young adults, particularly children and young adults, particularly

women, with a good diet (with enough calcium women, with a good diet (with enough calcium and vitamin D) and get plenty of exercise, will and vitamin D) and get plenty of exercise, will build up and maintain bone mass.build up and maintain bone mass.

• This will provide a good reserve against bone This will provide a good reserve against bone loss later in life. Exercise places stress on loss later in life. Exercise places stress on bones that builds up bone massbones that builds up bone mass