Robbins Ch 26 bone Flashcards
What occurs when there is an increased osteoprotegerin (OPG) binding to RANK ligand?
Decreased osteoclast activity
OPG binds RANK ligand which reduces the nuclear factor Kappa B transcription factor–diminishes osteoclast activity
What pathway increases OPG production and what does this favor?
WNT/B-catenin pathway–favors bone formation
What is generated from osteoclasts that promote bone resorption?
Matrix metalloproteinases
Result of a spontaneous new mutation in the fibroblast growth factor receptor 3 (FGFR3) gene leading to abnormal cartilage proliferation at growth plates and affecting endochondral bone growth…
Achondroplasia
What are the features of achondroplasia?
Infants torso and head are normal size
Extremities are short
Prominent forehead
What is seen on an XRAY of a patient with achondroplasia?
Shirt, slightly bowed long bones with NO osteopenia
May manifest at birth with multiple fractures from severe osteopenia and is due to abnormal type I collagen synthesis…
Osteogenesis imperfecta
What is seen with osteogenesis imperfect?
Osteopenia–predisposing to fractures
Blue sclerae
Dental abnormalities
Progressive hearing loss
May occur in childhood from a Vitamin D deficiency or decreased absorption of Vitamin D in the small intestine…
Rickets
What is the most common form of lethal dwarfism that results from a mutation in FGFR3 gene?
Thanatophoric dysplasia
Infants born with thanatophoric dysplasia often present with immediate respiratory distress, why?
Due to the markedly reduced thoracic size–leads to pulmonary hypoplasia
What are the characteristic findings of thanatophoric dysplasia?
Infant presents with immediate respiratory distress Short limbs Frontal skull bossing Small thorax Normal bone density without fractures
What syndrome is caused by the absence of HGPRT and is characterized by hyperuricemia?
Lesch-Nyhan syndrome
A decreased binding of what occurs in osteoporosis?
Decreased binding of osteoprotegerin (OPG) to the macrophage RANK ligand–leading to increased osteoclast activity
Ability of osteoblasts to divide and lay down osteoid is reduced and osteoblasts produce less OPG leading to accelerated bone loss. These are characteristics of what dz?
Osteoporosis
What characterizes postmenopausal osteoporosis?
Hormone-dependent acceleration of bone loss
Estrogen deficiency–> increased secretion of IL-1, 6 and TNFa
Estrogen deficiency seen in postmenopausal women leads to an increased secretion of IL-1 and 6 and TNFa. What does this increase and what does it decrease?
Increases the levels of RANK and RANKL
Decreases levels of OPG
Leading to increased osteoclastic activity and accelerated bone loss
The production of IL-6 from osteoblasts is seen in what disease?
Paget disease of the bone
What is seen on autopsy of a stillborn with evidence of type II lethal variant of osteogenesis imperfecta and what causes these findings? Also what mutation is seen with this disorder?
Marked osteopenia and multiple bone fractures caused by a deficiency in collagen I formation
COL1A1 mutation
What mutation is seen in cases of hereditary and sporadic osteochondromas?
EXT mutations
What mutation is seen in cases of achondrogenesis and how is it differentiated from osteogenesis imperfecta?
FGFR3 mutation
There is NO osteopenia or bone fractures at birth
Rare bone dz that results from mutations in genes that regulate osteoclast activity and bone resorption…
Osteopetrosis (albers-Schonberg dz)
There is a defect in the production in an enzyme seen in osteopetrosis, what is this enzyme?
Carbonic anhydrase
What are some physical findings seen with osteopetrosis (albers-schonderb dz)?
hepatosplenomegaly–due to marrow reduction
Palsies involving cranial nerves II, VII, VIII due to nerve compression in narrowed bony foramina
Pancytopenia
Difusely and symmetrically sclerotic bones–due to poorly formed metaphyses
The use of corticosteroids increases the risk of..
Developing Cushing syndrome with osteoporosis
What does corticosteroid use stimulate?
RANKL expression which inhibits osteoblast osteoprotegerin (OPG) synthesis–enhancing osteoclast proliferation-promoting bone resorption
What disease presents with a mosaic pattern of lamellar bone and has 3 phases–lytic, mixed, and sclerotic “burnt out” phases.
Paget disease of bone
What is the common presentation seen with Paget dz of bone?
Bone pain Reduced ROM No tenderness or swelling on palpation Sclerotic, thicked cortical bone with narrowed joint space on XRAY Mosaic pattern of lamellar bone has to buy larger hats loss of normal trabeculae
What are the 3 phases of Paget dz of bone?
Lytic phase
Mixed phase–osteosclerosis and osteolysis
Sclerotic “burnt out” phase
What bone disorder is seen in hyperparathyroidism?
Osteitis fibrosa cystica
Tumorlike projection of bone capped by cartilage protruding from the metaphyseal region of a long bone…
Osteochondroma
What gene mutations are seen in both hereditary and sporadic osteochondromas?
Loss of heterozygosity in EXT1 or EXT2 genes
Results in osteopenia from Vitamin D deficiency in an adult
Osteomalacia
Sporadic and genetic paget dz of bone have what mutation?
SQSTM1 mutation
What is elevated in the serum with a parathyroid adenoma?
Calcium
Phosphate
What activity increases with a parathyroid adenomas?
Increased secretion of PTH–leads to increased osteoclastic resorption of bone
What is the brown tumor of bone seen with parathyroid adenomas?
Microfracture–leading to hemorrhages and influx of macrophages–cystic lesion forms
What is contained within a brown tumor of bone caused by a parathyroid adenoma?
Osteoclasts and fibroblasts
Where does a giant cell tumor of bone occur and what does it contain?
occurs in epiphysis of bone and contains plump stream cells NOT fibroblast (like a brown tumor of bone-caused by microfractures)
Patients with a parathyroid adenoma who develop a brown tumor of bone caused by microfractures presents…
With chronic pain
can have a hx of urinary tract calculus
There is swelling in diaphysis of bone–without erosion of the cortex or soft-tissue mass
Increased osteoclasts and fibroblast proliferation
Bone is splintered into fragments…
Comminuted bone fracture
Fracture penetrates the skin…
Compound bone fracture
Nonaligned bone, possibly resulting in some deformity
Displaced bone fracture
Fracture where bone remains contiguous–does not extend completely across the shaft of the bone
Incomplete fracture
Fracture occurring in a location weakened by a preexisting dz…
Pathologic fracture
What are the underlying conditions that can lead to avascular necrosis of bone (osteonecrosis)?
Hemoglobinopathies (sickle cell dz) Fracture Barotrauma Hypercoagulable states Hyperlipidemia
What therapy can lead to avascular necrosis of bone (osteonecrosis)?
Glucocorticoid therapy–decreases osteoblastogenesis
What is seen on imaging when a patient presents with avascular necrosis of bone?
patchy radiolucency and densities within the bone
What is the most common site for avascular necrosis to occur?
Femoral head
Benign tumor of hyaline cartilage arising in the medullary space of young adults…
Enchondroma
How does enchodroma present and what causes it?
Pain with use of the joint and tenderness upon palpation
Caused by chondrocytes
What is the most common cause of pyogenic osteomyelitis?
Staphylococcus aureus
How does Pyogenic osteomyelitis present?
Seen in younger children
Elevated temp
Swelling with tenderness, pain and reduced ROM in affect area
Areas of osteolysis and comical erosion involving the metaphysis
Abscess formation
What is the sequence of events for the development of chronic osteomyelitis?
Compound fracture
Becomes infected
Inadequate subsequent care leading to the osteomyelitis
Patient has continued pain after some time
What is seen on X-ray in patients with chronic osteomyelitis and what is causing these two findings?
Sequestrum–infection of bone and associated vascular compromise causing necrosis
Involurcrum–shell of reactive new bone formed around dead bone
What is the hallmark for tuberculous osteomyelitis?
Destructive lesion in vertebrae with extension of dz along the posts muscle WITHOUT any signs of acute inflammation
Results from hematogenous spread of an infection in the lung. Long bones and vertebrae are the favored sites…
Tuberculosis of bone–osteomyelitis
Benign tumor of the bone with a central nidus of woven bone and sclerotic rim…
Osteoid osteoma
Young patient presents with severe pain that is relived with aspirin. XRAY shoes a well-defined lucent area surrounded by thin rim of bony sclerosis. Dx?
Osteoid osteoma
The activity of what is increased with an osteoid osteoma?
Osteoblast activity
Benign tumor of hyaline cartilage that arises in the medullary space in young adults?
Enchondroma
Localized area of developmental arrest of bone formation?
Fibrous dysplasia
Benign, locally aggressive lesion that arises in the epiphysis of long bones in young adults and has a “soap bubble” appearance on XRAY?
Giant cell tumor
What is the histological appearance of a giant cell tumor of bone?
Multinucleate cells in a storm predominantly composed of spindle-shaped mononuclear cells
A large, destructive lytic and plastic mass arising in the metaphysical region of the distal femur and extending into the surround soft tissue?
Osteosarcoma
What can call attention to an osteosarcoma?
trauma
What mutation is seen in individuals who develop osteosarcoma?
Sporadic cases–loss of both alleles of RB1
Familial cases–lost of just one allele of RB1
Ill-defined mass seen on XRAY involving the metaphysical area with elevation of adjacent periosteum?
Osteosarcoma
A biopsy is performed on a tumor located above the knee. It showed hyper chromatic, pleomorphic spindle cells forming an osteoid matrix. Dx?
Osteosarcoma
What are the two most common malignant bone tumors in children and what region of the bone do each usually arise from?
Osteosarcoma–arise in the metaphyseal region
Ewing sarcoma– arise in the diaphyseal region of long tubular bone
Young child presents with femoral bone pain with no hx of trauma or recent illness. On PE the affected area is warm and tender to palpation, fever and leukocytosis present. XRAY shows expansile mass in diaphyseal region extending into the soft tissue covered by layers of reactive bone. Histology shows sheets of closely packed primitive cells with small, uniform nuclei and scant cytoplasm. Dx?
Ewing sarcoma
What translocation is present in 85% of ewing sarcomas?
T(11;22)–giving rise to the EWS-FLI1 fusion gene
Focal lytic lesion within bone with recognizable plasma cells on histology?
Plasmacytoma
A benign tumor like condition that can weaken the bone to the point of pathologic fractures?
Fibrous dysplasia
Woven bone is middle of benign-looking fibroblasts–mostly occurs in ribs, femur, tibia, mandible, and calvaria?
Fibrous dysplasia
Patient presents with femur pain after recent fall while playing football. There is pain on palpation. A diaphysial lesion with central lucency and a thin sclerotic rim is discovered. The lesion is completely intramedullary and is well circumscribed. Biopsy shows scattered trabecular of woven bone in background of fibroblastic proliferation. Dx?
Fibrous dysplasia
The serum level of what substance raises the suspicion of bone mets in older adults, particularly when there is a pathologic fracture resulting from a bone lesion?
Alkaline phosphatase level
What are the primary sites where metastatic bone carcinoma can occur from?
Breast Prostate Lung Kidney Thyroid
A patient presents with increasing dull/constant bone pain in multiple locations. There is intense pain upon palpation. XRAY shows lytic area extending through entire thickness of bone. The patients alkaline phosphatase is elevated. Dx?
Metastatic bone carcinoma
Minimal joint stiffness in the morning that quickly subsides is characteristic of what disorder?
Osteoarthritis
Progressive involvement of large, weight-bearing joints and osteophytes in the interphalangeal joints in the elderly. This is a multifactorial dz in which genetic predisposition and biomechanics forces affect chondrocytes.
Osteoarthritis
A dz that is typically associated with symmetric involvement of small joints of the hands and feet. involves the infiltration of the synovium with CD4+ t-cells.
Rheumatoid arthritis
What are the features of chronic rheumatoid arthritis?
Bilateral symmetric involvement of joints
destruction of joints with characteristic deformities
Presences of rheumatoid nodules
What creates the pannus seen in rheumatoid arthritis and what does this eventually lead to?
Inflammatory cytokines–move into joint and eventually cause joint destruction
What is the treatment used for patient with chronic rheumatoid arthritis?
Anti-TNF agents
Rheumatoid arthritis patients are positive for?
Rheumatoid factor
Cyclic citrullinated peptides (CCPs)–which my indicate chronicity of dz
What is bisphosphonates treatment used for and how does it work?
Used to diminish osteoclast activity–treating conditions with bone loss
With respect to serology performed on patients with Juvenile rheumatoid arthritis, what is usually + and what is -?
rhumatoid factor negative
ANA positive
What is different with Juvenile rheumatoid arthritis when comparing it to adult RA?
More likely to have systemic manifestations
- Rash
- Myalgia
- Myocarditis
- Pericarditis
- Uveitis
- Glomerulonephritis
What disease is + for barrel burgodorferi and what is this associated with?
Lyme dz associated with migratory arthritis of large joints
What is the agent that produces the nongonococcal urethritis seen with reactive arthritis?
Chlamydia trachomatis
What joint is most commonly involved with a chlamydia trachmoatis infection?
Sacroiliac joint–like spondyloarthropathies
This disorder has a very strong association with HLA-B27, involves the lower back and pelvis and has a characteristic bamboo spine Xray..
Ankylosing spondyloarthritis
What are the extra-articular manifestations seen with ankylosing spondyloarthritis?
Anterior uveitis and aortitis
What is seen on XRAY in ankylosing spondyloarthritis?
loss of lumbar lordosis
narrowing with sclerosis of sacroiliac joints bilaterally
syndesmophyte formation at junction of vertebra
annulus fibrous of intervertebral discs
Name the seronegative spondyloarthropathies…
Ankylosing spondylitis
Reactive arthritis
Psoriatic arthritis
Eneropathic arthritis
What are the 4 common features of all the seronegative spondyloarthropathies?
Strong association with HLA-B27
Negative test result for rheumatoid factor
Infection-leading to back pain with recurrence after several months
Stiffness of lumbar spine and tenderness of the sacroiliac joints
What is the major difference btw Psoriasis with psoriatic arthritis and rheumatoid arthritis?
Psoriatic arthritis–does NOT have significant joint destruction
Patient presents with long standing history of silvery/salmon-colored skins lesions on elbows, knees, scalp and lubosacral area. Patient has unilateral increasing pain in joint areas. There is minimal reduction in mobility and NO swelling or warmth to the touch. There is minimal joint space narrowing and surface erosion. Dx?
Psoriatic arthritis
What is seen on the biopsy of a patient with psoriatic arthritis?
Epidermal thinning with hyperkeratosis and parakeratosis
Patients with sickle cell anemia are more likely to develop osteomyelitis due to what infectious agent?
Salmonella
Neonates who present with osteomyelitis most likely developed it from what infectious agent?
Group B strep
Chronic arthritis that tends to be remitting and migratory involving primarily that large joints and can cause extensive bony erosion if it becomes chronic is caused by what dz?
Lyme dz–borrelia burgdorferi
Sexually active young adults are most likely to develop suppurative arthritis from what infectious agent?
N. Gonorrhoeae
What usually occurs a few days before acute suppurative arthritis caused by N. Gonorrhoeae?
Urethritis
What is seen on PE and on biopsy with acute suppurative arthritis caused by N. Gonorrhoeae?
Swollen, warm and tender joint(s)
Biopsy–gram negative intracellular diplocoocus
Acute inflammation of the first MP joint caused by precipitation of needle-shaped negatively birefringent uric acid crystals in the joint space?
Gout
What is the first line of therapy for gout?
NSAIDs
What is seen on PE with Gout?
tenderness swelling and erythema of most commonly the first metatarsophalangeal joint
Precipitation of urate crystals into the joints producing an acute inflammatory reaction where neutrophils and and monocytes are found. If large enough it can erode the overlying skin
Gouty tophus
What are leukemia patients (especially patients with CML) who are treated with chemo at an increased risk of developing?
Secondary gout–chemo causes massive lysis of leukemic cell nuclei–produces large amounts of urate
Caused by deposition of calcium pyrophosphate dehydrate into joints?
Pseudogout
Pseudogout is most often seen secondary to what dz?
Hemochromatosis- causing skin pigmentation, HF, DM, Cirrhosis
What is seen on birefringent stains when its pseudo gout?
Blue–rhomdoidal calcium pyrophosphate crystals
A thin walled and clear structure with mucoid content that arises in the connective tissue of a joint capsule or tendon sheath?
Ganglion cyst
What is the most common site for a ganglion cyst to develop?
Extensor surfaces of the hands and feet–especially the wrist
What is the most common soft tissue tumor of the hand (that can also occur in the knee). Has translocation of coding sequence for M-CSF placed adjacent to promotor of the collagen COL6A3 gene. Its a benign lesion, but can be locally aggressive and extend into adjacent bone and soft tissue?
Tenosynovial giant cell tumor (pigmented villonodular synovitis)
What is seen on histology of a tenosynovial giant cell tumor?
synoviocyte-like tumor cells in a hyalinized storm contain osteoclast-like giant cells and hemosiderin
Benign soft-tissue neoplasm that is composed of mature adipocytes?
Lipoma
Tumor located in deep soft tissues, can be indolent, and can reach a large size. Its the most common sarcoma of adulthood?
Liposarcoma
What is the presentation for a liposarcoma
Dull, constant pain that worsens with movement
Is a deep solid mass with ill-defined soft-tissue
What is the karyotype translocation occurs with a liposarcoma and what gene amplification is seen?
Karyotype– t (12;16)(q13;p11)
Amplification of MDM2 gene
Reactive fibroblastic proliferation seen in the upper extremities and trunk of young adults. Sometimes occurs after trauma?
Nodular fasciitis
Hard-cord like lesion containing mature fibroblasts surrounded by dense collagen–lesion know as a dupuytren contracture?
Superficial fibromatosis
Most common sarcoma in children marked with antibody to vimentin?
Rhabdomyosarcoma
What is the histological appearance of a rhabdomyosarcoma?
Spindle-shaped markedly pleomorphic cells with pink cytoplasm
A well-circumscribed mass with a biphastic pattern of spindle cells and epithelial cells forming glands found around a joint or within deep soft tissues without bony erosion.
Synovial sarcoma
What is the translocation that occurs in most synovial sarcomas?
t(X;18)
