Bones, Joints & Soft Tissues (Martin) Flashcards
What type of ossification occurs in long bones?
Endochondral ossification; cartilage mold; new bone deposits are deposited at the bottom of growth plates leading to longitudinal growth
What type of ossification occurs in flat bones?
Intramembranous ossification; mesenchyme directly ossified by osteoblast; NO CARTILAGE; appositional growth
Osteomalacia
weakened, soft bone
Osteitis deformans
deforming bone-itis
Osteodystophy
difficult/bad growing bone
What is the most common type of collagen in osteoid?
type I collagen
Woven bone; increased cells and disorganized; produced rapidly (fetal development and repair); haphazard arrangement with less structural integrity; abnormal in adults
Lamellar bone; parallel collagen and strong; slow production; adult bone
In which decade of life do you tend to have more resorption of bone than formation?
fourth decade; see a decrease in skeletal mass
RANKL and OPG are expressed and produced by which cells?
Osteoblasts
Explain the pathophysiology of RANK?
receptor on osteoclast that activates NF-kB which promotes their survival and increases bone breakdown
Osteoprogenitor cells (osteocytes) produce which protein that triggers activation and production of OPG?
WNT proteins; they bind LRP5 and LRP6 on osteoblasts activates B-catenin and produces OPG; favors bone deposition/formation
Sclerostin
produced by osteoclasts; inhibits WNT/B-catenin; suppressing bone formation
What three hormones are important in bone formation?
estrogen, testosterone and Vit. D
What is the role of estrogen, testosterone and Vit. D in bone physiology?
they all favor bone formation
The role of M-CSF in bone homeostasis and remodeling?
M-CSF receptor on osteoclast that stimulates tyrosine kinase cascade; crucial for osteoclast generation
Dysostosis
localized disruption of migration and condensation of mesenchyme and differentiation into cartilage anlage
Supernumerary digit
extra bones or digits
Syndactyly or craniosynostosis
abnormal fusion of bones
What homeobox protein mutation is commonly associated with short terminal phalanges and a big toe?
HOXD13 mutation; brachydactyly
Achondroplasia
dwarfism; AD FGFR3 GOF mutation; short proximal extremities with normal trunk length, enlarged head and bulging forehead; NO change in longevity, intelligence or reproductive status
Thanatophoric dysplasia
most common death form of dwarfism; FGFR3 GOF mut (more severe phenotype); small chest cavity (respiratory insufficiency); die at birth or soon after
Osteogenesis Imperfecta involves which type of collagen?
Type I
Brittle bone disease
Osteogenesis imperfecta; deficiency in type I collagen will see BITE signs and symptoms; type I normal lifespan; type 2 most severe (die in utero); type 3 severe (if survive utero) and type 4 is mild
Osteogenesis imperfecta
brittle bone disease; deficiency in type I collagen; BITE signs and symptoms; accordion-like shortening of limbs
type I - COL1A1 mut
type II COL1A1 or COL1A2 mut (most severe) - respiratory problems (undeveloped lungs)
Treatment for osteogenesis imperfecta?
Surgical “rodding” of long bones; exercise and good nutrition; no smoking or steroid use
Pathology in osteopetrosis
decrease in bone resorption due to deficient osteoclast function causing diffuse, symmetric skeletal sclerosis
What is the mutation in achondroplasia?
Gain of function FGFR3 mutation
Defect in type II osteogenesis imperfecta?
there is no triple helix of collagen type I; uniformly fatal in utero (multiple intrauterine fractures)
Defect in type I osteogenesis imperfecta?
the collagen structure is normal, there is just less of it; these patients have a normal lifespan with most fractures occurring BEFORE puberty
What are the two types of osteopetrosis?
“marble bone disease”
1. Alber-Schonberg disease
2. Carbonic Anhydrase 2 deficiency
Alber-Schonberg disease
an AD osteopetrosis “marble bone disease”; mut in CLCN7 which encodes for a proton-chloride exchanger in osteoclast; decreased bone resorption leading to diffuse symmetrical skeletal sclerosis
What is the mutation in Alber-Schonberg disease?
mut in CLCN7 which encodes for a proton-chloride exchanger in osteoclast; decreased bone resorption leading to diffuse symmetrical skeletal sclerosis; an AD osteopetrosis “marble bone disease”
What is the typical clinical prevention of a patient with osteopetrosis?
diffuse symmetrical skeletal sclerosis; bones lack a medullary cavity and can present as an Erlenmeyer flask on imaging
Carbonic Anhydrase 2 deficiency
an AR osteopetrosis “marble bone disease”; lack CA2 that is needed for osteoclastic activity and renal tubular cells (renal tubular acidosis); decreased bone resorption leading to diffuse symmetrical skeletal sclerosis
What is a symptom that is seen in Carbonic Anhydrase 2 deficiency and NOT in Alber-Schonberg disease?
renal tubular acidosis because renal tubular cells also depend on CA2; both are osteopetrosis disorders
Why do you see repeated infections in osteopetrosis?
the bones lack a medullary cavity; there is no hematopoiesis = no immune cells (leukopenia); will see extra medullary hematopoiesis involving the spleen (hepatosplenomegaly)
Erlenmeyer flask on imaging as seen in osteopetrosis
Osteoporosis
severe osteopenia (below 2.5 SD mean peak bone mass); most common forms are senile and postmenopausal
What are the two most common forms of osteoporosis?
- senile - age related with low turnover (decreased activity of osteoblasts)
- postmenopausal - estrogen deficiency (increased osteoclast activity)
What are the 5 factors affecting bone mass in osteoporosis?
- Age - senile, decreased proliferation (low turnover)
- decreased physical activity - immobility, paralysis, astronauts in zero gravity
- genetics - LRP5 gene defect (rare)
- insufficient ca2+ intake (adolescent girls)
- Hormonal - post menopausal (estrogen deficiency)
Tamoxifen
treatment for breast cancer that can increase bone loss (drug induced osteoporosis)
Senile osteoporosis
age related with low turnover (decreased activity of osteoblasts); cortex is thinned by subperiosteal and endosteal resorption
Post menopausal osteoporosis
estrogen deficiency (increased osteoclast activity); the trabeculae is thinned which increases the risk for micro fractures and vertebral collapse
Osteoporotic vertebral body; loss of horizontal trabecular (post menopausal osteoporosis)
How does osteoporosis affect the axial spine?
lumbar lordosis and kyphoscoliosis
Risk factors for osteoporosis?
Caucasian, too much phosphorus in diet (sodas) and smoking
How do you diagnosis osteoporosis?
using a bone mineral density test (DEXA-scan)
(DEXA-scan)
bone mineral density test used to diagnose osteoporosis
Pathophysiology of Rickets?
impairment of mineralization of bone due to a Vit. D deficiency in kids; interferes with deposition of bone in the growth plate
Clinical presentation of Rickets?
frontal bossing, rachitic rosary of ribs, pigeon chest and bowed legs
Untreated primary hyperparathyroidism leads to what 3 skeletal abnormalities?
- osteoporosis - dissecting osteitis “railroad tracks”
- Brown tumor - vascular, hemorrhage and hemosiderin deposition leading to cystic degeneration
- von Recklinghausen disease of bone - generalized osteitis fibrosis cystica
“railroad tracks” appearance of trabecular seen in osteoporosis - dissecting osteitis caused by untreated hyperparathyroidism
a brown tumor; vascular, hemorrhage and hemosiderin deposition leading to cystic degeneration caused by untreated hyperparathyroidism
Paget Disease
aka Osteitis Deformans; an acquired bone disorder **axial skeleton and femur; can be associated with SQSTM1 gene mut that increases osteoclastic activity; “cotton wool” appearance; hallmark: mosaic pattern of lamellar bone - jigsaw-like appearance; bone growth compressed spinal and cranial nerves
Sporadic cases of Paget Disease are associated with what mutation?
SQSTM1 gene mut that increases osteoclastic activity
What bone disorder has a hallmark appearance of “mosaic pattern of lamellar bone”?
Paget Disease aka Osteitis Deformans; an acquired bone disorder
“cotton wool” appearance on imaging; seen in Paget Disease aka Osteitis Deformans; an acquired bone disorder
Labs and Treatment for Paget Disease?
increased alk phosphatase with NORMAL calcium AND phosphorus
TX: calcitonin and bisphosphonates
Hypervascularity in Paget Disease can lead to what potential fatal complication?
high-output heart failure
jigsaw puzzle-like pieces of lamellar bone seen in Paget Disease
“Greenstick” fracture?
a fracture extending only partially through the bone, common in infants when bones are soft
Stress fracture
slowly developing fracture that follows a period of increased physical activity (repetitive loads)
Comminuted fracture
bone is fragmented
Displaced fracture
ends of the bone at the fracture site are not aligned
a simpe vs a compound fracture
simple - overlying skin is intact
compound - bones shows through overlying skin
During the healing phase of bones; what changes would you observe at the end of the first week?
soft tissue callus or procallus; not structural rigidity for weight bearing
During the healing phase of bones; what changes would you observe at the end of the second week?
soft callus transformed into bony callus
Avascular necrosis (AVN)
infarction of the bone and marrow; most commonly caused by fractures or corticosteroids; the cortex is not usually involved due to collateral blood flow; subchondral infarcts are triangular or wedged shaped; can see “creeping substitution”
wedge-shaped osteonecrosis; most commonly caused by fractures or corticosteroids
What is the most common organism involved in pyogenic osteomyelitis?
staph aureus (80-90%)
Sequestrum
dead bone following subperiosteal abscess; seen in acute osteomyelitis
Involucrum
newly deposited bone that forms a shell of living tissue around devitalized bone; seen in chronic osteomyelitis
Brodie abscess
small interosseous abscess that is walled off by reactive bone; seen in chronic osteomyelitis
Pott’s disease
Tuberculous spondylitis involving the spine; can see loss of vertebral bodies on imaging; can cause permanent compression fractures leading to scoliosis or kyphosis
Bone pathology that has clinical presentation of “saber shin” and/or “saddle nose”
skeletal syphilis
What are the bone-forming tumors?
Osteoid osteoma - benign painful, worse at night, responds to NSAIDs, <2cm
Osteoid blastoma - benign, >2cm and does NOT respond to NSAIDs
Osteosarcoma - malignant painful enlarging mass
Osteosarcoma
most common malignant tumor of bone; painful enlarging mass; check for prior radiation; 50% involves knee; x ray will show mixed lytic and blastic mass and “Codman triangle”
X ray finding of a Codman triangle should make you suspect what bone pathology?
osteosarcoma; elevation of periosteum after bone breaks through cortex
What is a major risk factor for osteosarcoma?
prior radiation
70% of sporadic osteosarcoma cases involves a mutation to which gene?
RB gene mutation
Osteosarcoma can lead to what other bone pathology?
chondroblastic osteosarcoma (if abundant cartilage is present)
Osteosarcoma tends to spread to which organs?
lungs, bone and brain
Codman triangle seen in osteosarcoma; elevation of periosteum after bone breaks through cortex
What is the most common benign bone tumor?
ostechondroma; 85% are solitary and occur during early adulthood; a subtype - multiple hereditary exostosis which is AD can progress to a chondrosarcoma (malignant)
What type of bone tumor can progress to a chondrosarcoma?
multiple hereditary exostosis which is AD and 3X more likely in men
ostechondroma
benign bone tumor attached to skelton by a bony stalk capped by cartilage (bony mushroom appearance); can be painful if impinges on a nerve
benign bone tumor attached to skelton by a bony stalk capped by cartilage (bony mushroom appearance); osteochondroma
a well circumcised nodule of hyaline cartilage containing benign chondrocytes as seen in endochondroma (benign hyaline cartilage tumor)
Chondrosarcoma
second most common malignant bone tumor; onset in 40s yrs; commonly involves the shoulders; painful enlarging mass and can spread hematogenously to the **lungs; on imaging - flocculent densities
“flocculent densities” on imaging?
Chondrosarcoma - calcified matrix appears as foci of flocculent densities
Chondrosarcoma - calcified matrix appears as foci of flocculent densities
Chondrosarcoma - calcified matrix appears as foci of flocculent densities
Ewing sarcoma family tumors (ESFT)
bone tumor of unknown origin; predilection for Whites; “small blue round cell tumor” that is painful and frequently tender, warm and swollen; has onion-skin appearance on x-ray; affects long bones *femur; balanced translocation of EWSR1 gene
Ewing sarcoma family tumors (ESFT) typically affects which bones?
long bones *femur
What is typical appearance on x-ray of someone with a Ewing sarcoma family tumors (ESFT)?
onion-skin appearance on x-ray
Mutation involved with Ewing sarcoma family tumors (ESFT)?
balanced translocation of EWSR1 gene on chromosome 22; fusion of EWS-FL11
What is an important prognostic finding in Ewing sarcoma family tumors (ESFT)?
the amount of chemotherapy-induced necrosis - the more necrosis, the better because it is indicative of sensitivity to the treatment
What is the mutation in fibrous dysplasia?
somatic gain of function in GNAS1
What is the inherited genetic susceptibility in Rheumatoid arthritis (RA)?
HLA-DR4
hand deformities involved in Rheumatoid arthritis (RA)?
Boutonniere
Swan-neck
Ulnar deviation of fingers
radial deviation of wrist
Rheumatoid nodules typically grows where?
on the extensor surfaces at pressure points (forearm, elbows, occiput and lumbosacral area)
Characteristic of Rheumatoid nodules?
firm, nontender and round to oval; resemble necrotizing granulomas with a central zone of fibrinoid necrosis microscopically
OA vs RA
OA - disease of cartilage, “wear and tear”, large joints, heberdens and Bouchard nodes, no systemic effects or morning stiffness and worse with activity and better with rest
RA - disease of synovium, autoimmune, inflammatory, swan-neck and ulnar deviation deformities, systemic effects and morning stiffness, worse with rest and better with activity
Characteristics of OA?
disease of cartilage, “wear and tear”, large joints, heberdens and Bouchard nodes, no systemic effects or morning stiffness and worse with activity and better with rest
Characteristics of RA?
disease of synovium, autoimmune, inflammatory, swan-neck and ulnar deviation deformities, systemic effects and morning stiffness, worse with rest and better with activity
Gout
build up of crystallization of monosodium rate (MSU) due to hyperuricemia (>6.8 mg/dl); heavy alcohol consumption and obesity are risk factors
Pseudogout
build up of calcium pyrophosphate crystals; chondrocalcinosis; AD ANKH mutation; crystals form chalky, white friable deposits; they are rhomboid and positively birefringent
Liposarcoma
adipose malignancy; contain immature adipocytes = lipoblasts (irregular nuclei)
