Bone Path Flashcards
what are the components of the bone matrix?
osteoid
type 1 collagen
osteopontin
hydroxyapatite
woven bone
produced rapidly during fetal development and fracture repair
disorganized collagen structure
lamellar bone
slow production of stronger collagen structure
overtakes woven bone
osteoblasts
regulates mineralization
osteocytes
inactive osteoblasts
control calcium and phosphate levels
osteoclasts
multinucleated macrophages
bone resorption
what type of bones undergo endochondral ossification?
long bones
deposition of new bone at bottom of growth plates with longitudinal growth
bone growth
what type of bones undergo intramembranous ossification?
flat bones
deposition of new bone on the preexisting surface with appositional growth
bone remodeling
under control of hormones and growth factors
when is peak bone mass achieved?
in early adulthood after cessation of skeletal growth
when does bone resorption overtake bone formation?
fourth decade of life
decrease skeletal mass
what signaling pathways play a key role in homeostasis and remodeling of bones?
RANK, RANKL and OPG
WNT/B-catenin
M-CSF
Paracrine
what is the RANK?
receptor activator for NF-kB on osteoclast precursor
when stimulated by RANK-L, activates NF-kB for bone breakdown
where is RANK-L expressed?
osteoblasts and marrow stromal cells
what is OPG?
osteoprotegerin “decoy” receptor made by osteoblasts
can bind RANK-L and prevent interaction with RANK
bone building
what is the WNT/B-catenin pathway?
WNT proteins bind to LRP5 and LRP6 receptors on osteoblasts
trigger activation of B-catenin and OPG production
what inhibits the WNT pathway?
sclerostin produced by osteocytes
which factors stimulate bone growth?
estrogen
testosterone
vit D
what factors stimulate bone breakdown?
PTH
IL-1
glucocorticoids
what role does M-CSF play in bone homeostasis?
M-CSF receptor on osteoclast precursor stimulate tyrosine kinase cascade
results in generation of osteoclasts
describe the paracrine activity between osteoclasts and osteoblasts
breakdown of matrix by osteoclasts activates matrix proteins, GFs, cytokines and enzymes that activate osteoblasts
list the types of collagen and their location (boards only)
1 - bones and scaring 2 - cartilage 3 - skin, vessels, and granulation tissue 4 - basement membrane 5 - ligaments and lungs
generally describe dysostosis disorders
abnormal migration and condensation of mesenchyme and differentiation in cartilage
what factors lead to dysostosis?
transcription factor defects: homeobox or cytokines
syndromic
what defects are classified as dysostosis?
aplasia
supernumerary digit
syndactyly
craniosynostosis
generally describe dysplasia disorders
global disorganization of bone and/or cartilage caused by mutations in genes controlling development or remodeling
what is brachydactyly and what protein mutation is associated with it?
short terminal phalanges of thumb and big toe
HOXD13
what is cleidocranial dysplasia?
AD RUNX2 mutation leading to:
delayed closure of cranial sutures - patent fontanelles
wormian bones - additional bones within sutures
delayed eruption of secondary teeth
primitive clavicle
short height
what is achondroplasia?
AD mutation causing FGFR3 GoF
abnormal cartilage growth resulting in: short proximal extremities normal trunk length enlarged head bulging forehead depression root of the nose
*most common form of dwarfism
what is thanatophoric dysplasia?
lethal form of dwarfism
micromelic shortening of limbs frontal bossing macrocephaly small chest cavity bell-shaped abdomen die soon after birth
what factors result in abnormal bone density?
LPR5 receptor defect - osteoporosis or osteopetrosis
RANK-L mutation
what is osteogenesis imperfecta?
*BOARDS
mutation in a1 and a2 chains of type 1 collagen
most common inherited disorder of connective tissue
4 subtypes
type 1 OI
AD inheritance
decreased synthesis of a1 chain + abnormal a1 or a2 chain
normal collagen structure but decreased amount
best prognosis!
what is the clinical presentation of type 1 OI?
fractures before puberty blue sclera skeletal fragility abnormal dentition hearing impairment joint laxity triangular face
type 2 OI
AR or AD
abnormally short a1 chain + abnormal or insufficient a2 chain
lethal in utero or shortly after birth due to respiratory problems
OI treatment
surgical “rodding” of long bones
exercise, maintain healthy weight and nutrition
no smoking
no steroids
what differential dx is often seen with OI?
child abuse! types of fractures are similar to those in OI
fractures in multiple stages of healing
rib fractures
spiral fractures
no explanation of trauma
what is osteopetrosis?
marble bone disease/albers-schonberg disease
mutation in CLCN2 encoding proton pumps on osteoclasts resulting in carbonic anhydrase 2 deficiency
reduced bone resorption
acidification results in solubilized hydroxyapatite
what are the morphologic findings in osteopetrosis?
lack of medullary cavity
bulbous ends of long bones (Erlenmeyer flask)
neural foramina are small and compress nerves
describe the infantile form of osteopetrosis
SEVERE
AR
mediterranian or arab descent
what is the clinical presentation of infantile osteopetrosis?
optic atrophy deafness facial paralysis fractures anemia hydrocephaly
describe the adolescent form of osteopetrosis
MILD
AD
dx in adolescence or adulthood
what is the clinical presentation of adolescent osteopetrosis?
repeated fractures
mild cranial nerve deficits
anemia
describe mucopolysacchardoses
lysosomal storage diseases caused by a deficiency in acid hydrolase enzymes
mucopolysaccharides accumulate in chondrocytes causing structural defects in cartilage
what is the clinical presentation of mucopolysaccharidoses?
short stature
chest wall abnormalities
malformed bones
what is osteopenia?
decreased bone mass (1-2.5 SD below the mean)
precursor to osteoporosis
what is osteoporosis?
osteopenia severe enough to increase risk of fracture
at least 2.5 SD below mean
what fracture signifies osteoporosis?
atraumatic or vertebral compression fracture
what factors contribute to osteoporosis?
age physical activity genetics nutrition hormones
describe how age contributes to osteoporosis
senile osteoporosis
decreased proliferative and biosynthetic potential
decreased cell response to growth factors
describe how physical activity contributes to osteoporosis
mechanical forces stimulate bone remodeling
resistance exercises are best
decreased physical activity = decreased bone density
what genetic factors contribute to osteoporosis?
LRP5 RANKL OPG RANK HLA focus estrogen receptor gene vit D receptor gene
describe how nutrition contributes to osteoporosis
insufficient calcium intake during the period of rapid growth restricts peak bone mass
*girls more affected than boys
describe how hormones contribute to osteoporosis
post-menopausal estrogen deficiency results in decreased formation and resorption
also increases inflammatory cytokines which stimulate osteoclasts and increases RANKL
what breast cancer treatment can increase bone loss?
Tamoxifen
describe post-menopausal osteoporosis morphology
bone with an increased surface area
perforated thinned and lose interconnections
microfractures and vertebral collapse
describe senile osteoporosis morphology
cortex thinned by subperiosteal and endosteal resorption
who is predisposed to osteoporosis?
white women with light-colored hair and eyes
smokers
how do you dx osteoporosis?
DEXA-scan - bone mineral density test
labs to r/o secondary causes
what is the clinical presentation of osteoporosis?
thoracic and lumbar vertebral fractures
lumbar lordosis
kyphoscoliosis
what is a possible complication of fractures in osteoporosis?
pneumonia
PE
osteoporosis prevention
exercise
calcium
Vit D
osteoporosis tx
bisphosphonates
hormone therapy
denosumab (anti-RANKL)
what is Paget disease/osteitis deformans?
acquired disease of increased but disordered bone mass
either monostotic or polyostotic
what is the most common form of Paget?
familial polyostotic
what gene is associated with Paget?
SQSTM1
increased activity of NF-kB = increased osteoclast activity
what is the morphological hallmark of Paget?
mosaic pattern of lamellar bone (sclerotic phase)
*jigsaw appearance with prominent cement lines
describe the 3 phases of Paget
- lytic phase - large osteoclasts with 100 nuclei
- mixed phase - clasts + loss of blasts
- osteosclerotic phase - quiescent stage
what is the clinical presentation of Paget?
bowing of femurs and tibia chalk-stick type fractures of long bones spinal compression fractures kyphosis hypervascularity leading to CHF
what would be seen in labs with Paget?
increased serum alk phos
normal calcium and phos
Paget tx
calcitonin and bisphosphonates
what is a possible outcome of bone transformation in Paget?
sarcomatous transformation into osteosarcoma or fibrosarcoma
vit D deficiency in kids results in…
rickets
vit D deficiency in adults results in…
osteomalacia
what is the clinical presentation of rickets?
frontal bossing squared-off head rachitic rosary of ribs pigeon breast deformity lumbar lordosis bowed legs
how does hyperparathyroidism result in bone deformity?
PTH signals osteoclast activation to increase serum Ca
skeletal changes result from continued activation of PTH
what 4 skeletal abnormalities are associated with untreated hyperparathyroidism?
osteoporosis
brown tumor
dissecting osteitis
von Recklinghausen disease
what is dissecting osteitis?
clasts tunnel into and dissect centrally along the length of trabeculae creating the appearance of railroad tracks
what is a brown tumor?
bone loss leads to microfractures
microfractures elicit influx of macrophages and fibrous tissue
creates a mass of reactive tissue
also called osteitis fibrosis cystica
what is renal osteodystrophy?
skeletal changes associated with chronic renal disease
what is the clinical presentation of renal osteodystrophy?
osteopenia/osteoporosis
osteomalacia
secondary hyperparathyroidism
growth retardation
what are the 3 histologic subtypes of renal osteodystrophy?
- high turnover = resorption > formation
- low turnover = low activity overall
- mixed = areas with high and low turnover
describe the pathogenesis of renal osteodystrophy
tubular dysfunction - hydroxyapatite dissolution
generalized renal failure - hyperphos, hypoCa
decreased production of secreted factors - low vit D
what is known as the “silent crippler”?
renal osteodystrophy in kids
describe the healing of bone fractures
- hematoma formation
- callus formation - woven bone + cartilage
- callus ossification - woven bone
- bone remodeling - lamellar bone
what is osteonecrosis?
infarction of the bone and marrow secondary to vascular injury
most cases from fracture or corticosteroids
collateral flow preserves cortex
describe subcondral infarcts
causes pain only with activity at first and then constant pain
collapse and may lead to secondary arthritis
triangular or wedge-shaped
describe medullary infarcts
small, clinically silent infarcts that occur with Gaucher, dysbarism, and sickle cell anemia
involve trabecular bone and marrow
what is “creeping substitution”?
after bone death, trabecular that remain intact serve as scaffolding for deposition of new bone
what is osteomyelitis?
inflammation of the bone and marrow due to infection
usually a primary solitary focus but can be due to systemic infection
describe pyogenic osteomyelitis
bacterial infection from hematogenous spread, extension from contiguous site or direct implantation
in kids due to mucosal injuries or minor skin infections
in adults due to open fractures, surgery, or diabetic infection
what bacteria is the most common cause of osteomyelitis?
staph aureus
less common:
H. flu
Grp B strep
if a culture comes back as mixed bacteria, what would you suspect as the cause of osteomyelitis?
surgery or open fracture
sickle cell patients are predisposed to what bacterial infection?
salmonella
what is sequestrum?
dead bone following subperiosteal abscess
becomes draining sinus
what is involucrum?
newly deposited bone forms a shell of living tissue around the segment of dead bone
occurs in chronic osteomyeltitis
what is a Brodie abscess?
chronic, small interosseous abscess that frequently involves the cortex and is walled off by reactive bone
what is sclerosing osteomyelitis of Garre?
chronic jaw osteomyelitis associated with new bone formation that obscures the underlying osseous structure
what is the clinical presentation of acute osteomyelitis?
malaise
fever/chills
leukocytosis
intense, throbbing pain over the affected region
what will be seen on XR with acute osteomyelitis?
lytic focus of bone destruction surrounded by zone of sclerosis
osteomyelitis tx
abx and surgical drainage
what are some complications of chronic osteomyelitis?
pathologic fracture secondary amyloidosis endocarditis sepsis SCC in draining sinus sarcoma of infected bone
what is mycobacterial osteomyelitis?
blood borne infection originating from a focus of active disease during early stages of infection
bone infection may persist for years before detected
histo: caseous necrosis and granulomas
what is Pott disease?
tuberculous spondylitis
mycobacterial osteomyelitis of the spine
permanent compression fractures - scoliosis, kyphosis and neuro deficits
what are complications associated with Pott disease?
tuberculous arthritis
sinus tract formation
psoas abscess
amyloidosis
what skeletal abnormalities are associated with congenital syphilis?
saber shin - massive reactive periosteal bone deposition on medial and anterior surfaces of the tibia
what skeletal abnormalities are associated with acquired syphilis?
saddle nose deformity
palate, skull and long bone deformities
