Bone Path Flashcards
1
Q
what are the components of the bone matrix?
A
osteoid
type 1 collagen
osteopontin
hydroxyapatite
2
Q
woven bone
A
produced rapidly during fetal development and fracture repair
disorganized collagen structure
3
Q
lamellar bone
A
slow production of stronger collagen structure
overtakes woven bone
4
Q
osteoblasts
A
regulates mineralization
5
Q
osteocytes
A
inactive osteoblasts
control calcium and phosphate levels
6
Q
osteoclasts
A
multinucleated macrophages
bone resorption
7
Q
what type of bones undergo endochondral ossification?
A
long bones
deposition of new bone at bottom of growth plates with longitudinal growth
bone growth
8
Q
what type of bones undergo intramembranous ossification?
A
flat bones
deposition of new bone on the preexisting surface with appositional growth
bone remodeling
under control of hormones and growth factors
9
Q
when is peak bone mass achieved?
A
in early adulthood after cessation of skeletal growth
10
Q
when does bone resorption overtake bone formation?
A
fourth decade of life
decrease skeletal mass
11
Q
what signaling pathways play a key role in homeostasis and remodeling of bones?
A
RANK, RANKL and OPG
WNT/B-catenin
M-CSF
Paracrine
12
Q
what is the RANK?
A
receptor activator for NF-kB on osteoclast precursor
when stimulated by RANK-L, activates NF-kB for bone breakdown
13
Q
where is RANK-L expressed?
A
osteoblasts and marrow stromal cells
14
Q
what is OPG?
A
osteoprotegerin “decoy” receptor made by osteoblasts
can bind RANK-L and prevent interaction with RANK
bone building
15
Q
what is the WNT/B-catenin pathway?
A
WNT proteins bind to LRP5 and LRP6 receptors on osteoblasts
trigger activation of B-catenin and OPG production
16
Q
what inhibits the WNT pathway?
A
sclerostin produced by osteocytes
17
Q
which factors stimulate bone growth?
A
estrogen
testosterone
vit D
18
Q
what factors stimulate bone breakdown?
A
PTH
IL-1
glucocorticoids
19
Q
what role does M-CSF play in bone homeostasis?
A
M-CSF receptor on osteoclast precursor stimulate tyrosine kinase cascade
results in generation of osteoclasts
20
Q
describe the paracrine activity between osteoclasts and osteoblasts
A
breakdown of matrix by osteoclasts activates matrix proteins, GFs, cytokines and enzymes that activate osteoblasts
21
Q
list the types of collagen and their location (boards only)
A
1 - bones and scaring 2 - cartilage 3 - skin, vessels, and granulation tissue 4 - basement membrane 5 - ligaments and lungs
22
Q
generally describe dysostosis disorders
A
abnormal migration and condensation of mesenchyme and differentiation in cartilage
23
Q
what factors lead to dysostosis?
A
transcription factor defects: homeobox or cytokines
syndromic
24
Q
what defects are classified as dysostosis?
A
aplasia
supernumerary digit
syndactyly
craniosynostosis
25
generally describe dysplasia disorders
global disorganization of bone and/or cartilage caused by mutations in genes controlling development or remodeling
26
what is brachydactyly and what protein mutation is associated with it?
short terminal phalanges of thumb and big toe
HOXD13
27
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
28
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
29
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
```
30
what factors result in abnormal bone density?
LPR5 receptor defect - osteoporosis or osteopetrosis
| RANK-L mutation
31
what is osteogenesis imperfecta?
*BOARDS
mutation in a1 and a2 chains of type 1 collagen
most common inherited disorder of connective tissue
4 subtypes
32
type 1 OI
AD inheritance
decreased synthesis of a1 chain + abnormal a1 or a2 chain
normal collagen structure but decreased amount
best prognosis!
33
what is the clinical presentation of type 1 OI?
```
fractures before puberty
blue sclera
skeletal fragility
abnormal dentition
hearing impairment
joint laxity
triangular face
```
34
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
35
OI treatment
surgical "rodding" of long bones
exercise, maintain healthy weight and nutrition
no smoking
no steroids
36
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
37
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
38
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
39
describe the infantile form of osteopetrosis
SEVERE
AR
mediterranian or arab descent
40
what is the clinical presentation of infantile osteopetrosis?
```
optic atrophy
deafness
facial paralysis
fractures
anemia
hydrocephaly
```
41
describe the adolescent form of osteopetrosis
MILD
AD
dx in adolescence or adulthood
42
what is the clinical presentation of adolescent osteopetrosis?
repeated fractures
mild cranial nerve deficits
anemia
43
describe mucopolysacchardoses
lysosomal storage diseases caused by a deficiency in acid hydrolase enzymes
mucopolysaccharides accumulate in chondrocytes causing structural defects in cartilage
44
what is the clinical presentation of mucopolysaccharidoses?
short stature
chest wall abnormalities
malformed bones
45
what is osteopenia?
decreased bone mass (1-2.5 SD below the mean)
precursor to osteoporosis
46
what is osteoporosis?
osteopenia severe enough to increase risk of fracture
at least 2.5 SD below mean
47
what fracture signifies osteoporosis?
atraumatic or vertebral compression fracture
48
what factors contribute to osteoporosis?
```
age
physical activity
genetics
nutrition
hormones
```
49
describe how age contributes to osteoporosis
senile osteoporosis
decreased proliferative and biosynthetic potential
decreased cell response to growth factors
50
describe how physical activity contributes to osteoporosis
mechanical forces stimulate bone remodeling
resistance exercises are best
decreased physical activity = decreased bone density
51
what genetic factors contribute to osteoporosis?
```
LRP5
RANKL
OPG
RANK
HLA focus
estrogen receptor gene
vit D receptor gene
```
52
describe how nutrition contributes to osteoporosis
insufficient calcium intake during the period of rapid growth restricts peak bone mass
*girls more affected than boys
53
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
54
what breast cancer treatment can increase bone loss?
Tamoxifen
55
describe post-menopausal osteoporosis morphology
bone with an increased surface area
perforated thinned and lose interconnections
microfractures and vertebral collapse
56
describe senile osteoporosis morphology
cortex thinned by subperiosteal and endosteal resorption
57
who is predisposed to osteoporosis?
white women with light-colored hair and eyes
| smokers
58
how do you dx osteoporosis?
DEXA-scan - bone mineral density test
| labs to r/o secondary causes
59
what is the clinical presentation of osteoporosis?
thoracic and lumbar vertebral fractures
lumbar lordosis
kyphoscoliosis
60
what is a possible complication of fractures in osteoporosis?
pneumonia
| PE
61
osteoporosis prevention
exercise
calcium
Vit D
62
osteoporosis tx
bisphosphonates
hormone therapy
denosumab (anti-RANKL)
63
what is Paget disease/osteitis deformans?
acquired disease of increased but disordered bone mass
either monostotic or polyostotic
64
what is the most common form of Paget?
familial polyostotic
65
what gene is associated with Paget?
SQSTM1
increased activity of NF-kB = increased osteoclast activity
66
what is the morphological hallmark of Paget?
mosaic pattern of lamellar bone (sclerotic phase)
*jigsaw appearance with prominent cement lines
67
describe the 3 phases of Paget
1. lytic phase - large osteoclasts with 100 nuclei
2. mixed phase - clasts + loss of blasts
3. osteosclerotic phase - quiescent stage
68
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
```
69
what would be seen in labs with Paget?
increased serum alk phos
normal calcium and phos
70
Paget tx
calcitonin and bisphosphonates
71
what is a possible outcome of bone transformation in Paget?
sarcomatous transformation into osteosarcoma or fibrosarcoma
72
vit D deficiency in kids results in...
rickets
73
vit D deficiency in adults results in...
osteomalacia
74
what is the clinical presentation of rickets?
```
frontal bossing
squared-off head
rachitic rosary of ribs
pigeon breast deformity
lumbar lordosis
bowed legs
```
75
how does hyperparathyroidism result in bone deformity?
PTH signals osteoclast activation to increase serum Ca
skeletal changes result from continued activation of PTH
76
what 4 skeletal abnormalities are associated with untreated hyperparathyroidism?
osteoporosis
brown tumor
dissecting osteitis
von Recklinghausen disease
77
what is dissecting osteitis?
clasts tunnel into and dissect centrally along the length of trabeculae creating the appearance of railroad tracks
78
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
79
what is renal osteodystrophy?
skeletal changes associated with chronic renal disease
80
what is the clinical presentation of renal osteodystrophy?
osteopenia/osteoporosis
osteomalacia
secondary hyperparathyroidism
growth retardation
81
what are the 3 histologic subtypes of renal osteodystrophy?
1. high turnover = resorption > formation
2. low turnover = low activity overall
3. mixed = areas with high and low turnover
82
describe the pathogenesis of renal osteodystrophy
tubular dysfunction - hydroxyapatite dissolution
generalized renal failure - hyperphos, hypoCa
decreased production of secreted factors - low vit D
83
what is known as the "silent crippler"?
renal osteodystrophy in kids
84
describe the healing of bone fractures
1. hematoma formation
2. callus formation - woven bone + cartilage
3. callus ossification - woven bone
4. bone remodeling - lamellar bone
85
what is osteonecrosis?
infarction of the bone and marrow secondary to vascular injury
most cases from fracture or corticosteroids
collateral flow preserves cortex
86
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
87
describe medullary infarcts
small, clinically silent infarcts that occur with Gaucher, dysbarism, and sickle cell anemia
involve trabecular bone and marrow
88
what is "creeping substitution"?
after bone death, trabecular that remain intact serve as scaffolding for deposition of new bone
89
what is osteomyelitis?
inflammation of the bone and marrow due to infection
usually a primary solitary focus but can be due to systemic infection
90
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
91
what bacteria is the most common cause of osteomyelitis?
staph aureus
less common:
H. flu
Grp B strep
92
if a culture comes back as mixed bacteria, what would you suspect as the cause of osteomyelitis?
surgery or open fracture
93
sickle cell patients are predisposed to what bacterial infection?
salmonella
94
what is sequestrum?
dead bone following subperiosteal abscess
becomes draining sinus
95
what is involucrum?
newly deposited bone forms a shell of living tissue around the segment of dead bone
occurs in chronic osteomyeltitis
96
what is a Brodie abscess?
chronic, small interosseous abscess that frequently involves the cortex and is walled off by reactive bone
97
what is sclerosing osteomyelitis of Garre?
chronic jaw osteomyelitis associated with new bone formation that obscures the underlying osseous structure
98
what is the clinical presentation of acute osteomyelitis?
malaise
fever/chills
leukocytosis
intense, throbbing pain over the affected region
99
what will be seen on XR with acute osteomyelitis?
lytic focus of bone destruction surrounded by zone of sclerosis
100
osteomyelitis tx
abx and surgical drainage
101
what are some complications of chronic osteomyelitis?
```
pathologic fracture
secondary amyloidosis
endocarditis
sepsis
SCC in draining sinus
sarcoma of infected bone
```
102
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
103
what is Pott disease?
tuberculous spondylitis
mycobacterial osteomyelitis of the spine
permanent compression fractures - scoliosis, kyphosis and neuro deficits
104
what are complications associated with Pott disease?
tuberculous arthritis
sinus tract formation
psoas abscess
amyloidosis
105
what skeletal abnormalities are associated with congenital syphilis?
saber shin - massive reactive periosteal bone deposition on medial and anterior surfaces of the tibia
106
what skeletal abnormalities are associated with acquired syphilis?
saddle nose deformity
| palate, skull and long bone deformities
