Bones, Joints, Soft Tissue Flashcards
What is syndactyly or craniosynostosis?
abnormal fusion of bones
Define dysplasia
mutations in genes controlling development or remodeling–> disorganization of bone/cartilage that is not premalignant
What defect causes abnormal differentiation in osteoblasts and chondrocytes?
homeobox proteins
HOXD13: brachydactyly
RUNX2: cleidrocranial dysplasia w/ wormian bones
What is the most common skeletal dysplasia and major cause of dwarfism?
achondroplasia
Define achondroplasia, genes involved, and sx
AD FGFR3 gain of fxn
defect in endochondral ossification so long bones are short–> short extremities with normal trunk length
enlarged head with bulging forehead, depression root of nose
Are there changes in longevity, intelligence or reproductivity in achondroplasia?
no- all normal
What is the most common lethal form of dwarfism?
thanatophoric dysplasia
Describe thantophoric dysplasia
different FGFR3 GOF than achondroplasia
diminished proliferation of chondrocytes and disorganization in zone of proliferation
What do people with thantophoric dysplasia look like?
micromelic shortening of limbs
frontal bossing
macrocephaly
small chest cavity–> respiratory insufficiency
bell-shaped abdomen
die at or soon after birth
What is LPR5 receptor implicated in?
osteoporosis or petrosis, depending on defect
What do mutations in RANKL cause?
decreased or absent osteoclasts
on blasts, activate clast proliferation and activity normally
What is the most common inherited disorder of connective tissue?
osteogenesis imperfecta
What type of collagen is implicated in osteogenesis imperfecta?
type 1
found in bone, some joints, eyes, ears, skin, teeth
What aspects of type 1 collagen is mutated in osteogenesis imperfecta?
a1 and 2 chains
no triple helix formation
What happens in osteogenesis imperfecta?
decreased synthesis of normal collaged–> skeletal abnormalities
What is the best way to tell between potential abuse and osteogenesis imperfecta?
bone pathology
What is the worse type of osteogenesis imperfecta?
type 2
no triple helix–> fatal in utero
extraordinary bone fragility with multiple intrauterine fractures
What is the best and most common type of osteogenesis imperfecta?
type 1- AD
normal life span, childhood fractures decrease in frequency following puberty
Describe type 1 osteogenesis imperfecta
collagen structure is normal, but decreased amount
fractures before puberty
normal life span and stature
loose joints (increased mobility) and low muscle tone
blue, purple or gray sclera (normally whites of eyes)
triangular face
spinal curvature tendency
bone deformity is absent or minimal
brittle teeth
hearing loss in 20s-30s
Describe type 2 osteogenesis imperfecta
most severe
collagen improperly formed
lethal at or shortly after birth d/t resp problems (small chest cavity)
numerous fractures and severe bone deformity
small stature with underdeveloped lungs
Compare types 3 and 4 osteogenesis imperfecta
1 best, 2 worst
both have improperly formed collagen
4- intermediate
sclera white
shorter than average
3- intermediate to bad
fractures at birth, shows healed fx before birth
blue sclera
loose joints, low muscle tone
What is Albers-Schonberg disease?
osteopetrosis
aka marble bone disease
What is the pathogenesis of osteopetrosis?
deficiency in carbonic anhydrase 2
- -> clasts need acid, so can’t break down bone
- -> kidneys can’t get rid of acid, so renal tubular acidosis
mutation in CLCN7 (proton pump on clasts)
What do bones in osteopetrosis look like?
lack medullary cavity (blasts make bone that grows into it–> anemia)
Erlenmeyer flask look d/t bulbous ends of long bones
neural foramina small, compress nerves
Describe type 1 osteopetrosis
severe infantile form
AR (mediterranean, arab)
cranial nerve deficits
–> optic atrophy, deafness, facial paralysis (increased bone puts pressure on nerves)
postpartum mortality d/t:
–> fractures, anemia, hydrocephaly
Describe type 2 osteopetrosis
mild AD in adolescence or adulthood
repeat fractures
mild CN deficits and anemia
Describe mucopolysaccharidoses
lysosomal storage diseases caused by - in enzymes that degrade dermatan sulfate, heparan sulfate and keratan sulfate (acid hydrolase enzymes)
hunter and hurler syndromes
Describe presentation of patients with mucopollysaccharidoses
chondrocytes normally degrade ECM mucopolysaccharides, but since there is more of them they accumulate and kill chondrocytes–> defect in articular cartilage
–> problems at growth plate
short stature
chest wall abn
malformed bones
What is the difference between osteopenia and osteoporosis?
osteopenia
- decreased bone mass
- “lesser version of porosis”
- 1-2.5 SD below the mean
osteoporosis
~~osteopenia severe enough to increase risk of fracture
~~ at least 2.5 SD below the bean during peak bone mass in young adults
What signifies/ is a hallmark of osteoporosis?
atraumatic or vertebral compression fractures
What are the most common forms of osteoporosis?
senile and postmenopausal
What is the path behind senile osteoporosis?
low turnover variant
decreased proliferation and biosynthesis
decreased response to growth factors
Why does decreased physical activity lead to osteoporosis?
Mechanical forces stimulate normal bone remodeling
bone loss in immobility, paralysis, astronauts in zero gravity
resistance exercises better
Describe the defective nutrition in adolescent girls that leads to osteoporosis
insufficient calcium intake during period of rapid growth restricts peak bone mass
also increased PTH and decreased vitamin D
What is the path behind postmenopausal osteoporosis?
accelerated bone loss
estrogen deficiency promotes resorption and formation, but resorption more
high turnover variant
What medicine used in cancer treatment increases risk for osteoporosis?
tamoxifen used for breast cancer chemo adjunct
Is osteoporosis normal bone?
YES, just less of it
What does bone look like in senile osteoporosis?
cortex thinned by subperiosteal and endosteal resorption
haversian system widened
What does bone look like in postmenopausal osteoporosis?
bones have increased surface area d/t increased osteoclast activity
trabeculae are perforated, THINNED, lose interconnections–> microfractures and vertebral collapse
How to diagnose osteoporosis?
DEXA scan
(bone mineral density test)
blood test to check for secondary causes (renal/hepatic failure, hyperthyroid)
Genetic/environmental associations with osteoporosis
Caucasian, light colored hair and eyes
not enough calcium in teen years–>guaranteed
too much phosphorus (soda)
smoking
Prevention/treatment of osteoporosis
exercise, calcium, vitamin D
bisphosphonates (decrease clast activity)
hormone therapy (be careful of DVT and stroke)
denosumab (anti-RANKL)
Clinical course of osteoporosis
thoracic and lumbar vertebral fractures
–> PE and pneumonia
loss of height d/t lumbar lordosis and thoracic kyphoscoliosis
