Bones, Joints, Soft Tissue

Question 1

What is syndactyly or craniosynostosis?

Answer 1

abnormal fusion of bones

Question 2

Define dysplasia

Answer 2

mutations in genes controlling development or remodeling–> disorganization of bone/cartilage that is not premalignant

Question 3

What defect causes abnormal differentiation in osteoblasts and chondrocytes?

Answer 3

homeobox proteins

HOXD13: brachydactyly

RUNX2: cleidrocranial dysplasia w/ wormian bones

Question 4

What is the most common skeletal dysplasia and major cause of dwarfism?

Answer 4

achondroplasia

Question 5

Define achondroplasia, genes involved, and sx

Answer 5

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

Question 6

Are there changes in longevity, intelligence or reproductivity in achondroplasia?

Answer 6

no- all normal

Question 7

What is the most common lethal form of dwarfism?

Answer 7

thanatophoric dysplasia

Question 8

Describe thantophoric dysplasia

Answer 8

different FGFR3 GOF than achondroplasia

diminished proliferation of chondrocytes and disorganization in zone of proliferation

Question 9

What do people with thantophoric dysplasia look like?

Answer 9

micromelic shortening of limbs

frontal bossing

macrocephaly

small chest cavity–> respiratory insufficiency

bell-shaped abdomen

die at or soon after birth

Question 10

What is LPR5 receptor implicated in?

Answer 10

osteoporosis or petrosis, depending on defect

Question 11

What do mutations in RANKL cause?

Answer 11

decreased or absent osteoclasts

on blasts, activate clast proliferation and activity normally

Question 12

What is the most common inherited disorder of connective tissue?

Answer 12

osteogenesis imperfecta

Question 13

What type of collagen is implicated in osteogenesis imperfecta?

Answer 13

type 1

found in bone, some joints, eyes, ears, skin, teeth

Question 14

What aspects of type 1 collagen is mutated in osteogenesis imperfecta?

Answer 14

a1 and 2 chains

no triple helix formation

Question 15

What happens in osteogenesis imperfecta?

Answer 15

decreased synthesis of normal collaged–> skeletal abnormalities

Question 16

What is the best way to tell between potential abuse and osteogenesis imperfecta?

Answer 16

bone pathology

Question 17

What is the worse type of osteogenesis imperfecta?

Answer 17

type 2

no triple helix–> fatal in utero

extraordinary bone fragility with multiple intrauterine fractures

Question 18

What is the best and most common type of osteogenesis imperfecta?

Answer 18

type 1- AD

normal life span, childhood fractures decrease in frequency following puberty

Question 19

Describe type 1 osteogenesis imperfecta

Answer 19

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

Question 20

Describe type 2 osteogenesis imperfecta

Answer 20

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

Question 21

Compare types 3 and 4 osteogenesis imperfecta

Answer 21

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

Question 22

What is Albers-Schonberg disease?

Answer 22

osteopetrosis

aka marble bone disease

Question 23

What is the pathogenesis of osteopetrosis?

Answer 23

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)

Question 24

What do bones in osteopetrosis look like?

Answer 24

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

Question 25

Describe type 1 osteopetrosis

Answer 25

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

Question 26

Describe type 2 osteopetrosis

Answer 26

mild AD in adolescence or adulthood repeat fractures mild CN deficits and anemia

Question 27

Describe mucopolysaccharidoses

Answer 27

lysosomal storage diseases caused by - in enzymes that degrade dermatan sulfate, heparan sulfate and keratan sulfate (acid hydrolase enzymes) hunter and hurler syndromes

Question 28

Describe presentation of patients with mucopollysaccharidoses

Answer 28

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

Question 29

What is the difference between osteopenia and osteoporosis?

Answer 29

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

Question 30

What signifies/ is a hallmark of osteoporosis?

Answer 30

atraumatic or vertebral compression fractures

Question 31

What are the most common forms of osteoporosis?

Answer 31

senile and postmenopausal

Question 32

What is the path behind senile osteoporosis?

Answer 32

low turnover variant decreased proliferation and biosynthesis decreased response to growth factors

Question 33

Why does decreased physical activity lead to osteoporosis?

Answer 33

Mechanical forces stimulate normal bone remodeling bone loss in immobility, paralysis, astronauts in zero gravity resistance exercises better

Question 34

Describe the defective nutrition in adolescent girls that leads to osteoporosis

Answer 34

insufficient calcium intake during period of rapid growth restricts peak bone mass also increased PTH and decreased vitamin D

Question 35

What is the path behind postmenopausal osteoporosis?

Answer 35

accelerated bone loss estrogen deficiency promotes resorption and formation, but resorption more high turnover variant

Question 36

What medicine used in cancer treatment increases risk for osteoporosis?

Answer 36

tamoxifen used for breast cancer chemo adjunct

Question 37

Is osteoporosis normal bone?

Answer 37

YES, just less of it

Question 38

What does bone look like in senile osteoporosis?

Answer 38

cortex thinned by subperiosteal and endosteal resorption haversian system widened

Question 39

What does bone look like in postmenopausal osteoporosis?

Answer 39

bones have increased surface area d/t increased osteoclast activity trabeculae are perforated, THINNED, lose interconnections--> microfractures and vertebral collapse

Question 40

How to diagnose osteoporosis?

Answer 40

DEXA scan (bone mineral density test) blood test to check for secondary causes (renal/hepatic failure, hyperthyroid)

Question 41

Genetic/environmental associations with osteoporosis

Answer 41

Caucasian, light colored hair and eyes not enough calcium in teen years-->guaranteed too much phosphorus (soda) smoking

Question 42

Prevention/treatment of osteoporosis

Answer 42

exercise, calcium, vitamin D bisphosphonates (decrease clast activity) hormone therapy (be careful of DVT and stroke) denosumab (anti-RANKL)

Question 43

Clinical course of osteoporosis

Answer 43

thoracic and lumbar vertebral fractures --> PE and pneumonia loss of height d/t lumbar lordosis and thoracic kyphoscoliosis