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M&M Test 3 > B6-052 CBCL Osteoporosis > Flashcards

B6-052 CBCL Osteoporosis Flashcards

1
Q

characterized by loose arrangement of collagen fibers
forms during fracture repair and remodeling

A

primary (woven) bone

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2
Q

regular parallel arrangement of collagen
only visible on dried/ground sections

A

lamellar bone

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3
Q

inner layer of bone with spaces for marrow

A

trabecular bone

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4
Q

outer solid cortex of bone which encloses an inner layer of spongey bone

A

cortical bone

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5
Q

contains osteoprogenitor cells that can help with bone repair/remodeling [2]

A

periosteum
endosteum

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6
Q

organic matrix of bone is composed primarily of

A

type 1 collagen fibers

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7
Q

inorganic matrix of bone is composed primarily of

A

calcium hydroxypatite

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8
Q

99% of the bodies […] and […] is stored in bone

A

calcium
phosphate

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9
Q

osteoblasts come from what stem cell line?

A

mesenchymal

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10
Q

osteoclasts come from what stem cell line?

A

hematopoietic (monocyte/macrophages)

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11
Q

found in growing portion of bone, including periosteum and endosteum

A

osteoblasts

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12
Q

stimulates osteoclastogenesis

A

RANKL

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13
Q

decoy receptor of RANKL

A

ostoprotegerin

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14
Q

noncollagenous protein required for bone mineralization

A

osteocalcin

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15
Q

noncollagenous protein required for formation of sealing zone

A

osteopontin

**allow osteoblasts to have tight grip on bone

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16
Q

entrapped in matrix

A

osteocytes

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17
Q

function to maintain mineral concentration of matrix

A

osteocytes

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18
Q

primary function is bone formation

A

osteoblasts

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19
Q

mechanosensory sensors of bone

A

osteocytes

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20
Q

synthesize sclerostin which inhibits osteoblastic activity

A

osteocytes

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21
Q

found at bone surface and at sites of old, injured, or unneeded bone

A

osteoclasts

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22
Q

giant, mutlinucleate cells derived from monocytes

A

osteoclasts

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23
Q

genetic factors that influence peak bone mass

A

polymorphisms in vitamin D-R
LRP5/6 (males)
RANK, OPG, RANKL

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24
Q

how does menopause lead to osteoporosis?

A

decreased serum estrogen increases RANK/RANKL expression and stimulation of osteoclasts

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25
Q

compact bone remodeling occurs within the

A

osteon

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26
Q

trabecular bone remodeling occurs on

A

bone surface

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27
Q

inhibits osteoclastic activity

A

calcitonin

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28
Q

how does PTH stimulate bone reabsorption?

A

PTH binds to osteoblasts
osteoblasts release RANKL
RANKL binds to RANK on preosteoclasts
activates osteoclasts

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29
Q

what factors lead to the activation of osteoclasts? [2]

A

vitamin D
PTH

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30
Q

what factors lead to the inhibition of osteoclasts? [3]

A

estrogen
calcintonin
TGF-b

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31
Q

how does estrogen inhibit osteoclasts?

A

estrogen induces the secretion of OPG
OPG binds to RANKL and interferes with RANKL/RANK interaction
inhibits bone resorption

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32
Q

if OPG is greater than RANKL…

A

osteoclast apoptosis –> more bone formation

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33
Q

if OPG is less than RANKL…

A

osteoclast activation –> bone resorption

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34
Q

monoclonal antibody that binds to RANKL and competitively inhibits RANK binding

A

denosumab

can be used to treat osteoporosis

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35
Q

estrogen inhibits differentiation and promotes apoptosis of […]

A

osteoclasts

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36
Q

estrogen promotes differentiation and inhibits apoptosis of […]

A

osteoblasts

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37
Q

what does vitamin D do during positive calcium balance?

A

promotes intestinal calcium transport

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38
Q

what does vitamin D do during negative calcium balance?

A

induce osteoblastic expression of RANKL
suppresses bone matrix mineralization

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39
Q

WNT binds to LRP5/6 to stimulate [2]

A

osteoblastic activity
OPG

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40
Q

produced by osteocytes and has a negative effect on the WNT LRP5/6 pathway inhibiting osteoblasts

A

sclerostin

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41
Q

mechanical stress leads to the downregulation of […]

A

sclerostin

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42
Q

reduced muscle activity and reduced mechanical stress will lead to

A

higher slerostin
inhibition of ostoblasts

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43
Q

top genes associated with the development of osteoporosis [3]

A

RANK
OPG
RANKL

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44
Q

calcium nutritional state is key to […]

A

peak bone mass

**calcium deficiency in young life restricts PBM

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45
Q

vitamin D absorption and metabolism […] with age

A

decline

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46
Q

decreased estrogen after menopause increases

A

bone resorption and formation

**but bone resorption is greater

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47
Q

what cytokines increase as a result of low estrogen?

A

IL 6
TNF-a
IL-1

**any disease state/drug that reduces estrogen in premenopausal women will also have this effect and cause net bone loss

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48
Q

inflammation primarily promotes […] activity

A

osteoclast

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49
Q

TNF-a, IL-1, and IL-6 inhibits […]

A

osteoblasts

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50
Q

high doses of glucocorticoids […] RANKL and […] OPG

A

increase RANKL
decrease OPG

51
Q

prednisone doses of […]/day can increase fracture risk

A

5 mg/day

52
Q

why do males have a decreased risk of developing osteoporosis [2]

A

higher PBM
no sudden loss of estrogen

53
Q

most accurate and standardized way to measure bone mineral density

A

DEXA

54
Q

indications for BMD testing

A

women and men over 65
postmenopausal women and men aged 50-64 with risk factors

55
Q

compares bone density with that of healthy young adult

A

T score

**0 means equal

56
Q

a t score less than […] indicates osteoporosis

A

-2.5

57
Q

used to calculate 10 year risk of fracture

A

FRAX

58
Q

reversible causes of osteoporosis [5]

A

hyperparathyroidism
celiac disease
multiple myeloma
cushings
hypogonadism

59
Q

what is considered adequate intake of calcium and vitamin D for osteoporosis therapy?

A

1200-1500 mg Ca/day
800-1000 IU of vitamin D3

60
Q

indications for FDA meds treatment of osteoporosis

A
  1. hx of osteoporotic fracture
  2. T score less than -2.5
  3. FRAX score greater what 20% (3% in hip)
61
Q

selective estrogen receptor modulator

A

raloxifene

62
Q

medication often given to postmenopausal women with osteopenia/porosis and an increased risk of breast cancer

A

raloxifene

63
Q

bisphosphonates [4]

A

alendronate
ibandronate
risendronate
zolendronic acid

64
Q

considered first line for prevention/treatment of osteoporosis

A

bisphophonates

65
Q

administration instructions of bisphosphate

A

first thing in the morning, on empty stomach with a full glass of water
sit up for a while after

66
Q

most common side effect of bisphosphonates

A

esophageal reflux

67
Q

inhibit osteoclast-mediated bone resorption

A

bisphosphonates

68
Q

monoclonal antibody against RANKL that reduces osteoclastogenesis

A

denosumab

69
Q

what osteoporosis medications have evidence of fracture reduction in all three types? [4]

A

alendronate
risedronate
zoledronic acid
denosumab

70
Q

recombinant form of parathyroid hormone that is administered as a once daily injection

A

teriparatide

71
Q

previously had a black box warning for causing the side effect of osteosarcoma

A

teriparatide

72
Q

monoclonal antibody that binds/inhibits sclerostin

A

romosozumab

73
Q

main function of sclerostin

A

inhibit bone formation

74
Q

if oral bisphosphates are contraindicated, what medications can be used?

A

IV bisphosphonate (zoledronic acid)
teriparatide
denosumab
romosozumab

75
Q

with bisphosphonates there is evidence of plateau after […]

A

5 years

76
Q

options when you are approaching the 5 year mark of bisphosphonates

A

drug holiday (2 years)
switch to another class

77
Q

bone is classified as […] tissue

A

specialized connective

78
Q

outer, solid layer of bone

A

cortex

79
Q

inner layer of bone

A

cancellous

80
Q

immature bone that forms during fracture repair and remodeling

A

woven bone

81
Q

what part of bone contains the epiphyseal plate?

A

metaphysis

82
Q

ends of long bone that contain spongy bone covered by a thin layer of compact bone

A

epiphysis

83
Q

shaft of bone that contains compact bone around the medullary cavity

A

diaphysis

84
Q

outer layer of connective tissue that covers bone

A

periosteum

85
Q

inner layer of connective tissue that covers bone

A

endosteum

86
Q

arise from monocyte precursors

A

osteoclasts

87
Q

osteoid makes up the bulk of the organic matrix in bone and consists of [2]

A

proteoglycans
type 1 collagen

88
Q

have a ruffled border

A

osteoclasts

89
Q

opposes osteoclasts differentiation and activity

A

OPG

90
Q

prevents RANKL from binding to RANK on osteoclasts precursors

A

OPG

91
Q

opposes WNT signaling by binding to receptor LRP5/6 to

A

scelorstin

net effect is promote osteoclasts and inhibit osteoblasts

92
Q

increases the number of osteoclasts and the ruffled border activity of existing osteoclasts

A

PTH

93
Q

calcitonin receptors are found on

A

osteoclasts

94
Q

t score for osteopenia

A

-1 to -2.4

95
Q

factors associated with lower risk of osteoporosis in post-menopausal women

A

elevated BMI
former estrogen use

96
Q

why is elevated BMI thought to offer a protective factor for osteoporosis?

A

lower sclerostin production due to mechanical stress of increased load bearing

97
Q

concentrate at sites of active remodeling and remain in the matrix until bone is remodeled

A

bisphosphonates

98
Q

demonstrates greater percent change in lumbar spine BMD over treatment [2]

A

teriparatide
romosozumab

99
Q

drug that is functionally analogous to OPG

A

denosumab

100
Q

most significant challenge in management of osteoporosis after a fracture

A

treatment adherance

101
Q

what classes of drugs reduce all three fracture types

A

bisphosphonates
denosumab

102
Q

considered an option for primary drug in a patient with prior fractures or high risk,
but not considered first line in a patient with moderate risk or no prior fracture

A

teriparatide

103
Q

diagnostic definition of osteoporosis

A

history of atraumatic osteoporotic fracture

T score in any part of the body lower than -2.5

FRAX score greater than 20% in any part of the body, or 3% in the hip

104
Q

first line therapy for osteoporosis

A

bisphosphonates

105
Q

describe what happens to bone density following menopause

A

rapid decline for 3-5 year, then slower decline

106
Q

treatment for an individual with low fracture risk

A

calcium and vitamin D

107
Q

[…] can be used in adjunct to denosumab to help maintain gains in bone mineral density

A

bisphosphonates

108
Q

used to both treat osteoporosis and serve as prophylaxis in women with breast cancer

A

raloxifene

**unless patient currently taking aromatase inhibitor

109
Q

decoy receptor that binds RANKL

A

OPG

110
Q

secrete RANKL and OPG

A

osteoblasts

111
Q

monocytes/macrophages can bind M-CSF which will cause them to differentiate into

A

preosteoclasts

112
Q

once RANKL binds to RANK, it causes the differentiation of […] into […]

A

preosteoclasts
osteoclasts

113
Q

phase 1 of bone loss occurs when

A

in women in 3-5 years following onset of menopause

114
Q

what type of bone is most affected in phase 1 bone loss?

A

trabecular

115
Q

phase II of bone loss occurs when

A

in both men and women, with age

116
Q

what type of bone is lost in phase II bone loss?

A

cortical and trabecular

117
Q

calcitonin inhibits the activity of

A

osteoclasts

118
Q

T score of -1 to -2.4

A

osteopenia

119
Q

best next step for a patient who has a high risk of fracture?

A

get a bone density test

120
Q

why do bisphosphonates have such a long half life?

A

they get incorporated into hydroxyapatite crystals of bone

121
Q

used in metastatic cancer to prevent pathologic fractures

A

bisphosphonates

122
Q

IL-1, IL-6, and TNF-a promote the activity of

A

osteoclasts

123
Q

suppresses RANKL-induced osteoclast activation

A

denosumab

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