B6-052 CBCL Osteoporosis Flashcards
(123 cards)
1
Q
characterized by loose arrangement of collagen fibers
forms during fracture repair and remodeling
A
primary (woven) bone
2
Q
regular parallel arrangement of collagen
only visible on dried/ground sections
A
lamellar bone
3
Q
inner layer of bone with spaces for marrow
A
trabecular bone
4
Q
outer solid cortex of bone which encloses an inner layer of spongey bone
A
cortical bone
5
Q
contains osteoprogenitor cells that can help with bone repair/remodeling [2]
A
periosteum
endosteum
6
Q
organic matrix of bone is composed primarily of
A
type 1 collagen fibers
7
Q
inorganic matrix of bone is composed primarily of
A
calcium hydroxypatite
8
Q
99% of the bodies […] and […] is stored in bone
A
calcium
phosphate
9
Q
osteoblasts come from what stem cell line?
A
mesenchymal
10
Q
osteoclasts come from what stem cell line?
A
hematopoietic (monocyte/macrophages)
11
Q
found in growing portion of bone, including periosteum and endosteum
A
osteoblasts
12
Q
stimulates osteoclastogenesis
A
RANKL
13
Q
decoy receptor of RANKL
A
ostoprotegerin
14
Q
noncollagenous protein required for bone mineralization
A
osteocalcin
15
Q
noncollagenous protein required for formation of sealing zone
A
osteopontin
**allow osteoblasts to have tight grip on bone
16
Q
entrapped in matrix
A
osteocytes
17
Q
function to maintain mineral concentration of matrix
A
osteocytes
18
Q
primary function is bone formation
A
osteoblasts
19
Q
mechanosensory sensors of bone
A
osteocytes
20
Q
synthesize sclerostin which inhibits osteoblastic activity
A
osteocytes
21
Q
found at bone surface and at sites of old, injured, or unneeded bone
A
osteoclasts
22
Q
giant, mutlinucleate cells derived from monocytes
A
osteoclasts
23
Q
genetic factors that influence peak bone mass
A
polymorphisms in vitamin D-R
LRP5/6 (males)
RANK, OPG, RANKL
24
Q
how does menopause lead to osteoporosis?
A
decreased serum estrogen increases RANK/RANKL expression and stimulation of osteoclasts
25
compact bone remodeling occurs within the
osteon
26
trabecular bone remodeling occurs on
bone surface
27
inhibits osteoclastic activity
calcitonin
28
how does PTH stimulate bone reabsorption?
PTH binds to osteoblasts
osteoblasts release RANKL
RANKL binds to RANK on preosteoclasts
activates osteoclasts
29
what factors lead to the activation of osteoclasts? [2]
vitamin D
PTH
30
what factors lead to the inhibition of osteoclasts? [3]
estrogen
calcintonin
TGF-b
31
how does estrogen inhibit osteoclasts?
estrogen induces the secretion of OPG
OPG binds to RANKL and interferes with RANKL/RANK interaction
inhibits bone resorption
32
if OPG is greater than RANKL...
osteoclast apoptosis --> more bone formation
33
if OPG is less than RANKL...
osteoclast activation --> bone resorption
34
monoclonal antibody that binds to RANKL and competitively inhibits RANK binding
denosumab
**can be used to treat osteoporosis**
35
estrogen inhibits differentiation and promotes apoptosis of [...]
osteoclasts
36
estrogen promotes differentiation and inhibits apoptosis of [...]
osteoblasts
37
what does vitamin D do during positive calcium balance?
promotes intestinal calcium transport
38
what does vitamin D do during negative calcium balance?
induce osteoblastic expression of RANKL
suppresses bone matrix mineralization
39
WNT binds to LRP5/6 to stimulate [2]
osteoblastic activity
OPG
40
produced by osteocytes and has a negative effect on the WNT LRP5/6 pathway inhibiting osteoblasts
sclerostin
41
mechanical stress leads to the downregulation of [...]
sclerostin
42
reduced muscle activity and reduced mechanical stress will lead to
higher slerostin
inhibition of ostoblasts
43
top genes associated with the development of osteoporosis [3]
RANK
OPG
RANKL
44
calcium nutritional state is key to [...]
peak bone mass
**calcium deficiency in young life restricts PBM
45
vitamin D absorption and metabolism [...] with age
decline
46
decreased estrogen after menopause increases
bone resorption and formation
**but bone resorption is greater
47
what cytokines increase as a result of low estrogen?
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
48
inflammation primarily promotes [...] activity
osteoclast
49
TNF-a, IL-1, and IL-6 inhibits [...]
osteoblasts
50
high doses of glucocorticoids [...] RANKL and [...] OPG
increase RANKL
decrease OPG
51
prednisone doses of [...]/day can increase fracture risk
5 mg/day
52
why do males have a decreased risk of developing osteoporosis [2]
higher PBM
no sudden loss of estrogen
53
most accurate and standardized way to measure bone mineral density
DEXA
54
indications for BMD testing
women and men over 65
postmenopausal women and men aged 50-64 with risk factors
55
compares bone density with that of healthy young adult
T score
**0 means equal
56
a t score less than [...] indicates osteoporosis
-2.5
57
used to calculate 10 year risk of fracture
FRAX
58
reversible causes of osteoporosis [5]
hyperparathyroidism
celiac disease
multiple myeloma
cushings
hypogonadism
59
what is considered adequate intake of calcium and vitamin D for osteoporosis therapy?
1200-1500 mg Ca/day
800-1000 IU of vitamin D3
60
indications for FDA meds treatment of osteoporosis
1. hx of osteoporotic fracture
2. T score less than -2.5
3. FRAX score greater what 20% (3% in hip)
61
selective estrogen receptor modulator
raloxifene
62
medication often given to postmenopausal women with osteopenia/porosis and an increased risk of breast cancer
raloxifene
63
bisphosphonates [4]
alendronate
ibandronate
risendronate
zolendronic acid
64
considered first line for prevention/treatment of osteoporosis
bisphophonates
65
administration instructions of bisphosphate
first thing in the morning, on empty stomach with a full glass of water
sit up for a while after
66
most common side effect of bisphosphonates
esophageal reflux
67
inhibit osteoclast-mediated bone resorption
bisphosphonates
68
monoclonal antibody against RANKL that reduces osteoclastogenesis
denosumab
69
what osteoporosis medications have evidence of fracture reduction in all three types? [4]
alendronate
risedronate
zoledronic acid
denosumab
70
recombinant form of parathyroid hormone that is administered as a once daily injection
teriparatide
71
previously had a black box warning for causing the side effect of osteosarcoma
teriparatide
72
monoclonal antibody that binds/inhibits sclerostin
romosozumab
73
main function of sclerostin
inhibit bone formation
74
if oral bisphosphates are contraindicated, what medications can be used?
IV bisphosphonate (zoledronic acid)
teriparatide
denosumab
romosozumab
75
with bisphosphonates there is evidence of plateau after [...]
5 years
76
options when you are approaching the 5 year mark of bisphosphonates
drug holiday (2 years)
switch to another class
77
bone is classified as [...] tissue
specialized connective
78
outer, solid layer of bone
cortex
79
inner layer of bone
cancellous
80
immature bone that forms during fracture repair and remodeling
woven bone
81
what part of bone contains the epiphyseal plate?
metaphysis
82
ends of long bone that contain spongy bone covered by a thin layer of compact bone
epiphysis
83
shaft of bone that contains compact bone around the medullary cavity
diaphysis
84
outer layer of connective tissue that covers bone
periosteum
85
inner layer of connective tissue that covers bone
endosteum
86
arise from monocyte precursors
osteoclasts
87
osteoid makes up the bulk of the organic matrix in bone and consists of [2]
proteoglycans
type 1 collagen
88
have a ruffled border
osteoclasts
89
opposes osteoclasts differentiation and activity
OPG
90
prevents RANKL from binding to RANK on osteoclasts precursors
OPG
91
opposes WNT signaling by binding to receptor LRP5/6 to
scelorstin
net effect is promote osteoclasts and inhibit osteoblasts
92
increases the number of osteoclasts and the ruffled border activity of existing osteoclasts
PTH
93
calcitonin receptors are found on
osteoclasts
94
t score for osteopenia
-1 to -2.4
95
factors associated with lower risk of osteoporosis in post-menopausal women
elevated BMI
former estrogen use
96
why is elevated BMI thought to offer a protective factor for osteoporosis?
lower sclerostin production due to mechanical stress of increased load bearing
97
concentrate at sites of active remodeling and remain in the matrix until bone is remodeled
bisphosphonates
98
demonstrates greater percent change in lumbar spine BMD over treatment [2]
teriparatide
romosozumab
99
drug that is functionally analogous to OPG
denosumab
100
most significant challenge in management of osteoporosis after a fracture
treatment adherance
101
what classes of drugs reduce all three fracture types
bisphosphonates
denosumab
102
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
teriparatide
103
diagnostic definition of osteoporosis
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
first line therapy for osteoporosis
bisphosphonates
105
describe what happens to bone density following menopause
rapid decline for 3-5 year, then slower decline
106
treatment for an individual with low fracture risk
calcium and vitamin D
107
[...] can be used in adjunct to denosumab to help maintain gains in bone mineral density
bisphosphonates
108
used to both treat osteoporosis and serve as prophylaxis in women with breast cancer
raloxifene
**unless patient currently taking aromatase inhibitor
109
decoy receptor that binds RANKL
OPG
110
secrete RANKL and OPG
osteoblasts
111
monocytes/macrophages can bind M-CSF which will cause them to differentiate into
preosteoclasts
112
once RANKL binds to RANK, it causes the differentiation of [...] into [...]
preosteoclasts
osteoclasts
113
phase 1 of bone loss occurs when
in women in 3-5 years following onset of menopause
114
what type of bone is most affected in phase 1 bone loss?
trabecular
115
phase II of bone loss occurs when
in both men and women, with age
116
what type of bone is lost in phase II bone loss?
cortical and trabecular
117
calcitonin inhibits the activity of
osteoclasts
118
T score of -1 to -2.4
osteopenia
119
best next step for a patient who has a high risk of fracture?
get a bone density test
120
why do bisphosphonates have such a long half life?
they get incorporated into hydroxyapatite crystals of bone
121
used in metastatic cancer to prevent pathologic fractures
bisphosphonates
122
IL-1, IL-6, and TNF-a promote the activity of
osteoclasts
123
suppresses RANKL-induced osteoclast activation
denosumab
