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WorksheetsMorani OP LECOM P1
Total questions: 66
Worksheet time: 37mins
What are the three hormones that control serum calcium and phosphorus (P)
1,25-dihydroxyvitamin D (VD)
fibroblast growth factor 23 (FGF23)
Parathyroid hormone (PTH)
Testosterone
cAMP
What are the players in BMH (bone mineral homeostasis)
osteoclasts and osteoblasts
osteoclasts, osteoblasts, and osteocytes
osteoclast and osteocytes
osteocytes only
What does the osteoclasts do?
they synthesize new bone via the process known as bone mineralization
they break down bone via the process known as bone resorption
they are osteoblasts which encase beneath the bone lining. They form a base upon which mineralization occur
Bone reabsorption <<bone mineralization = bone loss (osteoporosis)
True
False
What is osteoblast?
They synthesize new bone via the process known as bone mineralization
They break down bone via the process known as bone resorption
They are osteoblasts which encase beneath the bone lining. They form a base upon which mineralization occur
They are osteoclasts which encase beneath the bone lining. They form a base upon which mineralization occur
Put the procedure for bone remodeling in order:
1. Osteoblast production
2. Osteocytes encase within mineralizing bone
3. Osteoclasts absorbing bone matrix
4. Osteoblast differentiation from myonuclear cells
5. Bone maturation followed by appearance of bone lining cells
6.Osteoblast differentiate into osteocytes
3,6,1,4,2,5
3,4,1,6,5,2
3,4,1,6,2,5
3,6,1,4,2,5
what is the role of calcium in various physiological function of the body?
fusion and release of storage vesicles
skeletal tissue remodeling
formation of bone matrix
muscle contraction
blood coagulation
What is the process of mobilizing out of the bone?
mineralization
osteoblasts
PTH
resorption
Which enzyme catalyzes the conversion of calcidiol to calcitriol?
25-hydroxylase
PTH
1-alpha hydroxylase
FGF-23
FGF-23 binds to FGF-1 and FGF-3c receptors in presence of the accessory _____ receptors
25-hydroxylase
Klotho
1-alpha hydroxylase
PHT
T/F Odanacatib is a cathapsin K inhibitor
True
False
What is the MOA of Densuomab?
RNAKL antagonist
cathapsin K inhibitor
mimics the biochemical effects of osteoprotegerin.
directly inhibit bone resorption without killing osteoclasts
What is the MOA of Odanacatib
permits complex coupling between bone resorption and formation to continue
cathapsin K inhibitor
RANKL antagonist
directly inhibiit bone resoprtion without killing osteoclasts
What is the SAR of Calcitonin-Salmon?
32 aa peptide secreted by the C cell of the thyroid gland
a recombinant human PTH 1-34
full-length PTH 1-84
T/F Raloxifene acts as an estrogen agonist on receptors in osteoblasts and osteoclasts but as an antagonist at breast and uterine estrogen receptors
True
False
What is true about Tamoxifen
linked with increased rates of uterine cancer, hot flashes, and thromboembolism
undergoes phase 1 metabolism in liver
does not increase risk of endometrial or breast cancer
undergo phase 2 metabolism
What are SERM's?
selective estradiol receptor modulators
selective endothelin receptor modulators
selective estrogen receptor modulators
selective enkephalin receptor modulators
T/F SERMS are compounds with estrogen beneficial effects having worse adverse effects profile compared to HRT
True.
False. SERMs are compounds with estrogen beneficial effects having better worse adverse effects profile compared to HRT
What is the effect of increased calcitonin signaling on calcium levels in circulating fluids?
Decreased bone resorption
Increased excretion of Ca2+ via kidneys and GIT
promote osteoblast and osteocyte apoptosis
inhibit osteoblast maturation and activity
RANKL is expressed on the:
osteoblast precursor
osteoclast precursor
RANK is expressed on the :
osteoblast precursor
osteoclast precursor
PTH has___amino acid residues
250
84
10
32
Which of the following vitamin D is obtained from plant source?
calcium
cholecalciferol
folic acid
erocalciferol
Which of the following decreases bone resorption?
estrogen
thyroid hormone
continuous administration of PTH
Glucocorticoids
T/F Long term use of Tamoxifene is associated with uterine cancer
True
False. Raloxifene
What are the important clinical instructions for the administration of bisphosphonates
administer first thing ion morning before consuming any food or water
administer bisphosphonate with orange juice or milk
administer bisphosphonate with at least 8 once of water
Remain in upright position for at least 30-60 min following drug administration
T/F R1 hydroxyl group is not essential for the clawing of the bisphosphonates to the bone resorption site
True
False. R1 hydroxyl group is essential for the clawing of the bisphosphonates to the bone resorption site
What is BMH?
process and regulation of skin remodeling
process and regulation of bone remodeling
process of osteoporosis
Factors that effect calcium homeostasis
hormones
diet and demographics
age
weight
disease states
Most calcium ingested is absorbed by ___
kidney
GIT
blood
What is false about VD (1,25-dihydroxyvitamin D) (pick 2)
increase the input of calcium and phosphorus from bone into the serum
increase calcium and phosphate absorption from the gut
less critical regulator of calcium homeostasis
in the kidney, decreases the excretion of both calcium and phosphorous
in the kidney, reduces calcium but increases phosphorous excretion
what are secondary regulators of BMH?
Calcitonin, Glucocorticoids, Thyroid hormone, Gonadal steroid
PTH, VD, FGF23
Calcitonin and thyroid hormone only
gluccorticoids, and gonadal steroids only
Intermittent PTH causes
bone resorption </= bone formation
bone resorption >>>>bone formation
T/F Continuous elevated PTH causes bone resorption >>>> bone formation
True
False
Klotho needs to be present but FGF receptor do not need to be present for signaling
True
False
Where is Calcitonin secreted from?
brain
liver
Thyroid gland
bone
What is false about corticosteroids?
induces bone resorption
inhibit born formation
increases interstitial absorption of calcium
decreases renal tubular absorption of calcium
T/F Prolonged use of glucorcorticoids lead to osteoporosis
True
False
T/F Excess thyroid hormone also increase bone turnover
True
False
Which type of osteoporosis decreases osteoblast activity and bone formation and decrease GI calcium absorption
Type 1
Type 2
Type 3
What type of osteoporosis is known as secondary osteoporosis and could be drug induced or because other disease states
type 1
type 2
type 3
What are risk factors of osteoporosis?
serotonin deficiency
estrogen deficiency
insufficient calcium intake
vitamin D deficiency
physical activity, smoking, and sedentary life style
Which medications are associated with osteoporosis?
Glucocorticoids
Thyroid hormones
depressants
immunosuppressants
aromatase inhibitors
Which disease state is not associated with osteoporosis?
Hypogonadal states
GI disorders
Hypogonadal states
endocrine disorders
what is the mechanism of antipsychotic drugs that leads to OP?
hypogonadism (anti-androgenic effects of pituitary gland suppressing testosterone)
increased osteoclast activation and RANKL
PPARy activation (suppreses osteoblast differentiation and functions)
hypogonadism (by stimulating prolactin secretion which decrease estrogen and testosterone secretion)
increased renal calcium secretion
What is the mechanism of thiazolidinedione drugs that leads to OP
hypogonadism (anti-androgenic effects on pituitary gland suppressing testosterone)
Increased osteoclast activation and RANKL
PPARy activation (suppresses osteoblast differentiation and functions)
increases renal calcium secretion
hyperparathyroidism
What is the mechanism of loop diuretics that leads to OP?
increased Osteoclast activation and RANKL
Hypogonadism (by stimulating prolactin secretion which decreases estrogen and testosterone secretion)
PPARy activation (suppresses osteoblast differentiation and function)
increases renal calcium secretion
What is the MOA for hormone replacement therapy (HRT)?
increases transcription of genes which codes for RANKL
suppresses of gene transcription for IL-6
promotes osteoclast apoptosis
promotes osteoblast and osteocytes apoptosis
suppresses transcription of genes which codes for RANKL
ART class of compounds acts via following principle mechanism
preventing bone degradation via arresting resorption
modulates cellular mechanism which interferes in osteoclasts apoptosis
prevents osteoclasts maturation
all of the above
Which therapy has an increased risk of breast cancer
Selective Estrogen Receptor Modulator
HRT
Bisphosphonates
What are 2 important binding sites between estrogen and estrogen receptor
OH at 3 binding to Arg394 (helix 3) and glutamate 353 (helix 6)
OH at 3 binding to Arg394 (helix6) and glutamate 353 (helix 3)
OH at 17 binds to histidine 524 (helix 11)
OH at 17 binds to histidine 524 (helix 3)
T/F A phenol ring on the estrogen interactions with activation facor-2 (Af-2) and the interaction changes the protein conformation allowing the interaction with estrogen response element (ERE)
True
False
T/F Depending on the tissue, a SERM is capable of acting as an estrogen agonist or an estrogen antagonist
True
False
Raloxifene hydrocholoride is based on which structure
anastrozole
exemestane
tamoxifen citrate
letrozole
T/F Tamoxifen is linked with increased rates of breast cancer, hot flashes, and thrombocytopenia likely due to the ethyl group of the tamoxifen stilbene core that is subject to allylic oxidative activation causing DNA alkylation and strand scission.
True
False
Which are third generation Selective Estrogen Receptor Modulators?
Ospemifene
Bezedoxifene
Toremifene
17bet-ethinyl estradio
T/F Raloxifene and bazedoxifene exhibit poor bioavailability
True
False
Raloxifene and ____decreases the risk of vertebral fracture
Raloxifene only
calcium supplementation
vitamin D
Why is it essential to chose a drug such as SERM over estrogen in treating a post-menopausal patient with OP??
SERMS produce beneficial effects on bone with reduced adverse effects compared to estrogen/HRT
SERMs are all antagonist agents
SERMs have better taste than estrogen/HRT
SERMs can be taken if you are breastfeeding and pregnant compared to estrogen/HRT
T/F Bisphosphonates have a long half life.
True
False.
once bisphosphonates are incorporated into bone they have a half life of ____
1 to 2 hrs
1 to 10 hrs
1 to 5 years
1 to 10 years
10 to 15 years
RANKL antagonists were designed to mimic what?
osteoclast
osteoprotgerin
osteoblast
Which is a RANKL antagonist?
Denosumab
Raloxifene
Tamoxifen
Cys-1 and Cys-7 are critical for the activity of calcitonin-Salmon and human calcitonin
True
False
T/F Odanacatib is a first line treatment for osteoporosis.
True
False
Bone anabolic agents
increase bone mass and strength
decreases BMD
increase BMD
protects from osteoporotic fragility fractures
