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pharmacology > osteoporosis > Flashcards

osteoporosis Flashcards

1
Q

Osteoporosis: Occurs when rate of bone _______ exceeds rate of bone _______

A

resorption

formation

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2
Q

what is the normal bone resorption process?

A

osteoclasts activation stimulated by RANKL

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3
Q

what is the activation of bone resorption in the pathologic process?

A

osteoclasts activation stimulated by PTH

metastatic disease

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4
Q

what is the process of bone formation? what are the 4 natural substances that promote this?

A 
Inhibition of osteoclast, stimulation of osteoblasts
Osteoprotegerin (OPG)
calcitonin
estrogen
 IL-10 inhibit osteoclast
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5
Q

what two main groups of natural substances regulate bone metabolism? what does is group include?

A

Hormones:
PTH, calcitonin, estrogen, androgens
Steroids:
Vitamin D, glucocorticoids

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6
Q

what do osteocytes do?

A
  • formed after osteoblast activity

- release chemicals that say we need more osteroblast or clast activity (regulators)

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7
Q

what is OPG? (where does it come from and what does it do?)

A

released by osteocyte, it inhibits bone resorption by binding RANKL (holding it hostage so it cant activate osteoclasts)

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8
Q

what does RANKL do?

A

binds to RANK on osteoclast - activates the osteoclast

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9
Q

how does PTH exposure differ with release low intermittent vs high chronic?

A

low intermittent- bone formation (anabolic axn)

high chronic- bone resorption (breakdown) (catabolic axn)

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10
Q

how does PTH increase bone turnover?

A

PTH stimulate osteoblast to secrete IL-1, IL-6 and RANKL to activate osteoclast activity
RANKL binds to RANK proteins triggering the osteoclasts
Result is bone turnover and remodeling

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11
Q

PTH regulates what two substances? using what 3 organs?

A

Regulates calcium & phosphate using bone, kidney, and intestines

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12
Q

what does PTH do in the kidney?

A

Stimulates 1- α hydroxylase to convert calcidiol to calcitriol (to give active vitamin D - allows us to absorb Ca+ from intestine)
-tell kidney to keep Ca+ (DistalT) but get rid of phosphate (ProximalT)

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13
Q

what does PTH do in the intestine?

A

Indirectly increases intestinal calcium absorption by stimulation of 1,25 dihydroxyvitamin D production

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14
Q

Vitamin D: Increases serum ___and contributes to bone ______

A

calcium, mineralization

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15
Q

why is it so important to maintain Ca+ and phosphate balance? - (what if they get too high?)

A

need to maintain so they dont precipitate and accumulate in places like the lungs

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16
Q

what is the net effect of calcitonin?

A

Increase serum calcium -> calcitonin secretion -> inhibition of osteoclast -> decreased serum calcium

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17
Q

what is a hypocalcemic hormone that OPPOSES the effect of PTH?

A

calcitonin

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18
Q

estrogen’s effect on osteocyte, blasts and clasts

A
  • decrease osteocyte and osteoblasts apoptosis

- increase osteoclast apoptosis

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19
Q

what is estrogen good for in regards to bone health? why is this important?

A

Estrogen is better at preventing bone loss than building bone.
dont give post- menopausal women estrogen to increase bone density unless last resort (other agents are better)

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20
Q

glucocorticoid’s effect on bones?

A

Antagonize vitamin D effect (decreasing intestinal calcium transport)
Blocks bone formation by inhibiting osteoblast activity
=overall : block bone formation

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21
Q

prolonged exposure to steroids can cause what effects in adults? children?

A

prolonged exposure to steroids can cause osteoporosis in adults and stunts skeletal development in children

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22
Q

what Can be useful at reversing hypercalcemia associated with lymphomas?

A

glucocorticoids

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23
Q

7 agents used to affect bone mineralization

A 
Bisphosphonates
Human parathyroid hormone related peptide analogs
Monoclonal Antibody
Sclerostin Inhibitor
Conjugated Estrogens/SERMS
Calcitonin
Calcium
Vitamin D
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24
Q

Drug of choice (first line) for treatment of osteoporosis

A

bisphosphonates

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25
Q

what are the bisphosphonate drugs?

A

*Alendronate (Fosamax)
*Risedronate (Actonel, Atelvia)
Ibandronate (Boniva)
Zolendronic acid (Reclast)- IV formulation (once a year infusion)

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26
Q

only bisphosphonate that is not first line b/c no help for hip/nonvertebral fractures

A

ibandronate (boniva)

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27
Q

which bisphosphonate is IV formulation - (once a year infusion)

A

zolendronic acid

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28
Q

bisphosphonate MOA

A

bind Ca+ - taken into bone in high concentrations
they are taken up by osteoclast (and destroy the proteins that make their fringe border so they can’t chew up the bone)
= osteoclast apoptosis = decr rate of resorption

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29
Q

what is important to remember about the abs. of oral bisphosphonates?

A

When given orally little is absorbed – less than 1%

must take on empty stomach for max absorption

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30
Q

any metabolism for bisphosphonates?

A

no!

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31
Q

1/2 life of bisphosphonates

A

After binding to bone, clearance is hours up to 10 years (what does get abs. - that 1%- stays around for a while)

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32
Q

1 ADR for bisphosphonates?

A

GI irritation

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33
Q

rare ADRs of bisphosphonates?

A

Osteonecrosis of jaw. AVN=avascular necrosis of jaw. (due to lack of blood flow to bone.)
-dental procedures in patients with cancer after prolonged chemo therapy

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34
Q

which type of administration of bisphosphonates has higher risk for AVN - high dose IV or oral?

A

High dose IV administration

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35
Q

contraindications for bisphosphonates? (3)

A

Renal dysfunction
Esophageal motility disorders (tablet sits in throat and erodes it)
PUD

36
Q

instructions for taking oral bisphosphonate

A

Taken alone on empty stomach in morning with 8 oz of water (Water reduces risk of tablet getting stuck in esophagus)
Remaining upright for 30 minutes to minimize risk of reflux (ibandronate is 60min)

37
Q

which is the one bisphosphonate that actually SHOULD be taken with food?

A

Risedronate sodium delayed release (Atelvia) must be taken with food

38
Q

what type of fractures are the fractures with greatest morbidity & mortality?

A

Vertebral and hip

39
Q

why are bisphosphonates so good for a first line for osteoporosis?

A

They increase bone density and prevent vertebral & hip fx (they hit BOTH)

40
Q

before starting bisphosphonates, what should pts be evaluated for?

A

to detect potentially treatable causes for osteoporosis - is there anything else causing the osteo that we can stop?

Labs: Calcium (hypocalcemia); 25-hydroxyvitamin D (Vit D Deficiency); Creatinine (Renal impairment)

41
Q

what is a “Tscore” ?

A

measurement of bone density - measured in std deviations (lower than -2.5 is definition of osteoporosis)

42
Q

for what pts can we discontinue bisphosphonates and reevaluate in 2-3 years? why can we do this?

A

if they were on alendronate or risendronate for 5 years
or Z. acid for 3 years
AND have stable BMD, no previous fractures and low risk for fracture.
*it stays in body for 10 years.

43
Q

what is the reevaluation rules for if a pt has a low Tscore?

A

this means they are at high risk for future fractures
Taking alendronate/risedronate-continue 10 years
Taking zoledronic acid – continue 6 years

44
Q

what are the human PTH -related peptide analogs (recombinant PTH)? what is the MOA?

A

Teriparatide (Forteo) & Abaloparatide (tymlos)

MOA: PTH in pulse form = osteoblast increase

45
Q

The only anabolic therapy for bone; it increases bone mineral density, bone mass & strength
(other meds prevent resorption)

A

recombinant PTH analogs- “paratides”

46
Q

3 contraindications for teriparatide & abaloparatide

A
  1. hx of bone metastases
  2. if at risk for osteosarcoma
  3. hypercalcemia
47
Q

whose at risk for osteosarcoma?

A

(Paget’s disease, unexplained increase in alkaline phosphatase, pediatric patient, h/o radiation therapy to the bones)

48
Q

teriparatide + abaloparatide- Only give for __ years (during a patients life time) then switch to _________ for further treatment. why?

A

2 years

Bisphosphonates for further treatment b/c of potential risk of bone cancer

49
Q

Human parathyroid hormone related peptide analogs (“paratides” ) are used for what 2 groups of pts?

A
  1. women at high risk of fracture, including those with very low BMD and a previous vertebral fracture
  2. hypogonadal osteoporosis in men w/ high risk of fracture
50
Q

“paratides” and bisphosphonated together?

A

no! it decreased BMD

51
Q

what should you remind pts when they are prescribed the “paratides” ?

A

take first dose lying down b/c of orthostatic hypotension

1xday injectable

52
Q

Denosumab (Prolia/Xgeva) MOA

A

binds to RANKL, prevents differentiation of osteoclast, leads to inhibition of osteoclast fxn and survival –> osteoclast apoptosis

53
Q

denosumab ( prolia or xgeva) what are they used for?

A

Prolia – osteoporosis/steroid induced osteoporosis
Xgeva – bone metastases from solid tumors, multiple myeloma
(same drug, just different dosing)

54
Q

what is our one sclerostin inhibitor drug?

A

Romosozumab-aqqg (Evenity)

55
Q

MOA of romosozumab (evenity)

A

inhibits axn of sclerostin . stimulating osteoblast activity while slightly decreasing osteoclast activity
(increases bone formation)

56
Q

sclerostin inhibitor (romosozumab-aqqg) is indicated for what use?

A

treatment of osteoporosis in postmenopausal women at high risk for fracture

57
Q

what defines “high risk of fracture”

A

Defined as a history of osteoporotic fracture
OR multiple risk factors for fracture
OR patients who have failed or are intolerant to other available osteoporosis therapy

58
Q

how long can you use the sclerostin inhibitor for? if osteoprosis remains after this time period, what can you switch to?

A

12 monthly doses (doesnt work anymore after a year)

* continued therapy with an anti-resorptive agent should be considered

59
Q

what is the one SERM we may use for osteoporosis?

A

Raloxifene (Evista)

60
Q

MOA of Raloxifene (Evista) ?

A

estrogen agonist used to reduce resorption of bone and decrease in overall bone turnover

61
Q

what is raloxifene (evista) good for?

A

Treatment and prevention of osteoporosis in postmenopausal women
Reduces risk of vertebral fractures by 30-50% (not for hip fractures)

62
Q

major ADR to look out for raloxifene (evista) ?

A

clots (First 4 months) (DVT)

63
Q

MOA of conjugated estrogen/bazedoxifene

A

Estrogen is agonist, Bazedoxifine is agonist on bone and antagonist in uterine tissue to prevent endometrial hyperplasia
(SERM)

64
Q

what does calcitonin (miacalcin) do to PTH? from where do they get this hormone ?

A

Antagonizes effects of PTH and inhibits bone resorption (increases bone density but DOES NOT prevent fractures)
-salmon derived hormone

65
Q

when would you use calcitonin for osteoporosis?

A

doesnt work very well - only really good for BONE PAIN

3rd line if you go to it at all

66
Q

why is Calcium recommended for all osteoporosis pts to take? (2 reasons)

A
  • maintain normal calcium concentrations

- to prevent hypocalcemia associated with other drug treatments

67
Q

what is the dosing for calcium?

A

1000 mg daily (19-50 years women & 51-70 years men)
1200 mg daily (51-70 years women & >70 men & women)
Avoid doses higher than 2000 mg/day

68
Q

what does total daily calcium include?

A

Total daily calcium includes diet and supplements - obtaining it naturally better than taking tablet

69
Q

why is Vit D recommended for all osteoporosis pts?

A

Maximizes absorption of calcium by intestine

70
Q

minimal dosing of vitamin D: men 70+ and post-menopausal women vs premenopausal women and men <70

A

Men over 70 and postmenopausal women is 800 IU/day

Premenopausal women and men < 70 is 600 IU/day

71
Q

*txt of osteoporosis: no prior fracture/moderate risk: 1st line (4)

A

Bisphosphonates: Alendronate, Risedronate, Zoledronic acid

Denosumab

72
Q

*txt of osteoporosis: no prior fracture/moderate risk: alternative options (3)

A

Bisphosphonate: ibandronate (for vert. fracture risk)
SERM: Raloxefine, Conjugated estrogen/Bazedoxifene (Duavee)

73
Q

*lifestyle measures for txt of osteoporosis (5)

A 
adequate calcium and vitamin D
exercise
smoking cessation
counseling on fall prevention
avoidance of heavy alcohol use
74
Q

*txt of osteoporosis: Hx fracture/high risk: 1st line (3)

A

Denosumab
Teriparatide, abaloparatide
Zoledronic acid (IV)

75
Q

*txt of osteoporosis: Hx fracture/high risk: 1st line (2)

A

Bisphosphonates: Alendronate or Risedronate

76
Q

special case of osteoporosis: men. txt? what if testosteron is low?

A

Avoid risk factors, treat with bisphosphonates.

If serum testosterone level is low can give testosterone injections

77
Q

special cases of osteoporosis: men - severe. what drugs can you use?

A

Denosumab, teriparatide

78
Q

special case: glucocorticoid-induced osteoporosis. txt?

A

higher doses Ca+ and Vit D

bisphosphonates

79
Q

special case: glucocorticoid-induced osteoporosis - severe. txt?

A

Severe cases: teriparatide

80
Q

special case: premenopausal women. what 3 things should be recommended as far as prevention?

A

Calcium, vitamin D, weight bearing exercise

81
Q

special case: premenopausal women- hypogonadism vs steroid-induced txt

A

Hypogonadism – estrogen replacement

Steroid induced – alendronate, risidronate; severe – teriparatide

82
Q

what 3 drugs to avoid for premenopausal women with osteoporosis

A

NO SERM’s, calcitonin, denosumab

83
Q

what is paget’s disease?

A

Resorb bone and then lay down, new poorly organized bone.

Results in overgrowth of bone at single or multiple sites - spikes and bony nodules- painful for pt

84
Q

goal of txt for paget

A

Goal of treatment is to reduce bone pain & reduce rate of bone remodeling

85
Q

txt options for bisphosphonates (2 main options)

A

Bisphosphonates 1st line agents - at higher dosing than for osteop.
Zoledronic acid
Alendronate
Risedronate

Calcitonin
Reserved for bone pain or when bisphosphonates not tolerated

pharmacology (24 decks)

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