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MSK Pharm > Osteoporosis > Flashcards

Osteoporosis Flashcards

1
Q

Osteoporosis progression is?

A

clinically silent!!

  • BMD (bone mass density) determined by DEXA
  • BMD is expressed a T-score!!
  • T-score: -1 to -2.5 - osteopenia
  • T-score: -2.5 to -4- osteoporosis
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2
Q

Drugs’ efficacy for prevention and treatment of osteoporosis depends on?

A

-adequate intake of vit D and Ca!

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3
Q

Calcium Supplements

A
  • Calcium carbonate- needs acid to dissolve and for abs

- Calcium citrate- doesnt need acid; higher cost

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4
Q

what promotes intestinal Ca absorption?

A

-1,25 (OH)3 Vit D3!!!

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5
Q

Vit D requirement

A 
(normally 400-800/day)
> 800/day in persons:
-GI malabs disorders
-corticosteroids, anticonvulsants, loop diuretics, heparin
-less exposure/response to sunlight
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6
Q

Drugs that lower serum Ca (secondary causes of osteoporosis)

A
  • glucocorticoids- impairs Vit D abs and impairs metabolic act in liver and kidney
  • anticonvulsants (carbamazepine, phenytoin)- induction of p450- hepatic inact of vit D
  • loop diuretics (furosemide)- Ca wasting
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7
Q

osteoporosis- risk factors

A
  • genetics (FH)
  • F > M
  • post-menopausal (estrogen level)
  • white, asian
  • small and thin
  • smoker, no exercise, alcohol
  • drugs, poor diet, eating disorder
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8
Q

osteoporosis- pharmacology

A
  • SERMs
  • Bisphosphonates
  • Biologicals
  • Ab’s
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9
Q

SERMs- drugs

A
  • Raloxifene

- Tamoxifen

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10
Q

Bisphosphonates- drugs

A

-Alendronate
-Ibandronate
-Pamidronate
-Risedronate
-Zoledronate
(AIPRZ)

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11
Q

Biologicals

A
  • Teriparatide
  • Calcitonin
  • Ab’s- Denosumab
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12
Q

Anti-Resorptive Therapy- inhibit osteoclasts- what drugs??

A
  • SERMs
  • Bisphosphonates
  • Biologicals
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13
Q

Anabolic therapy- act osteoblasts- what drugs?

A

-Teriparatide!!!!!

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14
Q

Postmenopausal women- prevention of osteoporosis

A

Estrogen H replacement!!

  • balance bone resorption and bone formation
  • optimal maturation of osteoclasts
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15
Q

Estrogen def- does what?

A

imbalances bone resorption and formation

-excess maturation of osteoclasts- excess bone resorption

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16
Q

HRT

A

-conjugated estrogens + medroxyprogesterone

17
Q

Hormone Replacement Therapy- benefits, risks

A 
Benefits
-inc bone health, dec menopause sx's
Risks
-inc breast and uterine cancer
-inc heart attack, stroke, thrombosis
18
Q

SERMs- drug

A

-Raloxifene

19
Q

SERMs- moa

A
  • recapitulate estrogens actions in bone
  • agonists at ER in osteoclasts!!!
  • antagonists at ER in breast epit!!
20
Q

SERMs vs HRT- risk vs benefits

A
  • Raloxifene- used for breast cancer prophylaxis!!!!
  • HRT- inc risk of breast, ovarian cancer
  • both prevent/treat osteoporosis in postmenopausal women
21
Q

Tamoxifen- risk of?

A

-inc uterine bleeding and cancer!!!

22
Q

HRT estrogens, Raloxifene, Tamoxifen- SE’s of all

A

-venous thromboembolism risk

23
Q

Bisphosphonates- moa

A
  • sequestered by bone near remodeling sites
  • accum in osteoclasts- inhibit osteoclast fxn:
  • inhibit FPP (Farnesyl Pyrophosphate) synthase- inhibit Prenylated G proteins (inhibit signal transduction)
  • osteoclast act and survival requires G-protein prenylation
24
Q

Bisphosphonates- complications

A
  • contraindication- pre-existing hypocalcemia
  • SE- esophagitis, esophageal ulcer!!
  • osteonecrosis of jaw (ONJ)
  • long-term use- inc fractures- BP remain in bone for decades!!!
25
Q

Osteonecrosis of Jaw- in who?

A
  • IV bisphosphonates
  • MM, breast cancer, prostate cancer
  • tooth extractions, dental trauma
26
Q

Zoledronate- moa

A
  • improved convenience, compliance, and efficacy for bisphosphonates
  • IV, 1x per yr
27
Q

Prevention and Tx- options

A
  • SERMs

- Bisphosphonates

28
Q

Treatment only- options

A
  • Calcitonin
  • Denosumab
  • Teriparatide (anabolic tx)
29
Q

Denosumab- moa

A
  • monoclonal ab against RANKL on osteoblasts (osteoclast diff factor)
  • inhibits osteoclast formation!
30
Q

Calcitonin- moa

A
  • inhibits osteoclast action

- dec pain w acute vertebral compression fracture

31
Q

Only Anabolic Therapy

A

-Teriparatide (SkeleGrow from Harry Potter)

32
Q

Teriparatide

A

(PTH fragment)

  • intermittent admin
  • stim osteoblast activity
  • for high risk pts
  • injection daily, expensive
33
Q

Osteoporosis and aging

A
  • senescence of osteoblasts

- persistent inc in PTH levels (due to dec renal Ca reabs and intestinal Ca abs in elderly)

34
Q

Cinacalcet- moa

A

Calcium Sensing R (CaSR) Activator

  • lowers PTH levels by inc the sensitivity of the Ca-sensing R to extracellular Ca
  • used to tx an overactive parathyroid gland in dialysis pts w chronic kidney dz; also to treat high blood Ca levels in pts w parathyroid cancer

MSK Pharm (10 decks)

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