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MSK II Midterm > Fitzy: Osteoporosis > Flashcards

Fitzy: Osteoporosis Flashcards

1
Q

What is the definition of osteoporosis?

A
  • 2.5 standard deviations from the mean bone density on DEXA scan
  • 1-5 to 2.5 is osteopenia
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2
Q

How T-score is calculated

A

(Patient’s BMD- young adult mean BMD)/(1 SD of young-adult Mean BMD)
-<2.5 is osteoporosis

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3
Q

What does the drugs’ efficacy for prevention and tx of osteoporosis depend on?

A

-adequate intake of Vit D and calcium

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4
Q

What are the 2 calcium supplements that a person can take?

A
  • Calcium carbonate

- calcium citrate

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5
Q

Describe calcium carbonate

A
  • 40% calcium, needs acid to dissolve and for absortion
  • take “at” or “after” meals
  • less stomach acid with aging
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6
Q

describe Calcium citrate

A
  • 20% calcium, no need for stomach acid for absorption
  • may be taken between meals
  • higher cost
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7
Q

What does 1,25 (OH)3 Vit D promote?

A

-intestinal Ca2+ absorption

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8
Q

What is the sufficient level of serum Vit D3

A

30-50

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9
Q

What are the drugs that lower serum Ca2+?

A
  • prednisone, methylprednisolone
  • budesonide, inhlaed
  • carbamazepine
  • phenytoin
  • Furosemide
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10
Q

So, if we are going to initiate glucocorticoid therapy, what would we have to do first?

A
  • a Bone densitometry and T-score

- glucocorticoids can impair Vit D absorption and metabolic activation n liver and kidney

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11
Q

What does Vit D make us do?

A

-absorb Ca2+ in the GI tract

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12
Q

what are the SERMs?

A
  • Raloxifene

- Tamoxifen

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13
Q

What are the Bisphosphonates

A
  • alendronate
  • ibandronate
  • pamidronate
  • resedronate
  • zolendronate
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14
Q

Biologicals

A
  • teraparatide

- calcitonin

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15
Q

Antibodies

A

-denosumab

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16
Q

What cells do osteoclasts come from?

A

-HSC’s

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17
Q

What cells do osteoblasts come from?

A

-Mesenchymal stem cells

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18
Q

What drugs inhibit osteoclasts?

A
  • SERMs
  • Bisphosphonates
  • calcitonin
  • Antibodies: denosumab
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19
Q

What causes osteoporosis in older women?

A
  • loss of estrogen during the aging process and at menopause

- E deficit leads to incrased rate ofbone resorption by osteoclasts

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20
Q

What does estrogen normally do?

A

-it’s usually a restrain on osteoclastic activity

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21
Q

Why is thrombosis such a big deal with estrogens?

A

-they stimulate the liver to make procoagulants

22
Q

What class of drugs do we use for prevention and tx of osteoporosis?

A
  • selective estrogen receptor modulators
  • Raloxifene
  • tamoxifen
23
Q

Which drugs are for tx only?

A
  • Calcitonin
  • teriparatide
  • denosumab
24
Q

Where are the receptors that SERMS are estrogen agonists at?

A

-the ER in OSTEOCLASTS

25
Q

Where are SERMS antagonists at ER’s

A
  • the breast epithelium

- the ER’s there are occupied by RIx

26
Q

When is Raloxifene usually chosen for osteoporosis prevention?

A

-when there is an independent need for breast cancer prophylaxis

27
Q

What is the risk with using tamoxifen?

A
  • increased uterine bleeding and cancer

- Raloxifene is not associated with vaginal bleeding or an increased risk of endometrial hyperplasia or cancer

28
Q

What other class of drugs do we use for prevention and tx of osteoporosis?

A

-aminobisphosphonates

29
Q

What do bisphosphonates do?

A
  • bind to hydroxyapatite crystals in bone and inhibit bone resorption through effects on osteoclasts
  • not metabolized, but either bind to hydroxyapatite in bone or are excreted unchanged into urine
30
Q

What is the required for the release of bisphosphonates from the body?

A
  • bone resorption

- they inhibit that… so they have a long time in bone

31
Q

What is the amino bisphosphonate prototype?

A

-alendronate

32
Q

What does alendronate accumulate in?

A
  • osteoCLASTS
  • sequestered by bone near remodeling sites
  • remember they just go into osteoclasts and make them do apoptosis
33
Q

What does osteoclast survival require?

A
  • G protein prenylation (for signal transduction)
  • FPP synthase does this
  • BP’s block FPP.. there ya go
  • more specifically, blocks conversion of Geranyl-PP to Farnesyl-PP
34
Q

What is a contraindication for BP’s?

A
  • pre-existing hypocalcemia

- we need bone, but we might also need the calcium from bone

35
Q

What are well recognized adverse events associated with oral bisphosphonates?

A

-Esophagitis and esophageal ulcer

36
Q

What do all of the BP’s end in?

A

-“dronate”

37
Q

Why do you NOT want to eat or drink anything for at least 30 min after taking BP’s
-you also do NOT want to lie down for at least 30 minutes

A

-you want to avoid esophagitis

38
Q

What is a rare but serious complication of BP’s that mainly happens in pts recieving it IV?

A

-Osteonecrosis of the Jaw (ONJ)

39
Q

What are the treatment only anti resorption therapies?

A
  • Calcitonin

- Denosumab

40
Q

Denosumab

A
  • monoclonal antibody
  • against RANKL
  • inhibits osteoclast formation b/c RANKL is a receptor activator of NFKB which is an osteoclast differentiating factor
  • so, normally, RANKL on the osteoblast will bind to RANK on a pre-osteoclast to make it turn into an actual osteoclast
41
Q

Calcitonin

A
  • inhibits osteoclast action… anti-resorptive
  • modest effect< BP
  • decreases pain with acute vertebral compression fracture***
42
Q

What is the Anabolic therapy that is used for tx only?

A

-Teriparatide (PTH fragment)

43
Q

What does teriparatide do?

A
  • stimulated osteoblast activity

- intermittent administration

44
Q

What is teriparatide reserved for?

A
  • high risk patients

- it has a greater increase in bone density as compared to alendrolate

45
Q

What are the indications for teriparatide?

A
  • postmenopausal women with osteoporosis at high risk for frature
  • high risk for fracture
  • high frisk for fracture!!!
46
Q

What fractures are more common in older men?

A

-incidence of hip fractures increases exponentially with age

47
Q

What drugs are effective in men?

A

-BP’s

48
Q

What is Cinacalcet?

A

-A Calcium sensing receptor (CaSR) activator

49
Q

What is Cinacalcet?

A
  • a calcimimetic agent

- lowers PTH levels by increasing the sensitivity of the CaSR to extracellular Ca2+

50
Q

What is Cinacalcet used for?

A
  • treating an overactive parathyroid gland in dialysis pts with chronic kidney disease
  • it is also used to treat high blood Ca2+ levels in pts with parathyroid cancer

MSK II Midterm (15 decks)

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