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Pharmacology - Winter > 14 - Osteoporosis > Flashcards

14 - Osteoporosis Flashcards

1
Q

What does osteoporosis mean?

A

Porous bones

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2
Q

What is osteoporosis?

A
  • Chronic condition w/ fragile bones

- Change in micro architecture of the bone, cause excessive loss of bone mass

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3
Q

When is osteoporosis most common and in which gender?

A

Post menopausal women

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4
Q

Can osteoporosis be prevented?

A

Yes

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5
Q

What are risk factors for osteoporosis?

A
  • Menopause
  • Age
  • Drugs (ex: glucocorticoids, prolonged use of coumadins)
  • Stress
  • Genetics
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6
Q

How is bone formed?

A

Osteoblasts secrete type 1 collage and Ca2+ and PO4- to form hydroxyapatite crystal (aka osteocytes) which connect to other osteocytes

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7
Q

What is the difference between osteoblasts and osteoclasts?

A
  • Osteoblasts build the bone

- Osteoclasts break down the bone

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8
Q

Do bones stay around the entire lifespan of a human?

A

No, they are constantly remodeled by the process of resorption and reformation

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9
Q

___ are responsible for resorption or erosin

A

Osteoclasts

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10
Q

____ are responsible for reformation

A

Osteoblasts

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11
Q

An abnormality in _____ leads to osteoporosis

A

Abnormality in resorption and reformation balance; excessive osteoclastic activity

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12
Q

How is osteoporosis diagnosed?

A
  • X-ray
  • Fragility fractures from minor trauma (ex: sneezing, coughing, bending)
  • Bone mineral density assessed be dual X-ray absorptiometry at hip and spine (T score of less than 2.5 = osteoporosis)
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13
Q

What are some strategies for preventing or delaying osteoporosis?

A
  • Weight bearing exercise
  • Cessation of smoking and limiting alcohol intake
  • Avoid drugs that increase bone loss (ex: glucocorticoids)
  • Diet containing calcium and vitamin D and supplements of protein and vitamin K (only if px needs drugs that increase bone loss)
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14
Q

Why do glucocorticoids cause osteoporosis?

A
  • Antagonize vitamin D stimulated Ca2+ absorption
  • Stimulate renal Ca2+ excretion
  • Block bone collagen formation
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15
Q

What regulates serum calcium levels in the body?

A
  • Calcitonin and parathyroid hormone (PTH)

- Calcitonin decreases and PTH increases serum Ca2+

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16
Q

What is the difference between vitamin D2 and D3?

A
  • D2 = ergocalciferol (plant source)

- D3 = cholecalciferol (animal source)

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17
Q

How does the body get the majority of its vitamin D3?

A

80-90% is synthesized in the skin

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18
Q

How is vitamin D3 synthesized?

A

7-dehydrocholesterol (precursor molecule) is cleaved by the energy from UVB light on the skin to form vitamin D3 (pro-hormone)

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19
Q

Are vitamin D2 and D3 active?

A

No, they are inactive

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20
Q

How is active vitamin D formed?

A

Hydroxylation occurs in the liver, then final hydroxylation occurs in the kidneys to form 1,25-dihydroxyvitamin D (calcitriol)

21
Q

What are the effects of calcitriol on bone?

A
  • Increase Ca2+ and phosphate absorption from gut
  • Decrease renal excretion of Ca2+ and phosphate
  • Increase bone turnover or remodeling
22
Q

What can cause a deficiency in calcitriol?

A
  • Poor diet
  • Inadequate sunlight
  • Hereditary receptor resistance
23
Q

What are some benefits of vitamin D that aren’t related to bone?

A
  • Muscle mass, strength, and balance
  • Multiple sclerosis
  • Psoriasis
  • Immune system
  • Anti-type 1 diabetes
  • Colorectal cancer
  • Asthma
24
Q

What is the difference between vitamin K1 and K2? What are sources of each vitamin?

A
  • Vitamin K1 required for coagulation; synthesized by plants and green vegetables
  • Vitamin K2 involved in bone metabolism; found in meat, fish, and fermented food
25
Q

What effect does vitamin K have on bone?

A
  • Regulates carboxylation of osteocalcin

- Undercarboxylated osteocalcin is frequent in post-menopause, but this can be corrected w/ supplementation

26
Q

What effect does warfarin have on bones?

A
  • Causes severe bone dysfunction in fetus and children, but less in adults
  • In adults, causes mild decrease in resorption, marked decrease in formation, and remodeling abnormalities
27
Q

Does vitamin K supplementation help w/ bone loss?

A

Not proven

28
Q

What can low doses of parathyroid hormone do to bone?

A

Increases bone turnover and remodeling, so may increase bone formation

29
Q

PTH secretion is reduced by increased _____

A

Ca2+ and 1,25-OH vitamin D (calcitriol)

30
Q

What effect does parathyroid hormone have on calcium and phosphate?

A
  • Increases calcium absorption from gut and reabsorption from kidney
  • Decreases phosphate absorption from gut and reabsorption from kidney
31
Q

What effect does parathyroid hormone have on vitamin D?

A

Stimulates hydroxylation (activation) of vitamin D in kidney

32
Q

What effect does parathyroid hormone have on osteoclasts and osteoblasts?

A

Activates osteoblasts, which activates osteoclasts through inducing a membrane-bound protein ligand, which increases both numbers and activity of osteoclasts

33
Q

What is teriparatide? What is it indicated for? What are the SE?

A
  • Endogenous parathyroid hormone; stimulates osteoblast activity
  • Indicated for severe osteoporosis in men, postmenopausal women, and glucocorticoid induced osteoporosis
  • SE = transient hypercalcemia 4-6 h post-dose, orthostatic hypotension, dizziness (so bedrest is recommended for 6 h post-dose)
34
Q

What effect does calcitonin have on bones?

A
  • Decreases osteoclastic bone resorption

- W/ longer exposure, decreases resorption and deposition

35
Q

Is calcitonin useful for osteoporosis?

A

No b/c doesn’t increase bone mass

36
Q

Is estrogen ever used for osteoporosis?

A

Yes, for post-menopausal osteoporosis w/ concomitant vasomotor sx

37
Q

What is RANKL?

A
  • Receptor activator of nuclear kappaB ligand (osteoprotegerin ligand)
  • Secreted by mature osteoblasts
  • Tells osteoclasts to be secreted
38
Q

What effect does estrogen have on bone?

A

Decreases bone resorption and RANKL

39
Q

Which SERM is indicated for osteoporosis? What are its effects?

A
  • Raloxifene for post-menopausal osteoporosis

- Decreases bone resorption, reduces RANKL, increases bone mineral density, and reduces number of incidence at spine

40
Q

____ are considered first line therapy for prevention and treatment of osteoporosis

A

Bisphosphonates (specifically nitrogen-containing)

41
Q

What is the mechanism of 1st gen bisphosphonates for osteoporosis? Are they first line therapy?

A
  • Bind directly to bone hydroxyapatite crystals
  • Are taken up by osteoclasts during remodeling and are incorporated in ATP
  • ATP analogues accumulate in osteoclasts and induce cell death
  • 2nd line b/c much less effective than 2nd and 3rd gen
42
Q

What is the mechanism of nitrogen-containing bisphosphonates?

A
  • Bind directly to bone hydroxyapatite crystals
  • Are taken up by osteoclasts during remodeling
  • Act by inhibiting enzymes in the mevalonate pathway
  • These enzymes are essential for osteoclast function and can lead to osteoclast death
43
Q

Which bisphosphonates are nitrogen-containing?

A
  • Alendronate
  • Risedronate
  • Zoledronic acid
44
Q

____ is an example of a 1st gen bisphosphonate

A

Etidronate

45
Q

How must bisphosphonates be taken?

A

In the A.M., w/ a full glass of water on an empty stomach

- Don’t consume beverages and food for at least 30 mins after dose

46
Q

What are some side effects of oral bisphosphonates?

A
  • GI disturbances (abdominal pain, acid reflux, nausea, esophagitis)
  • Bone, joint, and/or muscle pain
  • Ocular disorders
47
Q

What is denosumab? What are its effects?

A
  • Human monoclonal antibody
  • Targets RANKL in bloodstream and prevents it from binding to RANK receptor on osteoclasts in circulation
  • Inhibits development, activation, and survival of osteoclasts
48
Q

What are some SE of denosumab?

A
  • Severe infection
  • Dermatitis, eczema, rashes
  • Hypocalcemia
  • Musculoskeletal pain
  • Hypersensitivity reactions
49
Q

What is the proposed mechanism for the increased risk of infection w/ denosumab?

A

Activated T and B lymphocytes and lymph nodes express RANKL, and denosumab inhibits RANKL

Pharmacology - Winter (18 decks)

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