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Pharmacology B > Lecture 14 - Osteoporosis > Flashcards

Lecture 14 - Osteoporosis Flashcards

1
Q

Define osteoporosis

A

“porous bone” - chronic skeletal disorder of compromised bone strength associated with low bone density (quantity) and deterioration of bone microarchitecture (quality) which often results in fragility fractures

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2
Q

What 2 things does bone strength depend on?

A

1) bone mass (a quantity indicator measured as BMD)

2) bone microarchitecture (measure of quality)

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3
Q

What factors increase bone resorption > formation?

A

menopause
aging
disease
drugs

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4
Q

peak bone mass occurs when?

A

mid 30’s

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5
Q

bone loss accelerates at ____

A

menopause

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6
Q

OP is known as the ____ ____

A

silent thief

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7
Q

OP: describe it

A

slowly steals bone density over many years without signs of symptoms until a bone breaks or fractures

(1/3 women and 1/5 men over 50 will suffer an OP fragility fracture)

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8
Q

What is a compression fracture?

A

loss of > 25% vertebral height with end plate disruption

*compression fractures in the spine can cause losses of 6-9 inches in height

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9
Q

List some consequences of fractures

A
  • increased incidence of additional fractures
  • chronic pain
  • immobility
  • decreased quality of life
  • loss of independence
  • institutionalization
  • cost to healthcare
  • death (esp after hip or spine fracture)
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10
Q

What is the most serious consequence of OP?

A

fragility fractures (diagnosed by x-rays)

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11
Q

Fragility fractures occur ____ or from ____ _____

A

spontaneously or from minor traumas

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12
Q

What are the common sites for fracture

A

hip, spine, wrist

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13
Q

Describe the OP assessment:

A
  • Assess for fractures (diagnosed by x-rays)
  • Bone Mineral Density (BMD) is assessed by DXA (dual x-ray absorptiometry) at the hip and spine
  • WHO classification of OP based on BMD is a T-score < -2.5
  • BMD correlates with fracture risk but is only ONE component
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14
Q

see slide 8 and 9

A

ok

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15
Q

Can BMD (bone mineral density) alone determine fracture risk?

A

no - Bad result needs to be incorporated into a fracture risk calculator

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16
Q

Candidates for Osteoporosis Therapy:

Decision to treat is independent of ______ result based on _____ _____

A

BMD

fracture history

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17
Q

Candidates for Osteoporosis Therapy:

Based on fracture history

A
  • If had fragility fracture of the hip
  • If had fragility fracture of the spine (66% are asymptomatic)
  • If had > 2 non-spine, non-hip fragility fractures
  • If had 1 non-spine, non-hip fragility fracture after age 40 AND prolonged glucocorticoid use in the previous year
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18
Q

Who else is a candidate for Osteoporosis Therapy:

A
  • all men or women at high fracture risk should receive treatment
  • those at moderate risk may need treatment (depends on presence of other risk factors)
  • those who are deemed low risk do not treat treatment with OP medication
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19
Q

Exercise and fall prevention

A
  • strength training 2x/week
  • balance training or tai chi daily
  • > 30 min aerobic physical activity daily
  • walking is NOT enough without strength or balancing training
  • encourage attention to posture and exercises for back extensor muscles daily
  • hip protectors, home safety assessment, reassess meds
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20
Q

Recommended calcium for > 50 yrs old

A

1200 mg daily

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21
Q

Recommended calcium for 19-50 yrs old

A

1000 mg daily

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22
Q

Vitamin D recommended for adults under age 50 without OP or conditions affecting absorption ?

A

400 to 1000 IU daily

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23
Q

Vitamin D recommended for adults over 50 ?

A

800 to 2000 IU daily

*if they require > 2000 IU daily, monitor serum 25-OH D levels

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24
Q

List some other recommendations for basic bone health

A
  • Quit smoking
  • Limit alcohol to < 2 beverages per day
  • Follow Canada’s food guide: adequate protein intake, keep sodium intake < 2300 mg/day
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25
Q

What types of medications can increase the risk of falls?

A

Meds taken for:

  • Sleep
  • Mood/behaviour
  • Anxiety
  • Depression
  • Hypertension
  • Allergies
  • Pain
  • Muscle spasms

*these meds may impair balance, co-ordination, vision, may cause drowsiness, dizziness, hypotension, may increase confusion and forgetfulness

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26
Q

What regulates serum calcium levels?

A

tb to mechem

calcitonin and parathyroid hormone (PTH)

(Calcitonin decreases and PTH increases serum Ca concentration)

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27
Q

300 mg Ca in ??

A

250 mL milk

3/4 cup of plain yogurt

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28
Q

245 mg Ca in ??

A

3 cm cube cheese

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29
Q

Calcium supplements:

Less than or equal to ____mg Ca per dose maximizes absorption

A

500

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30
Q

Calcium supplements:

List some things about Calcium carbonate

A

widely available, cheap, must be taken with a meal for optimal absorption, may be associated with more GI complaints

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31
Q

Calcium supplements:

List some things about Calcium citrate

A

can be taken with or without meals, recommended if patient on PPI or H2 blocker, may be option for those unable to tolerate CaCO3

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32
Q

Why is Vitamin D important?

A
  • Helps body absorb & use calcium/phosphorus to build/maintain strong bones & teeth; can help protect older adults against OP; improves immune function
  • Vitamin D supplementation has been shown to reduce falls in elderly
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33
Q

Vitamin ___ (cholecalciferol) is synthesized in skin on exposure to UVB light from sun and is found in fish, meat, egg, fortified food and milk products and several plant species

A

D3

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34
Q

Vitamin __ (ergocalciferol) is found in wild mushrooms, fungi and yeasts

A

D2

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35
Q

Vitamin D2 and D3 must be converted to the active form in the ____ and ______

A

liver and kidneys

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36
Q

What does low serum vitamin D result in? (<30 nmol/L)

A
  • increased calcium resorption from bones

- associated with balance problems, high fall rates, low Bad and muscle weakness

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37
Q

What does excess vitamin D result in? (>250 nmol/L)

A

-hypercalcemia and increased calcium depositions in body and cause calcification of kidney, heart, lungs and blood vessels

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38
Q

Sources of Vitamin D?

A

fatty fish, egg yolks, milk/fortified food and beverages

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39
Q

How much Vitamin D in 2 large egg yolks?

A

80 IU

40
Q

How much Vitamin D in 250 mL milk?

A

100 IU

41
Q

How much Vitamin D in 3 oz sockeye salmon, cooked?

A

447 IU

42
Q

How much Vitamin D in tuna, canned in water, drained?

A

154 IU

43
Q

What is the optimal serum levels of Vitamin D?

A

> 75 nmol/L

44
Q

> _____ IU daily should be followed by serum monitoring

A

2000

45
Q

Vitamin D is a ___-soluble vitamin

A

fat

46
Q

Anti-resorptive agents do what?

A

inhibit bone loss

47
Q

List some anti-resorptive agents (inhibit bone loss)

A

Bisphosphonates (alendronate, risedronate, zoledronic acid)

Monoclonal Antibody (denosumab)

SERM (raloxifine)

Hormone Therapy (estrogen)

48
Q

What do anabolic agents do?

A

bone forming

49
Q

List an anabolic agent

A

PTH analogue (Teriparatide)

50
Q

What are some benefits of OP Meds?

A
  • Fracture risk reduction by approximately 50%
  • Bone density is stabilized or improved slightly
  • HIGH risk patient benefit the most
51
Q

What are some risks of OP Meds?

A
  • Side effects (as w all meds)
  • Safety based on benefits outweighing risks

*Benefits > risks for all patients at high risk of fracture and possibly for those at medium risk

52
Q

MOA of Teriparatide

A

PTH Analog

*remember PTH is released when Ca levels are too low

53
Q

MOA of Bisphosphonates

A

bind to bone, inhibit osteoclasts

*remember osteoclasts break down bone

54
Q

MOA of Raloxifene and Estrogen

A

reduce RANK ligand

RANK ligand works to differentiate and active osteoclasts to break down bone

55
Q

MOA of Denosumab

A

RANK Ligand Inhibitor

RANK ligand works to differentiate and active osteoclasts to break down bone

56
Q

see chart on slide 21

A

alllllllllrighttyyyy then

57
Q

________: considered 1st line therapy for prevention and treatment of OP

A

Bisphosphonates

58
Q

MOA of 1st gen BP (bisphosphonates)

A
  • Bind directly to bone hydroxyapatite crystals (crystalline form of calcium & phosphate), are taken up by osteoclasts during remodelling and are incorporated in ATP (a source of energy in the cell)
  • These ATP analogues accumulate in osteoclasts & induce cell death through inhibition of ATP-utilizing enzymes
  • Much less effective than 2nd and 3rd gen BP’s
59
Q

MOA of Nitrogen-containing BPs (N-BP’s)

alendronate, risedronate, zoledronic acid

A
  • Bind directly to bone hydroxyapatite crystals, are taken up by osteoclasts during remodelling and act by inhibiting enzymes in the mevalonate pathway
  • These enzymes are required for modification of proteins (GTPases) that are essential for osteoclast function and can also lead to osteoclast death
  • Indicated as 1st line therapy in OP in both males and females
60
Q

Bisphosphonates:

Must be taken when and how?

A

First thing in the AM with full class of water only on empty stomach

*beverages (esp milk, coffee, orange juice, mineral water) and food reduce absorption by up to 60%

Have to remain upright and refrain from taking other meds, food or beverages (except water) for at least 30 mins after dose

*Dairy rich foods, antacids, calcium and other divalent cations should ideally be taken 2-3 hours after BP

61
Q

Bisphosphonates:

Metabolism?

A

None

62
Q

Bisphosphonates:

Half-life elimination?

A

Varies from months to years; slowly released with process of bone turnover

63
Q

Bisphosphonates:

Excretion

A

Urine (up to 85%)

Feces (as unabsorbed drug)

64
Q

Bisphosphonates:

When are they CI?

A

CrCl < 35 mL/min

65
Q

Bisphosphonates:

Oral Adverse effects

A

may cause GI related problems such as abdominal pain, acid reflux, nausea, esophagitis, esophageal ulcers, erosions, gastric ulcers

66
Q

Bisphosphonates:

Oral and IV adverse effects

A

can contribute to bone, joint & or muscle pain; ocular disorders

67
Q

Bisphosphonates:

IV adverse effects

A

Acute-phase reaction with predominantly IV route; flu-like symptoms such as fatigue, fever, chills, myalgia and arthralgia; usually occurs 3-7 days following the infusion; generally mild-moderate but can last up to 2 weeks; reaction tends to lessen with subsequent infusions

68
Q

Bisphosphonates:

What are some rare adverse effects with long term use?

A

Osteonecrosis of the jaw (ONJ)

Atypical femur fractures (AFF)

69
Q

Bisphosphonates:

When are drug holidays recommended?

A

should be considered after 5 years of BP therapy in moderate-risk patients

70
Q

Bisphosphonates:

Who are not candidates for drug holidays?

A

Patients at high risk of fracture

71
Q

Denosumab is a ?

A

a fully human monoclonal antibody that targets RANKL in bloodstream

72
Q

MOA of Denosumab

A
  • Prevents RANKL from binding to RANK receptor on osteoclasts in the circulation
  • Inhibits development, activation and survival of osteoclasts
73
Q

AE of Denosumab?

A
  • rare incidence of ONJ & atypical fragility fractures similar to bisphosphonates
  • hypocalcemia
  • severe infection (cellulitis, endocarditis, infections of abdomen, urinary tract, and ear)
  • dermatitis, eczema, rashes
  • musculoskeletal pain
  • hypersensitivity rxns
74
Q

What is the proposed mechanism for increased risk of infections when taking Denosumab?

A

activated T and B lymphocytes and lymph nodes express RANKL and denosumab inhibits RANKL

75
Q

Dose of Denosumab?

A

60 mg SC every 6 months

76
Q

Teriparatide is a ??

A

parathyroid hormone analogue

77
Q

Describe the anabolic action of teriparatide?

A

-stimulates osteoblast activity
(osteoblasts build bone)
-increased GI calcium absorption
-increased renal reabsorption of calcium

**NOTE: intermittent PTH promotes bone formation and prolonged high PTH causes bone resorption

78
Q

Results of Teriparatide?

A

increased BMD, bone mass, and strength and decreased OP-related fragility fractures in postmenopausal women

79
Q

Teriparatide:

Who is it indicated for?

A

for severe OP (< -2.5 and fragility fractures) in men, postmenopausal women and glucocorticoid induced OP

80
Q

Teriparatide:

Dose?

A

20 mcg SC once daily for 24 months (lifetime maximum) followed by anti-resorptive therapy to maintain bone gain

81
Q

Teriparatide:

Adverse reactions?

A
  • transient hypercalcemia 4-6 hours post-dose
  • orthostatic hypotension
  • dizziness, headache, nausea, arthralgia
82
Q

Teriparatide:

Very ____

A

costly

83
Q

see slide 29

A

cool

84
Q

Who is estrogen indicated for?

A

postmenopausal OP with concomitant vasomotor symptoms

85
Q

Estrogen:

MOA

A
  • decreases bone resorption

- reduces RANKL

86
Q

Estrogen:

Must be prescribed with progestin if ??

A

uterus intact

87
Q

Estrogen:

AE?

A
  • Increased risk of breast cancer with long term therapy

- Increased risk of stroke, DVT in older postmenopausal women

88
Q

SERM (raloxifine):

Indicated for ?

A

OP in postmenopausal women

89
Q

SERM (raloxifine):

MOA

A
  • Decreases bone resorption
  • Reduces RANKL
  • Increases BMD
  • Reduces fragility fracture incidence in at spine
90
Q

SERM (raloxifine):

Agonist on ______

A

bone

91
Q

SERM (raloxifine):

Antagonist at ??

A

breast and endometrium (no hyperplasia)

92
Q

SERM (raloxifine):

Associated with invasive _____ cancer risk reduction in post menopausal women

A

breast

93
Q

SERM (raloxifine):

May increase risk of ??

A

DVT or PE, risk higher during first 4 months of treatment

PE = ??

94
Q

SERM (raloxifine):

Other adverse effects?

A

hot flashes

leg cramps/muscle spasms

95
Q

see chart on slide 31

A

okay

Pharmacology B (21 decks)

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