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Osteoporosis Flashcards

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1
Q

What is osteoporosis (OP)? What is it associated with?

A
  • Chronic skeletal disorder of compromised bone
    strength
  • Associated with low bone density (quantity) and bone deterioration (quality), leading to fragility fractures
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2
Q

What does bone strength depend on?

A
  • Bone mass (measured as bone mass density = BMD)

- Bone microarchitecture

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3
Q

At what age does peak bone mass occur?

A

~ mid 30s

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4
Q

When does bone loss accelerate for women?

A

Menopause (due to loss of estrogen)

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5
Q

What is a spine compression/fragility fracture?

A

Loss of ≥ 25% of vertebral height w/ end plate disruption

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6
Q

What are 2 possible results of spine fragility fractures?

A

1) 6-9 inches height loss

2) Extreme spine curvature (kymphosis or dowager’s hump)

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7
Q

What are 8 consequences of fractures?

A

1) Increased incidence of additional fractures
2) Chronic pain
3) Immobility
4) Decreased QOL
5) Loss of independence
6) Institutionalization (rehab and long-term care)
7) Immense healthcare costs
8) Death (esp after hip or spine fracture)

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8
Q

Why has it been suggested that OP be referred to as bone attacks?

A

Bc ≤20% of women and ≤10% of men get tx to prevent further fragility fractures

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9
Q

How do fragility fractures occur?

A
  • Spontaneously
  • Coughing/sneezing
  • Bending
  • Hugging
  • Minor traumas (for example, fall from: sitting, ≤ standing height, at ≤ walking speed, ≤ 3 stairs in height)
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10
Q

What are 3 common sites for fractures?

A

1) Hip
2) Spine
3) Wrist
(NOT feet, ankle, hands, cranio-facial)

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11
Q

How is BMD assessed?

A

Via Dual X-ray Absorptiometry at hip and spine

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12
Q

How does WHO classify OP?

A

Based on BMD (T-score ≤ -2.5)

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13
Q

What is T-score?

A
  • How much a person’s peak bone mass deviates from normal young adult (usually 20-29 y/o)
  • T-score units = standard deviation (-1 to 1 = normal)
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14
Q

What is Z-score?

A

Sex and age matched comparison of BMD

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15
Q

BMD does not determine fracture risk

A

BMD needs to be incorporated into risk calculator

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16
Q

Where is calcium stored in the body?

A

~99% stored in bones and teeth

1% stored in blood, muscle, other tissues

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17
Q

What regulates serum calcium levels?

A
  • Calcitonin (increased calcitonin, decreased Ca)

- Parathyroid hormone, PTH (increased PTH, increased Ca)

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18
Q

What is the recommended amount of elemental Ca/day (for ≥ 50 y/o)?

A

1200 mg

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19
Q

Ca + Vitamin D supplements (can be dosed separately) insufficient to prevent fractures in pts with OP

A

Must be used in adjunct with OP meds

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20
Q

What are the best food sources of Ca?

A
  • Milk products

- Fortified beverages

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21
Q

What is the recommended dose of Ca?

A

500 mg for max absorption

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22
Q

What are 2 Ca supplements?

A

1) Calcium carbonate

2) Calcium citrate: can be taken w/ or w/o meals

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23
Q

What are 2 issues with CaCO3?

A
  • Must be taken with meal for best absorption (compared to calcium citrate, which can be taken with or w/o food)
  • May be associated with GI issues
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24
Q

When is calcium citrate indicated?

A
  • If pt is on PPI or H2 blocker

- If CaCO3 intolerable

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25
What are 2 AEs of over-supplementation?
1) kidney stones | 2) if supplementation taken w/o Vit D, increased MI risk (?)
26
What are 3 roles of Vitamin D in the body?
1) Helps body absorb and use Ca and P to build/maintain strong bones and teeth 2) Helps protect older adults against OP 3) Improves immune function
27
What are 3 food sources of Vit D?
1) Fatty fish 2) Egg yolks 3) Milk/fortified food and drinks (not standardized)
28
How is Vit D monitored in serum?
- 25(OH)D is monitored in serum bc it has a long half life | - It reflects total Vit D from food, supplements, and sun
29
What is the optimal 25(OH)D serum levels?
≥ 75 nmol/L
30
Why is there a high prevalence of Vit D deficiency in Canada?
- Sunscreen and clothing - Northern latitude and seasons - Age/skin pigmentation * Most need supplements to meet recommended daily amounts*
31
Why is there a high prevalence of Vit D deficiency in Canada?
- Sunscreen and clothing - Northern latitude and seasons - Age/skin pigmentation * Most need supplements to meet recommended daily amounts*
32
≥2000 IU DAILY of Vit D requires...
serum monitoring
33
Since Vit D is a fat soluble vitamin, weekly or monthly doses are possible...
and may help in compliance (seen in OP pts who need higher doses)
34
When should 25(OH)D levels be checked to determine tx efficacy?
Check levels 3-4 months of supplementation/dose changes --> if target is achieved, re-check is not needed
35
Where is Vit D2/3 converted into the active form (calcitriol)?
Kidneys
36
What does low 25(OH)D serum levels (≤30 nmol/L) result in?
- Increased calcium resorption from bones (associated with balance problems) - High fall rates - Low BMD - Muscle weakness
37
What does high 25(OH)D serum levels (≥250 nmol/L) result in?
- Hypercalcemia --> calcification of kidney, heart, lungs, and blood vessels
38
What are 2 benefits of OP medication?
1) Fracture risk reduction (~50%) 2) Bone density stabilization/improvement * Most beneficial to high risk pts*
39
What is 1st line for OP prevention and tx?
Biphosphonates, BP (pyrophosphate analogue)
40
Newer generations of biphosphonates...
are more potent than the previous
41
Name a 1st generation BP:
Etidronate (less effective than 2nd/3rd gens)
42
Etidronate MOA:
1) Bind to hydroxyapatite crystals (Ca and P crystalline form) 2) Taken up into bone by osteoclasts during remodelling and incorporated into ATP 3) ATP analogues accumulate in osteoclasts, ATP-using enzymes are inhibited 4) Cell death
43
Name 3 second generation BPs (N containing):
1) Alendronate 2) Risedronate 3) Zoledronic Acid
44
2nd GEN BP MOA:
1) Bind to hydroxyapatite crystals 2) Taken up into bone by osteoclasts during remodelling 3) Inhibits enzymes (GTPase) involved in mevalonate pathway, which are needed for protein modification. These proteins are impt in osteoclast function and death
45
Why does BP have a strict dosing schedule?
Bc ≤ 1% of oral dose is absorbed
46
What is BP's dosing schedule?
- Take first thing in AM with full glass of water and on empty stomach (drinks like milk, coffee, OJ and food reduce abs by 60%) - Remain upright and do not eat/take meds for at least 30 min after taking dose - Eat dairy-rich foods, antacids, Ca 2-3 hours after taking dose
47
BP Metabolism:
None
48
BP half-life elimination:
Months-years (released during bone turnover)
49
BP excretion:
~85% via kidney, unabsorbed drug via feces
50
Oral BP AE:
- GI problems - Bone, joint, muscle pain - Ocular disorders
51
IV BP AE:
- Bone, joint, muscle pain - Ocular disorders - Acute-phase reactions include flu-like sx (lessens with subsequent infusions, lasts ~2 weeks)
52
What are rare risks associated with long-term BP use?
- Osteonecrosis of the jaw (usually seen in pts with existing jaw trauma) - Atypical femur fractures
53
Who should go on BP drug holidays?
- Mod risk pts after 5 years of BP tx | - NOT high risk pts (benefit vs risk)
54
Name a RANK ligand inhibitor:
Denosumab
55
Denosumab MOA:
1) Fully human monoclonal antibody that targets RANKL in bloodstream 2) Prevents RANKL from binding to RANK receptor on osteoclasts in circulation 3) Development, activation, and survival of osteoclasts inhibited
56
What is a special consideration for renally impaired pts taking Denosumab?
Monitoring Ca levels bc they are at increased risk of hypocalcemia (BUT dosing adjustment NOT necessary)
57
What are 6 AEs of Denosumab?
1) ONJ + atypical fractures (like BPs) 2) Hypocalcemia 3) Dermatitis/eczema 4) Musculoskeletal pain 5) Hypersensitivity reactions 6) Severe infection
58
Why is there a risk of infection associated with Denosumab?
Bc activated T and B cells and lymph nodes also express RANKL, which Denosumab inhibits
59
What is Teriparatide?
Parathyroid hormone analogue
60
Teriparatide MOA:
1) Stimulates osteoblast activity (anabolic) 2) Increased GI Ca absorption, increased GI renal absorption 3) Increased BMD, strength and decreased OP-related fractures in postmenopausal women
61
Intermittent PTH promotes bone formation
Prolonged high PTH causes bone resorption
62
Teriparatide indication:
- Severe OP (BMD = ≤ -2.5 + fragility fractures) in men and postmenopausal women**** - Glucocorticoid induced OP
63
Why is Teriparatide dosed for a lifetime maximum of 24 months?
Bc if taken for longer, there is an increased risk of osteosarcoma
64
What tx is Teriparatide tx followed with?
Anti-resorptive tx to maintain bone again
65
Teriparatide bioavailability:
95%
66
Teriparatide metabolism:
Hepatic
67
Teriparatide excretion:
Renal (as metabolites)
68
What are 4 AEs associated with Teriparatide?
1) Transient hypercalcemia (4-6 hours post-dose) 2) Orthostatic hypotension 3) Headache/nausea 4) Arthralgia
69
Estrogen indication (osteoporosis):
- (Younger) Postmenopausal OP presenting with vasomotor sx
70
Estrogen MOA:
Reduces RANKL, and therefore, bone resorption
71
What are 2 considerations to make when starting estrogen tx for osteoporosis?
- Adjust dose based on response to tx | - Must be prescribed with progestin if uterus is intact
72
What are 3 AEs associated with estrogen?
1) Increased risk of breast cancer with long-term tx 2) Increased risk of stroke 3) DVT in older postmenopausal women
73
Name a SERM used in OP tx:
Raloxifene
74
SERM indication (osteoporosis):
Postmenopausal women
75
Raloxifene MOA:
1) Reduces RANKL --> reduced bone resorption | 2) Bone agonist, breast and endometrium antagonist (no hyperplasia, so progestin is not needed)
76
What are 2 benefits associated with Raloxifene?
1) Increased BMD --> Reduced incidence of spine fractures | 2) Reduced risk of invasive breast cancer in postmenopausal women
77
What are 3 AEs associated with Raloxifene?
1) Increased risk of DVT/PE (higher risk in first 4 months of tx) 2) Hot flashes 3) Leg cramps/muscle spasms

Pharmacology (9 decks)

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