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Pharm Exam 3 > Exam 3: L26 Osteoporosis > Flashcards

Exam 3: L26 Osteoporosis Flashcards

1
Q

What are the major cell types involved in bone remodeling?

A

Osteoblasts, Osteoclasts, Osteocytes

Osteoblasts form and deposit bone, osteoclasts break down and resorb bone, and osteocytes signal the activity of both.

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2
Q

How do osteoblasts regulate osteoclast function?

A

By releasing RANK Ligand (RANKL) and interleukin-6 (IL-6)

RANKL stimulates osteoclast differentiation and activity, while osteoprotegerin (OPG) limits RANKL’s effects.

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3
Q

What is the definition of osteoporosis?

A

A bone disease where the amount of bone is decreased and structural integrity of trabecular bone is impaired

Osteoporosis results in weaker bones that are more likely to fracture.

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4
Q

What are the major hormones regulating bone remodeling?

A

Parathyroid Hormone (PTH), Vitamin D, Calcitonin, Estrogen

These hormones influence bone resorption and formation.

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5
Q

What is the main reason most osteoporosis drugs target resorption?

A

Because human bone remodeling is resorption dominant

It takes longer to fill resorption pits than to create them.

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6
Q

What role does estrogen play in the treatment of postmenopausal osteoporosis?

A

Increases osteoblast’s production of OPG and causes apoptosis of osteoclasts

This reduces osteoclast differentiation and activity, hence protecting bone density.

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7
Q

Which drugs have anabolic actions on bone?

A

Teriparatide, Abaloparatide, rhPTH (1-84)

These drugs stimulate bone formation.

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8
Q

What are the primary therapeutic agents for treating osteoporosis?

A

Calcium, Vitamin D, Hormones, Denosumab, Romosozumab, Bisphosphonates, Cinacalcet

Each category has specific drugs with unique mechanisms of action.

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9
Q

What is the mechanism of action of calcium in osteoporosis treatment?

A

Inhibition of PTH secretion and altering bone mineral properties

Adequate calcium is necessary for optimal bone health.

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10
Q

What are the three primary forms of Vitamin D?

A

Cholecalciferol (D3), Ergocalciferol (D2), Calcitriol

Calcitriol is the most active form of Vitamin D.

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11
Q

How does Vitamin D affect calcium levels in the body?

A

Increases intestinal absorption, decreases renal excretion

It works in conjunction with PTH to regulate calcium levels.

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12
Q

What are the adverse effects of calcium supplements?

A

Can inhibit iron absorption, affect thyroid medication absorption

It is important to space out the intake of calcium and iron.

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13
Q

What is the mechanism of action of calcitonin?

A

Inhibits bone resorption by osteoclasts

It antagonizes the actions of parathyroid hormone.

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14
Q

What are the indications for teriparatide and abaloparatide?

A

Treatment of osteoporosis by stimulating bone formation

These drugs are not recommended for cumulative use beyond 2 years.

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15
Q

What is the significance of RANK Ligand in bone remodeling?

A

Stimulates osteoclast differentiation and activity

It is a critical factor released by osteoblasts.

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16
Q

What indicates severe osteoporosis?

A

Osteoporosis with a fracture

It signifies a significant decrease in bone density and structural integrity.

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17
Q

What are the risk factors for developing osteoporosis?

A

Post-menopausal status, long-term glucocorticoid use, thyrotoxicosis, alcoholism, malabsorption syndrome

These factors can contribute to decreased bone density.

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18
Q

What is the role of sclerostin in bone remodeling?

A

Inhibits the WNT signaling pathway, reducing osteoblast activity

This leads to a shift toward bone resorption.

19
Q

What is the recommended daily intake of elemental calcium for adults?

A

1,000 to 1,500 mg/day

This includes both dietary sources and supplements.

20
Q

True or False: Osteopenia is always a bad condition that requires treatment.

A

False

Osteopenia can be part of the normal remodeling cycle and does not always require osteoporosis drugs.

21
Q

What is the primary effect of estrogen on bone density?

A

Increases bone mineral density (BMD) and strength

This is achieved through various mechanisms including reducing osteoclast activity.

22
Q

What is the affinity of PTH (1-34, aka teriparatide) for the RG conformation?

A

12X affinity

This refers to the increased activity of teriparatide when administered via daily injections.

23
Q

How does PTHrP (1-34, aka abaloparatide) compare in affinity to PTH (1-34) for the RG conformation?

A

1600X affinity

This indicates a significantly greater affinity for the RG conformation than the R0 conformation.

24
Q

Which conformation does rhPTH (1-84) tend to bind more stably?

A

R0 conformation

rhPTH (1-84) binds to both conformations but is more stable with R0.

25
Q

What are the therapeutic effects of PTHR1-RG activation?

A
  • Reduce bone turnover
  • Stimulate the formation of new bone
  • Increase bone mass
  • Increase skeletal mass and number of osteoblasts and osteoclasts
  • Increase bone strength
  • Reduce incidence of new vertebral and nonvertebral fractures

These effects are significant for osteoporosis treatment.

26
Q

What is a primary indication for the use of PTHR1-R0 activation with rhPTH (1-84)?

A

Treatment of hypoparathyroidism

This is given twice a day and is for patients not controlled with calcium and vitamin D supplements.

27
Q

What is the pharmacokinetics of teriparatide when injected subcutaneously?

A
  • Serum concentration peaks 30 minutes after administration
  • Effects are gone within 3 hours

This allows for intermittent effects on the PTH receptor.

28
Q

What are some common adverse effects associated with PTH treatments?

A
  • Increases serum calcium
  • Decreases serum phosphorous
  • Hypercalcemia
  • Hypercalciuria
  • Injection site reactions
  • Dizziness
  • Nausea
  • Headache
  • Arthralgia
  • Leg muscle cramps

Abaloparatide can also lead to hyperuricemia.

29
Q

What is the black box warning for PTH treatments?

A

Osteosarcoma

Increased incidence observed in rats, but no evidence in over 300,000 human trials.

30
Q

What is Denosumab (Prolia®) used for?

A

Treatment of osteoporosis in postmenopausal women and men at high risk for fractures

It is an alternative first-line treatment for those unable to tolerate bisphosphonates.

31
Q

What is the mechanism of action for Denosumab?

A

Inhibits bone resorption by blocking RANK-Ligand

RANK-Ligand is necessary for the formation of mature osteoclasts.

32
Q

What are the pharmacokinetics of Denosumab?

A

Subcutaneous injection, once every 6 months

There is no limit to the duration of Denosumab treatment.

33
Q

What are some adverse effects of Denosumab?

A
  • Hypocalcemia (2%)
  • Risk of severe hypocalcemia in advanced CKD
  • Serious cellulitis (0.4%)
  • Eczema (10%)
  • Bone and back pain
  • Atypical fractures
  • Osteonecrosis of the jaw (2% in high doses)

This side effect was not observed in osteoporosis studies.

34
Q

What are the absolute contraindications for Denosumab?

A
  • Hypocalcemia
  • Pregnancy

Denosumab is teratogenic.

35
Q

What is Romosozumab (Evenity®) indicated for?

A

Osteoporosis treatment in postmenopausal women at high risk for fractures

It is used for up to one year or 12 doses.

36
Q

What is the mechanism of action of Romosozumab?

A

Humanized monoclonal antibody against sclerostin

This increases bone formation and decreases bone resorption.

37
Q

What are the common adverse effects of Romosozumab?

A
  • Arthralgia
  • Headache
  • Serious cardiovascular events

These should be monitored during treatment.

38
Q

What are the FDA-approved bisphosphonates for osteoporosis?

A
  • Alendronate (Fosamax®)
  • Risedronate (Actonel®)
  • Ibandronate (Boniva®)
  • Zoledronic Acid (Zometa®, Reclast®)

These drugs are analogs of pyrophosphate.

39
Q

What is the mechanism of action of bisphosphonates?

A

Inhibits osteoclast activity and bone resorption

They bind to calcium salts, blocking hydroxyapatite formation.

40
Q

What are some adverse effects associated with oral bisphosphonate administration?

A
  • Abdominal pain
  • Heartburn
  • Upper GI irritation
  • Esophageal ulceration
  • Constipation
  • Diarrhea
  • Flatulence

Patients must remain upright for 30-60 minutes to reduce GI irritation.

41
Q

What should patients not take with oral bisphosphonates?

A

Calcium

Calcium inhibits the absorption of the medication.

42
Q

What is the mechanism of action for Cinacalcet (Sensipar®)?

A

Oral calcimimetic drug that binds to the calcium sensing receptor

This blocks PTH release.

43
Q

What are the adverse effects of Cinacalcet?

A
  • Nausea
  • Vomiting
  • Anorexia
  • Constipation
  • Dehydration
  • Hypocalcemia
  • Hypercalcemia
  • Asthenia
  • Bone fractures

Hypocalcemia occurs in 66-80% of cases.

Pharm Exam 3 (4 decks)

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