Exam 3: L26 Osteoporosis

Question 1

What are the major cell types involved in bone remodeling?

Answer 1

Osteoblasts, Osteoclasts, Osteocytes

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

Question 2

How do osteoblasts regulate osteoclast function?

Answer 2

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

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

Question 3

What is the definition of osteoporosis?

Answer 3

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.

Question 4

What are the major hormones regulating bone remodeling?

Answer 4

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

These hormones influence bone resorption and formation.

Question 5

What is the main reason most osteoporosis drugs target resorption?

Answer 5

Because human bone remodeling is resorption dominant

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

Question 6

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

Answer 6

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

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

Question 7

Which drugs have anabolic actions on bone?

Answer 7

Teriparatide, Abaloparatide, rhPTH (1-84)

These drugs stimulate bone formation.

Question 8

What are the primary therapeutic agents for treating osteoporosis?

Answer 8

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

Each category has specific drugs with unique mechanisms of action.

Question 9

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

Answer 9

Inhibition of PTH secretion and altering bone mineral properties

Adequate calcium is necessary for optimal bone health.

Question 10

What are the three primary forms of Vitamin D?

Answer 10

Cholecalciferol (D3), Ergocalciferol (D2), Calcitriol

Calcitriol is the most active form of Vitamin D.

Question 11

How does Vitamin D affect calcium levels in the body?

Answer 11

Increases intestinal absorption, decreases renal excretion

It works in conjunction with PTH to regulate calcium levels.

Question 12

What are the adverse effects of calcium supplements?

Answer 12

Can inhibit iron absorption, affect thyroid medication absorption

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

Question 13

What is the mechanism of action of calcitonin?

Answer 13

Inhibits bone resorption by osteoclasts

It antagonizes the actions of parathyroid hormone.

Question 14

What are the indications for teriparatide and abaloparatide?

Answer 14

Treatment of osteoporosis by stimulating bone formation

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

Question 15

What is the significance of RANK Ligand in bone remodeling?

Answer 15

Stimulates osteoclast differentiation and activity

It is a critical factor released by osteoblasts.

Question 16

What indicates severe osteoporosis?

Answer 16

Osteoporosis with a fracture

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

Question 17

What are the risk factors for developing osteoporosis?

Answer 17

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

These factors can contribute to decreased bone density.

Question 18

What is the role of sclerostin in bone remodeling?

Answer 18

Inhibits the WNT signaling pathway, reducing osteoblast activity

This leads to a shift toward bone resorption.

Question 19

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

Answer 19

1,000 to 1,500 mg/day

This includes both dietary sources and supplements.

Question 20

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

Answer 20

False

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

Question 21

What is the primary effect of estrogen on bone density?

Answer 21

Increases bone mineral density (BMD) and strength

This is achieved through various mechanisms including reducing osteoclast activity.

Question 22

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

Answer 22

12X affinity

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

Question 23

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

Answer 23

1600X affinity

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

Question 24

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

Answer 24

R0 conformation

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

Question 25

What are the therapeutic effects of PTHR1-RG activation?

Answer 25

* 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 ## Footnote These effects are significant for osteoporosis treatment.

Question 26

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

Answer 26

Treatment of hypoparathyroidism ## Footnote This is given twice a day and is for patients not controlled with calcium and vitamin D supplements.

Question 27

What is the pharmacokinetics of teriparatide when injected subcutaneously?

Answer 27

* Serum concentration peaks 30 minutes after administration * Effects are gone within 3 hours ## Footnote This allows for intermittent effects on the PTH receptor.

Question 28

What are some common adverse effects associated with PTH treatments?

Answer 28

* Increases serum calcium * Decreases serum phosphorous * Hypercalcemia * Hypercalciuria * Injection site reactions * Dizziness * Nausea * Headache * Arthralgia * Leg muscle cramps ## Footnote Abaloparatide can also lead to hyperuricemia.

Question 29

What is the black box warning for PTH treatments?

Answer 29

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

Question 30

What is Denosumab (Prolia®) used for?

Answer 30

Treatment of osteoporosis in postmenopausal women and men at high risk for fractures ## Footnote It is an alternative first-line treatment for those unable to tolerate bisphosphonates.

Question 31

What is the mechanism of action for Denosumab?

Answer 31

Inhibits bone resorption by blocking RANK-Ligand ## Footnote RANK-Ligand is necessary for the formation of mature osteoclasts.

Question 32

What are the pharmacokinetics of Denosumab?

Answer 32

Subcutaneous injection, once every 6 months ## Footnote There is no limit to the duration of Denosumab treatment.

Question 33

What are some adverse effects of Denosumab?

Answer 33

* 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) ## Footnote This side effect was not observed in osteoporosis studies.

Question 34

What are the absolute contraindications for Denosumab?

Answer 34

* Hypocalcemia * Pregnancy ## Footnote Denosumab is teratogenic.

Question 35

What is Romosozumab (Evenity®) indicated for?

Answer 35

Osteoporosis treatment in postmenopausal women at high risk for fractures ## Footnote It is used for up to one year or 12 doses.

Question 36

What is the mechanism of action of Romosozumab?

Answer 36

Humanized monoclonal antibody against sclerostin ## Footnote This increases bone formation and decreases bone resorption.

Question 37

What are the common adverse effects of Romosozumab?

Answer 37

* Arthralgia * Headache * Serious cardiovascular events ## Footnote These should be monitored during treatment.

Question 38

What are the FDA-approved bisphosphonates for osteoporosis?

Answer 38

* Alendronate (Fosamax®) * Risedronate (Actonel®) * Ibandronate (Boniva®) * Zoledronic Acid (Zometa®, Reclast®) ## Footnote These drugs are analogs of pyrophosphate.

Question 39

What is the mechanism of action of bisphosphonates?

Answer 39

Inhibits osteoclast activity and bone resorption ## Footnote They bind to calcium salts, blocking hydroxyapatite formation.

Question 40

What are some adverse effects associated with oral bisphosphonate administration?

Answer 40

* Abdominal pain * Heartburn * Upper GI irritation * Esophageal ulceration * Constipation * Diarrhea * Flatulence ## Footnote Patients must remain upright for 30-60 minutes to reduce GI irritation.

Question 41

What should patients not take with oral bisphosphonates?

Answer 41

Calcium ## Footnote Calcium inhibits the absorption of the medication.

Question 42

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

Answer 42

Oral calcimimetic drug that binds to the calcium sensing receptor ## Footnote This blocks PTH release.

Question 43

What are the adverse effects of Cinacalcet?

Answer 43

* Nausea * Vomiting * Anorexia * Constipation * Dehydration * Hypocalcemia * Hypercalcemia * Asthenia * Bone fractures ## Footnote Hypocalcemia occurs in 66-80% of cases.