Osteoporosis Drugs

Question 1

What is osteoporosis?

Answer 1

a condition of skeletal fragility characterized by reduced bone mass and microarchitectual deterioration

Question 2

What are the disease-related causes (3)?

Answer 2

hypogonadism (menopause, aging), hyperparathyroidism, hyperthyroidism

Question 3

What are the drug-induced causes (4)?

Answer 3

1) glucocorticoids (3rd leading cause overall)
2) thryroid replacements
3) GnRH agonist/antagonist suppression of gonadal steroid synthesis (prostate cancer, uterine cancer, endometriosis, breast cancer)
4) aromatase inhibitors (breast cancer)

Question 4

What mediates resorption?

Answer 4

osteoclasts

Question 5

What mediates reformation?

Answer 5

osteoblasts (secrete new matrix)

Question 6

Once the new matrix is formed, what happens?

Answer 6

calcification of matrix

Question 7

Osteoblast precursor + stress/circulating hormones = ____

Answer 7

RANKL

Question 8

RANKL-> ____ -> _____

Answer 8

RANK, osteoclast precursor

Question 9

An osteoblast precursor can become which two things?

Answer 9

a mature osteoclast (via RANKL) OR mature osteoblast

Question 10

What can also mediate the formation of an osteoblast from an osteoblast precursor (and not an osteoclast)?

Answer 10

secreted factors from mature osteoclasts

Question 11

What are the characteristics of osteoporosis (3) and what is the net result?

Answer 11

reduced bone mass and degraded bone architecture:
1) increased osteoclast number and activation
2) decreased osteoclast apoptosis
3) increased osteoblast apoptosis
Net result: deeper, larger resorption cavities in bone

Question 12

What are the anti-resorptive agents (5)?

Answer 12

bisphosphonates, calcitonin, denosumab, estrogen, reloxifene

Question 13

What is the selective estrogen receptor modulator?

Answer 13

raloxifene

Question 14

What is the bone forming agent?

Answer 14

teriparatide

Question 15

What does Vitamin D (calcitrol) supplementation cause?

Answer 15

increased calcium absorption from small intestine = increased bone mineralization

Question 16

What is the active metabolite of Vitamin D?

Answer 16

Calcitrol

Question 17

What happens with large doses of vitamin D?

Answer 17

increased bone resorption (increased osteoclast recruitment to bone sites)

Question 18

Bisphosphonates, aka…

Answer 18

pyrophosphate analogs

Question 19

What are the three bisphosphonates and how are the taken?

Answer 19

Alendronate - oral (daily, weekly)
Ibandronate - oral (daily, monthly), i.v. (3 months)
Zoledronate - i.v. (yearly)

Question 20

What are the properties of bisphosphonates (2)?

Answer 20

1) high affinity for bone, Ca chelator, incorporates stabilized structure
2) inhibits bone resorption: decreased osteoclast function and increased apoptosis

Question 21

What are the indications/uses for bisphosphonates (3)?

Answer 21

osteoporosis due to aging, postmenopausal women, steroids

Question 22

How are bisphosphonates administered?

Answer 22

oral, <10% absorbed, water only, upright position to prevent heartburn, esophageal irritation

Question 23

Why might high doses of bisphosphonates be used and what is the risk with high doses?

Answer 23

cancer treatment- risk for osteonecrosis of jaw

Question 24

What is the main risk of Zoledronate?

Answer 24

potential for renal toxicity

Question 25

What is Calcitonin?

Answer 25

thyroid gland hypocalcemic hormone

Question 26

How does Calcitonin work?

Answer 26

decreases bone resorption: calcitonin receptor on osteoclasts: decreased resorption border surface area (physical effect)

Question 27

What are the uses of calcitonin?

Answer 27

osteoporosis (PMW, steroids), low efficacy (fracture prevention?)

Question 28

How is Calcitonin administered?

Answer 28

human, salmon calcitonin (daily injection, nasal spray). less immune response to salmon calcitonin

Question 29

What is Denosumab?

Answer 29

human monoclonal antibody

Question 30

How does Denosumab work (2)?

Answer 30

1) binds to RANKL = decreased activation of RANK | 2) decreased osteoclast formation/activation = decreased resorption, increased bone mineral density (prevents fractures)

Question 31

How is Denosumab administered?

Answer 31

s.c. injection every 6 months

Question 32

What is the adverse effect of Denosumab?

Answer 32

increased infection risk?

Question 33

What is estrogen?

Answer 33

Hormone replacement therapy

Question 34

How does estrogen work?

Answer 34

decreases bone resorption: decreased RANKL and cytokines = decreased osteoclast proliferation and activation, decreased osteoblast apoptosis

Question 35

What are the long-term risks of estrogen use in PMW (4)?

Answer 35

breast cancer, thromboembolism, stroke, CV risk

Question 36

What is the limited use of estrogen?

Answer 36

non-responders with normal CV

Question 37

What is Raloxifene?

Answer 37

selective estrogen receptor modulator

Question 38

How does Raloxifene work on estrogen receptors?

Answer 38

estrogen receptor agonist in bone, antagonist in breast and endometrium

Question 39

How does Raloxifene work?

Answer 39

decreases osteoclast formation and activation = decreased resorption, increased bone mineral density, decreased fractures in PMW.

Question 40

What is the use of Raloxifene?

Answer 40

osteoporosis in PMW with breast cancer or family history

Question 41

How is Raloxifene administered?

Answer 41

oral, daily

Question 42

What are the adverse effects of Raloxifene (2)?

Answer 42

risk for venous thrombosis, pulmonary embolism

Question 43

What is Teriparatide?

Answer 43

bone forming agent, active peptide of PTH

Question 44

What does hyperparathyroidism cause and when can Teriparatide cause this?

Answer 44

bone resorption, decreased bone mineral density. can happen with high continuous doses

Question 45

How does Teriparatide work with low, intermittent doses (2)?

Answer 45

1) low, intermittent PTH = increased bone growth | 2) increases osteoblast number and activation, increased survival = bone formation

Question 46

What is the use of Teriparatide?

Answer 46

severe osteoporosis with high fracture risk

Question 47

How is Teriparatide administered?

Answer 47

daily s.c. injection, up to 2 years

Question 48

What is the adverse effect of Teriparatide?

Answer 48

may increase risk for osteosarcoma (rats)?

Question 49

What are the drugs to know (9)?

Answer 49

Alendronate, Ibandronate, Zoledronate, Calcitonin, Densumab, Raloxifene, Estrogen, Vitamin D, Teriparatide

Question 50

Should you go look at the review questions in the lecture?

Answer 50

Uh, JAHH!

Question 51

What did one ocean say to the other ocean?

Answer 51

Nothing, they just waved.