Osteoporosis Drug Treatment

Question 1

Osteoporosis drug classes:

Answer 1

PTH
Vitamin D analogs
Calcium
Bisphosphonates
Calcitonin
Selective estrogen receptor modulators
Thiazide diuretics
RANK-L inhibitors
Calcimimetics

Question 2

Osteoprotegerin affect?

Answer 2

Decreased osteoclastic activity

Question 3

What is a parathyroid hormone drug?

Answer 3

Teriparatide

Question 4

What does teriparatide do?

Answer 4

Makes structurally-normal new bone by binding PTH receptor

Question 5

Administration of teriparatide:

Answer 5

Sub Q once daily for up to two years to prevent bone fractures

Question 6

What are the fat soluble forms of vitamin D?

Answer 6

D2: Ergocalciferol
D3: Cholecalciferol

Question 7

Affect of PTH on vitamin D?

Answer 7

Stimulated 1,25-OH vitamin D3 formation

Question 8

Affect of FGF 23 on vitamin D?

Answer 8

Inhibits 1,25-OH vitamin D3 formation and increase renal phosphate excretion

Question 9

Vitamin D preparations:

Answer 9

Cholecalciferol (D3)
Ergocalciferol (D2)
Calcitriol (1,25-OH vitamin D3)
Paricalcitol (1,25-OH vitamin D2)

Question 10

When is the active for of vitamin D preparations (calcitriol and paricalcitol) needed?

Answer 10

When renal pathology is present

Question 11

Calcium preparations:

Answer 11

Calcium carbonate

Question 12

What is the treatment for osteoporosis?

Answer 12

Calcium + Vitamin D3 supplementation (each has mixed results when used alone)

Question 13

Bisphosphonates:

Answer 13

Alendronate

Etidronate

Question 14

Mechanism of bisphosphonates?

Answer 14

Non-hydrolysable analogs of pyrophosphates normally present in bone; reduce osteoclastic dissolution of hydroxyapatite in bone; no affect on osteoblasts

Question 15

Risk factors for bisphosphonates:

Answer 15

Osteonecrosis of jaw with dental procedures
Sickle cell disease
Radiation/chemotherapy
Local ischemia

Question 16

Mechanism of action for selective estrogen receptor modulators?

Answer 16

Binds both alpha and beta receptors in bone

Question 17

Where are alpha estrogen receptors (ERalpha) in bone found?

Answer 17

Cortical bone

Question 18

Where are beta estrogen receptors (ERbeta) in bone found?

Answer 18

Trabecular bone

Question 19

What specifically does estrogen cause in bones?

Answer 19

Decreased response of RANK-L receptor to RANK-L
Reduction of IL-6, TNF-alpha, and M-CSF
Stimulation of osteoprotegerin

Question 20

Net effect of estrogen:

Answer 20

Decreased osteoclast activation

Osteoblasts left unopposed

Question 21

What is a selective estrogen receptor agonist?

Answer 21

Raloxifene

Question 22

Raloxifene affect on estrogen receptors?

Answer 22

ERalpha: partial agonist
ERbeta: antagonist

Question 23

What does short-term administration of calcitonin cause?

Answer 23

Inhibits osteoclastic bone activity

Question 24

What does long-term administration of calcitonin cause?

Answer 24

Inhibits both osteoblastic and osteoclastic activity (rarely used)

Question 25

What do thiazide diuretics lead to?

Answer 25

Decrease in calcium excretion in the urine

Question 26

What channel do thiazide diuretics affect?

Answer 26

Inhibit NCC leading to decreased Na+ reabsorption

Question 27

What does inhibition of NCC lead to?

Answer 27

Decreased Na+ concentration in epithelial cells leading to increased basolateral Ca/Na antiporter leading to decreased Ca intracellularly driving the Ca reabsorption via apical membrane TRPV5

Question 28

What is a RANK-L inhibitor?

Answer 28

Denosumab

Question 29

What does binding to RANK cause?

Answer 29

Activation of nuclear factor kappa-B

Question 30

What is osteoprotegrin?

Answer 30

A soluble receptor for RANK-L released to bind and inactivate RANK-L

Question 31

What is Denosumab?

Answer 31

A monoclonal antibody against RANK-L

Question 32

How does Denosumab work?

Answer 32

Binds RANK-L to inactivate it therefore inhibiting osteoclastic activity

Question 33

Risks of Denosumab?

Answer 33

1. ) Mandibular necrosis with dental work | 2. ) Hip fractures

Question 34

What drug is a Calcimimetic?

Answer 34

Cinacalcet

Question 35

How does Cinacalcet work?

Answer 35

Allosteric activator of calcium sensing receptor (in PT gland)

Question 36

What does Cinacalcet cause?

Answer 36

PTH secretion inhibition

Question 37

What is Cinacalcet used for?

Answer 37

Hyperparathyroidism resulting from: 1. ) Chronic kidney disease 2. ) Parathyroid carcinoma

Question 38

What are the side effects of Cinacalcet?

Answer 38

Cardiac arrhythmia | Heart failure