Bone Mineral Drugs

Question 1

Where does most intracellular calcium exist?

Answer 1

mostly in mitochondria and the ER. Intracellular calcium tends to fluctuate greatly, but always less than 1uM

Question 2

How does most bone calcium exist?

Answer 2

99% is in mineral phase and the rest is in a pool that can rapidly exchange with extracellular calcium

Question 3

Where else is calcitonin secreted besides the thyroid C cells?

Answer 3

lung and intestinal tract

Question 4

How does PTH act at a molecular level?

Answer 4

Binds to a pasma membrane receptor and acts through Gs proteins to inrease cAMP and PKA (thus, urinary cAMP is a test for PTH)

Question 5

What are the pharm treatments for hypoparathyroidism?

Answer 5

hPTH is available has a short half-life (peptide) so it is more commonly treated with VitD, with or without dietary calcium supplements

Question 6

What are some hPTH hormones?

Answer 6

Teriparatide (1-34) (forteo)

Full length PTH (1-84)

Question 7

Describe the uses of Teriparatide?

Answer 7

stimulates bone formation at low doses (important for women with osteoporosis after bisphosphonate therapy). May stimulate IGF-1

Question 8

What is the use of Raloxifene (Evista)?

Answer 8

A selective estrogen receptor modulator approved for osteoporosis that has beneficial effects of estrogen without stimulating breast cancer

Question 9

What is Denosumab (Prolifa, Xgeva)?

Answer 9

A monoclonal Ab to RANKL on osteoblasts (60mg dose per 6 month) that blocks stimulation of osteoclast formation for osteoporosis treatment.

Can be used to increase bone mass in pts with breast or prostate cancer

Question 10

What are the roles of FGF23?

Answer 10

inhibits production of vitD and thus opposes PTH at the kidneys (produced by osteoblasts and osteoclasts)

Question 11

How does calcitonin work?

Answer 11

binds to plasma membrane receptors and decreases the ruffled border surface area on osteoclasts. Not a global inhibitor of PTH

Question 12

How is hypercalcemia treated in the short-term?

Answer 12

calcitonin (Calcimar and Miacalcin from salmon (pore potent)) great for short-term (Ab development occurs with long-term use even with hCT)

prednisone can also be used (takes 1-2 weeks) and shouldnt be taken for very long

Question 13

Other uses of calcitonin?

Answer 13

Paget’s disease

osteoporosis (injection and nasal spray)

Question 14

What are the uses of calcitriol in therapeutics?

Answer 14

• prophylaxis and cure of dietary rickets
• treatment of metabolic rickets and osteomalacia
• Tx of hypoparathyroidism
• prevention and Tx of osteoporosis

Question 15

What is Calcipotriol (an anlog of Calcitriol) used for?

Answer 15

Tx of psoriasis (topical Dovonex)-more effective than glucocorticoids

Question 16

What are bisphosphonates?

Answer 16

non-hydrolyzable analogs of inorganic pyrophosphate that inhibit bone resorption for treatment of things like Paget’s disease and osteoporosis

Question 17

What are the bisphosphonates used in Paget’s Tx?

Answer 17

Etidronate (Didronel),- first gen

alendronate (Fosamax) -second gen, and

risedronate (Actonel)- third gen

Question 18

What bisphosphonate is used for osteoporosis tx?

Answer 18

alendronate

Question 19

T or F. All bisphosphonates are very poorly absorbed from the Gi

Answer 19

T. Must be taken after an overnight with a full glass of water. No food for 30 min

Question 20

Other second gen bisphosphonates?

Answer 20

alendronate (Fosamax), panidronate (Aredia), and ibandronate (Boniva)

10-100x more potent

Question 21

Other third gen bisphosphonates?

1000-10000x more potent

Answer 21

risedronate (Actonel) and zoledronate (Zometa)

Question 22

AEs of bisphosphonates?

Answer 22

• osteonecrosis of the jaw (swelling and loosening of the teeth is often seen). Surgical correction makes elsions worse and 80% of cases follow dental extraction
• esophagitis

Much more common with 3rd gen drugs

Question 23

Osteonecrosis of the jaw

Answer 23

many cases are complicated by infection and occur mainly in pts. with cancer after prolonged therapy

Question 24

_______ are a common drug cause of osteoporosis in adults

Answer 24

Glucosteroids (by antagonizing Ca uptake in the intestine)

Question 25

Clinical utility of glucocorticoids?

Answer 25

useful in reversing lymphoma-induced hypercalcemia

Question 26

What bone issues can estrogen be used to treat? AEs?

Answer 26

effective in preventing osteoporosis (replacement therapy trials do increase risk of thrombosis though especially in women that smoke!!)

Question 27

Bisphosphonates in metastatic disease treatment

Answer 27

There is evidence to suggest utility of using bisphosphonates as the standard of care for pts. with bone mets from breast and prostate cancer. These pts. receive IV bisphosphonate therapy from the time of diagnosis (most commonly Zometa or Aredia)

The use of bisphosphonates shows a decrease in skeleal complications by up to 1/3rd.

Question 28

What are calcimimetics?

Answer 28

mimic binding to CaSRs

Cinacalcet (Sensipar) approved for hyperparathyroidism with parathyroid carcinoma

Question 29

What is Plicamycin (mithracin)?

Answer 29

ABX used for Paget’s disease and hypercalcemia for many years (now seldom used)

Question 30

What is Strontium ranelate?

Answer 30

Drug commonly used to Europe for osteoporosis that blocks differentiation of osteoclasts and promotes apoptosis, while also promoting bone formation and increasing bone mineral density.

Question 31

What is Fluoride used for?

Answer 31

dental caries prevention because it binds calcium (can also be used to prevent blood clotting) and can also be used to prevent osteoporosis

Question 32

AEs of Fluoride?

Answer 32

osteosclerosis (hyodrxyapatite is repalced by fluoroapatite)

mottled enamal (Fluorosis)

NO cancer risk

Question 33

Answer 33

Question 34