Agents affecting bone mineral homeostasis

Question 1

Ca is controlled by 3 calcitropic hormones. What are they?

Answer 1

PTH, calcitonin, calcitriol (active Vd)

Question 2

What are the 3 major sites of action for blood calcium regulation?

Answer 2

Bone, GI tract, Kidneys

Question 3

What are the 3 major actions of PTH?

Answer 3

increase bone resorption, increase kidney reabsorption, increase active form of VD

Question 4

PTH is released when concentration of Ca is _____ in the blood.

Answer 4

low

Question 5

Activation of calcium sensor has what 2 main transducing effect?

Answer 5

Activation of Phospholipase C and inhibition of adenylyl cyclase

Question 6

Where are PTH and Calcitonin secreting cells found?

Answer 6

parathyroid, and parafollicular cells in thyroid

Question 7

Other than pT and thyroid, where else is the calcium sensor expressed?

Answer 7

kidney, osteoblasts, hematopoietic cells, Gi mucosa

Question 8

Calcitonin functions to _____ plasma Ca.

Answer 8

decrease

Question 9

3 major actions of calcitonin

Answer 9

decrease bone resorption, decrease kidney resorption, decrease active form of vitamin D.

Question 10

In general, calcitonin _____ PTH actions.

Answer 10

opposes

Question 11

Calcitriol acts to ____ plasma Ca.

Answer 11

increase

Question 12

Where is calcitriol synthesized

Answer 12

skin and blood

Question 13

What are the most important physiological actions of calcitriol?

Answer 13

increase calcium uptake from GI, increase kidney reabsoprtion, increase bone reabsoprtion

Question 14

What can cause loss of Ca homeostasis?

Answer 14

estrogen deficiency, GC excess, GH deficiency, insulin deficiency, primary hypoparathydoidism, cancer

Question 15

Response to low Ca

Answer 15

detected by PT–> release of PTH–> increase absorption at kidney, increased synthesis of calcitriol, increased resoprtion of bone, more calcitriol results in increased GI absorption

Question 16

Response to high Ca

Answer 16

Detected by parafollicular cells causing release of calcitonin–> decreased synthesis of PTH, decreased resoprtion of bone, shift to inactive VD, decreased PTH causes increase excretion of calcium

Question 17

PTH MOA

Answer 17

binds plasma membrane receptor, activates adenylyl cyclase, increase cAMP–> activates PK–> increased urine cAMP

Question 18

What is the treatment for hypoparathyroidism?

Answer 18

bioengineered PTH, injectible daily form

Question 19

MOA of teriparatide

Answer 19

HRpth1-34 directly stimulates bone formation without stimulating resorption. IMportant for women after bisphosphonate, may stimulate IGF-1

Question 20

Uses of raloxifene

Answer 20

first SERM to be approved for osteoporosis. Has beneficial effects of estrogen without stimulating breast cancer.

Question 21

____ is a monoclonal antibody to RANKK

Answer 21

denosumab

Question 22

MOA of denosumab

Answer 22

blocks stimulation of osteocyte formation by RANKL and decreases osteoporosis. Increases bone mass in pt with breast or prostate cancer

Question 23

What does FGF23 do?

Answer 23

inhibits formation of VD, opposes PTH in the kidney, produced by osteoblasts and clasts

Question 24

MOA of calcitonin

Answer 24

binds to plasma membrane receptor, decreases ruffled border surface area on osteoclasts, not a global inhibitor of PTH, has direct renal effects

Question 25

What is calcitonin used in tx for?

Answer 25

Hypercalcemia- short term treatment, effective for short term tx, antibodies may develop
Pagets
Osteoporosis

Question 26

Calcitriol MOA

Answer 26

stimulates Ca and phosphate absoprtion in small intestine, induces synthesis of calbindin, binds to transcription factor to increase mRNA, protein synthesis, has additional effects to increase uptake of Ca from intestine

Question 27

Major uses of calcitriol in therapeutics

Answer 27

prophylaxis and cure of nutritional rickets, treatment of metabolic rickets and osteomalacia, treatment of hypoparathyroidism, prevention and treatment of osteoporosis

Question 28

Analogs of calcitriol

Answer 28

calcipotriol, dihydrotachysterol, paricalcitol, 22-oxacalcitriol

Question 29

Uses of calcipotriol

Answer 29

used in psoriasis

Question 30

What does paricalcitol do to PTH secretion? oxacalcitriol?

Answer 30

Both reduce

Question 31

What are bisphosphonates?

Answer 31

nonhydrolyzable analogs of inorganic pyrophosphate, inhibitors of bone resoprtion

Question 32

Which bisphosphonates are used in Pagets?

Answer 32

alendronate, risedronate

Question 33

What are bisphosphonates used for? Which are not effective orally in the management of hypercalciemia?

Answer 33

first used in pagets, effective in osteoporosis, etidronate, pamidronate

Question 34

Which bisphosphonates are used in osteoporosis?

Answer 34

alendronate

Question 35

What are the 2 3rd generation bisphosphonates?

Answer 35

risedronate, zoledronate (super potent)

Question 36

Describe absorption of bisphosphonates

Answer 36

all are poorly absorbed from intestine. Must be taken after overnight fast with full glass of water and no food for 30 minutes

Question 37

ADE of bisphosphonate

Answer 37

osteonecrosis of jaw- exposed bone under teeth, swelling and lose of teeth, may follow dental extraction, more common with 3rd generation drugs

Question 38

What does gc do to Ca uptake in intestine

Answer 38

antagonize

Question 39

Is estrogen effective in preventing osteoporosis

Answer 39

yes

Question 40

MOA of cinacalcet

Answer 40

calcimimetic that binds allosterically to CaSR and allows PTH suppression at lower Ca. Lowers PTH.

Question 41

Therapeutic use of cinacalcet

Answer 41

hyperparathyroidism in pt with parathyroid carcinoma

Question 42

Describe the use of fluoride

Answer 42

long used in cavity prevention, binds calcium and can be used to prevent clotting, potential agent in preventing osteoporosis. ADE: osteosclerosis, mottled enamel

Question 43

What are the 2 second generation bisphosphonates?

Answer 43

alendronate, ibandronate

Question 44

Role of prednisone in calcium therapuetics

Answer 44

Tx of hypercalcemia