Agents for Bone Mineral Homeostasis

Question 1

What are the actions of Calcitriol?

Answer 1

1) Increased Serum Ca

2) Increased Serum Phos

Question 2

What is calcitriol and how is it made?

Answer 2

It is active vitamin D3 and it it synthesized in skin and blood, activated in liver, then kidney (25 then 1)

Question 3

How does Calcitriol increase Serum Ca?

Answer 3

Increases duodenal absorption of Ca (increased calbindin), increases renal reabsorption of Ca, and increases bone resorption

Question 4

How are the PTH analogs mediated?

Answer 4

Gs mediated (activations of adenylyl cyclase to increase cAMP and the cAMP can be measured in urine to determine parathyroid function)
Used in hypoparathyroidism; but it is more commonly treated with Vit D3 +- Ca supplements

Question 5

What is Teriparatide? (specific)

Answer 5

It is a PTH analog; hrPTH 1-34 aa

Question 6

What is the MOA of Teriparatide?

Answer 6

It stimulates bone formation directly because low doses of PTH activate osteoblasts without activating osteoclasts; may stimulate IGF-1

Question 7

What is Teriparatide important in?

Answer 7

In women post bisphosphonate treatment

Question 8

What is the MOA of Raloxifene?

Answer 8

Selective Estrogen Receptor Modulator (SERM); It inhibits osteoclasts without causing breast cancer

Question 9

What is Raloxifene used for?

Answer 9

Osteoporosis

Question 10

What is the MOA of Denosumab?

Answer 10

it is an mAB to RANKL that blocks osteoclast activation by RANKL

Question 11

What is Denosumab used for?

Answer 11

Decrease osteoporosis and increase bone mass in patients with breast/prostate cancer; Biannual dose administration

Question 12

What is the most important calcium regulating hormone and for therapeutics?

Answer 12

Calcitriol

Question 13

What is Calcitriol used for?

Answer 13

Prophylaxis/Cure of rickets and osteomalacia; Treatment for hypoparathyroidism; Treatment for osteoporosis

Question 14

What is a Calcipotriol and what is it used for?

Answer 14

Synthetic Calcitriol; Used for psoriasis and is more effective than glucocorticoids

Question 15

What are bisphosphonates?

Answer 15

They are non-hydrolyzable analog of pyrophosphates that inhibit bone resorption. They are used in Paget’s and effective in osteoporosis.

Question 16

Describe the absorption and administration of bisphosphonates?

Answer 16

Poorly absorbed in gut and taken after overnight fast w/ water and no food for 30 minutes, there is a weekly dose form, and effective if given IV 4-24 infusion at lowering serum Ca for several weeks

Question 17

What is the big ADE of ALL of the Bisphosphonates?

Answer 17

Osteonecrosis of the Jaw! It is jaw bone exposure, swelling/loosening of teeth and dentists make it worse (80% follow dental work), it is complicated by infection and usually seen with 3rd generation drugs for cancer patients

Question 18

What is beneficial about bisphosphonates when used in cancer patients?

Answer 18

They can prevent bone loss due to chemotherapy, recommended w/ bone mets, breast, and prostate dx; use shows a 1/3rd decrease in skeletal complications

Question 19

What are Alendronate and Ibandronate?

Answer 19

The 2nd generation Bisphosphonates (10-100x more potent than 1st gen)

Question 20

What disease is Alendronate specifically indicated for?

Answer 20

Paget’s

Question 21

What are Risendronate and Zoledronate?

Answer 21

The 3rd generation Bisphosphonates (1k-10kx potent than 1st gen) Used in cancer patients with bone mets, given IV and may only need one dose

Question 22

What disease is Risendronate specifically indicated for?

Answer 22

Paget’s

Question 23

What is the MOA of Cincacalcet?

Answer 23

It allosterically binds to Ca sensing receptor and allows PTH suppression at lower blood Ca levels which will lower the circulating PTH

Question 24

What is Cincacalcet approved to be used in?

Answer 24

Hyperparathyroidism from parathyroid carcinoma

Question 25

What is Fluoride?

Answer 25

It is used to prevent cavities by binding calcium; it will mottle the enamel but prevent decay, it can prevent clotting, may prevent osteoporosis but toxicity can cause osteosclerosis