Bone Mineral Drugs

Question 1

What is the MOA of Vitamin D and its analogs?
• side effects?

Answer 1

• *Vitamin D/Vit D analogs:**
• *MOA:** works via intracellular and extracellular Vit. D receptors to increase BOTH calcium and phosphate reabsorption in the intestines, kidney, and to increase bone turnover.

Toxicity: All predicatable - Hypercalcemia, Hyperphosphatemia, Hypercalciuria

Question 2

What forms of Vitamin D are used to treat vitamin D deficiency?
• where can these be found naturally?

Answer 2

Ricketts:
Cholecalicferol/Ergocalciferol – non-hydroxylated Vit D. for Vitamin D Deficiency

Note: Cholecalicferol is the form of Vitamin D found in fish liver oil – it can remain in your fat stores for a long time

Question 3

What types of Vitamin D are used in the treatment of Hyperparathyroidism?
• Which can also treat hyperparathyroidism?
• which of these analogs are activated?

Answer 3

• *Calcitriol** – ACTIVATED vitamin D used as tx for:
  1. Secondary Hyperparathyroidism (CKD) 2. Hypoparathyriodism as tx for hypocalcemia

Doxercalciferol (– ½ Activated Vitamin D used for Secondary Hyperparathyroidism (CKD)

Paricalcitriol – Calcitriol analog (ACTIVATED) – for Secondary Hyperparathyroidism (CKD)

22-oxacalcitriol

Question 4

What vitamin D-based drug is used in the treament of psoriasis?

Answer 4

Calcipotriene (ala Calcipotriol) – Calcitriol analog (activated>) – for Psoriasis

Question 5

What type of Vitamin D is used in the treatment of osteoporosis?

Answer 5

Osteoporosis:
Dihydrotachysterol – much less potent than Calcitriol but is more effective at high doses
***Can be given as an injection or nasal spray***

Question 6

Bisphosphonates:
• Administration**
• MOA

Answer 6

Bisphosphonates
Administration: Oral but very poorly absorbed, take with glass of H2O and do not eat or do activities for 30 min to allow for absorption and to prevent esophageal problems.

MOA: Suppression of osteoclast activity and bone resorption

Question 7

Bisphosphonates:
• Toxicity

Answer 7

Bisphosphonates

Toxicity: increases as drug strength increases (3^rd gen most toxic)
Adynamic bone
Esophageal Irritation
Osteonecrosis of the Jaw

Question 8

What are the features of osteonecrosis of the Jaw and who is at the highest risk?

Answer 8

Bisphosphonates

Clinical Features of Jaw Osteonecrosis: pain, exposed bone under teeth, inability to correct surgically, superimposed infection

Risk Factors: dental extraction (80% of cases), often in patients on chemo

(bisphosphonates are often given to prevent bone loss from cancer tx – esp BREAST and PROSTATE)

Question 9

What are the 1st generation bisphosphonates?
• compare strength to other generations

Answer 9

Strength Increases with 10-100+x with each Generation
1^st Etidronate
2^nd Pamidronate, Alendronate, Ibandronate
3^rd Risedronate, Zoledronate

Question 10

What are the 2nd generation bisphosphonates?
• how does strength change with subsequent generations?

Answer 10

Strength Increases with 10-100+x with each Generation
1^st Etidronate
2^nd Pamidronate, Alendronate, Ibandronate
3^rd Risedronate, Zoledronate

Question 11

What are the 3rd generation bisphosphonates?
• how does strength change with each additional generation?

Answer 11

Strength Increases with 10-100+x with each Generation
1^st Etidronate
2^nd Pamidronate, Alendronate, Ibandronate
3^rd Risedronate, Zoledronate

Question 12

What conditions are commonly treated with bisphosphonates?

Answer 12

• *Paget’s Treatment** = EAR (etidronate, alendronate, risedronate)
• *Osteoporosis** = Aldendronate

Question 13

What bisphosphonates are used in the treatment of Paget’s?

Answer 13

Paget’s Treatment = EAR (etidronate, alendronate, risedronate)
Osteoporosis = Aldendronate

Question 14

What bisphosphonates are used in the treatment of osteoporosis?

Answer 14

Paget’s Treatment = EAR (etidronate, alendronate, risedronate)
Osteoporosis = Aldendronate

Question 15

Compare the effect of bisphosphonates on bone in comparison to agents like Vitamin D, Sr2+, and PTH.

Answer 15

Estrogen and the Bisphonates have less of an effect on increasing bone density relative to Vitamin D, PTH, and Sr2+

**Note: any prevention of loss is really the most important thing

Question 16

What are the thyroid hormone analogs?

Answer 16

Parathyroid Hormone Analogs – Teripartide

Question 17

Teripartide:
• Administration
• MOA

Answer 17

Teripartide

Administration: SC; PTH used in osteoporosis is administered in low-intermitent doses which leads to increased bone synthesis and less degradation by altering gene expression.

MOA: Just like PTH they increase renal reabsorption of Ca2+ and reduce reabsorption of phosphate. Additionally, they act directly on osteoblasts to increase bone turnover. Finally, they induce vitamin D synthesis to increase calcium and phosphate uptake in the intestines.

Question 18

Teripartide
• Toxicity
• Indication

Answer 18

Parathyroid Hormone Analogs – Teripartide

Toxicity: Same as hyperparathyroidism: hypercalcemia, hypercalcinuria (moans, stones, bones, groans)

Indication: Hypoparathyroidism, Women with Osteoporosis following tx with bisphosphonates

Question 19

What drug works as a selective estrogen receptor blocker?

Answer 19

Selective Estrogen Receptor Modulator – Raloxifene

Question 20

Raloxifene
• Administration
• MOA

Answer 20

Selective Estrogen Receptor Modulator – Raloxifene
Administration: Oral

MOA: works on estrogen receptors without binding estrogen receptors in the breasts

Question 21

Raloxifene
• Toxicity

Answer 21

Selective Estrogen Receptor Modulator – Raloxifene

Toxicity: Hot Flashes, Thromboembolism

Question 22

What drug works by preventing differentiation of monocytes into osteoclasts?

Answer 22

Denosumab

Question 23

Denosumab
• Administration
• MOA

Answer 23

Denosumab
Administration: SC

MOA: Anti-RANKL antibody blocking the stimulation of monocytes to become osteoclasts

Question 24

Denosumab
• Toxicity
• Indication

Answer 24

Denosumab

Toxicity: Blocking RANK compromises Immune function

Indication: increases bone mass in patients with breast and prostate cancer

Question 25

What are the drug names for calcitonin?

Answer 25

Calcitonin: Calcimar, Miacalcin (from Salmon)

Question 26

Calcimar
• Administration
• MOA

Answer 26

Calcitonin: Calcimar, Miacalcin (from Salmon)

Administration: SC, Intranasal – can only be administered for a few days to weeks because antibodies are easily developed against it.

MOA: Induces synthesis of Calbindin and increases Ca2+ uptake in the duodenum,

Question 27

Calcimar
• Toxicity
• Indication

Answer 27

Calcitonin: Calcimar, Miacalcin (from Salmon)

Toxicity: Rhinitis from nose spray

Indication: Paget’s, Osteoporosis, Acute Hypercalcemia

Question 28

Miacalcin
• Administration
• MOA

Answer 28

Calcitonin: Calcimar, Miacalcin (from Salmon)

Administration: SC, Intranasal – can only be administered for a few days to weeks because antibodies are easily developed against it.

MOA: Induces synthesis of Calbindin and increases Ca2+ uptake in the duodenum,

Question 29

Miacalcin
• Toxicity
• Indication

Answer 29

Calcitonin: Calcimar, Miacalcin (from Salmon)

Toxicity: Rhinitis from nose spray

Indication: Paget’s, Osteoporosis, Acute Hypercalcemia

Question 30

What is the use of glucocorticoids in bone health?

Answer 30

Glucocorticoids:
• useful in reversing lymphoma-induced hypercalcemia

Question 31

What drugs act as calcimimetics?

Answer 31

Calcimimetics – Cinacalcet

Question 32

Cinacalcet
• MOA
• Toxicity

Answer 32

Calcimimetics – Cinacalcet
MOA: acts on CaSR (calcium sensing receptor) to reduce the threshold of Ca2+ in the serum needed to activate the receptor and thus suppress PTH secretion from chief cells

Toxicity: Nausea, Hypocalcemia, Adynamic Bone

Question 33

Cinacalcet
• Indication

Answer 33

Calcimimetics – Cinacalcet

Indication: Hyperparathyroidism