Bone Mineral Homeostasis

Question 1

Bisphosphonates MOA

Answer 1

Etidronate, Alendronate, Pamidronate, Risedronate, Zoledronate

MOA: potent inhibitors of bone resportion that chelate with Ca2+ > cause osteoclast apoptosis and inhibition of compenents of cholester biosynthetic pathway

Question 2

1st generation Bisophosphonate?

Answer 2

• Etidronate: least potent and can even cause bone demineralization

Question 3

2nd generation Bisophosphonates AE?

Answer 3

• Alendronate: erosive esphagitis; must be taken on empty stomach
• Pamidronate: IV only can cause skin flushing, flu-like, muscle/joint aches, N/V/D, abd discomfort

Question 4

3rd generation Bisphosphonates AE?

Answer 4

• Risedronate: erosive esophagitis; must take on empty stomach
• Zoledronate: severe hypocalcemia, renal toxicity, Osteonecrosis of Jaw

Question 5

Denosumab MOA, Uses, AE

Answer 5

MOA: monoclonal RANKL inhibitor

Uses: Tx postmenopausal osteoporosis

AE: hypocalcemia, osteonecrosis of jaw, increased risk of infection

Question 6

SERMs MOA, uses, AE

Answer 6

Raloxifene, Tamoxifen

MOA: estrogen agonist in bone and liver

Uses: osteoporosis in postmenopausal women who cannot tolerate bisphosphonates

AE: Tamoxifen is also agonist at uterus so no recommended; raloxifene hot flashed and increase risk of venous thromboembolism

Question 7

Calcitonin MOA

Answer 7

MOA: PTH antagonist to inhibit osteoclastic bone resorption and increases bone mass in pts with osteoporosis

Question 8

Plicamycin MOA

Answer 8

MOA: RNA synthetis inhibitor that inhibits the effect of PTH upon osteoclast

Question 9

Pathphysiology behind CKDMBD

Answer 9

• Loss of functional renal parenchyma > decreased renal synthetic function
• Decreased calcitriol levels > reduced absorption of dietary calcium
• Hypocalcemia > upregulation of PTH secretion
• Loss of nephron function > decreased excretion of phosphate in urine
• Hyperphosphatemia > stimulation of PTH secretion
• Earlier CKD, FGF-23 is released by bone as phosphatonin to inhibit renal tubular reabsorprtion of phosphate
• FGG23 antagonized the effect of calcitriol on gut > hypocalcemia

Question 10

What is pathology of high bone turnover and low bone turnover and treatment?

Answer 10

• High bone turnover: hyperPTH > increase osteoclastic activity > osteitis fibrosa cystica; Tx with phosphate binder
• Low bone turnover: over-suppression of PTH > from agressive use of calcitriol and vit D analogs; vit D supplementation

Question 11

Sevelamer MOA, AE

Answer 11

MOA: nonabsorbable phosphate-binding polymer indicated for use in hemodialysis

AE: N/V/D, dyspepsia

Question 12

Vitamin D analog MOA

Answer 12

• Doxercalciferol: prohormone
• Paricalciferol: selective vit D receptor agonist for Tx of secondary hyperPTH

Question 13

Cinacalcet MOA, Uses

Answer 13

MOA: calcium receptor agonist which enhances the sensitivity of CaSR to extrecellular Ca2+

Uses: CKD pts on dialysis with secondary hyperPTH

Question 14

Gallium nitrate MOA, uses

Answer 14

MOA: inhibits bone resorption

Uses: management of hypercalcemia of malignancy

Question 15

Fluoride MOA

Answer 15

MOA: enchance osteoblast activity and increases bone volume

Question 16

Calcipotriol MOA, Uses

Answer 16

MOA: vitamin D3 analog regulates keratinocyte development > inhibit keratinocyte proliferation

Uses: psoriasis