Drugs that affect bone mineral homeostasis

Question 1

What are the effects of parathyroid hormone (PTH)?

Answer 1

Increases calcium, decreases phosphate –> increased bone resorption
- Also increases vitamin D metabolite through the kidneys

Question 2

What are the effects of vitamin D?

Answer 2

Increase in calcium and phosphate –> increased bone mineralization

Question 3

What are the effects of calcitonin?

Answer 3

Decrease in bone resorption

Question 4

Sources of Vitamin D

Answer 4

1. Diet= Vitamin D3, cholecalciferol, ergocalciferol
2. Exposure= UV rays

Question 5

What is the MAIN effect of vitamin D?

Answer 5

Increase in GI tract absorption of calcium and phosphate to then spit it out into circulation

Question 6

T/F: Calcitonin increases osteoclast activity

Answer 6

False, it inhibits osteoclast activity

Question 7

Teriparatide and abaloparatide

Answer 7

• Form of recombinant PTH
  MOA: binds to PTH receptor and causes greater amounts of OPG than RANKL
  Uses: osteoporosis
  AEs: hypercalcemia and osteosarcoma
  CI: osteosarcoma (BBW)
  Route: SC

Question 8

What is the function in OPG binding to RANKL?

Answer 8

It protects bone from excessive resorption and binds to this so that RANKL cannot bind to RANK–> helps bone mass and strength

Question 9

T/F: Use of teriparatide is not recommended for greater than 2 years

Answer 9

True

Question 10

Vitamin D (cholecalciferol, ergocalciferol, calcitriol)

Answer 10

MOA: regulate gene transcription via vit D receptor to produce beneficial effects on bone
Uses: diet supplement and off label for osteoporosis
AE: rare but can cause hypercalcemia
Note- take with calcium supplements

Question 11

Calcium supplements (calcium carbonate, calcium citrate)

Answer 11

Uses: osteoporosis prophylaxis with vitamin D
AE: constipation
DDI: space drugs apart by at least 2 hours
Note- take calcium carbonate with food

Question 12

Salmon calcitonin

Answer 12

MOA: agonist at calcitonin receptor (GPCR) and inhibits bone resorption by directly acting on osteoclasts
Uses: osteoporosis, hypercalcemia, and pagets disease
AEs: rhinitis (IN), allergy reactions (IN/IM/SC) , flushing (IM/SC) , malignancy, hypocalcemia
CI: fish hypersensitivity

Question 13

What drug is a SERM?

Answer 13

raloxifene

Question 14

Raloxifine

Answer 14

MOA: estrogen modulator and has positive effects on bone in liver (but has negative effects on breast, uterus, brain) and increases bone formation + decreases bone resorption
Uses: osteoporosis
AE: hot flashes, night sweats (common), increased risk of thromboembolism
CI: thromboembolic disease (BBW) and stroke (BBW)
DDI: levothyroxine (separate by 12 hours)

Question 15

What drugs are bisphosphonates

Answer 15

Alendronate (1/week), risendronate (1/week or 1/month), ibaundronate (1/3 months), and zoledronic acid (1/yr)
Note- Alendronate and risendronate are PO while ibaundronate and zoledronic acid are IV

Question 16

What is the MOA for bisphosphonates

Answer 16

Binds to hydroxyapatite in bone and inhibits osteoclastic bone resorption and benefits osteoblasts (prevents apoptosis)

Question 17

Bisphosphonates

Answer 17

PK: poorly absorbed orally so give on empty stomach with water and wait 30 min before eating
Uses: osteoporosis, hypercalcemia, paget disease
AE: upper GI side effects (reflux, esophagitis, ulcer) with oral; flu sxs and MSK pain with IV; for both rare AEs can occur like hypocalcemia, ONJ, atypical femur fractures
CIs: renal impairment, hypocalcemia, esophageal disorders
DDI: take apart from antacids, mineral supplements and NSAIDs

Question 18

T/F: You should monitor serum creatinine and calcium while taking bisphosphonates

Answer 18

True

Question 19

What are indications for bisphosphonates?

Answer 19

Ibandronate- vertebral fracture reduction
All others- vertebral fracture reduction, hip fracture reduction, non-vertebral fracture reduction

Question 20

Denosumab

Answer 20

MOA: fully humanized monoclonal antibody to RANKL and pretends its OPG
Uses: osteoporosis and hypercalcemia
AE: back pain, ONJ, atypical femur fraction
Dosing: SQ 2x per year

Question 21

What are indications for denosumab?

Answer 21

Decrease in vertebral fractures, non-vertebral fractures, and hip fractures (like alendronate, risendronate, and zoledronic acid)

Question 22

What are indications for raloxifene?

Answer 22

Decreases vertebral fractures

Question 23

What are indications for teriparatide?

Answer 23

Decreases vertebral fractures and non-vertebral fractures

Question 24

T/F: bisphosphonates and denosumab are non-hormonal therapies

Answer 24

True