Drugs that affect bone mineral homeostasis Flashcards
What are the effects of parathyroid hormone (PTH)?
Increases calcium, decreases phosphate –> increased bone resorption
- Also increases vitamin D metabolite through the kidneys
What are the effects of vitamin D?
Increase in calcium and phosphate –> increased bone mineralization
What are the effects of calcitonin?
Decrease in bone resorption
Sources of Vitamin D
- Diet= Vitamin D3, cholecalciferol, ergocalciferol
- Exposure= UV rays
What is the MAIN effect of vitamin D?
Increase in GI tract absorption of calcium and phosphate to then spit it out into circulation
T/F: Calcitonin increases osteoclast activity
False, it inhibits osteoclast activity
Teriparatide and abaloparatide
- 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
What is the function in OPG binding to RANKL?
It protects bone from excessive resorption and binds to this so that RANKL cannot bind to RANK–> helps bone mass and strength
T/F: Use of teriparatide is not recommended for greater than 2 years
True
Vitamin D (cholecalciferol, ergocalciferol, calcitriol)
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
Calcium supplements (calcium carbonate, calcium citrate)
Uses: osteoporosis prophylaxis with vitamin D
AE: constipation
DDI: space drugs apart by at least 2 hours
Note- take calcium carbonate with food
Salmon calcitonin
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
What drug is a SERM?
raloxifene
Raloxifine
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)
What drugs are bisphosphonates
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
What is the MOA for bisphosphonates
Binds to hydroxyapatite in bone and inhibits osteoclastic bone resorption and benefits osteoblasts (prevents apoptosis)
Bisphosphonates
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
T/F: You should monitor serum creatinine and calcium while taking bisphosphonates
True
What are indications for bisphosphonates?
Ibandronate- vertebral fracture reduction
All others- vertebral fracture reduction, hip fracture reduction, non-vertebral fracture reduction
Denosumab
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
What are indications for denosumab?
Decrease in vertebral fractures, non-vertebral fractures, and hip fractures (like alendronate, risendronate, and zoledronic acid)
What are indications for raloxifene?
Decreases vertebral fractures
What are indications for teriparatide?
Decreases vertebral fractures and non-vertebral fractures
T/F: bisphosphonates and denosumab are non-hormonal therapies
True
