Osteoporosis Drug Treatment Flashcards
Osteoporosis drug classes:
PTH Vitamin D analogs Calcium Bisphosphonates Calcitonin Selective estrogen receptor modulators Thiazide diuretics RANK-L inhibitors Calcimimetics
Osteoprotegerin affect?
Decreased osteoclastic activity
What is a parathyroid hormone drug?
Teriparatide
What does teriparatide do?
Makes structurally-normal new bone by binding PTH receptor
Administration of teriparatide:
Sub Q once daily for up to two years to prevent bone fractures
What are the fat soluble forms of vitamin D?
D2: Ergocalciferol
D3: Cholecalciferol
Affect of PTH on vitamin D?
Stimulated 1,25-OH vitamin D3 formation
Affect of FGF 23 on vitamin D?
Inhibits 1,25-OH vitamin D3 formation and increase renal phosphate excretion
Vitamin D preparations:
Cholecalciferol (D3)
Ergocalciferol (D2)
Calcitriol (1,25-OH vitamin D3)
Paricalcitol (1,25-OH vitamin D2)
When is the active for of vitamin D preparations (calcitriol and paricalcitol) needed?
When renal pathology is present
Calcium preparations:
Calcium carbonate
What is the treatment for osteoporosis?
Calcium + Vitamin D3 supplementation (each has mixed results when used alone)
Bisphosphonates:
Alendronate
Etidronate
Mechanism of bisphosphonates?
Non-hydrolysable analogs of pyrophosphates normally present in bone; reduce osteoclastic dissolution of hydroxyapatite in bone; no affect on osteoblasts
Risk factors for bisphosphonates:
Osteonecrosis of jaw with dental procedures
Sickle cell disease
Radiation/chemotherapy
Local ischemia
Mechanism of action for selective estrogen receptor modulators?
Binds both alpha and beta receptors in bone
Where are alpha estrogen receptors (ERalpha) in bone found?
Cortical bone
Where are beta estrogen receptors (ERbeta) in bone found?
Trabecular bone
What specifically does estrogen cause in bones?
Decreased response of RANK-L receptor to RANK-L
Reduction of IL-6, TNF-alpha, and M-CSF
Stimulation of osteoprotegerin
Net effect of estrogen:
Decreased osteoclast activation
Osteoblasts left unopposed
What is a selective estrogen receptor agonist?
Raloxifene
Raloxifene affect on estrogen receptors?
ERalpha: partial agonist
ERbeta: antagonist
What does short-term administration of calcitonin cause?
Inhibits osteoclastic bone activity
What does long-term administration of calcitonin cause?
Inhibits both osteoblastic and osteoclastic activity (rarely used)
What do thiazide diuretics lead to?
Decrease in calcium excretion in the urine
What channel do thiazide diuretics affect?
Inhibit NCC leading to decreased Na+ reabsorption
What does inhibition of NCC lead to?
Decreased Na+ concentration in epithelial cells leading to increased basolateral Ca/Na antiporter leading to decreased Ca intracellularly driving the Ca reabsorption via apical membrane TRPV5
What is a RANK-L inhibitor?
Denosumab
What does binding to RANK cause?
Activation of nuclear factor kappa-B
What is osteoprotegrin?
A soluble receptor for RANK-L released to bind and inactivate RANK-L
What is Denosumab?
A monoclonal antibody against RANK-L
How does Denosumab work?
Binds RANK-L to inactivate it therefore inhibiting osteoclastic activity
Risks of Denosumab?
- ) Mandibular necrosis with dental work
2. ) Hip fractures
What drug is a Calcimimetic?
Cinacalcet
How does Cinacalcet work?
Allosteric activator of calcium sensing receptor (in PT gland)
What does Cinacalcet cause?
PTH secretion inhibition
What is Cinacalcet used for?
Hyperparathyroidism resulting from:
- ) Chronic kidney disease
- ) Parathyroid carcinoma
What are the side effects of Cinacalcet?
Cardiac arrhythmia
Heart failure
