Osteoporosis drugs Flashcards
What are bisphosphonates? How do they work?
they are analogues of pyrophosphate
they bind the surface of hydroxyapatite crystals
they inhibit crystal resprotion: decr. osteoclast function and incr. osteoclast apoptosis (among other things)
What are the bisphosponates? (slash what is the suffix)
alendronate, risedronate, ibandronate: oral forms
IV forms: pamidronate and zolendronate. higher compliance for IV forms and may last up to a year for each injection
suffix: DRONATE
What are the advantages bisphosphonates
Advantages: long half life; cessation doesn’t lead to rapid bone loss because they get integrated into the bone
significant reduction in spinal fractures
can be used in men
What are the disadvantages of bisophosphonates?
Disadvantages:
varied effect on nonvertebral site fracture reduction
oral forms may cause esophageal irritation and are contraindicated in pts with severe GERD/Barrett’s esophagus
cause muscle aches
oral forms have poor oral absorption, so can be hard to take
small risk of osteonecrosis of the jaw
small risk of atypical fractures
What are SERMs? What are associated risks? What is the example drug?
“antiestrogens” with bone augmentation effects
antagonist to breast but agonist to bone
preserves bone mass and prevents vertebral fracture
no added risk of uterine cancer
slight incr. risk of DVT
drug: raloxifene
How does calcitonin work? Advantages
non-sex/non-steroid hormone
binds osteoclasts and decreases their activity and number
protects against vertebral fracture
Disadvantages of calcitonin
no effect on hip fractures
given as a nasal spray and causes nausea
increased risk of cancer:
not used for osteoporosis
PTH in osteoporosis: MOA, what is it?
anabolic agent
daily low dose injections increase bone mass
increases the lifespan of the osteoblasts by reducing apoptosis
basically only used for 2 yrs
When do you use PTH for osteoporosis
bone mass decline in a pt on bisphosphonates, estrogen, or SERMS
fracture on bisphosphonates
low turn over osteoporosis
premenopausal women
inability to tolerate other treatments
severe glucocortocoid induced osteoporosis
Contraindications for PTH
previous radiation therapy, Paget’s disease, history of osteosarcoma (among a few other diseases).
this is based on the fact that PTH casues osteosarcoma in rats
What is denosumab?
RANK-ligand inhibitor
given as a subq injection
causes a reduced fracture risk at 3 yrs
Denosumab: disadvantages
effect lost if not continued every 6 mo
can cause back and extremity pain, MSK pain, hypercholesterolemia, cystitis
can cause osteonecrosis of the jaw, hypocalcemia, and infections (all rare but serious)
metabolism of denosumab
not renally cleared so can be used in pts with reduced renal function
What is sclerostatin
influences wnt signaling
inhibition of sclerostatin increases bone mineral density
Calcium supplements
may be given as calcium carbonate or calcium citrate
calcium carbonate must be taken with a meal bc needs acidic environment to be dissolved. elderly and pts on H2 blockers may make less acid and calcium carbonate may not be well-absorbed.
calcium citrate is easier to dissolve but causes an incr. risk of kidney stones
