L8.Osteoporosis Flashcards
At what SD below the mean must bone density fall to be considered osteoporosis (measured by DEXA scanner)?
2.5 SD below mean
What is Cathepsin K?
The major degrader of collagen released by osteoclasts during bone resorption. So effective b/c can cut collagen in so many places.
What is the mechanism by which bisphosphanate works? Specifically N-containing BPs
Bisphosphonate modifies pyrophosphonate structure in the bone by replacing an O with a C w/ two R side chains (usually one is nitrogen containing). This change causes osteoclasts many problems.
- For N bisphosphonates: Disrupt osteoclast cholesterol metabolism b/c one of the intermediates is necessary for GTPases (small signaling molecules). W/o GTPases osteoclasts undergo apoptosis.
- Inhibit farnesyl diphosphate Synthase, enzyme that converts Geranyl-PP to Farnesyl-PP in cholesterol synthetic pathway.
How does Denosumab (Anti-RANKL mAB) fight osteoporosis?
Denosumab binds to RANKL on osteoblast, competitively inhibiting RANK and osteoclasts –> Apoptosis
How does Odanacatib work to fight osteoporosis?
Odanacatib is a Cathepsin K inhibitor. Big advantage of Odanacatib is that it doesn’t completely shut of osteoclasts, it just slows them way down. This is good b/c it allows osteoclasts to naturally secrete osteoblast recruiters. So odanacatib down regulates bone resorption AND increases bone formation.
What is osteonecrosis? Why is it relative to osteoporosis treatments and dentistry?
Osteonecrosis = Bone Death. This is sometimes seen as ONJ (Osteonecrosis of the Jaw), which occurs as a side-effect of osteoporosis medications such as N-containing bisphosphonates and Denosumab.
