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Iron
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What is Cathepsin K and how we can inhbibit it to increase bmd and periosteal bone expansion .
What is Cathepsin K ( simplified):
Cathepsin K is an enzyme ostoclasts secrete to break down collagen matrix ( type I collagen and elastin ) it plays a vital role in bone remodeling and bone resorption.
What happens when Cathepsin K is over expressed due to gene mutations in the CTSK gene:
In humans an over expression of Cathepsin K is linked with decreased bmd osteoporosis and Cortial bone loss . This would cause bones to become abnormally hollow and thin out due to the increase resorption rate . ( it’s also liked with loss of bmd in the mandible and changes in the length height and angles of the mandible )
Ok so now that we did a simple summary on what happens when Cat K is over expressed and it’s role in the skeleton we can now look on the effects of Cat K inhibition:
When Cat K is inhibited with a drug like odanacatib ( ODN ) we see very interesting things occur within the skeleton.
One of the unique things about OND is that it’s ability to keep ostoclast fully alive and working u might think why is this a good thing don’t ostoclast break down bone and ur right they do but the problem is when we nuke ostoclast number this creates a negative feed back loop and ur body lowers its osteoblast count to make up for it this puts the bone in a frozen like state where resorption won’t occur but also new bone deposition will also be frozen we see this happen in real life with Bisphosphonates. So as I was saying what makes Cat K so special is the fact that it keeps osteoclast numbers fully intact and it only inhibits their ability to break down bone so u never get the negative feed back loop u see with Bisphosphonates this results in osteoblasts not slowing down new bone deposition and they would keep on adding new bone over the old bone matrix resulting in periosteal bone expansion ( the increase in bone width ) and this has been proven in studies where OND caused a 3.5-6 fold increase in periosteal bone formation rate and an 21% increase in Cortial thickness even in adult monkeys. Further more cat k inhibition also prevents the break of periostin in bones this means periostin rapidly accumulates with in the periosteum of bones the high levels of periostin causes a spike in b-catenin signaling a crutial path way for wnt and modeling based formation. One last thing I forgot to add is that cat k inhibition preserves matrix derived growth factors from being broken down like igf-1 bmp2 and osteocalin.
One theory I made and I’ll try on my self is what if we use a drug what would increase ostoclast number since while using OND we know that they won’t be able to break down bone due to the Cat K inhibition but this would cause an increase in ostoblast count due to the feed back loop I mentioned when earlier as we know ostoclast secrete growth signals such as S1P wnt 10 ans bmp6 so an increase number of them would lead to an increase number of also ostoblast in the bone matrix what in theory would enhance the bone modeling rate . ( high dose of abalo or teri multiple times a day can be used to push out more ostoclast production via up regulation of RANKL I’ll be making a new post explaining more in detaail how we can use odn + abalo for my theory. )
pubmed.ncbi.nlm.nih.gov
https://www.esceo.org/sites/esceo/files/pdf/13.Cathepsin K controls...pdf
What is Cathepsin K ( simplified):
Cathepsin K is an enzyme ostoclasts secrete to break down collagen matrix ( type I collagen and elastin ) it plays a vital role in bone remodeling and bone resorption.
What happens when Cathepsin K is over expressed due to gene mutations in the CTSK gene:
In humans an over expression of Cathepsin K is linked with decreased bmd osteoporosis and Cortial bone loss . This would cause bones to become abnormally hollow and thin out due to the increase resorption rate . ( it’s also liked with loss of bmd in the mandible and changes in the length height and angles of the mandible )
Ok so now that we did a simple summary on what happens when Cat K is over expressed and it’s role in the skeleton we can now look on the effects of Cat K inhibition:
When Cat K is inhibited with a drug like odanacatib ( ODN ) we see very interesting things occur within the skeleton.
One of the unique things about OND is that it’s ability to keep ostoclast fully alive and working u might think why is this a good thing don’t ostoclast break down bone and ur right they do but the problem is when we nuke ostoclast number this creates a negative feed back loop and ur body lowers its osteoblast count to make up for it this puts the bone in a frozen like state where resorption won’t occur but also new bone deposition will also be frozen we see this happen in real life with Bisphosphonates. So as I was saying what makes Cat K so special is the fact that it keeps osteoclast numbers fully intact and it only inhibits their ability to break down bone so u never get the negative feed back loop u see with Bisphosphonates this results in osteoblasts not slowing down new bone deposition and they would keep on adding new bone over the old bone matrix resulting in periosteal bone expansion ( the increase in bone width ) and this has been proven in studies where OND caused a 3.5-6 fold increase in periosteal bone formation rate and an 21% increase in Cortial thickness even in adult monkeys. Further more cat k inhibition also prevents the break of periostin in bones this means periostin rapidly accumulates with in the periosteum of bones the high levels of periostin causes a spike in b-catenin signaling a crutial path way for wnt and modeling based formation. One last thing I forgot to add is that cat k inhibition preserves matrix derived growth factors from being broken down like igf-1 bmp2 and osteocalin.
One theory I made and I’ll try on my self is what if we use a drug what would increase ostoclast number since while using OND we know that they won’t be able to break down bone due to the Cat K inhibition but this would cause an increase in ostoblast count due to the feed back loop I mentioned when earlier as we know ostoclast secrete growth signals such as S1P wnt 10 ans bmp6 so an increase number of them would lead to an increase number of also ostoblast in the bone matrix what in theory would enhance the bone modeling rate . ( high dose of abalo or teri multiple times a day can be used to push out more ostoclast production via up regulation of RANKL I’ll be making a new post explaining more in detaail how we can use odn + abalo for my theory. )
Cathepsin K inhibitors prevent matrix-derived growth factor degradation by human osteoclasts - PubMed
The coupling between bone formation and resorption creates a therapeutic impasse in osteoporosis: antiresorptive therapy halts bone loss, but also inhibits bone formation, and therefore does not cure the condition. Surprisingly, recent preliminary reports suggest that inhibition of resorption by...
pubmed.ncbi.nlm.nih.gov
missing out fr im using my tism on this
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