LOOK:i am currently working on a detailed guide for compounds for bone growth this is a explanation of the pathways since i already know a good amount ab em and reading this before my compound guide (coming out before tuesday) will help.
THE GUIDE FOR BONE AUTISTS: THE PATHWAYS
hello i have done a small dive down this a while ago but i wish to revisit it and make a comprehensive thread. quick warning this is quite advanced and i am trying my best to explain but if you dont get anything please ask since i rlly do wish for this to be very understandable. I have backed up my claims with real studies and evidence im not saying like do masai jumps to grow 100 inches taller im not bsing here.
So before we get into the compounds we need to know how the bones grow and the pathways
simple explanation of how bones grow in general
so you have a thing called growth plates, the bones grow longer at the growth plates (epiphyseal plates is fancy term). these are soft cartillage zones at the end of bones like the femur,tibia,etc the growth plates have stages/zones
1.resting: this is where ur cells just chill
2.proliferating: this is where cells divide and get more cartillage
3.hypertrophic: this is where cells calcify
4.ossification: blood vessels form and the cartillage turns into bone
pathways what are they?
pathways are bassically signal chains, your hormones and special proteins tell the cells what they gotta do. for example HGH turns into IGF-1 which makes the chondrocytes (the cartillage cells) multiply (bassicaly triggers more of proliferating stage. there are also loops like Ihh/PTHrP keep plates balanced. if they mature too fast (turn into bone too fast) the whole thing closes early. there are a few more breaks like FGF/FGFR3 which slow shit down. CNP speeds up proliferating. estrogen (which is why girls shorter than boys) eventually fuse the plates by killing stem cells. testosterone helps by turning to estrogen and thickens bones. wnt and bmp flip switches for cell differentiation and bone formation
all of this is impacted by amount of sleep amount of stress and your nutrition, etc.ill explain each pathway better with how it works and the cons and back it with studies. now the detailed part
detailed explanations per pathway
pathway 1: GH/IGF-1 pathway
how it works: GH drops from ur pituitary mostly at night in sleep. it hits liver to make IGF-1 which binds to receptors on chondrocytes in prolif zone. this fires up PI3K/Akt and ERK1/2 signals leading to cyclin D1 so cells divide stack cartillage for length. GH can make IGF-1 local in plate too. for looksmaxxing high GH/IGF-1 means taller bassically. maxx it with 8-10hrs sleep and pinning hgh.
cons: too much like in tumors causes gigantism pre-closure but post-closure thick bones joint pain diabetes. low IGF-1 stunts growth like Laron syndrome. long term high IGF-1 cancer risk since it prolifs cells everywhere.
cited study/source: a study showed IGF-1 signaling is key for bone formation and remodeling with GH-independent actions too. (frontiersin.org 2013).
pathway 2: Ihh/PTHrP feedback loop
how it works: Ihh comes from pre-hypertrophic chondrocytes diffuses up to stim PTHrP in resting zone. PTHrP feeds back via PTH1R to delay hypertrophy keeping prolif zone active longer. this loop syncs prolif with maturation Ihh ramps as cells mature PTHrP brakes it. keeps plates open longer.
cons: mutations cause tumors or short limbs. over-Ihh delayed maturation weak bones. under premature closure short height. pharma risks kidney stuff since PTHrP hits calcium.
cited study/source: a study showed IRE1α regulates PTHrP-IHH loop for chondrocyte maturation knockouts cause short limbs from disrupted feedback. (sciencedirect.com 2022).
pathway 3: FGF/FGFR3 signaling
how it works: FGFs bind FGFR3 on chondrocytes activating STAT1/ERK to inhibit prolif push hypertrophy. its a brake high FGFR3 slows growth like in dwarfs with mutations. normal balances with accelerators.
cons: hyperactivation dwarfism joint deformities. inhibition risks overgrowth cancer since FGF prolifs other tissues. vosoritide sides injection pain low BP.
cited study/source: TYRA-300 FGFR3-selective inhibitor promotes bone growth in achondroplasia models normalizing prolif adding length in trials. (jci.org 2025).
pathway 4: CNP/NPR-B pathway
how it works: CNP binds NPR-B on chondrocytes raising cGMP PKG activation inhibits RAF1/ERK to boost prolif delay hypertrophy. gas pedal opposing FGFR3.
cons: mutations short stature or overgrowth syndromes. high CNP skeletal overgrowth but heart issues since natriuretic peptides regulate BP. injections site reactions headaches.
cited study/source: CNP stimulates endochondral bone growth expanding hypertrophic zones delaying mineralization via NPR-B/cGMP in mouse models. (pmc.ncbi.nlm.nih.gov 2007 foundational confirmed 2024 reviews).
pathway 5: estrogen in growth plate closure
how it works: estrogen E2 binds ERα/β on chondrocytes upregulating FGFR3 senescence genes p16/p21 depleting resting zone stems accelerating maturation fusion. high e2 accelerates closure. in dudes from test aromatization. maxxing avoid xenoestrogens plastics soy use AIs like letrozole off-label delay closure.
cons: too low E2 delayed closure but osteoporosis weak bones. high early closure short height. AIs risk low bone density mood swings.
cited study/source: estrogen accelerates prolif exhaustion senescence in growth plates leading to fusion in rodent models with E2 treatment. (e-cep.org 2024).
pathway 6: testosterone and aromatization
how it works: test boosts GH/IGF-1 for prolif aromatizes to E2 via CYP19 for closure signaling. direct AR on osteoblasts for periosteal growth wider bones/frame. if you wanna max this just pin test tbh
cons: excess early closure via high E2. low weak bones low density. TRT in teens risks stunting.
cited study/source: testosterone aromatization to estrogen key for male bone mass aromatase deficiency causes low BMD improved with E2 therapy. (nejm.org 1998 classic case study).
pathway 7: Wnt/β-catenin pathway
how it works: wnts bind Frizzled/LRP5/6 stabilize β-catenin nuclear translocation genes like Runx2 for osteoblast prolif/diff. in plate low wnt in prolif zone high in hypertrophy.
cons: over osteopetrosis dense but brittle bones. under low density fractures. mutations rare syndromes.
cited study/source: wnt/β-catenin regulates osteoblast diff bone homeostasis with components like sclerostin inhibiting for balance. (nature.com 2024).
pathway 8: BMP signaling
how it works: BMPs bind BMPRs activate Smads Runx2/MEF2C for hypertrophy ossification. stimulates prolif to diff transition.
cons: excess ectopic bone FOP disease. under delayed healing. pharma risks inflammation.
cited study/source: BMP signaling stimulates chondrocyte maturation Ihh expression in growth plates independent of maturation changes. (sciencedirect.com 2000 key mech study).
pros and cons lists per pathway simplified
stack em wisely like boost GH while inhibiting estrogen for max height (RISKY ESTROGEN HELPS BRAIN BUT STILL).
but this isnt my compound thread these are just pathways ill go WAY WAY WAY more in depth next thread so keep waiitng pls
GH/IGF-1:
pros: massive height gains better recovery frame density. easy to maxx naturally.
cons: cancer risk long-term insulin resistance pricey pharma.
Ihh/PTHrP:
pros: extends plate life syncs growth for even limbs.
cons: hard to target risks tumors if over.
FGF/FGFR3:
pros: inhibiting extra inches in shorties.
cons: drugs expensive/rare over-inhibit uncontrolled growth.
CNP/NPR-B:
pros: proven in trials for +cm/year opposes FGFR3.
cons: injections suck BP drops.
estrogen closure:
pros: delaying more time to grow.
cons: messing with hormones bone weakness making u a moodcel.
testosterone/aromatization:
pros: wider frame masculine bones easy to boost.
cons: accelerates closure if too high.
wnt/β-catenin:
pros: thicker bones from training no supps needed.
cons: overload risks injury.
BMP:
pros: speeds healing stronger bones.
cons: ectopic risks not height-specific.
Thanks for reading pls react this took a bit of time compiling sources and i am so thankful google exists imagine being a researcher in the 1970s having to find this information irl
THE GUIDE FOR BONE AUTISTS: THE PATHWAYS
hello i have done a small dive down this a while ago but i wish to revisit it and make a comprehensive thread. quick warning this is quite advanced and i am trying my best to explain but if you dont get anything please ask since i rlly do wish for this to be very understandable. I have backed up my claims with real studies and evidence im not saying like do masai jumps to grow 100 inches taller im not bsing here.
So before we get into the compounds we need to know how the bones grow and the pathways
simple explanation of how bones grow in general
so you have a thing called growth plates, the bones grow longer at the growth plates (epiphyseal plates is fancy term). these are soft cartillage zones at the end of bones like the femur,tibia,etc the growth plates have stages/zones
1.resting: this is where ur cells just chill
2.proliferating: this is where cells divide and get more cartillage
3.hypertrophic: this is where cells calcify
4.ossification: blood vessels form and the cartillage turns into bone
pathways what are they?
pathways are bassically signal chains, your hormones and special proteins tell the cells what they gotta do. for example HGH turns into IGF-1 which makes the chondrocytes (the cartillage cells) multiply (bassicaly triggers more of proliferating stage. there are also loops like Ihh/PTHrP keep plates balanced. if they mature too fast (turn into bone too fast) the whole thing closes early. there are a few more breaks like FGF/FGFR3 which slow shit down. CNP speeds up proliferating. estrogen (which is why girls shorter than boys) eventually fuse the plates by killing stem cells. testosterone helps by turning to estrogen and thickens bones. wnt and bmp flip switches for cell differentiation and bone formation
all of this is impacted by amount of sleep amount of stress and your nutrition, etc.ill explain each pathway better with how it works and the cons and back it with studies. now the detailed part
detailed explanations per pathway
pathway 1: GH/IGF-1 pathway
how it works: GH drops from ur pituitary mostly at night in sleep. it hits liver to make IGF-1 which binds to receptors on chondrocytes in prolif zone. this fires up PI3K/Akt and ERK1/2 signals leading to cyclin D1 so cells divide stack cartillage for length. GH can make IGF-1 local in plate too. for looksmaxxing high GH/IGF-1 means taller bassically. maxx it with 8-10hrs sleep and pinning hgh.
cons: too much like in tumors causes gigantism pre-closure but post-closure thick bones joint pain diabetes. low IGF-1 stunts growth like Laron syndrome. long term high IGF-1 cancer risk since it prolifs cells everywhere.
cited study/source: a study showed IGF-1 signaling is key for bone formation and remodeling with GH-independent actions too. (frontiersin.org 2013).
pathway 2: Ihh/PTHrP feedback loop
how it works: Ihh comes from pre-hypertrophic chondrocytes diffuses up to stim PTHrP in resting zone. PTHrP feeds back via PTH1R to delay hypertrophy keeping prolif zone active longer. this loop syncs prolif with maturation Ihh ramps as cells mature PTHrP brakes it. keeps plates open longer.
cons: mutations cause tumors or short limbs. over-Ihh delayed maturation weak bones. under premature closure short height. pharma risks kidney stuff since PTHrP hits calcium.
cited study/source: a study showed IRE1α regulates PTHrP-IHH loop for chondrocyte maturation knockouts cause short limbs from disrupted feedback. (sciencedirect.com 2022).
pathway 3: FGF/FGFR3 signaling
how it works: FGFs bind FGFR3 on chondrocytes activating STAT1/ERK to inhibit prolif push hypertrophy. its a brake high FGFR3 slows growth like in dwarfs with mutations. normal balances with accelerators.
cons: hyperactivation dwarfism joint deformities. inhibition risks overgrowth cancer since FGF prolifs other tissues. vosoritide sides injection pain low BP.
cited study/source: TYRA-300 FGFR3-selective inhibitor promotes bone growth in achondroplasia models normalizing prolif adding length in trials. (jci.org 2025).
pathway 4: CNP/NPR-B pathway
how it works: CNP binds NPR-B on chondrocytes raising cGMP PKG activation inhibits RAF1/ERK to boost prolif delay hypertrophy. gas pedal opposing FGFR3.
cons: mutations short stature or overgrowth syndromes. high CNP skeletal overgrowth but heart issues since natriuretic peptides regulate BP. injections site reactions headaches.
cited study/source: CNP stimulates endochondral bone growth expanding hypertrophic zones delaying mineralization via NPR-B/cGMP in mouse models. (pmc.ncbi.nlm.nih.gov 2007 foundational confirmed 2024 reviews).
pathway 5: estrogen in growth plate closure
how it works: estrogen E2 binds ERα/β on chondrocytes upregulating FGFR3 senescence genes p16/p21 depleting resting zone stems accelerating maturation fusion. high e2 accelerates closure. in dudes from test aromatization. maxxing avoid xenoestrogens plastics soy use AIs like letrozole off-label delay closure.
cons: too low E2 delayed closure but osteoporosis weak bones. high early closure short height. AIs risk low bone density mood swings.
cited study/source: estrogen accelerates prolif exhaustion senescence in growth plates leading to fusion in rodent models with E2 treatment. (e-cep.org 2024).
pathway 6: testosterone and aromatization
how it works: test boosts GH/IGF-1 for prolif aromatizes to E2 via CYP19 for closure signaling. direct AR on osteoblasts for periosteal growth wider bones/frame. if you wanna max this just pin test tbh
cons: excess early closure via high E2. low weak bones low density. TRT in teens risks stunting.
cited study/source: testosterone aromatization to estrogen key for male bone mass aromatase deficiency causes low BMD improved with E2 therapy. (nejm.org 1998 classic case study).
pathway 7: Wnt/β-catenin pathway
how it works: wnts bind Frizzled/LRP5/6 stabilize β-catenin nuclear translocation genes like Runx2 for osteoblast prolif/diff. in plate low wnt in prolif zone high in hypertrophy.
cons: over osteopetrosis dense but brittle bones. under low density fractures. mutations rare syndromes.
cited study/source: wnt/β-catenin regulates osteoblast diff bone homeostasis with components like sclerostin inhibiting for balance. (nature.com 2024).
pathway 8: BMP signaling
how it works: BMPs bind BMPRs activate Smads Runx2/MEF2C for hypertrophy ossification. stimulates prolif to diff transition.
cons: excess ectopic bone FOP disease. under delayed healing. pharma risks inflammation.
cited study/source: BMP signaling stimulates chondrocyte maturation Ihh expression in growth plates independent of maturation changes. (sciencedirect.com 2000 key mech study).
pros and cons lists per pathway simplified
stack em wisely like boost GH while inhibiting estrogen for max height (RISKY ESTROGEN HELPS BRAIN BUT STILL).
but this isnt my compound thread these are just pathways ill go WAY WAY WAY more in depth next thread so keep waiitng pls
GH/IGF-1:
pros: massive height gains better recovery frame density. easy to maxx naturally.
cons: cancer risk long-term insulin resistance pricey pharma.
Ihh/PTHrP:
pros: extends plate life syncs growth for even limbs.
cons: hard to target risks tumors if over.
FGF/FGFR3:
pros: inhibiting extra inches in shorties.
cons: drugs expensive/rare over-inhibit uncontrolled growth.
CNP/NPR-B:
pros: proven in trials for +cm/year opposes FGFR3.
cons: injections suck BP drops.
estrogen closure:
pros: delaying more time to grow.
cons: messing with hormones bone weakness making u a moodcel.
testosterone/aromatization:
pros: wider frame masculine bones easy to boost.
cons: accelerates closure if too high.
wnt/β-catenin:
pros: thicker bones from training no supps needed.
cons: overload risks injury.
BMP:
pros: speeds healing stronger bones.
cons: ectopic risks not height-specific.
Thanks for reading pls react this took a bit of time compiling sources and i am so thankful google exists imagine being a researcher in the 1970s having to find this information irl
