Get a Taller Stature with an Inversion Table(Microgravity)

Most height seekers know the story about how astronauts get taller in space.  The effect of space can be mimicked by inversion(Body Champ IT8070 Inversion Therapy Table).  Microgravity seems to have an effect on height above and beyond that of sleep.  Sleep is an important part of growth.  Weight loaded chicks who had sustained loading with no release from load had a shorter stature.  Decompression may be an important part of height growth.  Think about the physics of growing taller via the growth plate.  How can a bunch of hypertrophying chondrocytes push away two halves of a bone resulting in a longer bone?  It must need the period of sleep to stretch out the bone.  Perhaps the extra decompression provided by microgravity can result in bonus height growth.  Intermittent microgravity such as that by an inversion table(and maybe even something like a decline bench) may not only give you temporary height but may help with chondrogenic differentiation.  And temporary height can be useful in a situation where you need to meet a height requirement.

How does microgravity affect chondrogenesis and chondrogenic differentiation and how can we use this to grow taller both via LSJL and during natural development?

Differentiation of mesenchymal stem cells towards a nucleus pulposus-like phenotype utilizing simulated microgravity In vitro.

"Mesenchymal stem cells (MSCs) were induced into a nucleus pulposus-like phenotype utilizing simulated microgravity in vitro in order to establish a new cell-based tissue engineering treatment for intervertebral disc degeneration. For induction of a nucleus pulposus-like phenotype, MSCs were cultured in simulated microgravity in a chemically defined medium supplemented with 0 (experimental group) and 10 ng/mL (positive control group) of transforming growth factor β1 (TGF-β1). MSCs cultured under conventional condition without TGF-β1 served as blank control group. On the day 3 of culture, cellular proliferation was determined by WST-8 assay. Differentiation markers were evaluated by histology and reverse transcriptase-polymerase chain reaction (RT-PCR). TGF-β1 slightly promoted the proliferation of MSCs. The collagen and proteoglycans were detected in both groups after culture for 7 days[Microgravity resulted in collagen and proteoglycan expression even without TGF-Beta1, even though this study is analyzing spinal discs any expression of chondrogenic markers will help us grow taller]. The accumulation of proteoglycans was markedly increased. The RT-PCR revealed that the gene expression of Sox-9, aggrecan and type II collagen, which were chondrocyte specific, was increased in MSCs cultured under simulated microgravity for 3 days. The ratio of proteoglycans/collagen in blank control group was 3.4-fold higher than positive control group, which denoted a nucleus pulposus-like phenotype differentiation. Spontaneous differentiation of MSCs towards a nucleus pulposus-like phenotype in simulated microgravity occurred."

Now this study was not in the human body so the drawbacks of sustained microgravity could not be taken into account.  Sustained microgravity in rats was shown to reduce the growth plate cell count in rats.  The absence of TGF-Beta1 resulted in higher proteoglycan/collagen content than the control group with TGF-Beta1.  TGF-Beta1 is produced by osteoblast cells in the bone.  So, it's this TGF-Beta1 which is stimulated by loading that could be the difference between growth plate chondrocytes and articular chondrocytes(articular chondrocytes are surrounded by much less bone).

Microgravity is very helpful in inducing chondrogenic differentiation.  Intermittent microgravity could allow for the encouragement of a chondrogenic phenotype but still allow for the loading needed for the bone cells to secrete TGF-Beta1.

How do already more mature chondrocytes respond to microgravity?

Characterization of human chondrocytes exposed to simulated microgravity.

"We characterized human chondrocytes incubated on a random positioning machine (RPM) to simulate microgravity (microg).
When cultured in simulated microg, human chondrocytes start forming 3D cell assemblies within 5 days. After 24h, we could not detect caspase-3, Fas, p53 or Bcl-2 proteins in these cells, Annexin V flow cytometry, however, revealed 18% of apoptotic chondrocytes in 1g cultures but only 10% on the RPM[microgravity reduces chondrocyte apoptosis]. Both rates of apoptosis were not changed, when vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF) was added. 24 h, simulated microgravity also had significantly decreased collagen type I and X, but did not change collagen type IV and laminin, while collagen type II, chondroitin sulfate and aggrecan were elevated as compared with 1g controls[microgravity downregulated the bone marker type I collagen and the terminal differentiation marker type X collagen and upregulated hyaline cartilage marker type II collagen and proteoglycans]. The production of collagen type II/X, chondroitin sulfate and aggrecan was modified, when external bFGF or VEGF had been applied.
Chondrocytes exposed to simulated microg seem to change their extracellular matrix production behavior, while they rearrange their cytoskeletal proteins prior to forming 3D aggregates."

Microgravity may help chondrocytes aggregate and be more growth plate like.  It allows them to rearrange their cytoskeleton proteins which they could possibly not due under normal gravity.  So intermittent microgravity could allow chondrocytes to do things that they can't do under normal gravity helping you to grow taller.

The RPM machine may not be sustained microgravity and may only be intermittent so that could be what leads to the pure positive benefits.

The Effect of the Microgravity Rotating Culture System on the Chondrogenic Differentiation of Bone Marrow Mesenchymal Stem Cells.

"During chondrogenic induction, MSCs combined with polyglycolic acid (PGA) were cultured by static culture or microgravity rotating culture and chondrocyte formation was confirmed by toluidine blue staining. Furthermore, the mRNA and protein expressions of a specific cartilage extracellular matrix protein (collagen type II and Aggrecan) were evaluated by real-time RT-PCR and western blot, respectively. Toluidine blue staining indicated the OD values of proteoglycans semi-determination were higher in the microgravity rotating culture group than the static culture group. Following chondrogenic induction, mRNA and proteins of collagen type II and Aggrecan were more significantly expressed in cells of the microgravity rotating culture group compared with the controls."

"Gravity in the culture system usually results in the cells gathering in the bottom or out of the culture system rather than in the central vector."<-This could be a problem in the body as well.

"The lack of the cells in the center directly affected the growth of chondroid tissue because the transformation of MSCs to cartilage was closely related to the cell density"<-So occasional bouts of microgravity may help cells get to where they need to go and not forced to the bottom by gravity.

Neocartilage formation in 1 g, simulated, and microgravity environments: implications for tissue engineering.

"Porcine chondrocytes were seeded (100 x 10(6)/mL) into cylindrical culture chambers (n = 8) and cultured in the following environments: (i) microgravity during the Flight 7S (Cervantes mission) on the International Space Station (ISS), (ii) simulated microgravity in a random positioning machine (RPM), and (iii) normal gravity (1 g, control). After 16 days, each neocartilage tissue was processed for histology, immunohistochemistry, quantitative real-time reverse transcriptase-polymerase chain reaction, and histomorphometric analysis.
Weaker extracellular matrix staining of ISS neocartilage tissue was noted compared with both Earth-cultivated tissues[sustainedness of microgravity or other confounding variables make spaceflight different than the random positioning machine]. Higher collagen II/I expression ratios were observed in ISS samples compared with control tissue. Conversely, higher aggrecan/versican gene expression profiles were seen in control 1 g samples compared with microgravity samples. Cell density produced in microgravity was significantly reduced compared with the normal gravity neocartilage tissues.
Tissue cultivated on the RPM showed intermediate characteristics compared with ISS and 1 g conditions. These data indicate that the RPM system does not sustain microgravity. Although microgravity impacts the development of in vitro generated cartilage, simulated microgravity using the RPM may be a useful tool to produce cartilaginous tissue grafts with fewer cells."

So the RPM system likely does not produce sustained microgravity and likely mimics the results we would spending some time on an inversion table.  It's also possible however that the way the random positioning machine rotates cells could have another effect.

Gravity, a regulation factor in the differentiation of rat bone marrow mesenchymal stem cells.

"Rat BMSCs (rBMSCs) were cultured under hypergravity or simulated microgravity (SMG) conditions with or without inducement medium. The expression levels of the characteristic proteins were measured and analyzed using immunocytochemical, RT-PCR and Western-blot analyses. After treatment with 5-azacytidine and hypergravity, rBMSCs expressed more characteristic proteins of cardiomyocytes such as cTnT, GATA4 and beta-MHC; however, fewer such proteins were seen with SMG. After treating rBMSCs with osteogenic inducer and hypergravity, there were marked increases in the expression levels of ColIA1, Cbfa1 and ALP. Reverse results were obtained with SMG. rBMSCs treated with adipogenic inducer and SMG expressed greater levels of PPARgamma. Greater levels of Cbfa1- or cTnT-positive cells were observed under hypergravity without inducer, as shown by FACS analysis. These results indicate that hypergravity induces differentiation of rBMSCs into force-sensitive cells (cardiomyocytes and osteoblasts), whereas SMG induces force-insensitive cells (adipocytes).

Taken together, we conclude that gravity is an important factor affecting the differentiation of rBMSCs; this provides a new avenue for mechanistic studies of stem cell differentiation and a new approach to obtain more committed differentiated or undifferentiated cells."

"SMG led to collapse of microfilaments and the microtube cytoskeleton. In the present study, we provide the first evidence that HG increases organization of microfilament and microtubules, which may increase cell activity. "<-However this only happens after at least one day.

If we are operating under the hypothesis that intermittent microgravity allows chondrocytes to perform tasks that it isn't normally able to do during bed rest then we have to determine an optimal duration to perform the inversion.  Performing inversion is hard.  Perhaps 5 minutes of inversion a day and you might have to break that into 30 second intervals.

Fifteen days of microgravity causes growth in calvaria of mice.

"Bone growth may occur in spaceflight as a response to skeletal unloading and head-ward fluid shifts. While unloading causes significant loss of bone mass and density in legs of animals exposed to microgravity, increased blood and interstitial fluid flows accompanying microgravity-induced fluid redistribution may elicit an opposite effect in the head. Seven 23-week-old, adult female wild-type C57BL/6 mice were randomly chosen for exposure to 15days of microgravity on the STS-131 mission, while eight female littermates served as ground controls. Upon mission completion, all 15 murine calvariae were imaged on a micro-computed tomography scanner. A standardized rectangular volume was placed on the parietal bones of each calvaria for analyses, and three parameters were determined to measure increased parietal bone volume: bone volume (BV), average cortical thickness (Ct.Th), and tissue mineral density (TMD). Microgravity exposure caused a statistically significant increase in BV of the spaceflight (SF) group compared to that of the ground control (GC) group, the mean BV±SD for the SF group was 1.904±0.842mm3, compared to 1.758±0.122mm3 for the GC group. Ct.Th demonstrated a trend of increase from 0.099±0.006mm in the GC group to 0.104±0.005mm in the SF group (p=0.12). TMD was similar between the two groups with 0.878±0.029g/cm3 for the GC group and 0.893±0.028g/cm3 for the SF group (p=0.31). Our results indicate that microgravity causes responsive changes in calvarial bones that do not normally bear weight. Fluid shifts alone accompanying microgravity may initiate bone adaptation independent of skeletal loading by tissue."

"Calvaria from the spaceflight group showed an increase in cross-sectional thickness compared to calvaria from the ground control group. Bone also expanded into the cavity in the parietal bone adjacent to the suture."

There might be some longitudinal growth there as the suture is what separates the two bones.  Although I do not think the two bones are from the same mouse.

"in addition to increased average thickness of the calvaria in microgravity, there probably was some bone expansion into air sinuses within the parietal bones"  Does the expansion of the calvaria bone share the same properties as longitudinal bone growth?

Space and Height

In our analysis of what affects the differentiation and dedifferentiation of mesenchymal stem cells Runx2 was unveiled as a key compound that encourages osteogenic differentiation.  It was hypothesized that the down regulation of Runx2 by the lack of loading due to space flight followed by the upregulation after return on land could play a role in the astronaut height gain.  However, no official studies could be found that explored the height gain of the astronauts in space(the effects of microgravity on other organisms were explored however).  Just because a large component of the height gain is due to spinal decompression does not mean that a smaller component could be permanent.  According to one study "Simulated microgravity inhibits the proliferation and osteogenesis of rat bone marrow mesenchymal stem cells"<-title is the same.  Microgravity could also potentially induce dedifferentiation of osteoblastic cells allowing them to undergo into a chondrogenic lineage giving a more youthful taller growing bone.

The effect of a 5-day space flight on the immature rat spine.

"In September 1991, 8 neonatal rats were flown aboard the Space Shuttle Columbia flight STS-48 during a 5-day mission. Upon return to earth, the spines were dissected, frozen and shipped to our laboratory. Matched ground-based rats were used as controls. The spines were radiographed and then slowly thawed. Individual vertebrae were subjected to compressive biomechanical testing using an Instron tester and then processed for determination of calcium and phosphorus content. The intervertebral discs were placed in physiological saline and the stress-relaxation characteristics measured. The discs were then lyophilized and assayed for collagen and proteoglycan content. Disc height on radiographs was measured by image analysis.
After space flight, the heights of the discs were found to be 150 to 200 microns greater, although the values were not statistically significant[height of discs were greater explaining for some of the height gain]. There was no difference in the resiliency of the thoracic discs as determined by stress-relaxation. However, in the lumbar discs, space flight increased the resiliency. There was no difference in water content. In both the thoracic and lumbar discs there was a 3.3-fold increase in hydroxyproline-proteoglycan ratio after space flight. In the vertebrae, there was no difference in calcium-phosphate ratio or compressive strength.
Even after a short 5-day flight, the spine begins to undergo biomechanical and biochemical changes."

Nothing though about Runx2.  However, the problem is that non-microgravity seems to be essential to normal growth plate development.  The next study also studies the hypothesis that maybe a period of unloading followed by loading could help growth.

The Spacelab 3 simulation: basis for a model of growth plate response in microgravity in the rat.

"Data from Spacelab 3 (SL3) suggested that spaceflight significantly reduces the activity of the rat tibial growth plate. Animal processing after SL3 began twelve hours post-landing, so data reflect post-flight re-adaptation in addition to spaceflight effects. To determine if a twelve-hour period of weight bearing after seven days of unloading could affect the physes of spaceflown rats, the present study assessed the growth plate response to unloading with or without a reloading period. Rats were subjected to hind-limb suspension for seven days and then euthanized, with or without twelve hours of reloading. Activity of the growth plate was assessed. Rats suspended without reloading had reserve zone (RZ) height greater than controls[so there was less differentiation of cells], and shorter hypertrophy/calcification zone (HCZ) with fewer cells. The greater RZ was associated with a larger cell area, indicating a possible mitotic delay or secretion defect[likely due to a compound upregulated by loading such as Runx2 not being present]. Twelve hours of reloading decreased RZ height and cell number, and restored the number of cells in HCZ to control values, but the number of cells in the proliferative zone and height in HCZ were reduced. The rebound response to preserve/restore skeletal function after a period of unloading involves an acceleration of growth associated with a decreased cell cycle time in PZ. Changes during the reloading period in this simulation support our hypothesis that the effects of spaceflight on SL3 growth plates were altered by changes that occurred post-landing."

If cells were dedifferentiating due to absence of Runx2 you would expect that the number of cells in the twelve hours of reloading group to have a larger reserve cell number(due to osteoblasts dedifferentiating).

Gravitational changes affect tibial growth plates according to Hert's curve.

"Microgravity significantly affects chondrocyte differentiation within the tibial epiphyseal growth plate of space flown rats[it likely always affects chondrogenic differentiation including exogenously induced chondrogenic differentiation like with LSJL]. The changes produced in height and number of cells in different zones of the plate are associated with ultrastructural changes in the extracellular matrix. Given the importance of the growth plate in endochondral ossification, we began to assess the response of the plate to hypergravity, and the countermeasure value of excess G.
Rats of the strain used in Cosmos biosatellite missions were housed under conditions similar to Cosmos flights and subjected to continuous hypergravity (2 G) for 14 d, in a 12-ft radius centrifuge.Histomorphometrical analyses of tibial growth plates from these rats found the hypertrophic/calcification zone to be significantly reduced in both height and cell number, and the proliferation zone in cell number.
[The] rat growth plate responds to gravitational changes according to Hert's curve: i.e., a) an increased baseline (minimal) loading reduces cartilage differentiation; and b) a reduced baseline loading may lead to increased cartilage differentiation but only within a range, beyond which lack of differentiation results{So lowering the baseline to a specific point less than 9.8m/s^2 but greater than 0m/s^2 may help increase chondrogenic differentiation?}. The plasticity of the plate, i.e., its ability to increase or decrease its activity in response to changes in gravity suggests the possibility of a range of G that will produce the load necessary to maintain normal growth of the plate, i.e., possible countermeasures to the effects of either hypo- or hyper-gravity."

Baseline loading refers to the smallest loading you incur during a day.  So maybe experiencing microgravity during one short burst during the day may help encourage chondrogenic differentiation.  Like inversion maybe?

Height increase, neuromuscular function, and back pain during 6 degrees head-down tilt with traction.

"Spinal lengthening and back pain are commonly experienced by astronauts exposed to microgravity.
To develop a ground-based simulation for spinal adaptation to microgravity, we investigated height increase, neuromuscular function and back pain in 6 subjects all of whom underwent two forms of bed rest for 3 d. One form consisted of 6 degrees of head-down tilt (HDT) with balanced traction, while the other was horizontal bed rest (HBR). Subjects had a 2-week recovery period in between the studies.
Total body and spinal length increased significantly more and the subjects had significantly more back pain during HDT with balanced traction compared to HBR[The height increase lasted for two weeks following inversion for three days?]. The distance between the lower endplate of L4 and upper endplate of S1, as measured by ultrasonography, increased significantly in both treatments to the same degree[The inversion group grew taller than the bed rest group despite both groups having equal decompression of the spinal discs]. Intramuscular pressures in the erector spinae muscles and ankle torque measurements during plantarflexion and dorsiflexion did not change significantly during either treatment.
Compared to HBR, HDT with balanced traction may be a better method to simulate changes of total body and spinal lengths, as well as back pain seen in microgravity."

this is similar to the 100kg loading method that some height seekers have used.  The tilt is not as much as it could be and the load is not dynamic.  There could be constant inversion/eversion to stimulate more flow to the discs.

If you look at this image

Height was increased more than you'd expect than via disc height this is very promising because it could mean this method stimulates height in a novel mechanism.

So inversion seems to have effects other than just spinal decompression.  This inversion may allow for a lower threshold microgravity and may allow for bone to expand more than just bed rest.  Same with chondrocytes a lower threshold microgravity allows for chondrocytes to expand wider during the lowest microgravity point of the day(the inversion point).

Here's a study on weightlessness and height:

Structural and Mineral Content in Weight-bearing bones following hindlimb suspension in young rats

After 1 week suspension of growing rats bone length was lower by about 10% less change than control.  This study mentions studies where hindlimb suspension did not inhibit bone length.


So sustained microgravity followed by normal gravity(space flight) doesn't seem to have permanent height increasing effects.  However, intermittent periods of microgravity like those achieved by inversion may help increase height(Body Champ IT8070 Inversion Therapy Table) in addition to the temporary height achieved by changes in intravertebral disc shape.  To know for sure the effect of exposure to microgravity will have to be studied.

The Lateral Synovial Joint Loading Three Month Challenge

It's often said that if a method was found to increase height that it would be everywhere and the creator of the method would be a billionaire.  It's more complicated than that.  First, the method may be difficult, challenging, or time consuming and it can take a while to get results.  Second, there's a hierarchy which makes it hard for peons such as myself to have their voice heard.  So, how do I prove to you that Lateral Synovial Joint Loading works?  I want you to try it out.

This challenge will require three months of work.  The first thing I want you to do is go over to the Lateral Synovial Joint Loading Forums and post your starting measurements.  Then I want you to read over the Lateral Synovial Joint Loading Routine.  Now I don't want you to do the challenge if you're not going to post pictures of your results no matter what.  Be sure to do finger loading as well as you can get higher relative hydrostatic pressure in order to see if the issue is that not enough hydrostatic pressure is being generated.

Start out with 1 minute of clamping and 1 minute of dumbell loading.  I find that 30 seconds can lead to not giving the routine your full and extensive effort.  You can go up to three minutes if you chose(if you feel pain or it's intense then do not go three minutes but go 30 seconds).  Start out with a 10lbs dumbell(or less).  Start out lightly clamping and work your way up.  Do not use too heavy a dumbell because that can lead to the dumbell slipping which will cause shearing forces on the cartilage of the epiphysis.  If you've ever eaten chicken, the cartilage at the end of the chicken bone scratches right off.  Runners who endure shearing forces all the time often have bad knees.  We want compressive forces at the epiphysis and not shearing forces.

Go up in intensity and duration every week or so.

(*NEW*)You'll want to flex your muscles as your performing the clamping.  You want to get about 700 mmHg of hydrostatic pressure.  Studies have been performed using 1 MPa which is about 700 mmHg but 750 is the minimum recommended in one mechanical environment of bone marrow article.  Too fast of distraction in distraction osteogenesis may lead to a decrease in hydrostatic pressure(the blood clot created due to fracture is a region of high hydrostatic pressure) and that's why the periosteal stem cells there differentiate into fibroblasts rather than osteoblasts.  Now distraction osteogenesis involves more intramembranous ossification(meaning no cartilagenous template) versus endochondral ossification which we're trying to achieve with LSJL.  However, the reason that the periosteal stem cells don't differentiate into chondrocytes is likely due to the environment.  The stem cells differentiate in a medium involving a blood clot rather than a medium with type I collagen.  So even distraction osteogenesis may involve hydrostatic pressure at some level.

So we want to get to 700 mmHg of hydrostatic pressure by the end of the challenge.  We know know that human blood pressure typically varies between 80 to 120 mmHg.  So basically we want to increase the hydrostatic pressure in the bone marrow by 7 times.

While you're performing LSJL, contract the surrounding muscles in a pulsatile fashion.  Weightlifting at the gym will help with this.  It'll help you learn how to contract your muscles and build more muscles which will inhibit myostatin.  When nurses are checking for blood pressure they are making pulsatile squeezes of your arm.  That's sort of what you're trying to mimic with your muscular contracts.  You're trying to squeeze more blood into the target bone marrow epiphysis.


Eletric Muscle Stimulators(Complete Muscle Stimulation Unit with Carrying Case and Electrodes) may be worth looking into.  You'd want a high pulse rate to get more blood into the bone marrow.  LIPUS would help increase hydrostatic pressure but it's not really feasible to perform LSJL and LIPUS at the same time.


Alternate which bone side you load first(right or left) in case you're giving the muscle bone more effort than the second.


You want to load between 24(98% recovery of actin cytoskeleton activity) and 48 hours(100% recovery).  In the LSJL studies, they did a mixture with 5 days on and 2 non-consecutive days off.


There's no evidence that a week off or so will help as there doesn't seem to be a long term adaptation of the actin cytoskeleton.


In the Lengthening of Mouse Hindlimbs with Joint Loading study they seemed to use less load than would achieve 700 mmHg but there still seems to be signs of chondrogenic differentiation(you can see stem cells secreting white cartilagenous matrix outside of the growth plate zones).  They used only 0.5N which is less force than even 1 kg would generate but also remember that mice are small.  So it may not be necessary to get to 700 mmHg, however the rats growth plates were active and those rats rats had bone that was less vascularized(less ways for bone marrow to escape).  Thus, the hydrostatic pressure in that marrow was already higher than normal.

The first month you might have problems with clamping or not loading the dumbell properly.  It is a motor task.  It takes time to learn how to relax your ligaments and avoid slipping of the clamp.  You may think this is easy but you could say that throwing a jab is just sticking your arm out in front of you while taking a step forward.  If you get frustrated then just try again the next day.

The first month is about learning and conditioning.  If you want to do more then by all means do more but the easier you make the routine, the more likely you are to stick with it and then build up.  Just start with some light clamping and you'll have the routine established before you move up.

The second month, you should start being more aggressive.  Take another measurement and post your pictures on the forums again.  Don't expect height gain yet but expect a change in your bone shape.

At the end of the third month, you should have grown taller with LSJL.  If you haven't and you performed the exercises inducing sufficient hydrostatic pressure then you can say that all the pieces aren't there for LSJL yet.

How much height should you expect in three months?  Well, we're discounting the first month for learning so two months.

It's often thrown around that the bone completely remodels itself every ten years.  This is likely based on the average person and is likely modified by anabolic factors like HGH, leptin, etc.  Let's say that you have a tibia that's 15 inches long.  That would mean that every year the skeleton grows 1.5 inches of new tibia and 1.5 inches worth of new bone(now a confounding factor involved is chondrocytes which are involved in endochondral ossification which usually aren't typically involved in bone remodeling but are involved in LSJL induced height growth).  Coincidentally, I gained about 1.5 inches in one year of LSJL(well not quite since I'm 5'9 3/4"+ and not quite 5'10").  So in two months you can expect 0.25 inches or a quarter of an inch in your tibia.

According to the study, Lengthening of Mouse Hindlimbs with Joint Loading "In knee loading, the rate of lengthening with 0.5 N loads (peak-to-peak) was 0.1% per bout (femur) and 0.1% per bout (tibia) for 5-min loading per day."   So if the tibia is 15 inches long and you load 5 out of 7 days a week.  You'd grow 0.3 inches a month or 0.6 inches for two months.  But I don't think we can assume that as we won't do it as optimized as the scientists would.

Height Gaining by altering Bone Crystalization

Ozan Akkus from the university of Purdue where the Lateral Synovial Joint Loading modality was first developed, has an interesting theory of how bone changes with age.  Telomere length is one mechanism of how cells change with age but how does bone change with age and how do we revert it back to a more youthful and hopefully more chondrogenic state.

From Akkus:

• type-B carbonate content significantly increases with age(so reducing Type-B carbonate may be a way to grow taller and result in height gaining)
• the tissue composition gets more homogenous with age(less cartilage, hover the bone does begin as completely cartilage)
• tissue heterogeneity is a correlate of tissue strength(We know that microcracks increase bone strength)
• the crystallinity is a correlate of both fatigue and monotonic strength of bone.

Now, you might think that Type-B carbonate affects bone strength and not height.  However, it's bone heterogeneity that influences bone strength and the growth plates make the bone heterogeneous.  So therefore, Type-B carbonate may affect chondrogenesis in bone.

Effects of polyelectrolytic peptides on the quality of mineral crystals grown in vitro.

"Charged amino acids such as arginine, lysine, glutamic acid, and aspartic acid are abundant in noncollagenous proteins that regulate mineralization. Synthetic peptide forms of these amino acids affect crystal growth in precipitation of mineral crystals in solution{Remember that the mineralization does not necessarily stunt growth, if anything these amino acids will make you taller by increasing the mineralization growth when it does occur}. [Do] these peptides [affect] the viability and phenotype of bone marrow stromal cells (BMSCs){This will affect height growth as cartilage stem cell phenotypes make you taller} or on the in vitro mineralization process? Bone marrow was harvested from neonatal rat femora and cultured under conditions to induce mineralized nodule formation. Mineralized bone nodules were grown while supplementing the cultures with one of five polyelectrolytes: polystyrene sulfonate (PSS), poly-L: -glutamic acid (PLG), poly-L: -lysine (PLL), poly-L: -aspartic acid (PLA), and sodium citrate (SC), as well as a nontreated control group. The viability and the rate of collagen synthesis under the effect of these agents were characterized. [Analysis] was conducted on mineralized bone nodules to determine the effect of the polyelectrolytes on the mineralization, type-B carbonation, and crystallinity of the mineral phase. Morphology of resulting mineral crystals was investigated. PSS{Don't take polystyren sulfonate if you want to grow taller} had toxic effects on cells whereas the remaining agents were biocompatible, as the cell viability was either greater (PLG){Note that the Poly-L Glutamate is not compared with other forms of Glutamate so we can't be sure whether this form is superior, viability means larger cells and larger cells can make you taller} or not different from controls. The total collagen production by day 21 was 27% and 42% lower than controls for PLL{Lysine is needed but maybe the Lysine levels were too high} and PSS, respectively. Culture wells stained positively for alkaline phosphatase in the presence of polyelectrolytes, indicating that osteogenic differentiation was not impacted negatively. Type-B carbonation of the crystal lattice increased when treated with PLG, PLL, or PSS. Crystallinity of PLL and PSS was smaller than that of control. The mineral/matrix ratios of nodules did not change with polyelectrolyte treatment, with the exception of the PSS-treated group, which was less mineralized. XRD analysis of bone nodules indicated that PLA-treated samples were significantly longer{this is interesting, aspartame is used in artificial sweeteners, perhaps aspartame can make you taller?} than controls along the 002 direction{the 002 direction includes both length width and height}. The polypeptides consisting of charged amino acids are biocompatible and affect crystal quality and morphology in vitro in the presence of cells."

PLG increased the number of cells the most.  Since PSS was the least mineralized maybe it could be the most chondrogenic?  PSS had the highest levels of type-B carbonate.

So Aspartame may make you taller by increasing the size of bone nodules.  Glutamane may make you taller by increasing cell size.  Type-B carbonation may be a symptom rather than the cause of reduced chondrogenesis with age as this Type-B Carbonation is in itself caused by other things.

The compositional and physicochemical homogeneity of male femoral cortex increases after the sixth decade.

"The temporal and spatial fluctuations in the dynamics of secondary osteonal remodeling impart heterogeneity to the compositional quality of bone. Bone mineral density (BMD) fails to reflect this heterogeneity as being a single score. Specimens were prepared from mid-diaphyseal portions of human femora (age range 52-85 years old) and grouped based on the anatomical location (anterior, lateral, medial and posterior quadrants). Raman microscopy was used to obtain multiple measurements from each specimen which allowed the construction of histograms of mineralization, crystallinity and carbonation. Average mineralization of the medial quadrant and the data pooled over quadrants significantly increased with age{so bone mineralizaton continues to increase with age even post fusion}. The mean carbonation increased within the observed age range for the pooled data. The variations of values about the mean became tighter for mineralization, crystallinity and type-B carbonation with age, indicating an overall reduction in compositional heterogeneity of aging femoral cortex. Skewness values indicated that the distributions of histograms were not Gaussian. Age-related changes in mean tissue composition are confounded with changes in the variation of tissue make-up about the mean."

"bone tissue became more mineralized and more highly type-B carbonated with age"<-Note though that the youngest subjects were 52.

"The carbonate (CO₃²⁻) ion is distributed in three different locations in bone mineral. When a phosphate ion (PO₄³⁻) present in an apatite crystal is replaced by a carbonate ion (CO₃²⁻){The switch from a phosphate ion to a carbonate ion may affect the potential for chondrogenic differeniation}, the substitution is called type-B carbonate substitution, whereas carbonate ions occupying hydroxide ion (OH⁻) sites are designated as type-A substitution. Unstable free carbonate ions loosely bound on the crystal surface are called labile carbonate."Calcium Phosphate has been shown to activate MMPs.  Those MMPs could affect height growth.  The MMPs helping to build cartilage canals to allow for height growth.

It may be more beneficial to grow taller by having weaker crystals as that can make it easier for the debinding of neighboring crystals from collagen.  This would increase collagen elasticity and stretched collagen would make you taller.

Visualization of a phantom post-yield deformation process in cortical bone.

"A prominent opacity is evident in the process zone of notched thin wafers of bone loaded in tension. Being recoverable upon unloading{thus loading without unloading may alter the bone hindering height growth but loading with a period of unloading will not}, this opaque zone can be stained only when the sample is under load, unlike the classically reported forms of damage which take up the stain in the unloaded state. Furthermore, despite the stain uptake, microcracks are absent in the stained area examined by high magnification optical microscopy and atomic force microscopy (AFM). Therefore, the size scale and the electric charge of the features involved in the process zone were probed at the submicron level by using a wide range of fluorescent dyes of different molecular weights and charges. Negatively charged dyes penetrate the process zone and that dyes greater than 10 kDa (about 10-20 nm in size) were unable to label the process zone. The opacity initiates at about 1% principal strain and the strain accumulates up to 14%. While the opacity was largely recoverable upon unloading, the core regions which experienced large strains had permanent residual strains up to 2%, indicating that the observed deformation phenomenon can be interlocked within bone matrix without the formation of microcracks{If you induce large enough strains you could grow up to 2% taller with no microcracks}. Based on the similarity of size and their known affinity for negatively charged species, exposure of mineral nanoplatelets is proposed as prime candidates. Therefore, the deformation process reported here may be associated with debonding of mineral crystals from the neighboring collagen molecules{so the electrical attraction of mineral crystals to collagen affects how easy it is to grow taller, this could affect the slow down of pubertal height growth as perhaps the bonding of mineral crystals to collagen discourages a chondrogenic phenotype}. Overall, post-yield deformation of bone at the micron scale takes place by large strain events which are accommodated in bone matrix by the generation of nanoscale positively charged interfaces."

To grow taller by tensile strain you need to generate strains large enough for residual strains.

"the peak strain values (11%) observed in our study might be stemming from deformations of collagen fibrils themselves, as opposed to fibrillar sliding"<-the collagen fibers may actually be increasing in length rather than just the sliding of fibers thus making bone taller and longer.

So, Type-B Carbonation(the switching from Phosphorus to Carbonate) may impact pubertal fusion by reducing MMP levels.  It also might affect growing taller by bone stretching by strengthening the attachment of crystals to collagen.

LSJL Photo Proof

Many people have commented that their are no visible gains in the diaphysis of the tibia. As I mentioned here, most of the gains seem to occur in the epiphysis rather than the diaphysis.  People who have grown in the diaphysis like St.it likely have actively differentiating chondrocytes or left over type II collagen so that the stem cells are guided to differentiate near the shaft of the bone.  However, adults are likely to form new growth plates where there are stem cells and that's likely to be along the length of the horns of the tibia rather than at the very end of the tibia which would lengthen the diaphysis.  There's a lot more epiphysis after where the shin bone forks into two pieces than before thus if stem cells differentiate at the region of hydrostatic pressure they are more likely to differentiate along the horns then in the small portion where the tibia is one piece.

Growing along the horns will still make you taller.  It'll be interesting to continue to progress my finger growth as that has horns much shorter than the length of the clamp so if the diaphysis of the fingers grow then it could possibly be a positional problem and you need to clamp closer to where the tibia is one piece and on the epiphysis to grow taller along the diaphysis.

Here's the proof I grew along the horns:

In this picture the calf begins at 3 1/8" and the slope changes at 0(you can't see a lot past 0 but you can still see a change in slope).  The rotation of the calf may matter so the tibia epiphysis seems to be about 4 3/4".  So the length of the epiphysis is 3 1/8"

It may be hard to see the slope change in that picture so here's an earlier picture:

An inch is about 73.8 pixels.  The length of the line is about 262.3 pixels which is about 3.55 inches.  The black line on the ruler is what I used as an inch.  I think it's a little bit less than an inch.  If you go closer to what an inch is you would get a smaller number of total inches than 3.55 so there's still a definite height gain(given that later values are closer to 4).

Here's an early picture of my progress with LSJL.  The slope changes at about 1/8" and the calf changes at about 4".  So a about 3 3/8" of growth.   He's a picture of me with LSJL later.

Where the calf ends is at a little under 4(where the calf ends isn't quite where the epiphysis ends but it's less open to interpretation).  Where the slope changes is a hair under 0.  So we'll say about 4 inches.  You can see that I estimated the end of the epiphysis at 6" in the earlier picture whereas I estimated it at 5 inches in the later picture which is why I dropped it as a measurement.

Growing Tall by dedifferentiating cells into Pluripotent Stem Cells

Many have inquired that whether it's possible to induce height growth via bone modeling.  The bone completely replaces itself every ten years and bone is living tissue then shouldn't it be possible to completely replace the bone with a taller and longer bone?  The issue is that bone is primarily made up of Type I Collagen which is more matrix than bone.  That tissue it would be possible to grow taller via gap repair.  Remember that Marfan's Syndrome which results in tall stature involves a mutation involving genes related to Type I Collagen so there's anecdotal evidence of Type I collagen being able to increase height.   It's the osteoblasts and osteocytes that secrete the Type I Collagen bone matrix so it's those cells that ultimately have to be the ones that need to be reprogrammed in order to make a taller bone.

One way to do that is to cause the dedifferentiation of osteoblasts and osteocytes into Pluripotent Stem Cells and then get them to differentiate into chondrocytes.  Which would then secrete Type II collagen and a cartilagenous template could be formed much like the initial bone begins entirely by cartilagenous template.  If the Type I Collagen matrix proves to be an obstacle then it can be demineralized with acid.  This cartilagenous template would be much bigger than when you were a baby and you would grow much taller from this template as the template would be much bigger than when you were a baby.

But since bone is constantly being remodeled then the type I collagen would gradually be removed by the osteoclasts and the chondrocytes in place of the osteocytes would now be secreting Type II collagen and the bony template would gradually become a cartilagenous one and you would grow taller in your bone like you were a baby. The problem is that osteoblasts and osteocytes secrete TGF-Beta1 which is important for chondrogenesis.  TGF-Beta1 results in Smad 2/3 Phosphorylation.  So with no osteoblasts and osteocytes TGF-Beta1 levels would be lower discouraging chondrogenesis.  However, it's possible to use external sources of TGF-Beta1 and chondrogenesis can occur without TGF-Beta1 just not as well.

So how do we induce dedifferentiation of osteoblasts and osteocytes(we are of course using LSJL as an inducer of chondrogenesis)?

Influence of low oxygen tensions on expression of pluripotency genes in stem cells.

"[Stem cells] are residuing in defined microenvironments - "stem cell niches". The embryonic stem cells (ESC) are derived from embryos which exist in 3-5 percent oxygen condition. This environment is physiologically normal not only for ES cells but also for many other types of stem cells. These observations suggest that low oxygen condition plays a very important role in the maintenance of cell stemness. Pluripotency is regulated by the family of hypoxia inducible factors (HIFs), which are dependent on oxygen tensions[The initial primary ossification center is an hypoxic environment and the growth plate is also hypoxic]. HIF-2-alpha is an upstream regulator of Oct4, which is one of the main transcription factors used to generate the first induced pluripotent stem cells (iPSCs)[So HIF2-alpha upregulates Oct4 which can induce stem cell pluripotency]. It has been shown that knock-down of HIF-2-alpha but not HIF-1-alpha, leads to a decrease in the expression of Oct4, Nanog and Sox2[HIF1-alpha is important for inducing chondrogenesis whereas HIF2-alpha is important for inducing dedifferentiation of stem cells], which are important stem cells markers. The structure of hypoxia inducible factors as well as their behavior in hypoxia and normoxia was described. Therefore optimization of oxygen concentration seems to be crucial from the stem cell transplantation as well as iPS transplantation standpoint. Although many experiments with cell culture under low oxygen condition were performed, there is still much that is unknown. This short review presents some aspects on important issue of hypoxia induced regulation of stemness."

"cells grown in higher  oxygen tension (20% O2) accumulated more mutations  than cells in culture at 3% O2. Most of the mutations were transversions (G:C to T:A), which is a marker of mutation of oxidative DNA damage"

So inducing expression of HIF2-alpha can induce cellular dedifferentiation.  Remember, it's PHD that degrades the Hypoxia inducible factors in high oxygen environments.  So a PHD inhibitor is more important than the oxygen content.  Elevated levels of oxygen just enable PHD to work.  It's also possible that if you increase the levels of the Hypoxia inducible factors enough then they will be able to perform their actions properly regardless of being degraded by PHD.

Let's look specifically at osteoblast dedifferentiation.

Runx2, p53, and pRB status as diagnostic parameters for deregulation of osteoblast growth and differentiation in a new pre-chemotherapeutic osteosarcoma cell line (OS1).

"Osteosarcomas are the most prevalent primary bone tumors found in pediatric[children] patients. Many osteosarcoma cell lines (e.g., SAOS-2, U2OS, MG63) are derived from Caucasian patients. However, patients exhibit individual and ethnic differences in their responsiveness to irradiation and chemotherapy. This motivated the establishment of osteosarcoma cell lines (OS1, OS2, OS3) from three ethnically Chinese patients. OS1 cells, derived from a pre-chemotherapeutic tumor in the femur of a 6-year-old female, were examined for molecular markers characteristic for osteoblasts, stem cells, and cell cycle control by immunohistochemistry, reverse transcriptase-PCR, Western blotting and flow cytometry. OS1 have aberrant G-banded karyotypes, possibly reflecting chromosomal abnormalities related to p53 deficiency. OS1 had ossification profiles similar to human fetal osteoblasts rather than SAOS-2 which ossifies ab initio (P < 0.05). Absence of p53 correlates with increased Runx2 expression[Parathyroid Hormone targets Zfp521 which inhibits Runx2 activity, Runx2 encourages osteoblast differentiation, PTH, Zfp521, and p53 overexpression may be ways to cause osteoblast dedifferentiation], while the slow proliferation of OS1 cells is perhaps attenuated by pRB retention. OS1 express mesenchymal stem cell markers (CD44, CD105) and differ in relative expression of CD29, CD63, and CD71 to SAOS-2. (P < 0.05). Cell cycle synchronization with nocodazole did not affect Runx2 and CDK1 levels but decreased cyclin-E and increased cyclin-A (P < 0.05). Xenotransplantion of OS1 in SCID mice yields spontaneous tumors that were larger and grew faster than SAOS-2 transplants. Hence, OS1 is a new osteosarcoma cell culture model derived from a pre-chemotherapeutic ethnic Chinese patient, for mechanistic studies and development of therapeutic strategies to counteract metastasis and deregulation of mesenchymal development."

 p53 and pRB seem essential for proper cell growth and preventing cancerous tumors if you increase their expression you will potentially lower Runx2 expression, cause osteoblast dedifferentiation, and prevent osteosarcoma.

"the elevated levels of Runx2 present in OS1 cells may promote blood vessel growth in osteosarcoma cells to support tumor growth and increase its metastatic potential"<-so Runx2 increases blood vessal growth which may increase the oxygen content discouraging height growth and VEGF-A seems essential to height growth.  HIF2-alpha upregulates VEGFA.  Knockout of VEGF-A causes cell death in chondrocytes.  You might need permanently elevated levels of HIF1-alpha and HIF2-alpha as loss of VEGF-A may cause chondrocyte cell death.  The blood vessal growth induced by Runx2 may inhibit that.

Shear stress also induces Runx2.  LSJL induces fluid shear stress.  So LSJL itself may inhibit the dedifferentiation of osteoblasts meaning that an alternative method of inducing chondrogenesis may be needed if attempting to dedifferentiate osteoblasts.

Growth and cellular differentiation: a physico-biochemical conundrum? The example of the hand.

"Currently, the predominant hypothesis explains cellular differentiation as an essentially genetic intracellular process[this is the process we are operating on, we are trying to activate genes in stem cells to induce chondrogenesis with LSJL]. The goal of this paper is to suggest that cell growth and differentiation may be, simply, the result of physical and chemical constraints. Bone growth occurs at the level of cartilage conjunction (growth plate) in a zone of lesser constrain[So changing the level of constrain is a mechanism of growing taller, distraction osteogenesis changes the level of constrain, however this hypothesis doesn't explain growth abnormalities like gigantism]. It appears that this growth also induces muscle, tendon, nerve and skin elongation. This cartilage growth by itself seems to explain the elongation of the hand. Growth stops at puberty likely because of feed-back from an increasing muscle load[again Gigantism and myostatin deficient organisms would seem to refute this hypothesis as they are very tall and muscular]. The ossification (that is differentiation of cartilage into bone) appears to result from the shear stress induced[this is true, however, new stems can differentiate into cartilage replacing the ossified ones, this muscle load only increases growth rate and not adult height]. The study of bone age, obtained by X-ray picture of the hand, shows that ossification of epiphyses is very precise both in time and space. Computer modelization suggests that this ossification occurs where shear stress is greatest. The cartilage which does not ossify (joint, nose, larynx, ear, bronchus, etc.) is not exposed to high shear. Shear stress induces the secretion of extracellular matrix and a change of the biochemical environment of the cell. Precipitation of calcium phosphate, as in ossification, seems related to the alkalosis induced by shear stress. To speak in more general terms, loss of cellular differentiation, as occurs with cancer, can result from a change in the physical-chemical environments."

This hypothesis is not entirely correct but the environment may play a role in osteoblast differentiation.

"The use of rigid fixation for fracture of the extremity is common place. Epiphyses plated for a year show increased bone differentiation, premature closure and growth arrest"<-so yes the bone environment does affect height growth.  So rigid fixation reduces height growth likely because the elasticity of the bone is essential to height growth.  Some stretching of the bone is likely involved when you sleep and that can't occur when fixated.  How can hypertrophic chondrocytes push the bone apart from two ends when standing?  It likely can't.

"Extracellular matrix and/or low oxygen tension differentiates stem cells into chondrocytes"

The loss of shear stress may be enough to induce dedifferentiation of osteoblasts due to lower Runx2 levels.  As the study says, that the areas without ossification are those with lower shear stress.  So if you temporarily lowered shear stress(by say immobilization-like space flight) then would osteoblasts begin to dedifferentiate.  Then you could reinduce mobilization and grow taller than before?  However, astronauts do not experience permanent height growth.  Maybe they don't cycle enough to notice a difference.  Like say each space trip followed by landing induces a few millimeters of height growth that would not be enough to notice.


There are factors that can in general induce dedifferentiation like Oct4 and factors specific to osteoblasts like Runx2.  It may be possible to manipulate shear stress to grow taller but it wouldn't be as simple as cycling off and on LSJL.  You would have to be completely immobilized or in a low gravity environment.  It may also be possible to experiment with Runx2 inhibition or increase activity of Parathyroid Hormone or of Zfp521.


Bone regenerates via dedifferentiation of osteoblasts in the zebrafish fin.

"While mammals have a limited capacity to repair bone defects, zebrafish can completely regenerate amputated bony structures of their fins. Fin regeneration is dependent on formation of a blastema, a progenitor cell pool accumulating at the amputation plane. It is unclear which cells the blastema is derived from, whether it forms by dedifferentiation of mature cells, and whether blastema cells are multipotent. We show that mature osteoblasts dedifferentiate and form part of the blastema. Osteoblasts downregulate expression of intermediate and late bone differentiation markers and induce genes expressed by bone progenitors. Dedifferentiated osteoblasts proliferate in a FGF-dependent manner and migrate to form part of the blastema. Genetic fate mapping shows that osteoblasts only give rise to osteoblasts in the regenerate, indicating that dedifferentiation is not associated with the attainment of multipotency. Thus, bone can regenerate from mature osteoblasts via dedifferentiation, a finding with potential implications for human bone repair."

Maybe we can dedifferentiate our osteoblasts into stem cells and then into chondrocytes.

"In salamanders and fish, appendages (limbs, fins, and tails) regenerate via formation of a blastema, a mass of proliferative undifferentiated cells that contains the progenitors of the regenerating tissues"

"stump osteoblasts downregulate the expression of mature and intermediate differentiation markers in response to fin amputation. Amputation in the middle of a ray segment resulted in osteocalcin:GFP downregulation and distal shift of GFP signal also in the adjacent uninjured segment, suggesting that putative signals regulating osteoblast dedifferentiation spread from the injured segment to neighboring bone segments."

" glycoprotein secreted from immature bone cells, Tenascin , was induced in osteoblasts close to the amputation plane"

CXXC5

It looks like Cxxc5 could be an important factor.

CXXC5 mediates growth plate senescence and is a target for enhancement of longitudinal bone growth

"Longitudinal bone growth ceases with growth plate senescence during puberty. However, the molecular mechanisms of this phenomenon are largely unexplored. Here, we examined Wnt-responsive genes before and after growth plate senescence and found that CXXC finger protein 5 (CXXC5), a negative regulator of the Wnt/β-catenin pathway, was gradually elevated with reduction of Wnt/β-catenin signaling during senescent changes of rodent growth plate. Cxxc5−/− mice demonstrated delayed growth plate senescence and tibial elongation{If we can find a way to inhibit Cxxc5 we can grow taller}. As CXXC5 functions by interacting with dishevelled (DVL), we sought to identify small molecules capable of disrupting this interaction. In vitro screening assay monitoring CXXC5–DVL interaction revealed that several indirubin analogs were effective antagonists of this interaction. A functionally improved indirubin derivative, KY19382, elongated tibial length through delayed senescence and further activation of the growth plate in adolescent mice. Collectively, our findings reveal an important role for CXXC5 as a suppressor of longitudinal bone growth involving growth plate activity."

" CXXC5 expression progressively increased in the resting, proliferative, and hypertrophic chondrocytes undergoing growth plate senescence. We also found that estrogen, a sex hormone that is elevated during the pubertal period, induced CXXC5 expression followed by decrement of β-catenin in chondrocytes. Furthermore, Cxxc5−/− mice displayed enhanced chondrocyte proliferation and differentiation in the late pubertal growth plate as well as longer tibiae at adulthood. "

Chondroblastoma

Metaphyseal and diaphyseal chondroblastomas.

"There were four males and three females (age range 2-25 years) [with chondroblastomas]. Locations included proximal femur (n = 1), distal femur (2), proximal humerus (2), clavicle (1), and proximal radius (1). All lesions showed marginal sclerosis. A periosteal reaction was seen in five cases (71%), cortical expansion in four cases (57%), and chondroid matrix in four cases (57%). A CT (two cases) demonstrated a matrix in both cases. An MR (one case) showed extensive perilesional edema. Bone scan (one case) showed intense uptake."


"A 20-month-old female with swelling of the right forearm"<-that is certainly an alteration in bone shape and size.


"A 15-year-old female presenting with pain in the right shoulder""This lesion borders but does not transgress the closed growth plate"<-chondroblastomas can occur in closed growth plate.

25 year old male also with chondroblastoma and closed growth plate.

"chondroblastoma originates from a mesenchymal cell committed toward chondrogenesis via active growth plate signaling pathways"

Possible Risks of Lateral Synovial Joint Loading

If you look at the study The Role of Dynamic Flexion in Spine Injury you'll see that disc injury does not occur when loads exceed 30% of the disc's peak tolerance.  Discs are made of cartilage.  The point is that cartilage damage mostly occurs during light repetitive loads like marathon running.  Damage to cartilage is not anabolic.  Load to cartilage is anabolic and helps stimulate the genetic expression of the cartilage.  It's damage to bone that is anabolic to cartilage as exemplified by knee microfracture surgery.  Where drilling a hole into a bone in the knee releases stem cells that differentiate into chondrocytes thereby healing the cartilage(there is genetic blocking preventing endochondral ossification occurring from the articular cartilage).

To preserve cartilage health you have to cause enough damage to the bone to release microfractures allowing the cartilage to heal.  Cartilage damage is caused by low repetitive force which doesn't generate bone microfractures or extremely high forces which totally denatures the cartilage.  Cartilage damage is not usually caused by moderate forces with moderate duration like LSJL. 

Lifelong voluntary joint loading increases osteoarthritis in mice housing a deletion mutation in type II procollagen gene, and slightly also in non-transgenic mice 

"Objectives: To investigate the effects of voluntary running on the incidence and severity of osteoarthritis (OA) and associated changes in cartilage matrix and subchondral bone in a transgenic Del1 mouse model for OA. Methods: Del1 mice and their non-transgenic littermate controls were housed from the age of 5–6 weeks to 15 months in individual cages with running wheels. The running activity of each mouse was monitored for the entire 12 month period. Additional Del1 and control mice were housed in individual cages without running wheels. At the end of the experiment the severity of OA was evaluated by light microscopy, and the articular cartilage matrix changes by digital densitometry and quantitative polarised light microscopy.

Results: Lifelong voluntary running increased the incidence and severity of OA significantly in Del1 mice (transgenic runners), and slightly also in non-transgenic runners. Severe OA changes increased from 39% in transgenic non-runners to 90% in transgenic runners (p=0.006) in lateral tibial condyles, and from 24% to 80% (p=0.013) in lateral femoral condyles, respectively. The proteoglycan content of articular cartilage was reduced in transgenic runners in comparison with transgenic non-runners (p=0.0167), but a similar effect was not seen in non-transgenic runners compared with non-transgenic non-runners. No attributable differences were seen in the collagen network of articular cartilage or in the subchondral bone between any of the groups.

Conclusion: The Del1 mutation has earlier been shown to disturb the assembly of the cartilage collagen network and thereby increase the incidence and severity of OA with age. In this study, voluntary running was shown to increase further cartilage damage in the lateral compartments of the knee. This suggests that articular cartilage in Del1 mice is less resistant to physical loading than in control mice. Despite severe OA lesions in the knee joint at the age of 15 months, Del1 mice continued to run voluntarily 2–3 km every night."

Okay, so the issue is that joint loading reduces the proteoglycan content of the articular cartilage.  Chondroitin is a proteoglycan and you can supplement with that.  If the proteoglycan content of the cartilage is being lost at a faster rate than your body can generate it's own supply then supplementing with chondroitin is a good solution.

The main issue with LSJL is it not working.  I have grown 1 1/2" inch with LSJL.  There are two organic comments claiming results with LSJL.  I have received two or so other emails claiming LSJL results.  I have some people who have not gotten results but they also say that they gave up after a week.  It took me a month to find the right way to load the bones to gain height.  Myostatin inhibits cellular proliferation so you may have to increase the load to overcome that and other negative feedback mechanisms.

There are possible ways that LSJL could not work.  Maybe the genetic expression of the hyaline cartilage growth plate line alters so that no further growth occurs after puberty. But we know that mechanical loading can alter genetic expression(mechanotransduction), and H. Yokota plus P. Zhang got results in their rat study.  People are getting results from LSJL.

If you feel pain in your ligaments, then maybe you need to lighten the pressure you use on your joints and epiphysis.  When you first work out, your joints pop a lot but over time they adapt.  Your ligaments will adapt and will learn to relax when you perform LSJL.

You are trying to cause microfractures in the epiphysis of your long bones.  The ends of your bones may feel red or tender.  That is good.  Bone damage is anabolic.  When you feel pain, endorphins are released as well.  Focus on the endorphins rather than the pain.  The pain with the table clamp is not that bad.  Most of the pain occurs when releasing the table clamp rather than tightening it.  And the table clamp feels good increasing fluid flow in the bone.  The ankle for example is kind of hard to do as the end of the fibula doesn't always align to the end of the tibia but if you practice then you can find a place on your ankle where you can get both.

The elbow is hard to only get bone but I'm getting better.  The wrist I think I've got down. You need to focus on the benefits you're getting from doing your knee and then use that positive reinforcement to try to do the more complicated joints.  There is no substitute for practice.

Summary:

-Osteoarthiritis occurs as a result of a declining proteoglycan content.  Supplement with Chondroitin if you're worried about it.

-Your connective tissue will adapt over time to the demands placed on it due to LSJL.  Things should get easier.

-If you keep practicing your technique will improve allowing you to target more bone(although maybe articular cartilage loading at end of bone is needed) thus also reducing pain and other issues from LSJL.

Can Lateral Synovial Joint Loading cause Deep Vein Thrombosis due to the hydrostatic pressure it induces?  Let's look at the typical cause of DVT which is air travel.

Air travel and the risk of thromboembolism.

"Almost two billion people use commercial aircraft annually. Long-haul flights are taken by over 300 million people. A serious complication of long-distance travel (or prolonged time of flight) is thromboembolism. The real incidence of the problem is difficult to evaluate since there is no consensus about the diagnostic tests or limitation of time after landing connected to the VTE complication. A direct relation between VTE incidence and long-distance flights has been documented[DVT is caused mostly by long term increases in pressure of about 8 hours, far greater than the 30 seconds to 5 minutes that loading for LSJL should be]. The risk for DVT is 3–12% in a long-haul flight. The pathophysiologic changes that increase VTE risk at flight are stasis (sitting in crowded condition), hypoxia in the airplane cabin, and dehydration. Individual risk factors for air travel-related VTE include age over 40 years, gender (female), women who use oral contraceptives, varicose veins in lower limbs, obesity and genetic thrombophilia[All these factors involve sustained pressure not intermittent pressure, you don't have a high body fat percentage for short bursts of time]. Prevention measures include environmental protection such as keeping the pressure inside the airplane cabinet in hypobaric condition, avoiding dehydration and prolonged sitting. For individuals at increased risk, venous blood stasis can be reduced by wearing elastic stockings and prophylactic use of low-molecular-weight heparin."

Why don't people grow taller by traveling on airplanes?  That's atmospheric pressure rather than hydrostatic pressure.

Increasing height with Letrozole?

Estrogen is a needed compound that needs to be at an equilibrium point to maximize height.  Estrogen has positive effects on cellular proliferation however ER-alpha and ER-Beta receptors in the growth plate may reduce height.  However, some of the positive benefits of can be replicated by compounds like Alfalfa without the negative effects on the ER-alpha and ER-Beta receptors in the growth plate.  Tamoxifen is an aromatase inhibitor that has benefits independent of it's Estrogen inhibition.  However, sustained usage of Tamoxifen has negative consequences thus a proper cycling regime of Tamoxifen has to be in place before starting to take Tamoxifen to get only the good benefits of Tamoxifen.  Tamoxifen is unique as it targets directly the estrogen receptor that reduces height.

Can you use Letrozole and Alfalfa plus other estrogenic compounds to get the benefits of estrogen without the ER-Alpha and ER-Beta mediated side effects?

However, it may be that ER-Alpha can be activated even during Aromatase inhibition.

An “Omics” Approach to Determine the Mechanisms of Acquired Aromatase Inhibitor Resistance

"Although these drugs work effectively,  [individuals acquire] resistance to the AIs. To characterize the resistant mechanisms, a set of MCF-7aro cell lines that acquired resistance to the AIs was generated. Through an “Omics” approach, we found that the resistance mechanisms of the three AIs (anastrozole, letrozole, and exemestane) differ and activation of estrogen receptor alpha (ERα) is critical for acquired AI resistance. Our results reveal that growth factor/signal transduction pathways are upregulated after ERα-dependent pathways are suppressed by AIs, and ERα can then be activated through different crosstalk mechanisms[ER-alpha can still be activated after aromatase has been inhibited]."

"One clinical feature associated with AI treatment is the lack of crossresistance among the three AIs, suggesting that the different AIs use different resistance mechanisms or that AI-resistant cells developed supersensitive responses to ER"<-So you may want to cycle between three aromatase inhibitors

"We found that T or E2 induced proliferation of MCF-7aro cells at a rate six times faster than the untreated cells. In addition, the T-induced proliferation of MCF-7aro cells was effectively suppressed by LET, ANA, or TAM."<-this is the problem with aromatase inhibitors it decreases cellular proliferation by a factor of 1/6.  Although this can be mediated somewhat with Ipriflavone(Alfalfa).

If Letrozole can be effective without other compounds replicating the good effects of estrogen, imagine if letrozole was used with estrogen-like compounds that stimulated cellular proliferation.

A double-blind, placebo-controlled comparison of letrozole to oxandrolone effects upon growth and puberty of children with constitutional delay of puberty and idiopathic short stature.

"We compared the effects of letrozole with that of oxandrolone on predicted adult height (PAH), puberty, bone mineral density, serum insulin-like growth factor 1 (IGF-1) and blood lipoproteins.
 In a prospective, double-blind, randomized, placebo-controlled clinical trial, 91 CDGP boys (12.6-14.6 years old) with predicted short stature were treated with letrozole (2.5 mg/day), oxandrolone (2.5 mg/day), or placebo, at the outpatient pediatric endocrine clinic of Mofid Children's Hospital in Tehran for 2 years.[this is a pretty long time]
Letrozole differed from oxandrolone and placebo in significantly increasing PAH (p < 0.05), and slightly but significantly decreasing HDL-cholesterol. Oxandrolone, and to a lesser degree letrozole, significantly increased the height standard deviation score and bone age compared to placebo[interesting that both increased cellular proliferation rate which is not what you would expect with estrogen inhibition, maybe the boys had too high estrogen and the aromatase inhibitors knocked them down to the optimal range].
This first randomized controlled clinical trial in CDGD teenage boys with predicted short stature shows that letrozole increases PAH more than oxandrolone and advances pubertal stage and bone mineralization less."

"There was no significant difference [in BMD] between the letrozole and the placebo group during treatment[this is not what you'd expect as you'd think that with estrogen levels decreasing BMD would go down, this again makes it seem like the boys had above equilibrium levels of estrogen and these aromatase inhibitors knocked them down to equilibrium]. BMD in the oxandrolone group progressively increased over the 2-year period to 1.2 ± 0.8 in the lumbar spine and 1.1 ± 0.7 in the femoral neck. These both became significantly higher than on (p < 0.001) letrozole (–1.5 ± 0.9 and –1.2 ± 0.7, respectively) or placebo (–1.5 ± 1.1 and –1.2 ± 0.6, respectively), which did not differ significantly"


Aromatase inhibitors in pediatrics.


"Aromatase, an enzyme located in the endoplasmic reticulum of estrogen-producing cells, catalyzes the rate-limiting step in the conversion of androgens to estrogens in many tissues. The clinical features of patients with defects in CYP19A1, the gene encoding aromatase, have revealed a major role for this enzyme in epiphyseal plate closure, which has promoted interest in the use of inhibitors of aromatase to improve adult height. The availability of the selective aromatase inhibitors letrozole and anastrozole--currently approved as adjuvant therapy for breast cancer--have stimulated off-label use of aromatase inhibitors in pediatrics for short stature in boys.  Although aromatase inhibitors appear effective in increasing adult height of boys with short stature and/or pubertal delay, safety concerns, including vertebral deformities, a decrease in serum HDL cholesterol levels and increase of erythrocytosis, are reasons for caution."


Normal individuals would have to be treated with letrozole to see if the benefits of letrozole are due to high estrogen individuals knocked down to the equilibrium way as only people with short stature were used which are expected to have some differentiation from mean.  Alternatively, higher doses of letrozole could be used to see how much the benefits are dose dependent.  Given that letrozole was shown to decrease height in prepubertal rats and prepuberty it's expected that estrogen levels are below equilibrium, it is likely that the benefits of letrozole are based on your deviation from equilbrium in addition to acquired estrogen receptor alpha resistance.

Grow Tall with Tamoxifen?

Tamoxifen is an anti-estrogenic compound.  You need some estrogen levels for optimal growth however many of the beneficial effects of estrogen can be mimicked by Alfalfa.  Tamoxifen induces apoptosis in growth plate chondrocytes but apoptosis is a part of endochondral ossification both as both a part of terminal differentiation and to help align the growth plate.

Too high levels of estrogen seem to have a bigger height reduction effect than too low with too high estrogen levels increasing apoptosis whereas both too high and low levels of estrogen decreased cell proliferative capacity(thus both high and low estrogen will reduce height).  However, Alfalfa may be able to rescue the cell proliferating ability enabling you to safely lower estrogen without worrying about decreasing it too much.

Mice who were knockouts for GR30, which is an estrogen receptor, were found to be taller than the mice with GR30.  Males and females may respond differently to estrogen.

Tamoxifen + Alfalfa may be an intriguing modality in which to increase height during development.

Tamoxifen Stimulates Cancellous Bone Formation in Long Bones of Female Mice  

"Selective estrogen receptor modulators (SERMs) have been developed as a means of targeting estrogen’s protective effect on the skeleton. Although it is well established that SERMs such as tamoxifen inhibit bone resorption in a similar manner to estrogen, whether this agent shares estrogen’s stimulatory action on bone formation is currently unclear. To address this question, we compared the effect of treatment for 28 d with 17ß-estradiol (E2; 0.1, 1.0 mg/kg·d) and tamoxifen (0.1, 1.0, or 10 mg/kg·d) on cancellous bone formation at the proximal tibial metaphysis of intact female mice. E2 stimulated the formation of new cancellous bone throughout the metaphysis. A similar response was observed after administration of tamoxifen, the magnitude of which was approximately 50% of that seen after E2. As expected, E2 was found to suppress longitudinal bone growth, but in contrast, this parameter was stimulated by tamoxifen[tamoxifen also increased growth plate width]. We conclude that tamoxifen acts as an agonist with respect to estrogen’s stimulatory action on bone formation but as an antagonist in terms of estrogen’s inhibition of longitudinal growth, suggesting that the protective effect of SERMs on the skeleton is partly mediated by stimulation of osteoblast activity."

"the activity of tamoxifen requires biotransformation to 4-hydroxy-tamoxifen, which process may vary between mouse strains."<-this may explain why tamoxifen increases height in some studies but not in others.

So Tamoxifen was found to stimulate longitudinal growth in females and again male and female receptors may work differently.  Here's a study that says that Tamoxifen may lower height in males:

Tamoxifen impairs both longitudinal and cortical bone growth in young male rats.

"Tamoxifen (Tam) was recently shown to inhibit the growth of cultured fetal rat metatarsal bones and thus might also affect bone growth in vivo. Four-week-old Sprague-Dawley rats were gavaged daily with vehicle alone (peanut oil), Tam (40 mg/kg/d; 1 or 4 wk), or estradiol (40 microg/kg/d; 4 wk). Five of the 10 rats in each group were killed after 4 wk and the other five after 14 wk of recovery. Bone growth was followed by repeat DXA scans, whereas other bone parameters and spine length were evaluated by pQCT and X-ray at the time of death. Four-week Tam treatment significantly decreased body weight, nose-anus distance, spinal and tibial bone lengths, trabecular BMD, cortical periosteal circumference, and bone strength and also reduced serum IGF-I levels (424 +/- 54 versus 606 +/- 53 ng/ml in control; p < 0.05). Analysis of the tibial growth plate of treated rats showed elevated chondrocyte proliferation (BrdU) and apoptosis (TUNEL), as well as decreases in the number of hypertrophic chondrocytes and in the size of terminal hypertrophic chondrocytes. Despite a complete catch-up of body weight after 14 wk of recovery, the tibia was still shorter (p < 0.001) and its cortical region was smaller. We conclude that, when administered at a clinically relevant dose, Tam causes persistent retardation of longitudinal and cortical radial bone growth in young male rats. Our findings suggest that this inhibition results from local effects on the growth plate cartilage and systemic suppression of IGF-I production. Based on these rat data, we believe that Tam, if given to growing individuals, might compromise cortical bone growth, bone strength, and adult height."

"Tam induces permanent growth arrest of cultured fetal rat metatarsal bones, an effect associated with specific elimination of chondrocytes, primarily in the resting zone of the growth plate, through apoptosis"<-regardless of apoptosis' important of apoptosis you usually want apoptosis to occur later in endochondral ossification not in the "resting zone"

"the rate of chondrocyte proliferation was increased in the Tam 1-wk (p < 0.05) and Tam 4-wk (p < 0.01) group[This is good]. In addition, 4 wk of treatment with Tam significantly enhanced the frequency of apoptosis among the same cells[Maybe Tamoxifen needs to be cycled as the increased apoptosis may be a negative feedback mechanism to Tamoxifen]"<-The study with the positive benefits of tamoxifen only did the study for 28 days(exactly four weeks) so they didn't notice the apoptosis induction.

"The findings clearly showed that the growth retardation caused by Tam is associated with both elimination of chondrocytes through apoptosis and inhibition of chondrocyte differentiation. These results are consistent with our previous observation that Tam induces apoptosis of stem-like chondrocytes in cultured fetal rat metatarsal bones"

So Tamoxifen looks like it has potential but the appropriate cycling regime needs to be be in place and it needs to be clear why there's a negative feedback to Tamoxifen.  Tamoxifen has effects that cannot be rescued by Alfalfa.

And it's unknown how long off of Tamoxifen you have to be to get back the positive benefits from it.  You'd have to know things like the half-life to see how long it stays in your system.

So right now Tamoxifen is too risky to add to your height increase regime but if we keep forming our collective heads together maybe we can come up with an effective cycling regime.

Estrogen reduces cellular aging in human mesenchymal stem cells and chondrocytes.

[This is contrary to other evidence that estrogen accelerates both senescence and decreases proliferation thus decreasing height]

"Chondrocyte aging is associated with cartilage degeneration and senescence impairs the regenerative potential of mesenchymal stem cells (MSCs). Physiologic premenopausal concentrations of 17β-estradiol (E(2)) significantly decelerated telomere attrition in MSCs and chondrocytes while postmenopausal E(2) concentration had no significant effects[menopause lowers estrogen levels so too high estrogen levels inhibit telomere shortening]. The estrogen agonist-antagonist tamoxifen did not affect telomere biology, but inhibited the E(2) -stimulated reduction in telomere shortening. E(2) and tamoxifen did not influence cell proliferation, cell morphology, and β-galactosidase staining in chondrogenic cells. E(2) treatment did not affect the telomere-associated proteins TRF1 and TRF2. E(2) had no regulatory effects on the expression rates of the cell cycle regulator p21 and the DNA repair proteins SIRT1 and XRCC5. In spite of reducing telomere shortening in aging MSCs and chondrocytes, estrogen is not able to prevent somatic cells from replicative exhaustion and from finally entering senescence."

So just because estrogen reduces cellular aging by telomere shortening doesn't mean that estrogen can't accelerate senescence by some other mechanism.

"The cell division-dependent telomere shortening is prohibited by the enzyme telomerase, synthesizing telomeric repeats by reverse transcription"<-Hence why Astragalus may have some role in a height increase routine.

"E2 enhances telomerase activity and the expression of the catalytic subunit hTERT via ERα."<-which tamoxifen inhibits.