Monday, June 28, 2010

Growth Plates: They don't fuse

Note:  I am still a little sick.  I will start with pictures again this Thursday.  Virus is a confounding variable as the body may with-hold anabolic factors to stop the virus.  I'm still working out and performing LSJL but I'm waiting until I'm healthier to start measuring.  Also this page is inaccurate as the hyaline cartilage growth plate line does eventually fuse into bone but that does not inhibit height growth by new growth plate formation. 

Look at this page.  It's a pretty interesting explanation of all the ways that growth occurs but I want you to take note of one sentence:

6). The epiphysis ossify.

*Hyaline cartilage remains on the growth plate and the articulating surface.

The hyaline cartilage is not what's hypertrophying(differentiating) and then being ossified.  During primary ossification, stem cells turn into new chondrocytes(differentiate into chondrocytes) and then those chondrocytes are fused into bone.  The hyaline cartilage does not fuse into bone because there is already an extracellular matrix.  Stem cells within or transported to the hyaline cartilage by methods such as LSJL differentiate into chondrocytes.  Those chondrocytes hypertrophy and those chondrocytes are ossified into bone.  The chondrocytes within the hyaline cartilage do hypertrophy and eventually ossify.

Bone formed at the primary and secondary ossification centers push the articular(hyaline) cartilage away.  Some being at the end of the bone and others at the growth plate line.  The reason that growth doesn't occur indefinitely is a lack of stem cells in the hyaline cartilage growth plate line which is what LSJL tries to rectify.  The hyaline cartilage environment has genetic markers that shape the stem cells into hypertrophying and differentiating chondrocytes.  Methods like IGF-1 increase height growth by increasing stem cell proliferation thereby increasing growth.

Now, the reason that a growth plate line does not remain after fracture healing like in limb lengthening surgery is that in fracture healing endochondral ossification occurs as a result of periosteal progenitor cells which differentiate into chondrocytes and so on.  There's never any hyaline cartilage matrix so the entirety of the homeless chondrocytes are ossified.

So you see growth plates don't fuse.  New chondrocytes are created from stem cells and those chondrocytes are ossified.  Not the ones in the growth plate.

Mechanisms of Growth Plate Maturation and Epiphyseal Fusion

"Longitudinal growth occurs within the long bones at the growth plate. During childhood, the growth plate matures, its total width decreases and eventually it disappears at the end of puberty with complete replacement by bone along with cessation of longitudinal growth. The exact mechanism of epiphyseal fusion is still not completely understood and experimental studies are complicated by the fact that there is a species difference between humans and rabbits that do fuse their growth plates and rodents that do not. This mini review summarizes hypotheses and theories postulated in the literature regarding growth plate maturation and epiphyseal fusion. Growth factors, local regulators and hormones involved in growth plate maturation are described as well as four postulated hypotheses and theories regarding the final steps in epiphyseal fusion: apoptosis, autophagy, transdifferentiation and hypoxia. A better insight into the mechanisms of epiphyseal fusion may ultimately help to develop new strategies for the treatment of cartilage and growth disorders. "

Remember that growth plates have to do more than merely transform into bone otherwise they would never increase in length they have to deform the bone into a longer shape which is why I think apoptosis is the most logical final step as that could generate force deforming the bone.

"Senescence is a term for the structural and functional changes over time in the growth plate, such as a gradual decline in the overall growth plate height, proliferative zone height, hypertrophic zone height, size of hypertrophic chondrocytes and column density"<-senescence is what we try to prevent not fusion

"A new hypothesis is that proliferation is influenced by a multiorgan genetic program and that proliferation declines when this genetic program has reached a critical point"<-although this would not explain individuals of different proportions

"A most widely held hypothesis is that at the chondro-osseous junction site of the growth plate, terminally hypertrophic chondrocytes die by undergoing apoptosis leaving behind a scaffold of cartilage matrix for osteoblasts that invade and lay down bone[this apoptosis also releases water that generates force to induce bone deformation]. It is assumed that the same mechanism eventually also results in epiphyseal fusion. Studies in the rat showed that apoptosis-regulating proteins (the so-called caspases, which are cysteine proteases) are expressed in the growth plate and that there is an increased expression of proapoptotic factors with age. Typical morphological changes when cells undergo apoptosis include cell shrinkage with intact organelles and integrity of membranes, pyknotic nuclei by aggregation of chromatin, fragmented DNA, partitioning of the cytoplasm and nucleus into membrane-bound vesicles (apoptotic bodies) and absence of an inflammatory response. Interestingly, several recent studies failed to demonstrate a typical apoptotic appearance in the terminal hypertrophic chondrocytes and, therefore, these studies have questioned whether apoptosis is the final mechanism through which chondrocytes die in the terminal hypertrophic zone. Furthermore, we recently analyzed a unique piece of fusing human growth plate tissue during epiphyseal fusion and were not able to find signs of classical apoptosis"<-Note that if apoptosis is a critical role during endochondral ossification than it is logical not to find signs of apoptosis during fusion as this stage of growth may release factors to encourage further growth.  It may be at time of senescence apoptosis ceases and other forms of cell death occur.

"The oldest hypothesis is that at the chondro-osseous junction site of the growth plate terminal hypertrophic chondrocytes can transdifferentiate into osteoblasts. This theory is based on mostly organ and cell culture models, like for example chondrocytes in mice and murine metatarsal bone cultures that were able to transdifferentiate into osteoblasts producing bone matrix. Adams and Shapiro discussed that evidence in support of transdifferentiation is mostly circumstantial. It is based on microscopic examination of chondrocyte and osteoblast populations at the chondro-osseous junction and results from different studies are inconsistent. Although direct evidence is lacking, others speculate that transdifferentiation is present at the chondro-osseous junction because terminally differentiated cells are producing collagen type 1 together with extracellular matrix factors. In addition, to our knowledge human studies on transdifferentiation at the chondro-osseous junction in the growth plate have not been described."<-some chondrocytes may transdifferentiate into osteoblasts whereas others may undergo apoptosis.  Transdifferentiation is unlikely to induce bone deformation.

"In a unique human growth plate tissue specimen in the process of undergoing epiphyseal fusion, we observed a dense border of thick bone surrounding growth plate remnants at the site where normally the growth plate is located[just because apoptosis is not involved during fusion does not mean that it may not be involved in earlier stages of development]. In addition, signs of hypoxia and early necrosis were found. We postulated that the border of dense bone might function as a physical barrier for oxygen and nutrients to reach the fusing growth plate resulting in hypoxia and eventually cell death in a nonclassical apoptotic way through necrosis or a mixture of apoptosis and necrosis[if this is the case than osteoclasts can help continue endochondral ossification by degrading this dense bone]. In line with this new hypothesis, White et al recently demonstrated bridging bone in the center of a distal human tibial growth plate obtained from a 12.9-year-old girl, which might be an early sign of this shelling process. Signs of a hypoxia-related process were also reported by Stewart et al who observed an upregulated expression of hypoxia-inducible factor 2α mRNA during chick and murine chondrocyte differentiation in vitro. Hypoxia-inducible factor 2α knockout mice are small, which might indicate that this gene has an important role in the growth plate and subsequently in the regulation of longitudinal growth. Thus, epiphyseal fusion might be a hypoxia-related process leading eventually to cell death of growth plate chondrocytes."

It is likely that all four methods are involved with apoptosis being the most important but apoptosis is likely not present near fusion.


  1. Good, don't measure if you are sick, the lifestyle is different when sick and measurement are too falsed... wait...

    But consider the method of sitting/stand up ratio that I have speack about in your last LSJL post... You eliminate measure noise of vertebral disk compression...

  2. Does the growth plates thing imply that there's a possibility for future clinical methods to come out? I'm looking forward to it.

  3. how do we increase the presence of IGF-1??

  4. btw, tyler, what do you tink of sky shinbone routine 2011? do you think its feasible?

  5. Interesting, but what then is seen on x-rays when they say the growth plates have fused?

  6. Re: Clinical Methods. I think they should try injecting stem cells into the hyaline cartilage growth plate line and activating the appropriate genetic expression.

    Re: X-rays & Growth Plate Fusion. X-rays mostly show bone. If you look at X-rays, the articular cartilage(which is the same as hyaline cartilage) shows up but mostly as just whiter bone. On an X-ray the growth plate just looks like a fracture gap. You can see a little bit of whiteness here around the growth plate line.

    I see whiteness really high up on the tibia that's about the same texture as what the articular cartilage shows up as. In that picture the femur is too blurry to make out a growth plate line.

  7. So, when they believe the growth plate has fused, it is because they no longer see a gap where the growth plate is, because the hyaline cartilage has shrunk?

  8. No the hyaline cartilage doesn't shrink. It's just that the hypertrophic chondrocytes look like a gap in an x-ray because there's no extracellular matrix. The hyaline cartilage resting zone is always there. It's the other areas like the proliferating and hypertrophy zone that are not there.

    How's LSJL going for you by the way?

  9. Ah so these other areas are what disappear from the x-ray.

    It's going well. I haven't measured in a couple weeks though. The data I do have shows a continual increase in height. Judging by eye, it looked like somewhere around an inch between my initial measurement and my latest. I'll actually measure the distance with my next measurement.

  10. any recent data on this, is it verified in the field?


  12. i grew a centimeter with this. i verified this with a wall measure.but i stoped growing soon after starting.i think my bones got stronger and now they dont allow fluid flow. i tried taking months off, but alas, the bones did not seem to soften any..
    later i tried steroids(dianobol bucause its a igf1 booster. i tried just one leg to see if it worked.the wall sais it didnt.Next time im doing testosterone. 650 mg a week and ill try again.

  13. any recent data on this, is it verified in the field?
    BUMP^^^^^ we need you to do a follow up on this ,
    is it the consensus of the scientist that the growth plate fuses?
    can you explain this, in a updated blog post?