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Can bone remodeling contribute to height?

Microfracture theory and bone remodeling theory are two theories floated around that can possibly contribute to height. Here’s a review paper about bone remodeling, is there anything in it related to height?

Toward a Unifying Theory of Bone Remodeling

“remodeling increases both when mechanical loading is excessively low{there’s a training program called Hypertrophy Specific Training or HST that involves using periods of low mechanical loading to make muscle more susceptible to high mechanical loading would it be possible to use the same principles for bone?}, that is, in a disuse state, and when it is excessively high, producing substantial fatigue damage, is contrary to the widely held assumption that a signal generated by osteocytes in proportion to mechanical loading stimulates bone lining cells to activate remodeling. The new theory resolves this disparity by assuming that lining cells are inclined to activate remodeling unless restrained by an inhibitory signal{so if we remove this inhibitory signal we can can have bone remodeling all the time?}, and that the mechanically provoked osteocytic signal serves this inhibitory function.
Consequently, remodeling is elevated when signal generation declines due to reduced loading, or when signal generation or transmission is interrupted by damage due to excessive loading{Thus we could potentially get bone remodeling without mechanical loading}. Otherwise, remodeling is kept at a relatively low level by inhibitory signals produced through physiologic loading.
Furthermore, the inhibitory signal is postulated to be identical to that proposed by Marotti as the mechanism for conversion of osteoblasts to osteocytes, and responsible for the diminishment of apposition rate during refilling of osteonal basic multicellular units. Consequently, a single, mechanically derived signal, produced in the osteocytic syncytium, may control osteoblast and bone lining cell functions, and thereby a variety of important phenomena in bone biology{Thus it would be really easy to produce some sort of pill if there is only one signal}.”

“when an osteocyte becomes buried to a critical depth in the bone matrix, an additional osteocyte is recruited to maintain contact with the bone surface as the BMU wall thickness increases. the osteocyte sends an inhibitory signal through its processes to the osteoblasts forming bone above it. This causes the most affected osteoblast to slow its production of osteoid, and it is buried in the matrix by the adjacent osteoblasts.”

“microcracks and more diffuse disturbances of the calcified matrix structure. It seems clear from observing such damage that it could easily interfere with both the normal flow of fluids over osteocyte processes within canaliculae (signal generation) and with the passage of signals from one cell to another through these processes (signal transmission).“<-this suggests that it is not the microfractures themselves that stimulate growth but rather the fluid flow that is changed by the microfractures. This suggests that it is possible to get bone growth via fluid flow alone and microfractures are not needed.

“diffuse damage to the calcified matrix could release Ca ions or cytokines that could act to reduce
the inhibitory signals produced by the osteocytes, or their transmission from cell-to-cell. microdamage results in osteocyte apoptosis, again interrupting both signal generation and transmission”

“remodeling is known to be activated is local bone matrix necrosis—that is, when osteocytes die. This may occur from microdamage or when the haversian blood supply is interrupted following fracture”<-again fluid flow driven changes not the microfracture itself.

Concluding thoughts: It’s difficult to imagine a possible way in which osteocytes can help you grow taller as bone is a tissue not capable of interstital growth(growth from within) thus needing a cartilage or fibrous intermediate. Unless new bone is deposited at longitudinal ends. But this paper does enforce the idea that it is not microfractures themselves that cause new bone formation but rather the change in fluid flow caused by those microfractures. It is also likely that any soft tissue caused by an exercise routine within the bone would benefit more from changes in fluid flow than the microfractures themselves.

Huge news someone other than Yokota/Zhang use a joint loading device

This is huge that someone else is doing a LSJL like device it means that something could be close to being put into practice.

Micromechanical Loading Studies in Ex Vivo Cultured Embryonic Rat Bones Enabled by a Newly Developed Portable Loading Device

“Mechanical loading has been described as having the potential to affect bone growth{we want it to affect bone growth post skeletal maturity of couse}. In order to experimentally study the potential clinical applications of mechanical loading as a novel treatment to locally modulate bone growth, there is a need to develop a portable mechanical loading device enabling studies in small bones. Existing devices are bulky and challenging to transfer within and between laboratories and animal facilities, and they do not offer user-friendly mechanical testing across both ex vivo cultured small bones and in vivo animal models. To address this, we developed a portable loading device comprised of a linear actuator fixed within a stainless-steel frame equipped with suitable structures and interfaces. The actuator, along with the supplied control system, can achieve high-precision force control within the desired force and frequency range, allowing various load application scenarios{the potential would be to use the device to induce longitudinal bone growth on skeletally mature individuals}. To validate the functionality of this new device, proof-of-concept studies were performed in ex vivo cultured rat bones of varying sizes. First, very small fetal metatarsal bones were microdissected and exposed to 0.4 N loading applied at 0.77 Hz for 30 s. When bone lengths were measured after 5 days in culture, loaded bones had grown less than unloaded controls (p < 0.05). Next, fetal rat femur bones were periodically exposed to 0.4 N loading at 0.77 Hz while being cultured ex vivo for 12 days. Interestingly, this loading regimen had the opposite effect on bone growth, i.e., loaded femur bones grew significantly more than unloaded controls{femurs have different proportions than metarsal bones, one possibility is that femur bones shape makes it more susceptible to fluid based forces and pressure gradients, due to the femurs longer shape it is possibly more susceptible to deforming forces than metatarsals}. These findings suggest that complex relationships between longitudinal bone growth and mechanical loading can be determined using this device. We conclude that our new portable mechanical loading device allows experimental studies in small bones of varying sizes, which may facilitate further preclinical studies exploring the potential clinical applications of mechanical loading.”

“two use-cases were devised: repetitive impact loading of small force (0.05–0.5 N) at a range of  30–180 repetitions and continuous sinusoidal loading of medium force (0.5–5 N) at a frequency range of 5–20 Hz.”<-something like a massage gun does something similar of repetitive impact loading.

Above is the device used.

So unfortunately for metarsals it does look like yes the device suppressed growth. However, initially the 0.1N load enhanced growth. More studies would have to be done.
In contrast femur bones grew pretty uniformly and the difference is pretty significant. Again, I think it is possible that this could be due to the different shape of the femur bones or maybe the load was too strong for the smaller metatarsal bones.

“Its square shape securely covers the entire cartilage area on each side of the embryonic femur bone, allowing the indenter to apply mechanical loading specifically to the growth plate in a stable manner.”<-just because the growth plate was the thing that was loaded does not necessarily mean that the growth plate was solely responsible for the growth there could be effects elsewhere as well including that which induces longitudinal bone growth.

“we identified that the same load applied to bones of different dimensions has opposing effects on bone growth, suggesting that the effects of mechanical loading on growth are dependent on the magnitudes and relative dimensions of the bones.”<-so they too think that the shape of the bone has an impact on whether growth is induced or not. The fact that the shape of the bones matter also suggests that yes it is possible that not all of the growth is due to the growth plate.

“Embryonic metatarsal bones from Day 19.5 of gestation are approximately 1 mm in length, whereas femur bones are approximately 4 mm, indicating that the level of mechanical loading that stimulates or inhibits bone growth is likely dependent on bone size.”

This is the sentence where the cite Yokota/Zhang’s joint loading study: ” The device’s controller enables sinusoidal loading, which has been demonstrated to have a bone growth-promoting effect in mice “

Study finds that vibration can affect longitudinal bone growth

I am studying vibration due to some anecdotal success using the massage gun on fingers. Looking at vibration results I am seeing mixed results. Sometimes it results in degenerative changes but it is likely that vibration needs to be applied correctly to see results. I believe that like Lateral Synovial joint Loading, vibration would be more effective when applied laterally as that would be more effective in driving fluid flow within the bone. I have written about vibration in the past and in one study I saw that when vibration was applied growth plate parameters increased in the vibrated growth but bone length was about the same so it is possible that bone length at skeletal maturity could be longer in the vibrated group.

Attempt to stimulate longitudinal growth in the dog by mechanical vibration

“In animals, right- and left-handedness leads to larger bones on the dominant side.”

“six miniature partly threaded and self-tapping stainless-steel pins 3 mm in diameter (similar to Denham pins used in orthopaedic surgery) were inserted and allowed to penetrate the skin of the medial sides of the forelegs. The incision was loosely sutured between the pins. Stainless-steel bars were fixed to the ends of the protruding pins. These were grooved and cut to match the yokes on the vibrating rig described below.”<it’s possible these surgical incisions are a confounding factor to longitudinal bone growth.

“The amplitude of vibration was not markedly reduced; this was achieved by incorporating a stiff spring web in the system”

Here’s some images of the vibration mechanism:

“

“The vibrator enabled the foreleg to be vibrated longitudinally with respect to the radius and ulna”<-so there’s some lateral and torsional loading here.

“In all, seven animals were experimented upon. The first (Dog 1) was experimented upon alone to see if
the study was humane and feasible. Subsequently, and after an encouraging result, four dogs were used
(Dogs 2A-D). In all of these the vibration was sinusoidal, the frequency 20 Hz and the peak-topeak amplitude 4 mm. Finally, in two more dogs (Dogs 3A and B) the same frequency was used but
the amplitude increased to 6 mm”

“As stated above, Dog 1 was used to test the feasibility of the experimental protocol. The result from this single test was an obvious lengthening of the vibrated side{!!!!!} and it indicated to us that
the study should be expanded. Therefore in Group 2, four animals were used, the experimental procedure
being similar except that the daily average vibration period was increased from 1-7h to 2.1h{so it’s possible that these animals did not increase in bone length due to “overtraining”}. The results of Group 2 were disappointing in that, in two dogs, there was actually a small reduction in growth in length on the vibrated side. Group 3 was a more vigorous test in which the amplitude of vibration was increased to 6-8 mm (peak-to-peak). The dogs tolerated this well but, again, no increase occurred. (In one other animal, pins were inserted on one side only and here there was a slight increase in length of both radius and ulna compared with the undisturbed side{so yes this means that the pins are a confounding variable}.)”

Here’s the exciting increase in bone length:

That is frigging massive. The bone looks a lot different in the length increased bone.

“The arteriograms obtained from Dog 1 before sacrifice showed a slight real increase in calibre of the digital vessels on the vibrated side. The difference did not warrant further arteriograms.”<-So vascularity could contribute to part of the increase?

“Histological examination of the growth plates and of the cortical bone at the site of the pins was unremarkable.”<-this is huge as it means that the increase in size could be unrelated to the growth plate i.e. meaning that it could work post skeletal maturity!!!!!

I think there is an overtraining aspect at play here that is possible. As 2 and 3 had stronger stimulus applied and that is why they did not get results.

“The forces were transferred from the radius through the elbow and wrist joints to the arm and paw
respectively. In order to reach these joints, the forces must have passed through the upper and lower
growth plate respectively of the radius, and these will have been subjected to alternating compressive
and distracting forces.”<-one possibility is that the vibration may have induced longitudinal bone growth on the bone but damaged the growth plates. In skeletally mature individuals this would not be an issue as they do not have growth plates. Thus, it would be worthwhile to repeat the experiment on skeletally mature animals.

Here’s the study that was cited in the paper as being about vibration:

The effects of mechanical vibration on bone development in the rat

The study found bone decreased calcium content. This could play a role as the hardness of bone impedes intersititial(longitudinal) bone growth.

And this study too finds slight increase in longitudinal growth!:

Here’s the vibration applied:

“In one series of experiments. lasting for 5 weeks. 20 and 25 Hz was applied for 2.5 hr twice daily with 6
hr of rest intervening. In another series, which lasted for 4 months. the animals received 25 Hz for 12 hr each day without interruption”

So another result that indicates that perhaps by optimizing the vibration stimulus longitudinal bone growth is possible. Also interesting to note that in this study the non vibrated groups grow faster at first. I don’t know what conclusion to draw from that but it is something to explore.

So overall there is not a smoking gun to vibration and longitudinal bone growth but there is some smoke. So it is worth it to keep testing the massage gun method to see if the anecdotal reports continue to have promise. And it is entirely possible that once the method is optimized the results will be stronger than what is reported here.

Yokota/Zhang LSJL related study finds stem cell migration

If migration of stem cells can occur it means that potentially stem cells could migrate to form new growth plates and that cartilage could regenerate at articular cartilage sites potentially leading to height increase via articular cartilage endochondral ossification.

Mechanical Loading Promotes the Migration of Endogenous Stem Cells and Chondrogenic Differentiation in a Mouse Model of Osteoarthritis

“This study evaluated whether mechanical loading can enhance anabolic activities by facilitating the recruitment of stem cells for chondrogenesis{anabolic effects could potentially be used for non-osteoarthritic ie normal cartilage}. We evaluated cartilage degradation in a mouse model of OA through histology with H&E and safranin O staining. We also evaluated the migration and chondrogenic ability of stem cells using in vitro assays, including immunohistochemistry, immunofuorescence, and Western blot analysis. The result showed that the OA mice that received mechanical loading exhibited resilience to cartilage damage. Compared to the OA group, mechanical loading promoted the expression of Piezo1 and the migration of stem cells was promoted via the SDF-1/CXCR4 axis. Also, the chondrogenic diferentiation was enhanced by the upregulation of SOX9, a transcription factor important for chondrogenesis. Collectively, the results revealed that mechanical loading facilitated cartilage repair by promoting the migration and chondrogenic diferentiation of endogenous stem cells. This study provided new insights into the loading-driven engagement of endogenous stem cells and the enhancement of anabolic responses for the treatment of OA.”

A vacuole is a space within a cell that is empty of cytoplasm, lined with a membrane, and filled with fluid. Reduction in vacuoles could potentially that new bone is being formed.

“Mechanical stimulation affects the migration and differentiation of MSCs”

“We developed joint loading modalities in which dynamic lateral loads are applied to synovial joints”

“mechanical loading caused cyclic alteration of the intramedullary pressure, driving oscillatory
fluid flow and molecular transport in the lacunocanalicular network in the bone matrix and the medullary cavity”

“female C57BL/6 mice (~ 14 weeks of age, Animal Center of Academy of Military Medical Sciences, China) were used.”

Piezo1 is greater in loading groups even than non ostearthritic controls meaning LSJL(lateral synovial joint loading) meaning that joint loading should enhance stem cell migration in healthy controls.

joint loading promotes adhesion and migration compounds even above controls. These compounds could potentially help induce new cartilage and bone formation.

“Dynamic loads were sinusoidal at 1 N (peak-to-peak) and the frequency was 5 Hz for 6 min/day (each knee, 3 min).”

joint loading increases sdf1 over non-osteoarthritic controls a compound which is again involved in cellular migration.

“After 2 weeks of mechanical loading, the level of Piezo1 in OA mice was significantly increased”

Again strong increase in stem cell migration over controls.

“knee loading contributed to repairing damaged cartilage by recruiting endogenous stem cells and stimulating chondrogenic differentiation.”

Here’s a diagram which explains how loading could be anabolic to cartilage and bone and potentially non osteoarthritic cartilage and bone as well.

Tachypleus tridentatus potential height increase supplement

Tachypleus tridentatus is also known as horshoe crab. According to The Beneficial Effects of Edible Kynurenic Acid from Marine Horseshoe Crab (Tachypleus tridentatus) on Obesity, Hyperlipidemia, and Gut Microbiota in High-Fat Diet-Fed Mice, compounds like Kyurenic acid could be beneficial effects of horshe crab.

Proteomic Identification of Plasma Components in Tachypleus tridentatus and Their Effects on the Longitudinal Bone Growth Rate in Rats

“Tachypleus tridentatus (T. tridentatus) is a marine animal and traditional Chinese medicine. T. tridentatus plasma is a valuable resource for important medical and health-based functions. In this experiment, in order to evaluate the effect and mechanism of T. tridentatus plasma with respect to the promotion of bone tissue growth in rats, the processes of ultrafiltration and mass spectrometry were first used to separate and identify the components of T. tridentatus plasma. Then, a comparison of the effects of the T. tridentatus plasma samples, which each possessed different molecular weights, regarding the growth of the long bones of rats was conducted. Finally, transcriptomics, proteomics, and bioinformatics were all used to analyze the biological functions and related signaling pathways of the T. tridentatus plasma in order to promote rat bone growth. The results showed that the contents of amino acid residues in peptides are related to the growth promotion that was contained in the 10–30 kDa plasma group. Moreover, the T. tridentatus plasma samples were found to be higher in this respect than those in the whole plasma group. In addition, the 10–30 kDa plasma group could significantly promote bone growth activity in rats. The proteomic analysis showed that the proteins that were differentially expressed in the 10–30 kDa plasma group were mainly enriched in the PI3K-AKT signal pathway. Our study suggested that the T. tridentatus plasma possesses promising potential for the purposes of clinical use, whereby it can serve the role of a growth-promoting agent.“

The fact that they think that horshoe clab has clinical use is promising but we have to see what unique benefits it has over other compounds. Lots of things stimulate the PI3K-AKT pathway. We have to see if there’s anything the plasma does that is unique or superior in promoting growth.

“T. tridentatus possesses anti-inflammatory, analgesic, hemostatic, and antidysentery medicinal effects. It is also worth noting that T. tridentatus blood that contains hemocyanin possesses important medical application value. The blood extract can be made into a Limulus-reagent (LR), which is widely used for the purposes of endotoxin detection and quantification in injections, as well as in radiopharmaceuticals, vaccines, and other biological products”

“T. tridentatus plasma can promote the growth and development of Wistar rats by increasing body weight, body length, and tail length in adolescent Wistar rats; in addition, despite this range of growth, the rats do not appear obese.”

” IGF-1, BMP2, and ALP are applied to monitor bone growth indicators.”<-lots of things can increase those things. The question is does Horshoe Crab does anything that is unique?

“the plasma group showed macroscopic changes in total longitudinal bone length after 14 days of treatment. In addition, morphological changes were observed, such as the increased height of the growth plate area and an increased number of proliferating cells. Furthermore, T. tridentatus plasma treatment significantly increased the total serum levels of BMP-2, IGF-1R, and IGF-1, as well as induced the upregulated expression of IGF-1 and IGF-1R in the growth plate region.”

So the fact that scientists like that this compound can enhance longitudinal bone growth is interesting but the question is is whether it is really better than say other things in the diet?

Study mentions that bone length is plastic and mentions nutrition and mechanical loading as two potential means by which bone length can be manipulated

The below study suggests that growth is manituable not only be nutrition but also by mechanical loading(tool use). It states that growth of some elements of the body is prioritized over others in times of nutrient restriction(“the thrity phenotype” hypothesis). Although this study is more geared to that nutrition can alter body height and skeletal length growth. Proving the plasticity(ability of bone to change in length) of bone is essential in proving that bone can change in response to mechanical loading.

Plasticity in the growth of body segments in relation to height-for-age and maternal education in Guatemala

“Plasticity in the growth of body segments between populations has been researched in relation to migration, temporal change and high-altitude studies{height seekers could potentially manipulate altitude or temperature}. We study the within population variation in body segments, thus controlling for some of the environmental and genetic differences that could be at play in between populations studies. We test a version of the thrifty phenotype hypothesis, where the growth of head-trunk and hand are prioritized due to their functional significance over height and leg growth.

A total of 3913 Guatemalan, rural, semi-urban and urban, Maya and Ladino children 6 to 15 years old were studied. Height, sitting height, leg length, and metacarpal length were studied in relation to three proxies for living conditions: height- and leg length-for-age, and maternal education. Estimation statistics and null hypothesis significance testing were used to analyze the data.

Metatarsal length and sitting height values were higher than height and leg length respectively. Relative metacarpal length was conserved across height-for-age groups. Females were less affected than males for metacarpal length and sitting height, but more affected for leg length.

Our results agree with the thrifty phenotype hypothesis, where metacarpal and sitting height growth would be prioritized over height and leg length due to greater functional significance.“

“Plasticity refers to the ability of an organism to modify its biology to respond to changes in the environment, particularly when these changes are physiologically stressful”<-plasticity in height is a very promising idea for height as it means height and bone length can be manipulated.

“in conditions of environmental stress, leg length is often more sensitive than is the head-trunk segment, and that tibia and ulna lengths are also more sensitive than humerus, hand and foot lengths. A proximate reason for this sensitivity is due to the allometry of skeletal growth, where the more proximal body segments grow fastest prenatally and are less exposed to extra-uterine environmental stress, but more distal segments grow most rapidly after birth and are more exposed to environmental stress. The thrifty phenotype hypothesis offers an ultimate evolutionary explanation; the growth of human body segments with greater functional significance, such as “head-brain,” “trunk-major organs,” and “hands-tools” will be prioritized over forearms and legs.”

“the thrifty phenotype hypothesis over the predictions of the distal blood flow and cold adaptation models in the growth of different body segments in living populations “

“According to this hypothesis, the growth of the head-trunk segment would be prioritized due to the important organs that it houses (brain, heart, lungs), and the growth of the hand would be prioritized due to its manipulative function in human tool technology, thus offering an ultimate evolutionary explanation for the differential plasticity in the growth of body segments under different conditions of stress.”

the thrifty phenotype hypothesis is basically that growth is conserved based on nutrients with some bones being prioritized over others in times of nutrient restriction.