There is a lot of evidence that shows that bite jumping appliances and other dynamic loading methods can induce growth of the jaw. This growth seems to be due to the lateral pterygoid muscle applying dynamic load on the mandibular condylar cartilage. There, is a possibility of applying these same techniques to other long bones. Other bones however do not have this muscle insertion so directly into the cartilage. We would have to think hard to find a way to apply this technique.

Long-Term Effect of Diet Consistency on Mandibular Growth within Three Generations: A Longitudinal Cephalometric Study in Rats

<-harder foods likely work by forcing the lateral pterygoid muscle to work harder in a more dynamic way thus placing a stronger load on the mandibular condylar cartilage. One thing that would be interesting to try is if this worked on adults.

“Craniofacial growth has been shown to be affected by different factors, including environment. It is thought that environmental changes could possibly affect the growth of the mandible. The question of how diet consistency affects mandibular growth within one generation of rats has been answered to some extent by various studies, according to which diet consistency may result in different masticatory forces that affect mandibular growth. There is no study so far that examined possible quantitative and qualitative growth changes in the mandible within different generations. The present experiment evaluated the impact of different food consistencies on mandibular growth within three generations. The results of this study indicate that a soft diet could be responsible for less mandibular growth, and this information might be passing through generations.”

“A total breeding sample of 60 female and 8 male Wistar rats were used in this study. Measurements took place only on female animals. Twenty female Wistar rats at 30 days old and four male rats at 30 days old comprised the primary breeding sample of the first generation, and from these animals two different generations were reproduced. Lateral cephalometric X-rays were taken from all female rats at the age of 100 days.”

“Means of measurements of all soft diet groups compared to hard diet groups were significantly smaller. According to linear measurements, there was a significant difference only between the first-generation soft diet with the third-generation soft diet group. According to geometric morphometric analysis, the statistical differences appeared on the condylar process and the angle of the mandible”

“muscular loading forces play their own part in bone growth and development. One of the most critical muscular systems is the orofacial, which is necessary for feeding in vertebrates. Mandibular growth is closely associated with the movement of the jaws and loads of the orofacial region. Mastication, as one of the environmental factors, seems to be responsible for a variety of developmental changes in the craniofacial region and more specifically in the mandible”

“The coordinated actions of osteoclasts and osteoblasts result in the resorption and replacement of the existing cortical bone, a process known as intracortical bone remodeling (or simply remodeling). Secondary osteons, which are cylinder-shaped structures, are created as a result of this process. Due to their concentric lamellae and surrounding cement line, secondary osteons are apparent in cross-section. The remodeling process’ resorption phase releases mineral reserves to support mineral homeostasis, but it also leads to the development of microcracks as a result of mechanical deformation. Both significant mechanical deformations (high strain) and repeated cycles of loading have been linked to microcracks. Therefore, areas of the skeleton with more severe loading conditions should have increased rates of remodeling since those areas should sustain more microdamage. When the load situation is unknown, it is less evident if increased remodeling may be attributable to high strain or cyclical loading.” <-they suggest that the loading may cause microcracks and that could cause the change in bone shape but I think the increase in size is due to articular cartilage endochondral ossification.

“high strain may not be necessary for substantial remodeling to occur and that cyclical loading may be more likely to result in elevated remodeling”<-this alludes to fluid flow theory.

“various epigenetic mechanisms are now known that consist of intracellular macromolecular chain reactions and extend from the membrane to the cell nucleus. In this way, information is transferred between the extracellular environment and the nucleus. The osteocyte network detects and responds to mechanical stimuli and thus plays an important role in triggering bone remodeling. In addition, loading applied to the tissues can change the shape of the cells. As a result, deformation of the intracellular content, including the cytoskeleton, is observed, and processes are activated that even change the mechanisms of action of the genome”

“Increased mineralization was found on the trabecular bone in the condyle of the hard diet group than in the soft diet group”

“chewing hard food enhances nearly all physiological masticatory parameters, muscular coordination, and masticatory side modifications as compared to chewing soft food”<-the question becomes whether we can keep chewing harder food to gain more in the mandible.

Every dimension was superior in the harder food group.

“The indications for the posterior mandibular height were Co-Go, Co-Go’ linear measurements. There were statistically significant differences between all soft diet groups when they were compared with the hard diet groups in all linear measurements. There were no statistically significant differences between all hard diet generations due to linear measurements.”

Definitely noticable difference in the G group.

“In 2014, Hichijo et al. found that there was no significant difference between the hard diet and soft diet groups in the mandibular length and the mandibular base length”

“It is important to mention that we used a similar methodology to previous studies, but with some of these studies, our results differ in terms of one-generation outcome. This could be possibly explained because we used a different rat strain than some of the previous studies. Another possible reason could be the limitations of 2D X-rays and the procedure that each study followed to take those.”

So this study provides further evidence that mechanical loading can influence growth of the mandible and we can possibly apply those principles to alter the growth of other long bones.

Continuing Periosteal Apposition I: Documentation, Hypotheses, and Interpretation

“This paper reviews 42 studies published since 1964 that have found both significant and nonsignificant
age-related change in various skeletal size dimensions, e.g., length, diameter, width, and area”

“Continuing periosteal apposition (CPA) of lamellar bone in adulthood leads to greater skeletal dimensions in older individuals.”

The paper mentions several citations that show changes in skull shape with age including length of skeletal elements. If skull bones can increase in length it is possible that other bones could increase in length too.

This review paper mentions a Harry Isreal paper as showing that the vertebral body can increase in height past skeletal maturity:

PROGRESSIVE ENLARGEMENT OF THE VERTEBRAL BODY AS PART OF THE PROCESS OF HUMAN SKELETAL AGEING

“Both longitudinal and cross-sectional evaluation of the body of the third cervical vertebra reveal
that age-associated continuing enlargement occurs in women through adulthood and into the later
years.“<-this is exciting stuff as it means it is possible to gain torso height and it could explain the height gain in pregnancy.

So only one person did not have a age related vertebral body height increase. And amazingly this was a longitudinal study with some people well past their twenties.

This is the third cervical vertebrae

The paper Continuing growth in sella turcica with age also looks promising as Sell Turcica is a bone but I could not get the paper.

Here’s another one of the papers mentioned that measured length:

Sex Differences in Age-Related Remodeling of the Femur and Tibia

“In a previous study of a preindustrial sample with high activity levels, both men and women exhibited bone subperiosteal expansion and increase in second moments of area with aging.”

“In preliminary analyses of the data, we found that there was a significant negative trend in femoral and
tibial length with age, particularly among men, where bone length decreased 34 mm per decade on
average”<-if bone length can decrease it is possible that it can increase.

I emailed Susan Pfeiffer regarding her paper “Age Changes in the External Dimensions of Adult Bone” which showed bioarcheological data that stated that persistent physical activity could stimulate bone growth in length. This paper showed archeological evidence that limb assymetry continued to widen post puberty. The issue with that paper is that it is not a longitudinal study(not on the same subjects over time) so there could be methodological issues. The paper is quite old so I sent her an email about it and she replied ” It looks to me that my paper joins a number of others. Its core conclusions appear to remain valid.”

I asked her to expand on the papers that provided evidence to contribute to the theory that lengthening post epiphyseal fusion is possible and this is one of the ones she suggested. Unfortunately, she stated that her research did continue to go down the direction. I of course was not satisfied with this but I’m lucky I got a response at all. Her is the paper she mentioned: Now it does not show proof of longitudinal growth but it show evidence that appositional growth increase is possible post maturity.

IF you look at figure 3 you can see that in some individuals cortical bone continued to increase for the 3rd metacarpal between the ages 20 and 25.

Cortical index is a radiogrammetric parameter that assesses cortical bone stock using a bone X-ray. It is calculated using the ratio between the thickness of the cortical bone and the diameter of the bone shaft.

The exciting statement of course is that appositional continues post fusion at least but not necessarily limited to the ages of 20 and 25.

It looks though if anything and in measuring on gimp that the second metacarpal is longer in the second photo in figure 3. The third metacarpal is too close to call. This is despite the increase in appositional growth being more in the third metacarpal. It is extremely difficult to do an accurate measurement via gimp.

For 6 years old, who have more deformable bones. However, it is possible that strengthening the stimulus could make it worker for older and even skeletally mature individuals. If stretching works via articular cartilage endochondral ossification.

Exercise combined with lysine-inositol vitamin B12 promotes height growth in children with idiopathic short stature

Short stature is short stature of an unknown cause(not familial or genetic or unknown genetic origin). One of these causes could be inadequate nutrition including B12 deficiency. So using idiopathic short stature individuals is not ideal. The ideal test subjects would be normal stature individuals. Then ideally you’d try to find a way to reproduce the results in skeletally mature individuals by strengthening the stimulus.

“Researchers observed that many patients with ISS whose genetic target height is around the 50th percentile have no symptoms, and their bone age was only slightly lower than the age in the auxiliary examination. For these children, regular exercise of moderate intensity was employed. Stretching exercise, combined with oral lysine-inositol vitamin B12 (VB12), can effectively promote height growth. Based on
this, we systematically observed the clinical efficacy of regular stretch exercise of moderate-intensity combined with lysine and VB12 oral liquid in the intervention of ISS.”<-One possibility to make this paper work on the skeletally mature is to increase the intensity of the stretching exercise. It is possible that the exercise may work by increasing nutrient uptake in the growth plate in which case it won’t work in the skeletally mature.

“A total of 60 children with ISS who met the inclusion criteria and were treated at the traditional Chinese medicine dwarfism clinic of the Henan Children’s Hospital from June 2018 to July 2020 were selected.”

“The observation group consisted of 23 males and 7 females, aged 4.33–8.33 years. The control group consisted of 22 males and 8 females, aged 4.00–7.92 years.”

“(1) age < 3 years, or age > 10 years (male) or age > 8 years (female); (2) not meeting the ISS diagnostic criteria; (3) height growth rate ≥ 5 cm per year; (4) family history of hereditary diseases or underlying diseases of the heart, liver, kidney, etc.; (5) mental or emotional disorders or history of malnutrition.”<-it’s good that they removed malnutrition but that does not rule out vitamin deficiencies.

“The control group was given oral lysine-inositol VB12 oral solution (10 mL bid). Meanwhile, the observation group was given oral lysine-inositol VB12 oral solution (10 mL bid) and exercised according to the “ISS exercise guidance sheet”, which was developed in terms of exercise items, exercise intensity, exercise time, exercise days per week and so on. The children were instructed to perform aerobic exercises, such as brisk walking, running, jumping rope, etc., followed by stretching activities.”<-so really no unusual exercise activities

“The exercise could be broken down into two or three sessions per day to prevent children from
being overworked. Both groups were undergoing treatment for 12 months.”

“after 6 and 12 months of treatment, GV, serum GHRH, GH, IGF-1, and IGFBP-3 levels in the observation group were significantly higher than those in the control group whereas its HtSDS[Height Standard Deviation Score] was significantly lower than that in the control group{there was less height variance in the exercised group}. The difference between the two groups was statistically significant); after 12 months of treatment, Height in the observation group was significantly higher than that in the control group, and the difference between the two groups was statistically significant“

“The micronutrient Zn has been reported to promote growth rate in children with dwarfism.”

“Lysine VB12 is a complex of lysine, inositol, and VB12 that can be used to treat lysine deficiency symptoms, such as lack of appetite and poor growth. Lysine is an essential amino acid for all proteins in the human body and is a precursor substance for peptide hormones and coenzymes. In addition to maintaining metabolic balance in the body, lysine is an essential substance for children’s growth and development, since it can improve immune function, promote intellectual and physical development, improve nutritional status, and increase appetite”

So height is greater in the exercised group but so is starting height which is not ideal but still this is promising but this really needs follow up studies.

So interesting stuff here but we need more studies to see how it could play out. What would be interesting is spreading out the exercise more throughout the day to see if that reduce the negative correlation between minutes per day and growth velocity. Watching follow up studies will be helpful. Also we want to really optimize the optimal exercises. And find a way for any of the exercises to potentially work on adults.

Deer antlers are a mammalian appendage capable of regeneration. I don’t believe that eating deer antlers could induce growth plate regeneration but possibly the study of deer antlers could help enable growth plate regeneration. And perhaps studying deer antlers could enable the growth plates to be open for longer. One of the problems with limb lengthening surgery remains muscle and other soft tissue tightness. The growth plate is connected to these soft tissues via the enthesis so it is logical to think that perhaps the enthesis can help provide the cellular ingredients for those soft tissues to grow as needed via the enthesis.

A population of stem cells with strong regenerative potential discovered in deer antlers

<-perhaps for example there could be an osteotomy and an injection of these stem cells in a region near the enthesis to form new growth plates.

“The annual regrowth of deer antlers provides a valuable model for studying organ regeneration in mammals. We describe a single-cell atlas of antler regrowth. The earliest-stage antler initiators were mesenchymal cells that express the paired related homeobox 1 gene (PRRX1+ mesenchymal cells). We also identified a population of “antler blastema progenitor cells” (ABPCs) that developed from the PRRX1+ mesenchymal cells and directed the antler regeneration process.{could we use similar cells to form new growth plates?} Cross-species comparisons identified ABPCs in several mammalian blastema. In vivo and in vitro ABPCs displayed strong self-renewal ability and could generate osteochondral lineage cells. Last, we observed a spatially well-structured pattern of cellular and gene expression in antler growth center during the peak growth stage, revealing the cellular mechanisms involved in rapid antler elongation.”

“Lower vertebrates have a remarkable capacity to heal in a scar-free manner and regenerate lost appendages, even at the adult stage”

“deer antler offers a singular model to study spontaneous regeneration in mammals because its
regeneration is similar and clinically relevant to mammalian long-bone development”

“hard antlers are cast from their pedicles, then both antler bone and cartilage are regenerated from the pedicle periosteum located in the pedicle stumps”

“We further identified a population of regenerative progenitor cells, ABPCs, in the antler blastema, with impressive capacities for self-renewal, osteogenic–chondrogenic differentiation, and bone-tissue repair.”<-in the paper it goes over more what the cell characteristics of the progenitor cells might be. The question is: How do we translate what’s going on in the deer antlers to bone?