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.
There have been studies that have shown that it is possible to induce longitudinal bone growth in the jaw even potentially past skeletal maturity. Either the cells of the cartilage of the jaw are different than the cells of other joints(they could express different genes), in which case things that affect the jaw may not affect other joints, or it is not the cells themselves but rather the mechanical environment of the jaw. The jaw undergoes much more dynamic loading than other joints because the jaw is more moveable and the lateral pterygoid muscle is almost directly attached to the cartilage of the jaw providing it with a unique stimulation. Even if the cells of the jaw are different than the cells of other cartilaginous regions it is possible that these cells are different because of the unique mechanical loading that the jaw undergoes. The unique loading that the jaw cartilage undergoes maybe what alters the genetic expression that the cells of the jaw have. It is possible that if we load the joint cartilage of other cartilaginous regions in a similar way we may be able to induce growth longitudinally similar to what occurs in the jaw.
“A new technique in plastic surgery termed Osteogenesis Modulation is described. This technique uses a surgically implanted, battery-operated medical device to deliver customized electrical pulses to produce mandibular bone growth{trying to surgical implant the device to other joints may be challenging as it could potentially affect movement, we would want a way to implement the electric pulses to other joints in a way that does not require surgery}. This device was designed to be a temporary, nonpermanent implant. The purpose of this study was to review both the safety and efficacy of Osteogenesis Modulation.
This study comprises two phases. Phase I involved experimental technology development and animal experiments. Phase II included technology development for clinical use and a clinical trial. In Phase II, four patients with a diagnosis of mandibular hypoplasia and microgenia underwent surgical implantation of the novel medical device over the chin bone. Once a satisfactory change of contour of mandibular bone was achieved, the devices were removed. In all patients, the devices were left in place for 12 months, then surgically removed under local anesthesia. Preoperative and long-term postoperative cephalometric controls were done.
In all patients, symmetrical mandibular bone growth was observed with good-to-excellent aesthetic results. The overall follow-up period was 39 months. Cephalometric controls taken 3 to 6 months after the device removal showed an average increase in mandible length of 5.26mm (range, 2.83–7.60mm){this increase is not not exciting but it could improved upon}.
Preliminary clinical results suggest that Osteogenesis Modulation is a safe, minimally invasive, and effective alternative treatment for the correction of mandibular hypoplasia in selected cases.”
“he mandible thickness when low-intensity, moderate-intensity, or high-intensity negative pulses were applied was 2.70mm, 3.43mm, and 3.58mm, respectively. The thickness of the mandible on high-intensity positive pulses was 2.15mm.”<-it is very exciting that there was no decrease in results with more stimulus as it means that the stimulation may not be biphasic and it could be possible to increase the results with stronger stimulus.
Here is a before and after xray:
Before and after pic:
There are several before and after pics and x-rays in the study.
The next steps would be to try to apply this to other joints. I would try the hand and toe joints next because they are more movable compared to say the knee and ankle. Even though the stimulus to the jaw is electrical it is still possible that the enhanced jaw movement enhanced the results. Ideally we’d want only the electrical stimulation to produce the results that would make it easier to translate to other joints. That was the problem with possibly trying to mimic the bite jumping appliance on other joints. The jaw just undergoes so much more dynamic loading.
This is a very exciting study and here’s hoping it can translate to cheaper possibly greater height growth than limb lengthening surgery.
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.
<-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?
If vibration increases cartilage thickness. It is possible too that vibration could induce articular cartilage endochondral and stimulate growth plate growth. There are studies that show that vibration may be do this but the results have been non-overwhelming and mixed. It is possible however that it may be that the vibration stimulus needs to be improved. For example, laterally applying the vibration to the epiphysis and applying the vibration directly to the bone may improve the stimulus. But there are still several studies that show vibration is promising. It’s just the lack of a “smoking gun” study.
“1) 14-days of immobilization of young healthy subjects using a 6°-“head-down-tilt-bed-rest”-model (6°-HDT) would reduce cartilage thickness in the knee and serum Cartilage oligometric matrix protein (COMP) concentration and 2) isolated whole body vibration training would counteract the bed rest effects.”
“While the control intervention resulted in an overall loss in average cartilage thickness of −8% (pre: 3.08 mm±0.6 mm post: 2.82 mm±0.6 mm) in the weight-bearing regions of the tibia, average cartilage thickness increased by 21.9% (pre: 2.66 mm±0.45 mm post: 3.24 mm±0.63 mm) with the vibration intervention. No significant differences were found in the weight-bearing regions of the femur. During both interventions, reduced serum COMP concentrations were observed (control intervention: −13.6±8.4%; vibration intervention: −9.9±3.3%).”<-it is possible that a thickness in cartilage could increase height and induce articular cartilage endochondral ossification it could also stimulate growth plate growth. The thickness of the cartilage was increased versus control which is good but COMP is reduced compared to control which is bad.
“Cartilage presumably maintains and responds to the loads placed on joints during activities of daily living. For instance, the loads generated at the knee during walking correlate with cartilage thickness in the weight-bearing regions of the knee”<-so we could potentially change the way we load to alter cartilage thickness.
“COMP plays a major role in stabilizing the extracellular matrix through its interaction with collagen fibrils and other matrix components. Serum COMP concentrations are elevated in patients with knee osteoarthritis and rheumatoid arthritis but also after a moderate walking exercise in healthy adults and after intense running exercise in athletes. Thus, serum COMP concentration appears to be sensitive to physiological loading.”
“Vibration frequencies between 15 Hz and 90 Hz have been used to achieve adaptations in muscle and bone”
“Training sessions were scheduled at least 30 min after breakfast and lunch. Subjects walked the distance between their room and the training room each session (∼25 steps). Each vibration training unit was composed of five times 60 s of isometric exercise bouts on a vibration platform (Galileo 900, Novotec Medical GmbH, Pforzheim, Germany) in an upright standing position with a knee flexion angle of 30°. Subjects carried an additional load of 15% of their body mass on a diving belt around their pelvis. Between exercise bouts subjects rested for 60 s while sitting on a chair. The vibration platform vibrated at 20 Hz with approximately 3 mm amplitude at the centre of the foot.”<-the vibration in this study could be improved.
“Average and maximum thicknesses in the tibial cartilage increased significantly by 21.9% and 26.6%, respectively[due to vibration]. The percentage change in average and maximum cartilage thicknesses did not differ between the medial and the lateral compartments of the tibia for both study phases. Cartilage thickness in the lateral and the medial compartments of the femoral cartilage did not show significant changes due to the bed rest or to the training intervention”<-maybe the way we as humans typically load does not adequate load the lateral and medial compartments of the femoral cartilage and that’s why we don’t typically gain height there. It’s possible that if all parts of the femoral cartilage was engaged we would gain height and therefore if we change our loading we could stimulate all components of the femoral cartilage and thereby gain height.
“the increased cartilage thickness after the vibration training if the mechanical stimulus increases proteoglycan content of cartilage.”
“Proteoglycans are negatively charged and thus exert a large swelling pressure that causes tensile stress on the surrounding collagen network”