Gloxi Height Enhancer Ingredient Analysis

Michael has provided his thoughts on Gloxi Height Enhancer here.  I also want to note that I could not find any information on promodulin which is mentioned in the video as being a key to grow taller. I did find something on uromodulin which is connection to their calcium thesis.

I wanted to do a detailed analysis on the ingredients I obtained from this page on Gloxi Height Enhancer.

In the analysis on Alfalfa, it was discovered that Alfalfa may result in increased height but only during development.  One study found that some Lectins could encourage chondroinduction, but wheat germ actually encouraged adipoinduction.  Here’s what Michael had to say about Casein Phosphopeptide.  I think the existing research suggests that Casein Phosphopeptide can accelerate and possibly enhance existing endochondral ossification but it doesn’t look like it can induce new growth plates.  Hydrolyzed collagen has been shown to enhanced longitudinal bone growth in some cases.  According to Effects of Chlorella vulgaris on bone marrow progenitor cells of mice infected with Listeria monocytogenes., Chlorella can reduce lead levels of bone marrow cells.  Lead stimulates TGF-Beta signaling of chondrogenesis but inhibits BMP-2 signaling of chondrogenesis.  BMP-2 signaling seems to be preferably over TGF-Beta signaling for enhanced growth.  Thus Chlorella could contribute to longitudinal bone growth benefits by it’s beneficial effects against lead.  Jujube seems to be a typical antioxidant in which I couldn’t find any novel effects.  Anyone know any?

According to Ancordin, the major rhizome protein of madeira-vine, with trypsin inhibitory and stimulatory activities in nitric oxide productions., Madeira-vine could stimulate nitric oxide production.  It has an inhibitory effect on trypsin and trypsin seems to have a beneficial effect on growth.

The remainder of the ingredients are just too common and well studied and sufficient levels are likely already present in your diet.

Based on this evidence, it’s possible that Gloxi Height Enhancer might enhance height growth in growing individuals but will not re-induce height growth in adults unless these ingredients have novel effects that were previously undocumented.

According to [Effects of astragalus and angelica on bone marrow stem cells proliferation and VEGF protein expression in vitro]., Angelica(and astragalus) could increase stem cell proliferation and stem cells would be the foundation for new growth plates.  Also this study: Angelica sinensis polysaccharide nanoparticles as novel non-viral carriers for gene delivery to mesenchymal stem cells., states that an ingredient from Angelica could be used for gene delivery to MSC.  This could be a very powerful effect for inducing new height growth but it’s not possible to be used in this gel.  I couldn’t find much on Chiang Ziong Rhizonia(more common name is Huang Xiong).

The primary ingredient of rhizoma discoreae is diosgenin.  I studied diosgenin but couldn’t find a connection between it and longitudinal bone growth.

The promoting effects of geniposidic acid and aucubin in Eucommia ulmoides Oliver leaves on collagen synthesis.

“collagen synthesis was stimulated by the administration of a hot water extract from the leaves of Eucommia ulmoides OLIVER, Eucommiaceae (Du-Zhong leaves) in false aged model rats. In this paper, we set out to examine the compounds in Du-Zhong leaves that stimulated collagen synthesis in false aged model rats. In experiment 1, a methanol extract of Du-Zhong leaves also stimulated collagen synthesis in aged model rats. An acetone fraction was derived from the methanol extract by silica gel chromatography in experiment 2. The acetone fraction mainly contained iridoides mono-glycosides such as geniposidic acid and aucubin. The administration of geniposidic acid or aucubin stimulated collagen synthesis in aged model rats in experiments 3 and 4 (significance (p<0.05)). The reported pharmacological effects of Du-Zhong leaves, including healing organs and strengthening bone and muscle, are closely related to collagen metabolism. It appears that geniposidic acid and aucubin are the actual compounds in Du-Zhong which caused the effect in our experiments.”

So could possibly have an effect. Since there’s collagen in the skin using this gel could make your skin thicker.

According to Clove (Syzygium aromaticum Linn) extract rich in eugenol and eugenol derivatives shows bone-preserving efficacy., Clove does alter the serum bone levels of things such as Calcium or Phosphate but nothing that could induce new height growth.

Most of the research regarding Ocimum gratissimum deals with it’s beneficial affects against radiation damage.

Finally, there’s Astragalus which has actually been shown to have a connection to longitudinal bone growth.

If you look on the other part of the brochure you can see that they don’t list any novel effects for the ingredients.  I also don’t see any means of how total calcium absorption will increase height.

Biggest Growth Spurt of 24 inches In 3 Months by 12 Year Old Boy from Hodgkin’s Chemotherapy Treatment

Biggest Growth Spurt of 24 inches In 3 Months by 12 Year Old Boy from Hodgkin’s Chemotherapy Treatment

OLYMPUS DIGITAL CAMERARecently I have been reading the Pulitzer Prize Winner book on the history of cancer called The Emperor of All Maladies by Siddhartha Mukherjee. My cousin which has been trained as an oncologist recommend the book to me and I finally managed to buy the Audible.com version of the book from Amazon and have been spending about hours in the last few days of traveling in Airports and Planes listening to this incredible story on how physicians for the last few millennia have been fighting against this most difficult of diseases.

Some surprising figures I would learn is that 1 out of every 3 people in the USA would be diagnosed with cancer at some point in their life. Every year about 3 million people die from the disease in the world but the CDC reports that it is probably closer to 8 million people die from some version of Cancer each year. The struggle of doctors to fight and try to win this war against cancer is probably going be the defining medical endeavor for our generation, if not this century.

Maybe during the 19th century and the early 20th century, the focus of physicians was on finding ways to fight against infectious diseases like TB, Smallpox, Polio, and Influenza, those type of diseases caused by the bacteria or parasites have been taken care of ever since the advent of Penicillin and various other vaccinations. The defining types of disorders that are affecting this new generation is going to be degenerative diseases as man kind learn how to extend his life expectancy from 65 to maybe to double that. Our great-grandparents didn’t have to worry about Osteoporosis, Arthritis, High Blood Pressure, or Alzeheimers as much as us since their life expectancy was not as long as ours will be. Cancer will be the other major type of disease which we will have to deal with.

Our Main Point

Biggest Growth SpurtIn a certain passage of the audible book Dr. Mukherjee mentioned that after one case of cancer remission for a boy which had his weight reduced greatly to just 50 lbs by cancer, the 12 year old boy managed to grow 2 feet within 3 months after the oncologists managed to find the right type of chemical compound, (usually a type of anti-folate derivative) to stall the multiplication and spread of the cancer cells in his system. In addition, His weight increased by 50%, which does not seem like a lot since a 50% increase from 50 lbs is just 25 lbs to a total of 75 lbs.

(Read the clipping we did of the PDF of the audio book on the right. It was under the chapter called “An Army On The March“)

This type of story is the strangest which I have ever heard of any growth spurts. It is definitely the biggest growth spurt which I have ever heard off. To grow 2 feet in 3 months would mean that the kid would be growing at around over 1/4 inch every single day!!!

Of course we have to remind ourselves that this is a 12 year old boy we are talking about but this rate is still insane to comprehend.

I am not sure how it is possible that a person can grow that fast, even if we take into account catch up growth. I personally would suspect that after his 3 months of intense height increase, the growth plates probably completely ossified, due to over extension of the process in the cartilage.

(It seems that the growth plates, just like almost every other system/unit in the body that has not been infected by cancer has a natural negative feedback loop controller if one variable becomes too high. This is known collectively as Homeostasis. If you over exert the growth plates, they will go through bone maturity at a faster rate. If your growth is stunted, the senescence of the growth plates actually slows down, leading to catch-up growth after the inhibitory effect is removed. It seems that maybe the chondrocytes in the resting zone have some type of internal, intrinsic rate at which they can replicate and enlarge before some receptor or protein in the ECM causes them to stop.)

We have written before a few times about how catch up growth works.

While we were studying the longitudinal diurnal growth patterns of the tibia, we found that the long bones don’t grow in any type of linear pattern, or even predictable variable and/or intermittent pattern. (For Reference, read “Modulation of vertebral and tibial growth by compression loading: diurnal versus full-time loading“). They go through what can only be described as micro-growth spurts which were irregular . We realized from looking at the pattern on how major growth spurts work, there are certain short durations of time where the hypertrophy process of the chondrocytes seem to go crazy.

The Possible Case and the Growth Curve

What we speculate, without going into the deep research to find the exact case, is that based on the growth curve provided by the pamphlets created annually by WHO (World Health Organization) and the NIH (National Institute of Health) that before the treatment, the boy would probably have been around 3 feet tall. Let’s remember what we learned from previous posts before where we both uploaded and analyzed the charts provided by both the CDC and the WHO.

The average (median, NOT mean) American 12 year old boy would be around 150 cm tall with a 1 standard deviation range of 7-8 cm. The information was obtained by typing in the term “Average Height of 12 Year Old Boy” into the Wolfram Alpha Search Engine. (Based on the 2000 CDC Report).

In addition, the average weight (we are again talking about median) would be 40 kg, with an uneven distribution bell curve. It would range as high as 50 kg or as low as 34 kg.

We assume that the boy did not have Hodgkin’s his whole life, but only developed it probably in the last 2-3 years. That meant that his growth would have been stunted only within the last 3-5 years, although there might have been a few cancer cells in his system before that. From what I can personally remember about this particular type of cancer, which is usually called Lymphoma, it is one of the few cancers which is not too fatal and people who get it treated early enough can have a very high life expectancy past diagnosis.

Since the growth rate per year for an American boy between the ages of say 7-12 or 9-12 is about 2-3 inch/year and also correct that for the factor that increased bump in linear growth in long bones for puberty, we would guess that his height around the age of 12 was stunted by around 10-13 inches of height. Obviously the body was trying to catch up.

If this boy did not have his height stunted, the 2 extra feet of height would have pushed him to be almost 7 feet tall. If we we assume that this boy at the age of 12 was about the 12-13 inches shorter than average, which is at 150 cm (or 4′ 11″), than his increase of 2 feet would put his final height to be around 6 feet tall. Of course, that would still seem a little ridiculous. It is hard for us to imagine a 12 and a half year old boy who has been suffering for a few years from Hodgkin’s growing to the height of 6 feet tall. We probably won’t be provided private information about that boy who lived in the early 20th Century, but we guess that if we are to assume that his height was dramatically stunted to less than 4 feet, then his growth to a final adult height (assuming the boy lived to adulthood) would not seem so extreme.

The case of this boy who at the age of 12 with stunted growth growing 24 inches in height in 3 months shows that the potential for increased bone longitudinal growth is much higher than I would have ever predicted. Could we possibly use a mechanism to stunt our growth at the later stages of bone maturity (ages 16-18) for an extra push in bone longitudinal growth to reach a higher adult height from the rebounding effect of catch-up growth?

Reply To Geoffrey Arnold and His Blog The Social Complex

Reply To Geoffrey Arnold and His Blog The Social Complex

We have a tracking program for our website Natural Height Growth and can see most people who quote or link to the website. We found out from the tracking software that Mr. Arnold wrote on a Reddit thread that we on this website were selling a product so we had to be some type of major scam. We are not selling anything of our own, at least right now.

This is what Geoffrey Arnold has said about us, which we found insulting and rude, since he didn’t even give us a chance and look over what we have been doing for the last few years. Maybe the only way to describe this guy is to call him a “Hater”. He feels like he can’t play in the game since the world is discriminating against him and people of his “kind” unfairly so the only way he know how to respond is just to hate and write.

The back story, on what Geoffrey wrote on the specific Reddit Post…

“….This guy actually sent a message to my blog, advertising his site, as if I was going to publish it. I might get around to reading it later, but I’m sure it’s mostly gibberish. Hard to trust anyone who is talking about heightism while selling a product aimed at people who want to be taller.

That would be like getting information about racism from a company that sells skin bleaching cream…”

The clipping is from below…

Geoffrey Arnold

Our intention was to write two different books, one for people who are still growing and another for people who have stopped growing. At this point, we have looked at the science and say that it is possible for us to write one book for people who still have their growth plate cartilage and can possibly stlll grow. We can’t write the 2nd book for people with no cartilage left. We may never be able to write that 2nd book since we have found very little evidence that it would be possible.

There is a store section on the website but if he had look at it carefully, then he would see we don’t have anything of our own to sell. As for everything else, we give them for free. We even had DMCAs from the people at (Company That Will Not Be Named) and GT4I given to stop us from giving their products for free. We are putting our skin into the game and have come close to legal actions against people because we are trying to make the internet and the world a better place. We are trying to change the way the world operations in a fundamental way.

What don’t think that his work is that impressive. He has said that he has written over 1200+ post for the website. We are now at over 1100+. In terms of quantity, we will overwhelm his website soon.

He would have realized that our motives are not just a financial one. We’d love to actually find a solution and make some big profit from it but we keep the site going from google ads. We are a part of the Amazon Affiliate program but that doesn’t earn enough money since people don’t seem to click those links. This website is not as profitable as most people would believe. We are trying to build up a way to monetize the website to let us continue to pay off the monthly operating costs.

I wrote to him before because I thought he cared enough to want to help and maybe try to look for a solution. He sure has a lot of stuff written about heightism. Everything he says is more or less right, but would he would be willing to put in some type of effort to maybe change the system, and help people? If he doesn’t believe there is a solution, that is fine. He doesn’t need to lift up a medical textbook and go through the real research to see what is possible. He has the complete  right to just spend the next 10+ years and keep writing another 3000+ posts about how the world is bias towards short men and short people.

He’ll get a small following of people on Reddit who agree with him and he will probably will get some type of self satisfaction in knowing that he can only be half-fulfilled. He can justify his own existence in his small circle of influence and control. We get it, the way that the ego works to protect itself is to just be right about something. We might not be able to get what we really, REALLY want, but as long as we can sit back, be pessimistic, sceptical, cynical, or pragmatic about how bad the world treats us because of something which we can’t change, as least we can be partially fulfilled and satisfied. Instead of finding self-esteem in knowing that we can change this problem, he finds validation in his ego from knowing that he is “right” since he just talk about how bad the world is. He can be the sceptic who does nothing, but takes no time or effort to look for a way out of the problems that they vent about. 

What he wrote about us I would consider to be unfair since he never made the full effort to read any of our large posts and research extensively. He brushed us off without ever looking at the science. Why? It is the same reason why I have brushed off any type of height increasing pill or potion or herbal concoction sold by websites using the type of design from the 2004-2009 era. It seems to be too crazy and improbably to believe. However, at least I spend the time to look over what the websites have to say. Maybe they do have something of worth to say and something to contribute. He apparently did not take the time to look over what our research is, and dismissed us without ever looking into our content.

Could meditation affect height related genes?

Previously, scientific studies have shown that meditation could affect free radical levels and biophoton emissions.  There have been a few studies on meditation and it’s affects on gene expression but no genes seemed to be altered that could increase height during development or reinstate height growth in adults.

Rapid changes in histone deacetylases and inflammatory gene expression in expert meditators

“Here we explored the impact of a day of intensive practice of mindfulness meditation in experienced subjects (n = 19) on the expression of circadian, chromatin modulatory and inflammatory genes in peripheral blood mononuclear cells (PBMC){Ideally we’d like gene expression of the growth plate and bone marrow but this could give us some insight if meditation can alter any genes involved in development processes}. In parallel, we analyzed a control group of subjects with no meditation experience who engaged in leisure activities in the same environment (n = 21). PBMC from all participants were obtained before (t1) and after (t2) the intervention (t2 − t1 = 8 h) and gene expression was analyzed. Both groups were also presented with the Trier Social Stress Test (TSST).
Core clock gene expression at baseline (t1) was similar between groups and their rhythmicity was not influenced in meditators by the intensive day of practice. Similarly, we found that all the epigenetic regulatory enzymes and inflammatory genes analyzed exhibited similar basal expression levels in the two groups. In contrast, after the brief intervention we detected reduced expression of histone deacetylase genes (HDAC 2, 3 and 9), alterations in global modification of histones (H4ac; H3K4me3) and decreased expression of pro-inflammatory genes (RIPK2 and COX2) in meditators compared with controls. We found that the expression of RIPK2 and HDAC2 genes was associated with a faster cortisol recovery to the TSST in both groups.”

HDAC2 binds to the cartilage promotor Sox9 which is a height increase link there.  Although it is not necessarily a positive binding as HDAC2 did repress some cartilage specific genes like Col2a1 in one study.  Since Meditation reduces HDAC2 expression that could be beneficial to height growth.

H3K4me3 is associated with gene activation.  Thus raising the possibility that meditation alters genes other than those listed.  Jeffrey Baron thinks that declining H3K4me3 levels are associated with declining organ growth with ageElevated levels of H3K4me3 is associated with chondrogenesis.

“Increased telomerase activity was detected in response [to yogic meditation]”

” Rapid epigenetic changes in response to environmental exposures such as diet and physical exercise have also been detected in human peripheral tissues”

It seems with the genes above mentioned, that meditation has the ability to accelerate but not induce or increase chondrogenesis.  So, you’ll grow taller faster but not taller than you would have.
Meditation would accelerate growth by inhibiting HDAC2 which supresses chondrogenesis.  The elevated levels of H3K4me3 could be a sign of increased gene activation but it’s not likely that H3K4me3 is driving the gene activation.  Whether meditation can activate growth plate inducer genes or genes that enhance growth remains to be seen.

 

Could pulling your fingers make them longer?

Even if you could grow taller via your articular cartilage, it’s likely that the periosteum would constrain additional growth.  Note the studies that shows that articular cartilage longitudinal growth can continue in bones without periosteum such as the fingers.

By mimicing the effects of the bite-jumping device on the mandible and the way it increases growth in that region it could be possible to increase in the same way in the fingers by pulling on them.

Repeated mechanical loading enhances the expression of Indian hedgehog in condylar cartilage.

Indian hedgehog (Ihh) acts as a mechanotransduction mediator that converts mechanical strain into cellular proliferation and cartilage formation in mandibular condylar cartilage{But could Ihh act as a signal to induce mesenchymal stem cell differentiation into chondrocytes?  Ihh has been shown in some instances to be a chondrogenic inducer of mesenchymal stem cells.}. The aim of this study was to examine the effect of repeated mechanical strain on the level of expression of Ihh and type II collagen mRNA in condylar growth. Two hundred and eighty 35 days old Sprague-Dawley rats were divided into 10 experimental and 10 control groups. Repeated mechanical loading was applied by advancing the mandible in a stepwise manner by fitting a stepwise bite jumping appliance{Bite jumping devices have been shown to induce adaptations in 135 day old rats(almost five months old), this bite jumping device was explained as reactivating endochondral ossification in the old rat condyle}. Animals were sacrificed together with their matched controls on 10 different time points. Total RNA was extracted from condylar cartilage immediately after dissection. Ihh and type II collagen mRNA was quantified. In the experimental group, Ihh mRNA increased significantly on experimental day 7. Upon the second advancement, another peak was elicited 7 days later. Type II collagen showed a significant increase on days 21 and 44 of advancement. Mechanical loading in a repeated manner, triggers the expression of Ihh which in turn increases the number of replicating mesenchymal cells as well as the amount of the cartilage formed. Taken together these events increase condylar growth.”

Here’s what a bite jumping appliance looks like:

bite jumping applianceHere’s more info on the bite jumping device.  This device seem like it would place a distraction force on the bone and cartilage.

“Mandibular forward positioning led to changes in the biophysical environment that caused deformation of the mesenchymal cells and other cells in the extra-cellular matrix. Thus create strain alignment that causes deformation of the cytoskeleton of these cells and trigger the expression of Ihh. The expression of Ihh elicited by mechanical loading of the mandibular joint promoted mesenchymal cell proliferation and initiated a cascade of cellular and molecular responses that led to condylar growth”

“Mechanical stress stimulated Ihh expression in chondrocytes in vitro by 18-fold. Over expression of Ihh in transgenic mice led to an increase in the number of replicating chondrocytes in the growth plate”

“the number of replicating mesenchymal cells in the condyle directly impacts the growth potential of the condyle. Furthermore, the number of replicating chondrocytes impacts the amount of cartilage to be formed and subsequently influences condylar growth because cartilage acts as the template onto which bone will form. Therefore, over expression of Ihh in the condylar cartilage in response to mechanical loading could result in enhanced condylar growth. ”

“Ihh mRNA expression showed a decrease with age during natural growth. Forward mandibular positioning led to a significant increase of Ihh mRNA, with the peak identified on day 7 and dropped to control level after 14 days of appliance wearing. The peak increment corresponded to a fold change of 5 in the stepwise advancement group. ”

“Upon the second advancement on experimental day 30, Ihh mRNA showed a significant increase on experimental day 33 and reached another peak on experimental day 37, which has a corresponding fold change of 12.5. After the peak, the level of expression started to decrease again to the normal level. ”

“In the experimental group, collagen II mRNA started to increase on days 14. Although the critical values were statistically insignificant when compared with the control, a greater amount of mRNA was detected on experimental days 14 and 21. The fold change identified was 2.5 and 2.8 respectively.  The second advancement on days 30 led to a significant increase in type II collagen mRNA, which reached the peak on days 51 with a fold change of 21.8. The amounts of mRNA detected on experimental days 44 and 51 were significant when compared with natural growth. ”

The first mandibular advancement was by 2mm.  It would be interesting to measure any temporary change in leg length during LSJL.  The second advancement was also by 2mm.

Factors regulating condylar cartilage growth under repeated load application.

“280 Sprague-Dawley rats were used in this experiment. The animals were randomly allocated into experimental and control groups. Repeated mechanical loading was applied through a bite-jumping device in the experimental group. The experimental animals were sacrificed on 10 different time points together with the matched control. Total RNA was extracted from the mandibular condylar cartilage for PTHrP and SOX9 genes quantification using real-time RTPCR. PTHrP expression was increased and reached a peak level on the seventh day after mechanical loading was given. Repeated mechanical loading triggered a significant increase of PTHrP expression leading to another peak increment. The expression of SOX9 was highly correlated with the PTHrP expression, and its pattern of expression was similar to that of PTHrP after repeated mechanical loading. In conclusions, repeated mechanical loading on the condyle triggers the expression of PTHrP and SOX9, which in turn promotes condylar cartilage growth.”

“The set-up involves an intra-oral [bite-jumping] device that positions the mandible forward, therefore, generating tension at the condyle and the glenoid fossa. ”

“t mechanical loading led to a significant increase in the expression of PTHrP, which delayed cartilage cells maturation and endowed the condyle with more potential to buildup cartilage. This increase in PTHrP was associated with the increase of new chondrocyte populations. Furthermore, it was documented that PTHrP up-regulated SOX9 transcription, which has been shown to promote differentiation of mesenchymal cells into chondroblasts in the mandibular condyle. It is convincible that repeated mechanical load applications through mandibular advancement in a stepwise manner could re-trigger the expression of these factors and lead to further growth.“<-there does seem to be periosteum in the mandible so it could mean regions with periosteum can be stretched via increased articular cartilage growth.

“PTHrP also up-regulates the expression of SOX9, which in turn acts upon the mesenchymal cells, and induces their differentiation into chondrogenic cells. ”

Note that some bones you can pull thereby immediately increasing the length of the skeleton examples include the wrist, fingers, and jaw.  Pull your finger and make it instantly longer but this seems far more difficult with the elbows and knees but perhaps still possible.

This would be a possible experiment to do on a finger.  There could be a device that pulls the finger away from the hand.  Would it be safe and healthy to the hand to do this for a long period of time?  There’s already a multitude of anecdotal evidence of intermittant tensile on the hand via knuckle cracking.  Although that could be more of a bending force rather than a pure longitudinal stretching one.  But I know that some people crack their knuckles by pulling them.

Does anyone have any anecdotal advancement of people with longer hands due to cracking their knuckles by pulling on their fingers?

In addition, any exercise like deadlifts and farmer’s walk would put a pulling force on the arms.  Does anyone have any anecdotal evidence of people getting longer arms by doing farmer’s walks?

Do Bisphosphonates decrease height?

The bisphophonate Aldronate reduces height.  Other bisphophantes such as zoledronate have an impact on the growth plate and may have an impact on height.  I don’t know for sure what affect bisphophonates have on height but if I had to guess I would say that they result in decreased height.

Effect of Bisphosphonates on the Rapidly Growing Male Murine Skeleton

“C57Bl6/J male mice were treated from 18 to 38 days of age with vehicle, alendronate, pamidronate, zoledronate or clodronate at doses selected to replicate those used in humans. Treatment with alendronate, pamidronate and zoledronate, but not clodronate led to a decrease in the number of chondrocytes per column in the hypertrophic chondrocyte layer. This was not associated with altered hypertrophic chondrocyte apoptosis or vascular invasion at the growth plate.

The effects of pamidronate on trabecular microarchitecture were less beneficial than those of alendronate and zoledronate. Pamidronate did not increase cortical thickness or cortical area/total area relative to control mice. These studies suggest that bisphosphonate administration does not adversely affect skeletal growth.”

“Technicium, 99mTc-labeled 1-hydroxy-methyledene bisphosphonate, a compound closely related to clodronate, is used for bone scans. In children and growing animals, this agent is avidly taken up in the region of the growth plate where cartilage is being replaced by bone”

“first generation bisphosphonates (ethane-1-hydroxy-1,1-diphosphonate and dichloromethylene diphsophonate), performed in growing rats more than four decades ago, demonstrated expansion of the growth plate and persistence of columns of calcified cartilage”<-note that expansion of the growth plate does not always lead to increased height.

“Pamidronate decreases basal ERK1/2 phosphorylation in hypertrophic chondrocytes”<-other bisphosphonates did not alter ERK1/2 phosphorylation.

“Treatment of hypertrophic chondrocytes with phosphate leads to rapid phosphorylation of Erk1/2 which is required for phosphate-mediated hypertrophic chondrocyte apoptosis”

“Bisphosphonates do not impair hypertrophic chondrocyte apoptosis in vivo”<-although the pamidronate group had a slight increase in hypertrophic chondrocyte apoptosis.

“zoledronate suppresses MMP-9 expression, whereas pamidronate increases MMP-9 mRNA
levels in cells of the monocyte/macrophage lineage, and clodronate has no effect”

“The number of osteoclasts in this region [metaphysis] (350 microns) was significantly decreased in the mice treated with alendronate and zoledronate relative to control mice (2.3  and 3.3 respectively vs 7.5 in control mice). Pamidronate and clodronate treatment resulted in a small and insignificant decrease in cortical osteoclasts in this region relative to control animals (6.0 and 7.0 respectively).”

“Femoral length did not differ between control and treated mice, nor among treatment groups(data not shown).”<-This is unfortunate as any non-signficiant difference in femur length could be notable.

“the non-nitrogen containing bisphosphonate, clodronate, did not alter the number of hypertrophic chondrocytes per column and led to fewer growth plate changes than the nitrogen-containing bisphosphonates.”