Monthly Archives: October 2012

High Impact Sports Improves Bone Strength And Bone Geometry

Me: It is important to note that only two sports were compared side by side, specifically soccer and swimming for the first study. What we see is that when the swimmers and soccer players are compared to control groups, the loading from weight by the soccer players resulted in an increase in bone mineral density (BMD) which results in an increase in bone strength, and increased thickness of the cortical area. Apparently the bone strength of swimmers seems to be even lower than the controls, which makes sense since we have seen astronauts who go into space will increase in height from decompression of spine but will drop dramatically bone mineral density, bone loss, and bone strength. This might suggest that the viscoelastic nature of water might do a similar effect on the human body allowing for it to expand longitudinally in the water but probably goes back to normal when the swimmer gets out of the water just like how the astronaut gets back to their normal height after spending time back on earth. We know the loading from soccer leads to stronger bones and thicker bones. However we are not clear whether it would lead to longer bones as well, which is what we have been trying to achieve.

For the second study, it seems that with old age, the medullary cavity decreases in apposition and increase in size. Exercise can help increase the endocortical apposition and cortical area from the inside thus resulting in slight shrinkage of the cavity. With boys, during puberty and post puberty, the periosteal apposition is higher than the cortical resorption so for males, the cortical area is larger. With females from the tennis study, the periostral apposition is also higher from exercise and loading before puberty but the cavity seems to increase from endocortical resorption. What is important to note is that the rising estrogen levels in the pubertal tennis players will result in less bone sensitivity to loading. 

From PubMed study link HERE

J Bone Miner Metab. 2011 May;29(3):342-51. Epub 2010 Oct 21.

Bone geometry and strength adaptations to physical constraints inherent in different sports: comparison between elite female soccer players and swimmers.

Ferry B, Duclos M, Burt L, Therre P, Le Gall F, Jaffré C, Courteix D.

Source

Laboratoire Interuniversitaire de Biologie des APS, EA 3533, PRES Clermont Université, Université Blaise Pascal, 24 avenue des Landais, BP 80026, 63177 Aubiere Cedex, France.

Abstract

Sports training characterized by impacts or weight-bearing activity is well known to induce osteogenic effects on the skeleton. Less is known about the potential effects on bone strength and geometry, especially in female adolescent athletes. The aim of this study was to investigate hip geometry in adolescent soccer players and swimmers compared to normal values that stemmed from a control group. This study included 26 swimmers (SWIM; 15.9 ± 2 years) and 32 soccer players (SOC; 16.2 ± 0.7 years), matched in body height and weight. A group of 15 age-matched controls served for the calculation of hip parameter Z-scores. Body composition and bone mineral density (BMD) were assessed by dual-energy X-ray absorptiometry (DXA). DXA scans were analyzed at the femoral neck by the hip structure analysis (HSA) program to calculate the cross-sectional area (CSA), cortical dimensions (inner endocortical diameter, ED; outer width and thickness, ACT), the centroid (CMP), cross-sectional moment of inertia (CSMI), section modulus (Z), and buckling ratio (BR) at the narrow neck (NN), intertrochanteric (IT), and femoral shaft (FS) sites. Specific BMDs were significantly higher in soccer players compared with swimmers. At all bone sites, every parameter reflecting strength (CSMI, Z, BR) favored soccer players. In contrast, swimmers had hip structural analysis (HSA) Z-scores below the normal values of the controls, thus denoting weaker bone in swimmers. In conclusion, this study suggests an influence of training practice not only on BMD values but also on bone geometry parameters. Sports with high impacts are likely to improve bone strength and bone geometry. Moreover, this study does not support the argument that female swimmers can be considered sedentary subjects regarding bone characteristics.

PMID: 20963459        [PubMed – indexed for MEDLINE]

Changes in bone geometry during growth

Growth in the external size of a long bone, its cortical thickness and the distribution of cortical bone about the neu- tral axis is determined by the absolute and relative behavior of the periosteal and endocortical bone surfaces along the length of the bone8,13. Before puberty, periosteal apposition accounts for most of the increase in cortical area, this is part- ly offset however by the enlarging marrow cavity due to endocortical resorption. The net result is an enlarged corti- cal area located further from the neutral axis, leading to increased resistance to bending4. Late in puberty, periosteal apposition continues and is now accompanied by endocorti- cal apposition14, leading to an increase in cortical thickness.

The temporal sequence of events in boys tracks that of girls before puberty. Sexual dimorphism occurs during puberty and is characterized by boys exhibiting greater perisoteal expansion late in and post-puberty, and the absence of any endocortical contraction. Thus, in boys, the net result is the attainment of a greater cortical area that is located further from the axis of rotation compared to girls13.

The skeleton’s temporal sequence of events due to growth are not only surface-specific but also region-specific with more rapid maturation of distal than proximal regions. Distal segments of the appendicular skeleton mature before the proximal segments14. Similarly, contraction of the medullary cavity occurs in a distal to proximal pattern8,14.

The effect of additional loading on bone geome- try during growth

If additional loading does enhance the effect of growth then it would follow that exercise during childhood would result in an increase in periosteal but not endocortical apposition. Late in puberty, and in the immediate years following puberty the predominant effect would be narrowing of the medullar cavity due to endocortical apposition. This maturity-dependent preferential change in cortical surfaces with mechanical loading has been demonstrated in animals15-17. Younger animals showed greater periosteal expansion, while older animals showed greater medullar cavity narrowing. Reduced mechanical loading through limb immobilization or weightlessness also leads to preferential changes at the cortical surfaces: younger animals show a greater periosteal response (inhibition of bone formation), while older animals showed a greater endocortical response (increased resorption)7,16,18.

The results of human studies however are equivocal; for instance, consistent with this proposal is the finding that pre- pubertal female gymnasts had a larger total bone area (periosteal expansion) of the forearm despite a smaller stature19. While the playing arm in adult tennis players resulted in no detectable change to the total bone area of the radius, it did however result in thicker trabeculae20. Exercise also led to medullary contraction (but no periosteal expan- sion) at the tibia in adult military recruits21. In contrast, load- ing in pre-pubertal female gymnasts and non-athletic boys resulted in increased cortical area at the mid-femoral shaft due to endocortical contraction, not periosteal expansion2.

The aforementioned inconsistencies in the literature are likely to partly reflect the limitations imposed by two-dimen- sional measures (i.e., X-ray) of a three-dimensional struc- ture (i.e., bone). Radiographs and dual energy X-ray absorp- tiometry (DEXA) provide a two-dimensional projection of bone in the coronal plane which integrates periosteal and endocortical changes in the medio-lateral, not antero-poste- rior direction. Predicting changes using two-dimensional projections makes the flawed assumption that the bone is cylindrical and that the osteogenic response is uniform. These measurements in one plane do not provide informa- tion about changes that may occur cross-sectionally because of bone modelling. The cortical bone could be contracting in one plane but expanding in the other to resist bending moments. For this reason analysis of the cross sectional bone geometry is imperative. Furthermore, inferences from one or two measures at a site may not provide an accurate representation of changes that occur along the length of the bone8,22. Measuring techniques (MRI or CT) that provide a cross sectional view in the transverse plane is required for a more accurate assessment of surface specific changes in long bones. MRI is useful (particularly in children) because of the ability to collect images along the whole length of the bone without any radiation exposure.

In a recent study, MRI was used to compare the side-to- side differences in bone traits in the arms of competitive female tennis players during different stages of maturation8. The key findings were that loading did magnify the structural changes produced during growth. Prior to puberty, loading

magnified periosteal apposition along the length of the shaft; at the mid-humerus loading resulted in increased endocorti- cal resorption (medullary expansion). During the post-puber- tal period loading magnified the effect of endocortical appo- sition (medullary contraction), which makes an important contribution to cortical thickness in females. In fact, endo- cortical apposition accounted for most of the greater side-to- side difference attained in the post-pubertal years.

Most of the structural changes due to loading occurred early in the pre-pubertal years because adaptive changes in response to loading were sufficient to reduce the strains in bone that may lead to microdamage if not decreased23,24. The only additional benefit achieved from tennis training later in puberty was contraction of the medullary cavity. The rising estrogen levels during puberty are thought to lower the bone (re)modeling threshold on this surface, and thus sensitize bone next to marrow to the effect of mechanical loading25. Interestingly, medullary contraction did not confer any addi- tional increase in the structural rigidity of the bone.

Is Growth Differentiator Factor 5 GDF5 Gene The Most Influential Gene Towards Height?

Me: This article on the link between height and the susceptibility for the risk of osteoarthritis seems to show that the most common area in the genome which show height variation effects is around the GDF5 producing gene area. I must do more research on the GDF5 gene and GDF5 in general.

What I do want to note is that the study and article was published in 2008, before the news of HMGA2 or LIN28B or the world wide gene project was published in Nature. The study looked at over 35,000 people and looked at over 2 million genetic variants. The thing is that this gene was fond to have less than 1% influence over the entire genetic influence. The effect was only about 4 milimeters on average, which ranged up to over 1 cm in height difference.

The most important part of the sciencedaily articles is….

The variants most strongly associated with height lie in a region of the human genome thought to influence expression of a gene for growth differentiation factor 5, called GDF5, which is a protein involved in the development of cartilage in the legs and other long bones. Rare variants in the GDF5 gene have been associated with disorders of skeletal development, and more common variants recently have been tied to susceptibility to osteoarthritis of the hip and knees in Asian and European populations.

It says that GDF-5 is involved in the development of cartilage in the legs and other long bones. This might be a real breakthrough in our understanding of which genes control over height. The lack of the gene producing its proteins leads to a moderate decrease in height and increased susceptibility to osteoarthritis.

From the article on Science Daily

Genetic Connection Between Short Stature And Arthritis Uncovered

ScienceDaily (Jan. 17, 2008) — Common genetic variants linked to arthritis may also play a role in human height, a new study shows.

The new study confirms observations by health professionals of a connection between decreased height and increased risk of osteoarthritis, the most common form of arthritis. Researchers speculate that both extremes of height may be associated with osteoarthritis for different reasons. Shorter bones and/or less cartilage may render the joints more susceptible to damage, while longer bones may produce greater levels of damaging stress on the joints.

The findings are exciting for several reasons, said Gonçalo Abecasis, assistant professor in the School of Public Health. For one, there are many genes that control height, but only a few associated with osteoarthritis, he said. The international study was co-led by the University of Michigan School of Public Health.

“In this case the gene we picked also is important in osteoarthritis and it’s actually quite hard to find genes for osteoarthritis,” said Abecasis, who co-directed the study with Karen Mohlke of the University of North Carolina. “One of the things we were excited about is you could study (height) in many people, and once you’ve done that you have a short list of genes that you can then study for what they do in terms of osteoarthritis.”

The findings also add to the general understanding of height.

“It is useful to know all genes responsible for height variation, so we are reassured if our baby is shorter than others because he has a collection of “short” alleles on his DNA, and not because he has something wrong, like a metabolism disorder,” said Serena Sanna, co-author who worked on the paper as a post-doctoral student in Abecasis’ group and who is now at the National Research Council di Cagliari in Italy. Anne Jackson, a research specialist at U-M, is also a co-author.

To arrive at their findings, researchers from the United States and Europe analyzed the genomes of more than 35,000 people. If there were average height differences for individuals with certain genetic variants, this indicated that something in that genomic region containing the variants likely influenced height. In this particular study, researchers initially examined the effects of more than 2 million genetic variants.

The new variant accounts for less than 1 percent of the genetic basis of height, and is associated with an average difference in height of about 0.4 centimeters, or a little more than an eighth of an inch. The range went from 0.3 cm to 1.4 cm, depending on the population and whether an individual had one or two copies of the so-called taller version of the variant. A variety of factors, including genetics, diet and prenatal environment, interact to determine how tall someone grows. It is currently thought that genetic factors are responsible for at least 80 percent of the variation in height among people.

The variants most strongly associated with height lie in a region of the human genome thought to influence expression of a gene for growth differentiation factor 5, called GDF5, which is a protein involved in the development of cartilage in the legs and other long bones. Rare variants in the GDF5 gene have been associated with disorders of skeletal development, and more common variants recently have been tied to susceptibility to osteoarthritis of the hip and knees in Asian and European populations.

The researchers speculate that genetic variants that reduce production of the GDF5 protein may affect the amount of cartilage in the spine, the proportion of limbs and/or the angles of joints, resulting in both a modest decrease in height and increased susceptibility to osteoarthritis.

The completion of the map of human genetic variation, or HapMap, has fueled a surge in this type of genome-wide association study, with most of the growth coming in the past 10 months. Researchers around the globe have now associated more than 60 common DNA variants with the risk of more than 20 common diseases or related traits.

The journal Nature Genetics will publish the findings online Jan. 13.

The research received major support from National Human Genome Research Institute, National Institute on Aging, National Institute of Diabetes and Digestive and Kidney Diseases, and the National Heart, Lung and Blood Institute, all of which are part of the National Institutes of Health.

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Gonadotropin Releasing Hormone (GnRH) AKA Luteinizing Hormone Releasing Hormone (LHRH) Can Delay Puberty

Me: I found from this study that it may be possible to slow down or delay the closure of the growth plates at least for growth hormone deficiency adolescents with using LHRH. As stated by the study, “These results indicate that delaying puberty with LHRH-A in GHD children during treatment with GH increases final height“. Of course keep in mind that the LHRH was used in combination with GH. The test was done with a control, a group only subjected to GH, and the last group who was treated with LHRH and GH.

What I found fascinating is how the GnRH releases the right type of hormones in the anterior pituitary…“At the pituitary, GnRH stimulates the synthesis and secretion of the gonadotropins, follicle-stimulating hormone (FSH), and luteinizing hormone (LH). These processes are controlled by the size and frequency of GnRH pulses, as well as by feedback from androgens and estrogens. Low-frequency GnRH pulses lead to FSH release, whereas high-frequency GnRH pulses stimulate LH release.”

The results are…”We observed a significant decrease in the rate of BA maturation in the group treated with GH+LHRH-A (1.5 ± 0.2 yr) compared with the group treated with GH alone (4.2 ± 0.5 yr) during the 3 years of LHRH-A therapy (P < 0.05)…These results indicate that delaying puberty with LHRH-A in GHD children during treatment with GH increases final height“

Interpretation: it would seem that children treated with just GH treatment might have only increase grow velocity but did not slow the bone maturation process down. With the LHRHa, we did slow it down. This tells us a critical clue on what can be done for future research and potential ideas.

From the Wikipedia article on GnRH aka LHRH HERE we learn first what is the Luteinizing hormone releasing hormone and how it functions.

Gonadotropin-releasing hormone (GnRH), also known as Luteinizing-hormone-releasing hormone (LHRH) and luliberin, is a trophic peptide hormone responsible for the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary. GnRH is synthesized and released from neurons within the hypothalamus. The peptide belongs to gonadotropin-releasing hormone family.

Neurohormone

GnRH is considered a neurohormone, a hormone produced in a specific neural cell and released at its neural terminal. A key area for production of GNRH is the preoptic area of the hypothalamus, which contains most of the GnRH-secreting neurons. GnRH neurons originate in the nose and migrate into the brain, where they are scattered throughout the medial septum and hypothalamus and connected by very long >1-millimeter-long dendrites. These bundle together so they receive shared synaptic input, a process that allows them to synchronize their GnRH release.[1]

GnRH is secreted in the hypophysial portal bloodstream at the median eminence. The portal blood carries the GnRH to the pituitary gland, which contains the gonadotrope cells, where GnRH activates its own receptor, gonadotropin-releasing hormone receptor (GnRHR), a seven-transmembrane G-protein-coupled receptor that stimulates the beta isoform of Phosphoinositide phospholipase C, which goes on to mobilize calcium and protein kinase C. This results in the activation of proteins involved in the synthesis and secretion of the gonadotropins LH and FSH. GnRH is degraded by proteolysis within a few minutes.

Control of FSH and LH

At the pituitary, GnRH stimulates the synthesis and secretion of the gonadotropins, follicle-stimulating hormone (FSH), and luteinizing hormone (LH). These processes are controlled by the size and frequency of GnRH pulses, as well as by feedback from androgens and estrogens. Low-frequency GnRH pulses lead to FSH release, whereas high-frequency GnRH pulses stimulate LH release.

There are differences in GnRH secretion between females and males. In males, GnRH is secreted in pulses at a constant frequency, but, in females, the frequency of the pulses varies during the menstrual cycle, and there is a large surge of GnRH just before ovulation.

GnRH secretion is pulsatile in all vertebrates, and is necessary for correct reproductive function. Thus, a single hormone, GnRH1, controls a complex process of follicular growth, ovulation, and corpus luteum maintenance in the female, and spermatogenesis in the male.

Activity

The GnRH neurons are regulated by many different afferent neurons, using several different transmitters (including norepinephrine, GABA, glutamate). For instance, dopamine appears to stimulate LH release (through GnRH) in estrogen-progesterone-primed females; dopamine may inhibit LH release in ovariectomized females.[2] Kisspeptin appears to be an important regulator of GnRH release.[3] GnRH release can also be regulated by estrogen. It has been reported that there are kisspeptin-producing neurons that also express estrogen receptor alpha.[4]

Next the PubMed study link HERE

Near Final Height in Pubertal Growth Hormone (GH)-Deficient Patients Treated with GH Alone or in Combination with Luteinizing Hormone-Releasing Hormone Analog: Results of a Prospective, Randomized Trial

  1. M. Veronica Mericq, Martha Eggers, Alejandra Avila, Gordon B. Cutler Jr. 2 and Fernando Cassorla

–Author Affiliations

  • Institute of Maternal and Child Research (M.V.M., M.E., A.A., F.C.), University of Chile, Santiago, Chile; and DEB, NICHD (G.B.C.), National Institutes of Health, Bethesda, Maryland 20892
  • Address correspondence and requests for reprints to: M. Verónica Mericq, IDIMI, University of Chile, Casilla 226-3, Santiago, Chile.

Abstract

To study the effects of delaying puberty in GH-deficient (GHD) children, we studied 21 GHD (9 boys, 14 girls), treatment-naive, pubertal patients in a prospective, randomized trial. Their chronological age was 14.3 ± 1.6 yr, and their bone age was 11.3 ± 1.1 yr (mean ± SD) at the beginning of the study. Four patients who developed hypogonadotropic hypogonadism were subsequently excluded from the study. Patients were randomly assigned to receive GH + LH-releasing hormone analog (LHRH-A) (n = 7), or GH alone (n = 10). GH and LHRH-A treatment started simultaneously in each patient. GH (Nutropin) was administered at a dose of 0.1U/kg·day sc, until patients reached a bone age (BA) of 14 yr in girls and 16 yr in boys, and LHRH-A (Lupron depot) was administered at a dose of 300 μg/kg·every 28 days in during 3 yr. We defined GH deficiency as patients with a growth velocity less than 4 cm/yr, BA delay more than 1 yr in relationship to chronological age, GH response to two stimulation tests less than 7μ g/L, associated with low serum insulin-like growth factor I and insulin-like growth factor binding protein 3 levels. Statistical analysis was performed by ANOVA or Kruskall Wallis when variances were not homogeneous. We observed a significant decrease in the rate of BA maturation in the group treated with GH+LHRH-A (1.5 ± 0.2 yr) compared with the group treated with GH alone (4.2 ± 0.5 yr) during the 3 years of LHRH-A therapy (P < 0.05). This delay in BA maturation produced a significant gain in final height in the group treated with GH+LHRH-A, which reached −1.3 ± 0.5 SDscore compared with −2.7 ± 0.3 SD score (P < 0.05) in the group treated with GH alone. These results indicate that delaying puberty with LHRH-A in GHD children during treatment with GH increases final height.

  • Received August 31, 1999.
  • Revision received October 12, 1999.
  • Accepted October 25, 1999.

Combining The Effect Of Gonadotropin Releasing Hormone Analogue And Growth Hormone Together In Treatment

Me: The point of this post is to show that for children who suffer from idiopathic short stature, precious puberty, and impaired height the use of using a combination of Gonadotropin releasing hormone analogue and growth hormone is better than using any of the two types of hormones by themselves. Of course it is interesting to realize that the three studies and articles published are from the same group of researchers. 

From the first study…”Our results suggest that combined therapy with Gn-RH analogues and recombinant GH can improve growth velocity and predicted adult height in girls with central precocious puberty and impaired height prognosis during Gn-RH analogue treatment.” The baseline growth velocity increased from around 3 cm/year to 6.5 cm/year and the final height increased from around 1552 cm to 156 cm.

From the 2nd study…”In conclusion, a gain of 7.9 cm in adult height represents a significant improvement, which justifies the addition of GH for 2-3 yr during the conventional treatment with GnRHa, especially in patients with CPP, and a decrease in GV so marked as to impair PAH, not allowing it to reach even the third centile.” What we seem to see is that the GnRH treatments can slow down growth velocity and bone maturation, which can result in a little bit of extra height but if the growth velocity is lowered too little, then it overrides the effect that decreasing the rate of bone maturation would have. This can be corrected by adding hGH into the treatment to increase the the growth velocity rate but still keeping the effect of the GnRH which slows down the bone maturation.

From the 3rd study…”Our experience suggests that the combination of GH and GnRHa is significantly more effective in improving adult height than GH alone in girls with idiopathic short stature, early or normal onset of puberty, and low PAH well below the third percentile and TH.“.. We see that if you use treatment ot the GnRHa you really get very little increase in final height (only 6 cm) but with the hGH and GnRHa treatment the final height is on average 10 cm larger. This is usually for idiopathic short stature girls who have precious puberty and bone maturation.

From PubMed study link HERE

Acta Paediatr. 1995 Mar;84(3):299-304.

Effect of combined treatment with gonadotropin releasing hormone analogue and growth hormone in patients with central precocious puberty who had subnormal growth velocity and impaired height prognosis.

Saggese G, Pasquino AM, Bertelloni S, Baroncelli GI, Battini R, Pucarelli I, Segni M, Franchi G.

Source

Department of Pediatrics, University of Pisa, Italy.

Abstract

Growth hormone-insulin-like growth factor-I status and response to growth hormone therapy (0.6 IU/kg/week sc, six times a week for 12 months) were evaluated in 12 girls (chronological age 9.4 +/- 1.6 years) suffering from central precocious puberty with growth velocity less than 4 cm/year and no substantial increase or decrease in predicted adult height during gonadotropin releasing hormone Bn-RH) analogue treatment (D-Trp6-LH-RH, 60 micrograms/kg im/28 days). At baseline, large variations were observed in nocturnal growth hormone (GH) means (pathological values stimulated levodopa GH peaks (pathological values (< 10.0 micrograms/l) 28.6%) and serum insulin-like growth factor-I (IGF-I) levels. Neither GH-nor IGF-I levels were correlated with growth velocity. During recombinant GH therapy, growth velocity increased significantly (baseline 3.0 +/- 0.9 cm/year; 6 months 6.4 +/- 1.9 cm/year, p < 0.001 versus baseline; 12 months 6.0 +/- 1.3 cm/year, p < 0.0001 versus baseline). There was a significant increase in height SDS for bone age (baseline -1.6 +/- 0.5 SDS; 12 months -1.04 +/- 0.6 SDS; p < 0.002) and in predicted adult height (baseline 152.0 +/- 3.6 cm; 12 months 155.9 +/- 3.4 cm; p < 0.002). Our results suggest that combined therapy with Gn-RH analogues and recombinant GH can improve growth velocity and predicted adult height in girls with central precocious puberty and impaired height prognosis during Gn-RH analogue treatment.

PMID: 7780252   [PubMed – indexed for MEDLINE]

From PubMed study link HERE

J Clin Endocrinol Metab. 1999 Feb;84(2):449-52.

Adult height in girls with central precocious puberty treated with gonadotropin-releasing hormone analogues and growth hormone.

Pasquino AM, Pucarelli I, Segni M, Matrunola M, Cerroni F.

Source

Pediatric Department, University La Sapienza, Rome, Italy.

Erratum in

J Clin Endocrinol Metab 1999 Jun;84(6):1978. Cerrone F [corrected to Cerroni F].

Abstract

GnRH analogues (GnRHa) represent the treatment of choice in central precocious puberty (CPP), because arresting pubertal development and reducing either growth velocity (GV) or bone maturation (BA) should improve adult height. However, in some patients, GV decrease is so remarkable that it impairs predicted adult height (PAH); and therefore, the addition of GH is suggested. Out of twenty subjects with idiopathic CPP (treated with GnRHa depot-triptorelin, at a dose of 100 microg/kg im every 21 days, for at least 2-3 yr), whose GV fall below the 25th percentile for chronological age, 10 received, in addition to GnRHa, GH at a dose of 0.3 mg/kg x week s.c., 6 days weekly, for 2-4 yr; and 10 matched for BA, chronological age, and duration of GnRHa treatment, who showed the same growth pattern but refused GH treatment, served to evaluate the efficacy of GH addition. No patient showed classical GH deficiency. Both groups discontinued treatment at a comparable BA (mean +/- SEM): 13.2 +/- 0.2 in GnRHa plus GH vs. 13.0 +/- 0.1 yr in the control group. At the conclusion of the study, all the patients had achieved adult height. Adult height was considered to be attained when the growth during the preceding year was less than 1 cm, with a BA of over 15 yr. Patients of the group treated with GH plus GnRHa showed an adult height significantly higher (P < 0.001) than pretreatment PAH (160.6 +/- 1.3 vs. 152.7 +/- 1.7 cm). Target height (TH) was significantly exceeded. The group treated with GnRH alone reached an adult height not significantly higher than pretreatment PAH (157.1 +/- 2.5 vs. 155.5 +/- 1.9 cm). TH was just reached but not significantly exceeded. The gain in centimeters obtained, calculated between pretreatment PAH and final height, was 7.9 +/- 1.1 cm in patients treated with GH combined with GnRHa; whereas in patients treated with GnRHa alone, the gain was just 1.6 +/- 1.2 cm (P = 0.001). Furthermore, no side effects have been observed either on bone age progression or ovarian cyst appearance and the gynecological follow-up in the GH-treated patients (in comparison with those treated with GnRHa alone). In conclusion, a gain of 7.9 cm in adult height represents a significant improvement, which justifies the addition of GH for 2-3 yr during the conventional treatment with GnRHa, especially in patients with CPP, and a decrease in GV so marked as to impair PAH, not allowing it to reach even the third centile.

PMID: 10022399     [PubMed – indexed for MEDLINE]  Free full text

From PubMed study link HERE

J Clin Endocrinol Metab. 2000 Feb;85(2):619-22.

Adult height in short normal girls treated with gonadotropin-releasing hormone analogs and growth hormone.

Pasquino AM, Pucarelli I, Roggini M, Segni M.

Source
Pediatric Department, University La Sapienza, Rome, Italy.

Abstract

Combined treatment with GH and GnRH analogs (GnRHa) has been proposed to improve final adult height in true precocious puberty, GH deficiency, and short normal subjects with early or normal timing of puberty with still controversial results. We treated 12 girls with idiopathic short stature and normal or early puberty with GH and GnRHa and followed them to adult height; 12 girls comparable for auxological and laboratory characteristics treated with GH alone served to better evaluate the efficacy of addition of GnRHa. At the start of combined treatment, the chronological age of the girls (CA; mean +/- SD) was 10.2 +/- 0.9 yr, bone age (BA) was 10.6 +/- 1.9 yr, height SD score for BA was – 1.81 +/- 0.8, PAH was 146.3 +/- 5.0 cm. PAH was significantly lower than target height (TH 152.7 +/- 3.6 cm; P < 0.005). GH was given at a dose of 0.3 mg/kg x week, sc, 6 days weekly, and GnRHa (depot-triptorelin) was given at a dose of 100 microg/kg every 21 days, im. The 12 girls were treated with GH alone at the same dose; at the start of therapy their CA was 10.7 +/- 1.0, BA was 10.1 +/- 1.4 yr, height SD score for BA was – 1.65 +/- 0.8, PAH was 145.6 +/- 4.4 cm, and TH was 155.8 +/- 4.6 cm. Pubertal Tanner stage in both groups was B2P2 or B3P3. LHRH test and pelvic ultrasound showed the beginning of puberty. The GH response to standard provocative tests was 10 g/L or more. The mean period of treatment was 4.6 +/- 1.7 yr in the group treated with GH plus GnRHa and 4.9 +/- 1.4 yr in the group treated with GH alone; both groups discontinued treatment at comparable CA and BA. Adult height was considered to be attained when growth during the preceding year was less than 1 cm, with a BA of over 15 yr. Patients in the group treated with GH plus GnRHa showed an adult height significantly higher (P < 0.001) than the pretreatment PAH (156.3 +/- 5.9 vs. 146.3 +/- 5 cm); the gain in centimeters calculated between pretreatment PAH and adult height was 10 +/- 2.9 cm, and 7 of 12 girls had a gain over 10 cm. Target height was significantly exceeded. Height SD score for BA increased from – 1.81 +/-0.8 to -0.85 +/- 1.0. The GH alone group reached an adult height higher than the pretreatment PAH (151.7 +/- 2.7 vs. 145.6 +/- 4.4 cm); the gain in final height vs. pretreatment PAH was 6.1 +/- 4.4 cm, and 5 of 12 girls did not gain more than 4 cm. TH was even not reached. The height SD score did not significantly change. No adverse effects were observed in either group. All of the girls showed good compliance and were satisfied with the results. Our experience suggests that the combination of GH and GnRHa is significantly more effective in improving adult height than GH alone in girls with idiopathic short stature, early or normal onset of puberty, and low PAH well below the third percentile and TH. As the cost-benefit of such invasive treatment must be seriously considered, further studies are needed due to the small sample of our patients as well as in other studies reported to date.

Comment in

Final adult height in short healthy children treated with growth hormone and gonadotropin-releasing hormone analogs. [J Clin Endocrinol Metab. 2001]

PMID: 10690865  [PubMed – indexed for MEDLINE]     Free full text

Differential Effects Of HGH And IGF-I On Body Proportions

Me: This post shows that the effects of HGH and IGF-1 are actually different for different areas in the body. I showed in a recent post that the inject of IGF-2 in a localized region of the long bone (distal femoral epiphysis) lead to the long bone (femur) to lengthen. We know that from growth plate analysis that the growth plates have receptors for both GH and IGF-2, but from my personal research, the IGF-2 might have a more regional localized effect leading to increased limb length then torso/body length. However this study was done for IGF-1, bot IGF-2. 
Analysis & Interpretation of study: It is important to realized that the upper/lower body segment interpretation means the lower body is the leg/limbs while the upper body is the torso. So a higher U/L value means there was more lengthening effect on the torso than the limbs. A lower U/L value means there was more lengthening on the limbs then the torso. It seems that with kids who have some form of growth hormone deficiency (isolated and multiple pituitary hormone deficiency) the limbs were the primary area of lengthening from using the hGH injections. However with kids who suffered from Laron’s Syndrome, intrauterine growth retardation, or idiopathic short stature the treatment with either IGF-1 or hGH did not change the U/L but did result in increase height so it seems that with these types of disorders, the distributed effect by the GH or IGF-1 was even throughout the body. 
From PubMed article link HERE…
Anthropol Anz. 2012 Jul;69(3):255-9.

Differential effects of hGH and IGF-I on body proportions.

Laron Z, Silbergeld A, Kauli R.

Source

Endocrinology and Diabetes Research Unit, Schneider Children’s Hospital, WHO Collaborating Center for Diabetes in Youth Petah Tikva and Sackler School of Medicine, Tel Aviv, Israel. laronz@clalit.org.il

Abstract

The differential growth effects of hGH and IGF-I on the upper/lower (U/L) body segment in relation to height (Ht) were analyzed in 15 patients with isolated Growth hormone deficiency (IGHD,:7M, 8F) mean age 5.0 +/- 3.2 (SD) years treated with hGH; 21 patients with multiple pituitary hormone deficiency including growth hormone (MPHD: 14M, 7F) aged 10.0 +/- 3.8, treated with hGH; 9 patients with Laron Syndrome (LS) (4M,5F) aged 6.9 +/- 5.6 years treated with IGF-I; 9 boys with intrauterine growth retardation (IUGR) aged 6.3 +/- 1.25 years treated by hGH; and 22 boys with idiopathic short stature (ISS) aged 8.0 +/- 1.55 years treated by hGH. The dose of hGH was 33 microg/kg/day, that of IGF-I 180-200 microg/kg/day. RESULTS: the U/L body segment ratio in IGHD patients decreased from 2.3 +/- 0.7 to 1.1 +/- 0.7 (p <0.001), and the Ht SDS increased from -4.9 +/- 1.3 to 2.3 +/- 1 (p < 0.001) following treatment. In MPHD patients the U/L body segment decreased from 1.1 +/- 1.1 to -0.6 +/- 1.0 (p < 0.001), and the Ht SDS increased from -3.3 +/- 1.4 to -2.5 +/- 1.0 (p < 0.009). In the LS group the U/L body segment ratio did not change with IGF-I treatment but Ht improved from -6.1 +/- 1.3 to -4.6 +/- 1.2 (p < 0.001), The differential growth response of the children with IUGR and with ISS resembled that of the children with LS. CONCLUSIONS: hGH and IGF-I act differentially on the spine and limbs.

PMID: 22928349   [PubMed – indexed for MEDLINE]

Mind Hack XVI: A Complete Resource Guide For All Of Your Cognitive Enhancement And Intelligence Increase Needs

Note: This post will be one of those that will be continuously edited and added upon as the site goes on

To enhance your life, life quality, and life expectancy, these are very nice resource websites or forum boards you can checkout which I have found throughout the internet space. They deal with nutrition, supplements, and

1. Life-Enhancement.com

2. TheLimitlessMan.com

3. LongCity.Com

4. AnabolicMinds.com

5.

To enhance your mind, cognitive ability, mental fitness, memory, intelligence, power of focus and concentration, and everything else related, these are the resource that I have found which I think are rather informative and good.

1. BrainMeta.com

2. MindNutrition.com

3. NootropicSupplements.com

4.

5.