The effects of delayed puberty on the growth plate.
"Many athletes are beginning intense training before puberty, a time of increased bone accrual when up to 25% of total bone mineral accrual occurs. Female athletes experiencing late or delayed pubertal onset may have open epiphyseal plates that are vulnerable to injury. This investigation's purpose was to determine whether a delay in puberty (primary amenorrhea) affects the growth plate immediately postpuberty and at maturity.
Forty-eight female Sprague-Dawley rats (23 d old) were randomly assigned to 4 groups (n=12); short-term control (C-ST), long-term control (C-LT), short-term GnRH antagonist (G-ST), and long-term GnRH antagonist (G-LT). At 25 days of age, daily gonadotropin-releasing hormone antagonist (GnRH-a) injections were administered delaying pubertal onset. Left tibias were analyzed. Stained frontal slices of proximal tibia (5 µm thick) were analyzed in hypertrophic, proliferative, and reserve zones for total height, zone height, and cell/column counts.
Growth plate height was 19.7% wider in delayed puberty (G-ST) group and at maturity was 27.9% greater in G-LT group compared with control (C-LT). No significant differences were found in short-term or long-term growth plate zone heights or cell/column counts between groups. Growth plate zone height normalized to total height resulted in 28.7% larger reserve zone in the short-term GnRH-a group but the proliferative zone was 8.5% larger in the long-term group compared with the control group. Normalized to growth plate height a significant decrease was found in column counts in proliferative zones of the short-term and long-term GnRH-a groups.
Current data illustrate that delayed puberty using GnRH-a injections results in significant growth plate height and decreases proliferative column counts and zone height, thus potentially contributing to decreases in bone mass at maturity.
Growth plate height increases indicate increased potential for growth and bone accrual. However, previous models report decreased bone volume following delayed puberty via GnRH-a injections that may have detrimental effects in the long term."
"Estrogen in low doses stimulates growth hormone and results in the chondroblast progenitor cells in the reserve zone beginning clonal expansion. Suppressed estrogen levels during delayed puberty and secondary amenorrhea may have a direct negative effect on the growth plate and thus bone development"
"The GnRH-a model significantly delays the onset of puberty resulting in suppressed estradiol levels during growth"
"proximal growth plates of the tibia of IGF-1-deficient and acid-labile subunit knockout mice (LID+ALSKO) were smaller in total height and in the height of the proliferative and hypertrophic zones of chondrocytes compared with controls"
"delayed pubertal onset in the GnRH-a groups resulted in increased height[growth plate height not body height] but bone bridging would indicate that even though statistically growth plates are at different heights senescence was near with growth plate fusion at a time point similar to control animals. Delayed growth plate senescence following the dexamethasone injections was indicated by the lack of growth plate fusion in the experimental animals. After the 16-week period, the control group had 74% more fused growth plates in comparison with the dexamethasone group."
According to the author, there was no statistically significant differences in bone length between either the long term or short term groups.
"Means were very similar between groups at both time points."
Benefit of postponing normal puberty for improving final height
"In children with central precocious puberty, a GnRH analog (GnRHa) alone is efficacious in increasing final height, but in other conditions a combination of growth hormone (GH) and GnRHa is needed. In GH-deficient children with early onset of puberty and poor height prediction, the combination of GH and GnRHa increases final height by 1.0-1.3 s.d. In children with idiopathic short stature and persistent short stature after intrauterine growth retardation, the combination also appears to be beneficial. Potential side effects include weight gain, a negative effect on bone mineralization, and psychosocial consequences. More data on long-term safety have to be collected before the combination of GH and GnRHa in children with idiopathic short stature should be considered for clinical use outside clinical trials. "
"within the normal range, late developers have a greater leg length:sitting height ratio than early developers"
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