Hypothalamic Suppression Decreases Bone Strength Before and After Puberty in a Rat Model

Abstract

The incidence of menstrual irregularities, both primary and secondary amenorrhea, has been reported to be as high as 60%, with the highest incidence in younger athletes, suggesting possible adverse effects on bone development. It was hypothesized that in a rat model, suppressed hypothalamic activity via a gonadotropin-releasing hormone antagonist (GnRH-a) before onset of puberty would result in a relatively larger bone strength deficit compared with suppression after puberty. Hypothalamic suppression was achieved by providing GnRH injections. Animals received injections for 25 days either before puberty (pre group) (age 23–46 days) or after puberty (post group) (age 65–90 days). Body weights and uterine weights were measured. Serum estradiol was assayed. Mechanical strength of the right femora and histomorphometry of the left femur were measured. Suppression of the hypothalamic– pituitary–gonadal axis was confirmed by significant atrophy of uterine tissue and suppressed estradiol levels. The peak moment was significantly lower in the pre and post GnRH-a groups compared with control. The percentage difference of the average peak moment and stiffness values from the respective age-matched control groups yielded a greater percentage difference in the pre group. The cortical area was less in the GnRH-a-treated groups, but no significant difference between the relative deficits between pre and post groups were found. Hypothalimic–pituitary–gonadal axis suppression before puberty resulted in a significantly larger deficit in mechanical strength compared with postpubertal animals. The time before puberty may represent a time when skeletal strength is more compromised. Women experience both primary and secondary amenorrhea; however, the treatment may need to be different for each condition.

Abrogation of Cbl–PI3K Interaction Increases Bone Formation and Osteoblast Proliferation

“…Given that YF mice have increased cancellous bone (Fig. 1 d; Table 1 ) and increased cortical bone size (Table 1 ), we examined the mechanical properties of the long bones using a three-point bending assay, as previously described [ 24 , 25 ]. There was a significant increase in peak moment and yield displacement in YF mice compared to WT, but no differences were observed in the other parameters listed in Table 2 .…”

“…Breaking strength of the right femur was measured under three-point bending using a material testing machine (ElectroForce Systems Group, Bose, Eden Prairie, MN) fitted with a 1,000 N load cell as previously described [ 24 , 25 ]; to minimize the effect of shear loading, the distance between the lower support points was maximized. Femora were placed on the loading fixture anterior side down and loaded in the anterior–posterior plane at a span length of 19.26 mm.…”

L-Plastin deficiency produces increased trabecular bone due to attenuation of sealing ring formation and osteoclast dysfunction

“…Breaking strength of the left femur was measured under three-point bending using a material testing machine (ElectroForce Systems Group, Bose, Eden Prairie, MN) fitted with a 1 000 N load cell as previously described. [78][79][80] The effect of shear loading was minimized via maximizing the distance between the lower support points. Femurs were placed on the loading fixture anterior side down and loaded in the anterior-posterior plane at a span length of (Femur: 9 weeks-9.2 mm, 13 weeks-9.6 mm; Tibia: 9 weeks-13.0 mm, 13 weeks-13.8 mm).…”

Spinal Cord Injury Induced Arrest in Estrous Cycle of Rats is Ameliorated by S-nitrosoglutathione: Novel Therapeutic Agent to Treat Amenorrhea

“…Estrogen is produced primarily by developing follicles in the ovary in response to gonadotropic hormones, with the peak of production occurring at ovulation. Decreases in estrogen level result in infrequent menstrual cycles [13]. In addition to controlling reproductive physiology, estrogen also targets the brain [14], significantly affecting individuals' cognitive, psycho‐emotional, and depressive status [15].…”