Bone loss in ovariectomized rats: Dominant role for estrogen but apparently not for FSH

Abstract

Estrogen deficiency as the sole factor underlying post-menopausal osteoporosis was challenged, in light of reports that both follicular stimulation hormone (FSH) receptor and FSHβ knockout mice were resistant to bone loss, suggesting a detrimental role for FSH. We assessed whether lowering FSH levels by gonadotropin realizing (GnRH) analog decapeptyl in ovariectomized female rats (OVX) affects bone. Wistar-derived 25 days old OVX female rats were injected for 10 weeks with estradiol-17β (E(2)), with GnRH analog (decapeptyl) or with both. FSH and luteinizing hormone (LH) serum levels were markedly increased in OVX rats, with smaller growth plates with disrupted architecture; heavy infiltration of bone marrow with numerous adipocytes and reduced thickness of cortical bone. In OVX rats treated with E(2), FSH, and LH levels were intermediate, the tibia was similar to that of intact rats, but there was reduced thickness of cortical bone. In decapeptyl treated OVX rats, FSH and LH levels were suppressed, the organization of growth plate and the trabecular bone were disrupted, and there were fewer proliferative and chondroblastic cells and a large adipocytes population in bone marrow, but an increased trabecular bone volume (TBV). In the E(2) + decapeptyl treatment, FSH and LH levels were suppressed, with partially restored growth plate architecture and improved TBV. In conclusion, E(2) deficiency is the dominant factor impairing bone loss in OVX and concomitant changes in FSH/LH levels achieved by decapeptyl have some modulating, though complex role in this setting. The role of high FSH levels in post-menopausal bone loss requires further investigation using combined sub-optimal doses of the different hormones.

Effects of polymorphisms in gonadotropin and gonadotropin receptor genes on reproductive function

“…However, this study only suggests that FSH could be indirectly involved in the bone loss mechanisms since a correlation between FSH levels and bone metabolism has never been observed in other populations. Conversely, some studies are in complete disagreement with the model which provides a direct FSH regulation of the bone mass [164][165][166]. The presence of direct transcriptional targets of sex steroid hormones in bone [167] and the evidence of a clear association between estrogen receptors subtypes with the features of the bone metabolism [168][169][170][171][172][173][174][175], suggest that gonadotropins and their receptors do not have a predominant role in regulating the bone turnover mechanisms.…”

Decreased Bone Mineral Density in Rats Rendered Follicle-Deplete by an Ovotoxic Chemical Correlates with Changes in Follicle-Stimulating Hormone and Inhibin A

“…For example, the partial reversal of trabecular bone loss in OVX animals in response to FSH inhibition is suggestive of in vivo catabolic bone effects of elevated FSH [22]. However, conversely, bone mass in intact mice overexpressing FSH is also increased [23].…”

Using three-point bending to evaluate tibia bone strength in ovariectomized young mice

“…There have been conflicting results that suggest that the elevation in follicle stimulating hormone (FSH) due to estrogen deficiency is associated with a decline in bone mass [24,25]. However, Ozbek et al [26] recently found that elevated levels of FSH due to hypogonadotropic and hypergonadotropic hypogonadism in adolescent girls did not have an impact on femur bone mineral density.…”