Effects of estrogen on growth plate senescence and epiphyseal fusion

Abstract

Estrogen is critical for epiphyseal fusion in both young men and women. In this study, we explored the cellular mechanisms by which estrogen causes this phenomenon. Juvenile ovariectomized female rabbits received either 70 g/kg estradiol cypionate or vehicle i.m. once a week. Growth plates from the proximal tibia, distal tibia, and distal femur were analyzed after 2, 4, 6, or 8 weeks of treatment. In vehicle-treated animals, there was a gradual senescent decline in tibial growth rate, rate of chondrocyte proliferation, growth plate height, number of proliferative chondrocytes, number of hypertrophic chondrocytes, size of terminal hypertrophic chondrocytes, and column density. Estrogen treatment accelerated the senescent decline in all of these parameters. In senescent growth plates, epiphyseal fusion was observed to be an abrupt event in which all remaining chondrocytes were rapidly replaced by bone elements. Fusion occurred when the rate of chondrocyte proliferation approached zero. Estrogen caused this proliferative exhaustion and fusion to occur earlier. Our data suggest that (i) epiphyseal fusion is triggered when the proliferative potential of growth plate chondrocytes is exhausted; and (ii) estrogen does not induce growth plate ossification directly; instead, estrogen accelerates the programmed senescence of the growth plate, thus causing earlier proliferative exhaustion and consequently earlier fusion.

The aromatase inhibitor letrozole increases epiphyseal growth plate height and tibial length in peripubertal male mice

“…Rather, it is estrogen that, by enhancing osteogenesis at the expense of chondrogenesis, accelerates the epiphyseal fusion rate and terminates linear growth (Cutler 1997). Furthermore, in a study in rabbits, Weise et al (2001) suggested that epiphyseal fusion is triggered when the proliferative potential of growth plate chondrocytes is exhausted, and that estrogen accelerates the programmed senescence of the growth plate, thereby causing earlier epiphyseal fusion.…”

Frequency of osteoporosis in children with Turner Syndrome and determining the optimal age of the onset of estrogen replacement theraphy

“…Düşük dozlarda büyümeyi uyarırken, yük-sek dozlarda büyümeyi baskılamaktadır (11)(12)(13)(14)(15) . Yüksek doz östrojen, kısmen epifiz füzyonu üzerine direkt etkisiyle, kısmen de büyüme hormonu antagonisti gibi davranarak büyümeyi kısıtlar (16)(17)(18)(19) . Turner sendromlu olgularda gonadal yetersizliğe bağlı olarak östrojen düzeyleri düşük saptanır ve bu olguların çoğu östrojen tedavisi olmaksızın puberteye girememektedir.…”

Epiphyseal growth plate and secondary peripheral chondrosarcoma: the neighbours matter

“…The epiphyseal growth plate's fate is to be resorbed after the pubertal growth spurt, at the time of sexual maturation [37]. The resorption and fusion of the growth plate follow the cessation of growth and are regulated by both systemic mechanisms (ie oestrogen hormone) and local mechanisms, intrinsic to the growth plate [38,39].…”

“…It has been described that the growth plate chondrocytes have a finite proliferative capacity [39]. Therefore, the fusion of the growth plate is triggered when the proliferative potential of the chondrocytes is exhausted and finally all the remaining chondrocytes are replaced by bone, in which the epiphysis fuses with the metaphysic [37].…”