Histomorphology of the metaphysis of the tibia of ovariectomized rats treated with estradiol-17ß or Cimicifuga racemosa

Estradiol-17ß (E2) and the extract of Cimicifuga racemosa (CR) protect against development of osteoporosis following ovariectomy (ovx) of rats. This was previously shown utilizing quantitative computer tomography which measures bone mineral density, i.e. the degree of bone mineralisation. Bone stability, however is largely dependent on the microarchitecture particularly of the trabecular apparatuses of long bones. Therefore we investigated by means of quantitative histomorphometry the microarchitecture of the metaphysis of the tibia of ovx rats either treated with E2 (14µg/day/animal) or with the special extract BNO 1055 (30mg per day) over a period of 3 months given immediately after ovx (prophylactic approach) or starting 30 days after ovx (therapeutic approach). CT scans were taken prior to 45 and 90 days after ovx and animals were sacrificed after the last CT-scan, the tibiae harvested and embedded in epoxy resin, cut in 3µm preparations and stained according to Goldner. By means of computer aided program the surface of the trabeculae within the endosteal area of the metaphysis of the tibia were evaluated. The qCT data indicated that sham treated animals lost more than 50% of their cancellous bone mineral density within 3 months after ovx. This loss was almost totally prevented by E2 and partially by the Cimicifuga racemosa extract in the prophylactic approach. This reflected also in the histomorphometric data: A massive loss of the number of trabeculae was observed in the sham treated ovx animals and this loss was largely prevented by E2 and the CR extract BNO 1055. The periosteal circumference at the level of the metaphysis of tibia was significantly enlarged in the ovx animals and the total cortical bone mass was also increased. This effect was also largely prevented by E2 and the CR extract BNO 1055. Osteocalcin is a surrogate parameter of osteoblast activity which can be measured in the serum. E2 caused lowest osteocalcin concentration at the end of the study while levels in BNO 1055 treated animals were significantly elevated compared to controls. In the therapeutic approach trabecular rarification had occurred prior to treatment (˜35%) but a further loss of cancellous density and of trabeculae was prevented by E2 and BNO 1055. Thus E2 and substance(s) present in BNO 1055 were able to maintain the structure of the bone although the underlying mechanisms appear to be different. E2 has more antiresorptive effects whereas CR BNO 1055 may stimulate osteoblast activity.