Effect of weight manipulation on bone loss due to ovariectomy and the protective effects of estrogen in the rat

Abstract

While characterizing the effects of estrogen on an ovariectomized (OVX) rat model of bone loss, we examined several weight-matching regimens [e.g., ad libitum (feed bins continually full), weight matched (rate of weight gain for OVX and Sham-OVX groups was equalized), and weight restricted (weight gain rates for all groups were equalized to that of estrogen-treated OVX rats)] for possible effects. Bone loss following ovariectomy is primarily the result of an increase in bone resorption and is extremely sensitive to the effects of estrogens. Thus, in all of our analyses, treatment with 17 beta-estradiol served as a positive control for the prevention of bone loss. Each weight-matching study had three groups: control (Sham-OVX), OVX, and OVX + 17 beta-estradiol (0.1 mg/kg/day), and lasted for either 2, 4, or 6 weeks. Throughout the study, each Sprague Dawley rat was weighed every other day, and following sacrifice, a femur was removed for bone mineral density (BMD) analysis at the distal metaphysis by single photon absorptiometry. Following 2 weeks of dietary modifications, no significant differences were detected in BMD among the ad lib or weight matched groups. However, an estradiol-preventable reduction in BMD in restricted OVX rats was detected at 2 weeks postovariectomy. Additionally, OVX rats in all three dietary regimens displayed an estrogen-preventable reduction in proximal femur BMD at 4 and 6 weeks postovariectomy. These results indicate that a 4-week rat ovariectomized model of bone loss, under conditions of ad libitum feeding, shows great potential for pharmacologic manipulation.

Evaluation of a soybean product fujiflavone P40 as an antiosteoporotic agent in rats

“…1 and Table 3) which has been postulated to provide a partial protection against the development of osteoporosis (Roudebush et al, 1993). The increase in the food consumption in ovariectomized rats (25% increase in OVX over Sham rats in 2-7 weeks) may correlate with the increase of body weight (Clark and Tarttelin, 1982).…”

Bone quality in animal models of osteoporosis

“…Bone loss following ovariectomy has been consistently observed in the spine [Ammann et al, 1992[Ammann et al, , 1993Kimmel and Wronski, 1990], as well as at the metaphyses of long bones, such as proximal tibia [Ammann et al, 1992[Ammann et al, , 1993 and distal femur [Griffin et al, 1993;Kimmel and Wronski, 1990;Roudebush et al, 1993]. However, the BMD of the proximal femur (which is a clinically important site of fracture in humans) showed much less response to ovariectomy, with no statistically significant difference after 1 month [Griffin et al, 1993].…”

Soy Isoflavones Attenuate Ovariectomy-Induced Bone Loss in Stroke-Prone Spontaneously Hypertensive Rats (SHRSP).

“…Similar but significant inhibitions were noted with respect to estrogen treatment for ovarian hormone deficiency [18,19]. Current observations indicate that estrogen, via the regulation of leptin production, is related to the regulation of feeding behavior [20].…”