Influence of Aging on Cortical and Trabecular Bone Response to Estradiol Treatment in Ovariectomized Rats

Gaumet, N.; Braillon, P.; Seibel, Markus J.; Pointillart, Alain; Coxam, Véronique; Davicco, Marie-Jeanne

doi:10.1159/000021996

Cited by 13 publications

(13 citation statements)

References 38 publications

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“…Consistent with our findings in C57BL/6 mice, Gaumet et al (17) found that the skeletal response to estrogen was similar in young (6 month) versus old (12 month) rats, but the uterus of the old rats was much less responsive to estrogen as compared with the young rats. It is also of interest that recent data indicate that very low doses of estrogen can prevent bone loss in elderly postmenopausal women without significant uterine stimulation (18,19).…”

Section: Discussionsupporting

confidence: 92%

“…Indeed, previous studies have found that in mature rats subcutaneous injections of E 2 (10 mg/kg/48 h) resulted in a distinct increase in uterine weight (21%) compared with sham-operated rats at doses that were less effective on bone, whereas similar doses of E 2 (18 mg/kg/day) given by subcutaneous pellets led to an increase in cancellous bone area with no increase of the uterine weight above the weight of the sham-operated rats (17,23). Also of interest is the study by Erben et al (24) in rats, where a dose of estrogen given by subcutaneous pellets (5.2 mg/kg/day) resulted in an increase in cancellous bone area with a concomitant decrease in uterine wet weight over the course of the treatment.…”

Section: Discussionmentioning

confidence: 99%

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Dose-response of estrogen on bone versus the uterus in ovariectomized mice

Riggs

Spelsberg

et al. 2004

Eur J Endocrinol

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Background: Estrogen is known to have important effects on both reproductive and non-reproductive tissues. Moreover, there is increasing interest in developing compounds that may have selective effects on bone versus reproductive tissues. Methods: Since mouse models are often used in these studies, we administrated increasing doses of estradiol (E 2 ) (0 to 500 mg/kg/day) by slow release pellets to ovariectomized 6-month-old C57BL/6 mice and assessed skeletal and uterine responses following 2 months of treatment. Results: The mice lost bone at multiple sites following ovariectomy (OVX); however, while the lowest E 2 dose of 5 mg/kg/day completely prevented loss of cancellous bone (at the lumbar spine and tibial metaphysis), it had no stimulatory effects on the uterus. Higher doses of E 2 resulted in further increases in bone mineral density, with eventual stimulation of the uterus at a dose of 40 mg/kg/day. By contrast, when 3-month-old C57BL/6 mice were administered the same doses of E 2 and studied after 1 month, the 5 mg/kg/day dose resulted in uterine hypertropy, but was not able to prevent loss of cancellous bone. Conclusions: Thus these results (i) provide data on the dose -response for the effects of E 2 on mouse bone and (ii) indicate that the relative effects of E 2 on bone versus the uterus are highly dependent on the particular experimental conditions used. This issue needs to be considered in evaluating agents with potential 'selective' effects on bone versus reproductive tissues.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Dose-response of estrogen on bone versus the uterus in ovariectomized mice

Riggs

Spelsberg

et al. 2004

Eur J Endocrinol

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“…However, the clinical features of osteoporotic patients in bone remodeling were reported as follows. According to several reports, in patients with postmenopausal osteoporosis, the rate of trabecular bone loss is greater than that of normal subjects34; however, the rate of cortical bone loss is only slightly above normal 31. In contrast, Riggs and Melton11 reported that patients with senile osteoporosis showed a proportionate loss of cortical and trabecular bone and that the rate of bone loss was slightly higher than normal.…”

Section: Discussionmentioning

confidence: 99%

Effect of the difference of bone turnover on peri‐titanium implant osteogenesis in ovariectomized rats

Okamura

Ayukawa

Iyama

et al. 2004

J Biomedical Materials Res

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High and low bone turnover situations, both of which are typically observed as postmenopausal and senile osteoporosis, were created by ovariectomy (OVX), and then an investigation of whether or not the difference of bone turnover affected peri-titanium (Ti) implant osteogenesis in rats was conducted. Female rats were divided into four groups. The experimental and control groups underwent OVX or sham operations at 15 or 27 weeks of age, as high or low bone turnover groups, respectively. Ti implants were inserted into the tibiae at 30 weeks, then fluorochromes were injected 10 or 20 days after the implantation for histometry. The implants were retained for 30 days and then ground sections were prepared. Afterward, the cortical bone growth rate, bone contact ratio (BCR) of the implant in both the cortical bone area and medullary canal area, and the average trabecular bone thickness around the implant were evaluated. Biochemical markers of bone turnover were also measured. Biochemical measurements indicated both increasing osteocalcin production in OVX rats and decreasing tartrate-resistant acid phosphatase activity in the low-turnover group. Histometrical measurements showed decreasing cortical growth and low BCR in the medullary canal of the low-turnover group. The high-turnover group demonstrated BCR as high as that of the control group. There was no significant difference in the average trabecular bone thickness around the implant among the groups. As a result, two types of osteoporotic situations were confirmed and it was shown that the difference of bone turnover was clearly due to the diverse osteogenesis around the Ti implant.

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“…This may be caused by the insufficient decrease in mechanical properties in OVX rats as compared with sham‐operated rats at 12 weeks after the surgery. A previous report has shown that neither OVX nor E 2 replacement had a significant effect on tibial mechanical properties at 2 months after the surgery on 6‐, 12‐, and 30‐month‐old rats (30) . Another report also has shown that the decrease in femoral bone strength by OVX is not seen before 9 months after the surgery on 6‐month‐old rats (27) .…”

Section: Discussionmentioning

confidence: 97%