This study describes an increase in biochemical and histomorphometric markers of bone resorption prior to increased bone formation and trabecular bone loss in the ovariectomized rat. Six-month-old, female Sprague Dawley rats were either sham operated or ovariectomized (Ovx) and killed at 0, 6, 9, 15, 18, 21, and 42 days postoperation when femora were collected and trabecular bone volume (BV/TV) was determined from von Kossa silver-stained sections using the Quantimet 520 image analysis system in the distal region. A number of these sections were also examined unstained for fluorochrome labels, and stained for acid phosphatase to detect osteoclast-like cells (ACP surface). At 18 days postoperation, lumbar vertebrae were examined. Blood and urine specimens were analyzed for bone-related biochemical variables. ACP surface was significantly greater in Ovx rats compared with sham at 6 days postoperation (mean ACP surface (%TS) +/- SEM: sham 36.4 +/- 1.9; Ovx 40.3 +/- 1.2, P < 0.05) as was urinary hydroxyproline excretion. Serum osteocalcin and alkaline phosphatase activity were not elevated in Ovx rats compared with Sham until 9 days postoperation. Mineral apposition rate (MAR) was increased at 12 days after ovariectomy (mean MAR (microm/day) +/- SEM: sham 0.85 +/- 0.06; Ovx 1.23 +/- 0.06, P < 0.05). Trabecular bone volume (BV/TV) at a specific site in the metaphyseal-diaphyseal core area was significantly lower at 15 days postoperation (mean (%) +/- SEM: Sham 7.40 +/- 1.23, Ovx 4.25 0 0.65, P < 0.05). There was no difference in lumbar vertebral BV/TV between the two groups at 18 days postoperation, however, ACP surface was elevated in the Ovx rats (P < 0.05). A systemic increase in bone resorption at 6 days postovariectomy precedes increased formation whereas the length of time required for the dissolution of trabeculae postoperation is determined locally.

The effect of ovariectomy (OVX) on cancellous bone in the rat is not uniform at all sites of the skeleton. We report variation in the short-term effects of adult OVX in three regions of the distal femur: the diaphysis (DIA), the metaphysis (META), and the epiphysis (EPI). Cancellous bone parameters were estimated in the three separate zones of the femora and compared with changes in bone cell activity, as estimated by osteoclast surface (Oc.S) and bone formation rate (BFR). Changes were studied for 30 days in a series of rats either sham-operated (Sham) or ovariectomized (OVX) at 7 months of age. Oc.S and BFR were elevated following OVX in all regions. The time course for the OVX-induced changes differed between regions: DIA, both Oc.S and BFR were elevated at day 9; META, Oc.S was also elevated at day 9, while the rise in BFR was delayed until day 21; EPI, Oc.S remained stable but increased relative to ovary-intact rats by day 18 due to reduced levels in the latter, but BFR did not rise until day 28. These changes in bone cell activity following OVX produced a 71% reduction of cancellous bone in the DIA and a 35% reduction in the META. In contrast, no OVX-induced bone loss was observed in the EPI. This study shows that bone cell activity increases in each region of the distal femur within the first 30 days following OVX, independent of bone loss. However, the time course of increased bone cell activity is not uniform. These data highlight the role of local factors in the response to ovarian hormone deficiency.

Mechanical strain maintains bone architecture even under conditions of increased bone turnover such as occurs with ovarian hormone deficiency. The rat distal femur contains two sites that apparently experience different levels of mechanical strain and therefore the rat is a suitable model for investigating such effects. The femoral epiphysis experiences higher strain energy compared with the metaphysis and we report the effects of aging between 7 and 12 months and the postovariectomy effects over the same time period on cancellous bone variables measured at these two sites. Age-related bone loss in sham-operated ( .7] [NS]). Osteoblast cell activity and osteoclast surface were increased after ovariectomy in both regions. The mineral apposition rate decreased at 9.5 months of age in both regions (p < 0.0001), independent of ovariectomy, and was coincident with a reduction in trabecular number in the epiphyses of both operative groups and in the metaphysis of the ovary-intact group. These data suggest that local mechanical strain governs bone balance with aging and that architectural changes resulting from age-related bone loss may mirror those following estrogen deficiency but occur via a different cellular

Female Sprague-Dawley rats (n = 72), 6 months old, underwent either sham operation, oophorectomy, adrenalectomy, or combined oophorectomy and adrenalectomy (O&A). They were all maintained on normal saline ad libitum and 20 g/day 1.1% calcium chow. Nine weeks after operation, the trabecular bone volume of the distal femoral shaft was significantly lower (P less than 0.001) in the adrenalectomized (11.1%), oophorectomized (7.0%), and O&A (8.3%) animals than in sham-operated animals (19.8%). Eighteen weeks after operation, the trabecular bone volume in O&A animals had fallen to a mean of 3.8% (sham 17.0%), and the length of the femur had increased to 38.8 mm after O&A (sham 36.8 mm, P less than 0.01). O&A animals treated with 0.35 mg/kg/week nandrolone decanoate from 9 weeks postoperatively onward, had twice the femoral trabecular bone volume of untreated animals at 18 weeks (P less than 0.05). By contrast, no significant differences were found in vertebral body trabecular bone between any groups, including groups receiving treatment with androgens. We have found that, by 9 weeks after operation, adrenalectomy alone causes significant loss of metaphyseal trabecular bone, similar to the progressive loss seen after oophorectomy.

No abstract