Drug-induced prevention of gastrectomy- and ovariectomy-induced osteopaenia in the young female rat

Abstract

Both ovariectomy (Ovx) and gastrectomy (Gx) induce osteopaenia in rats and humans. While the effect of Ovx has been ascribed to oestrogen deficiency, the underlying mechanism behind Gx is poorly understood. Alendronate, oestrogen and parathyroid hormone (PTH) are known to prevent the osteopaenia induced by Ovx in rats. The purpose of the present study was to determine whether alendronate, oestrogen or PTH could also prevent Gxevoked osteopaenia. Rats were Ovx-, Gx-, or were sham-operated (Sham) and were then treated with alendronate (50 µg/kg/day), oestrogen (10 µg/kg/day) or PTH(1-84) (75 µg/kg/day) for eight weeks. At sacrifice, serum PTH was unaffected by surgery (Ovx, 64 8 pg/ ml; Gx, 75 13 pg/ml; Sham, 58 11 pg/ml). The bone mineral density (BMD) of the fifth lumbar vertebra (L5) was analysed. Ovx and Gx reduced the BMD (ash weight/volume) of the L5 by 15 4% and 22 3% respectively. Trabecular BMD and the cortical bone mineral content (BMC) of the femur were assessed using peripheral computed tomography. Both Ovx and Gx markedly reduced trabecular BMD in the metaphyseal area of the distal femur (Ovx, 37 7%; Gx, 49 7%). The cortical BMC of the femur was only slightly reduced. Alendronate prevented trabecular bone loss after both Ovx and Gx, while oestrogen and PTH prevented trabecular bone loss after Ovx but not after Gx.In conclusion, the bisphosphonate alendronate prevented both Ovx-and Gx-induced trabecular bone loss. In contrast, PTH and oestrogen prevented Ovx-induced but not Gx-induced trabecular bone loss, suggesting that the mechanism behind the trabecular bone loss in Ovx rats differs from that in Gx rats. The results support the notion that the mechanism of action for the bone-sparing effect of these drugs differs. The ability of alendronate, and probably also other bisphosphonates, to prevent Gx-evoked osteopaenia in the rat might be of potential clinical interest when dealing with post-Gx osteopaenia in humans.

Pharmacological treatment of osteopenia induced by gastrectomy or ovariectomy in young female rats

“…However, in the GX group, estrogen increased the trabecular BMD. Although estrogen had no significant effect in the SHAM-operated rats in this study, we have reported earlier that the same daily dose of estrogen increased the trabecular bone mass in SHAMoperated rats (Andersson et al 2002). Moreover, higher daily doses of estrogen have been shown to increase the trabecular bone mass in normal, intact rats (Wronski et al 1988).…”

“…In an earlier study, we showed that OVXinduced osteopenia could be prevented by treatment with alendronate, estrogen or PTH. However, GX-induced bone loss can be prevented by giving alendronate, but not PTH or estrogen (Andersson et al 2002). Here we studied whether alendronate, estrogen or PTH is an effective treatment of established osteopenia induced by OVX or GX in rats.…”

“…pQCT was performed with the Stratec peripheral quantitative computed tomograph (pQCT) XCT Research M (Norland Corp., Fort Atkinson, WI) specifically modified for use on small bone specimens (software version 5.4B; operating at 70 µm resolution) (Rosen et al 1995, Andersson et al 2002. The machine was calibrated with a standard of hydroxyapatite embedded in acrylic plastic.…”

“…The trabecular bone region was defined as the inner 45% of the scanned bone area. Hence, no cortical bone was included in the trabecular BMD measurement (Andersson et al 2002). The middiaphysis of the rat femur contains cortical bone alone.…”

“…We have previously evaluated the effectiveness of alendronate, estrogen and PTH in preventing the development of OVX-or GX-evoked osteopenia in the rat (Andersson et al 2002). We found that alendronate prevented trabecular bone loss after GX and OVX, while estrogen and PTH prevented trabecular bone loss after OVX, but not after GX.…”