The purpose of this study was to assess peripheral quantitative computed tomography (pQCT) imaging for measurement of volumetric bone mineral density (BMD) in vivo in mouse tibia following ovariectomy, and following treatment with 17 beta-oestradiol (E2). Two studies were undertaken. In study 1, three groups (n = 10) of mature mice were ovariectomized (OVX) or sham operated (SHAM); one of the OVX groups was dosed weekly with E2 (OVX.E2). Images of the proximal tibia were acquired on the day of surgery and at intervals following surgery until week 6. In study 2, four groups (OVX, SHAM, OVX.E2 and a SHAM group dosed with E2, SHAM.E2) of immature mice (n = 10) were imaged weekly up to 10 weeks post-surgery. Precision of pQCT for measurement of total (trabecular plus cortical) BMD was 2.4%, trabecular 5.2% and cortical 2.6%. In mature animals, significantly slower net bone formation was seen in OVX compared with SHAM animals using paired analysis with each animal as its own control. Group analysis detected no significant difference in BMD between SHAM and OVX at any time point. In immature animals, using paired analysis, with each animal as its own control, a significant difference between SHAM and OVX animals was detectable 3 weeks post-surgery (P < 0.05). As in study 1, group analysis of total BMD failed to detect any significant difference between SHAM and OVX at any time point. Treatment with E2 caused an easily-detected increase in BMD and led to osteopetrosis in both groups. The statistical power of this technique is adequate for testing antiresorptive or bone-forming therapies in the mouse.

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The use of peripheral quantitative computed tomography (pQCT) was investigated for the measurement of volumetric bone mineral density (BMD) in mg x cm-3. Two studies were undertaken. In the first study, the precision of pQCT in vivo and ex vivo was tested at 14 weeks postovariectomy (OVX). In the second study, the efficacy of a standard antiresorptive treatment, 17beta-estradiol (E2), was tested 6 weeks post-OVX. The precision for total (compact plus trabecular) BMD was 1.3-1.9%, and that for trabecular BMD was 2.4-2. 7%. There was excellent agreement between trabecular BMD measurements in vivo and ex vivo (r = 0.91). Significant reductions in trabecular BMD were observed in vivo at 14 and 6 weeks following ovariectomy in the femur, in each study. The loss of trabecular BMD depended on slice location, and varied from 0 to 22% at 6 weeks, and from 0 to 26% at 14 weeks (P < 0.001, at the affected locations). The antiresorptive effect of treatment was demonstrated in the 6-week study: there was no significant difference in BMD between sham-operated and E2-treated OVX rats.

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