Stimulation and inhibition of bone formation: use of peripheral quantitative computed tomography in the mouse in vivo

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.