Bone Abstracts

We have previously shown that female neuronal nitric oxide synthase knockout (nNOS KO) mice have increased trabecular bone volume. However, this study was performed in mice at 10 weeks of age only. To investigate whether the high bone volume is maintained during ageing, we compared 3-month- and 12-month-old wild type (WT) and nNOS KO mice using μCT. The tibias from 8 WT and 8 nNOS KO mice at each age were dissected, fixed for 24 h in buffered formalin, stored in 70% ethanol, scanned using a Skyscan1272 μCT scanner at a resolution of 4.5 μm and the proximal tibia analysed.

As before, the 3-month old nNOS KO mice had increased trabecular bone volume, with BV/TV increased by 35% (P<0.01), trabecular thickness by 11% (P<0.05), trabecular number by 20% (P<0.01), and connectivity density by 26% (P<0.05). In addition we found a change in the bone shape, with tissue volume increased by 17% (P<0.01) and periosteal circumference increased by 10% (P<0.001), indicating an enlargement of the bone and leading to an increase of the polar moment of inertia of 39% (P<0.01). At 12 months of age, the WT mice showed significant age-related bone loss, with a reduction in BV/TV and trabecular number of 63% (P<0.0001), a 79% increase in trabecular separation (P<0.001), and no change in trabecular thickness. At 12 months, there was no significant difference between WT and nNOS KO mice in BV/TV, trabecular number or trabecular separation. A significant increase of 20% was observed in the trabecular thickness of nNOS KO mice (P<0.01).

In conclusion, our results show that the high bone volume phenotype of female nNOS KO mice is not maintained during ageing As bone metabolism in nNOS KO mice is hypersensitive to changes in oestrogen levels, this may be due to an age-related decrease in oestrogen.