Effect of prostaglandin and bisphosphonate on cancellous bone volume and structure in the ovariectomized rat studied by quantitative three-dimensional nuclear magnetic resonance microscopy

Abstract

The purpose of this work was to evaluate the potential of nuclear magnetic resonance microscopy (NMRM) in conjunction with a processing technique to monitor the effect of preventive agents in an ovariectomized (OVX) rat. Twenty-five female Sprague-Dawley rats were OVX at 6 months of age (except for the intact control group), allowed to lose bone for 60 days, and then treated for 60 days. During treatment, animals were administered vehicle, prostaglandin E2 (PGE2; 6 mg/kg), or alendronate (3 μg/kg) subcutaneously once a day. Subsequently, tibiae were harvested and the marrow removed. NMRM was carried out at 9.4 T, with the specimens immersed in 1.2 mM diethylenetriaminepentaacetic acid-gadolinium salt (Gd-DTPA) aqueous solution. A three-dimensional (3D) partial flip-angle pulse sequence was used, providing a 1283 array of (46 μm)3 isotropic voxels. Fifty of the 128 axial images in the 3D data set comprising ~2.4 mm volume distal to the growth plate were processed from each specimen using a probability-based method for determining bone volume fraction (BVF), tubularity, contiguity, as well as the mean trabecular plate thickness and separation. PGE2 and alendronate altered BVF consistently at all tibial regions. The effect of alendronate was to keep BVF about midway between intact and OVX, whereas PGE2 returned BVF to intact levels. The other parameters showed similar responses to treatment. The strongest discriminator was trabecular BVF, which could obviously differentiate the groups. The study establishes NMRM as a nondestructive histomorphometric method for the quantitative evaluation of drug response in a rat ovariectomy model.