Elsevier

Bone

Volume 30, Issue 4, April 2002, Pages 594-598
Bone

Differences of three-dimensional trabecular microstructure in osteopenic rat models caused by ovariectomy and neurectomy

https://doi.org/10.1016/S8756-3282(02)00684-1Get rights and content

Abstract

We investigated the differences in three-dimensional microstructure of bone in cases of osteopenia caused by two different procedures: ovariectomy (ovx) and sciatic neurectomy (nx). Thirty-nine 8-week-old female Lewis rats were divided into two groups: (1) ovx and sham operation; and (2) nx and sham operation. At 12 weeks of age these rats were killed to sample the right tibiae. The samples were scanned using microcomputed tomography to obtain metric parameters such as bone volume fraction (BV/TV), trabecular thickness (Tb.Th), and trabecular separation (Tb.Sp), and nonmetric parameters such as structure model index (SMI), trabecular bone pattern factor (TBPf), and degree of anisotropy (DA). The changes in all microstructural parameters were significant in both the ovx and nx groups, with those of BV/TV, Tb.Th, Tb.Sp, and SMI more significant in the ovx group than in the nx group, in comparison to their respective controls. The significantly higher coefficient of variance for Tb.Th across the entire analyzed area of the individual samples indicated that the trabecular thinning occurred heterogenously and that the microstructural deterioration induced by ovx and nx appeared to be locally accelerated, so as to induce perforation and disappearance of trabeculae. The DA increased significantly in the ovx rats, whereas it decreased in the nx rats. The appearance of microstructural deterioration differed between the two osteopenic models. The three-dimensional (3D) images from the nx rats showed flake-like trabeculae, whereas the ovx rats exhibited a diffuse disappearance of trabeculae, especially in the central part of the tibia, but with a preservation of shape for those trabeculae that were retained. The reduction in cortical area was more significant in the nx group. nx and ovx resulted in significant changes in bone microstructure, showing perforation and removal of trabeculae due to locally accelerated bone resorption. The 3D microcomputed tomography images demonstrated the different microstructural changes that occurred in the ovx and nx groups. Loading during bone resorption increased the anisotropy, whereas immobilization increased the isotropy. In addition, immobilization had a more significant effect on the cortical area.

Introduction

Primary osteoporosis is a disease characterized by low bone mass, deterioration of bone microstructure, increased bone fragility, and a consequent increase in fracture risk.

The various mechanisms responsible for bone loss are not fully understood. Estrogen withdrawal is associated with a more prominent increase in bone resorption than in bone formation for the first 10 years following menopause.8 Increased bone resorption and inhibited bone formation are the two major causes of bone loss in immobilization.11, 13 Unilateral sciatic neurectomy has been shown to induce limb paralysis and cause a rapid decrease in bone mass.7, 12

The changes just described for these osteopenic conditions were obtained merely by bone histomorphometric analyses. This method provides important information concerning bone structure, but is limited to two-dimensional analysis. Three-dimensional analysis is needed to fully understand bone alterations in osteopenic conditions.

To investigate the mechanisms inducing bone loss and its microstructural deterioration, we designed a study using two different osteopenic rat models, one subjected to estrogen withdrawal and another with immobilization due to sciatic neurectomy. Our purpose was to examine differences in patterns of deterioration with regard to trabecular microstructure as a result of immobilization and/or hormonal alteration. For each model, the trabecular bone of the tibia was analyzed using the most recent three-dimensional microstructural analysis.

Section snippets

Osteopenic animal models

Two osteopenic rat models were studied: (1) estrogen withdrawal by ovariectomy (ovx); and (2) immobilization due to sciatic neurectomy (nx). The rats were not pair-fed. These experiments were performed according to our institute’s guidelines for animal care, which are based on NIH guidelines. Each model was matched with its respective control.

Comparisons of microstructural parameters of osteopenic models with their respective controls

Figure 2 demonstrates typical features of the 3D trabecular microstructure of the tibia in a ovx rat (upper left) and its corresponding sham-operated rat (lower left), and in a nx rat (upper right) and its corresponding sham-operated rat (lower right). The microstructure was deteriorated in each osteopenic model in comparison to each respective control model. Images from the nx rat show flake-like trabeculae, whereas the ovx rat images demonstrate a diffuse disappearance of trabeculae,

Discussion

Previous reports describing changes in trabecular microstructure secondary to osteopenia due to hormonal disorders or immobilization were made using histomorphometry in both human and experimental animal studies. The microstructure analysis was performed typically on one section of specimen applying a parallel-plate model. Micro-CT provides 3D data developed from multiple slices. Our analysis system provides direct calculation of both histomorphometric parameters and nonmetric parameters such

Acknowledgements

The authors greatly appreciate the valuable suggestions of Prof. Akira Yamaguchi, Department of Oral Pathology, Nagasaki University School of Dentistry.

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