Comparative study of skeletal response to estrogen depletion at red and yellow marrow sites in rats

Abstract

Background: Skeletal sites with red and yellow marrow may respond differently to estrogen depletion. To investigate this possibility, bone histomorphometric changes were compared at skeletal sites with different marrow composition in ovariectomized (OVX) rats, an animal model for postmenopausal bone loss. Methods: Female rats were OVX or sham-operated at 3 months of age and sacrificed at 1 month or 1 year postsurgery. Eight rats were sacrificed at the beginning of the study as baseline controls. The proximal tibial metaphysis (PTM) and first lumbar vertebra (LV), bone sites with red marrow, as well as the distal tibial metaphysis (DTM) and fifth caudal vertebra (CV), bone sites with yellow marrow, were processed undecalcified for quantitative bone histomorphometry. Results: In control rats, an age-related decrease in bone turnover was observed at all bone sites. Indices of bone turnover, such as osteoclast surface, mineral apposition rate, and bone formation rate, were lower in the DTM and CV compared to the PTM and LV. At 1 month postovariectomy, most bone resorption and formation indices at all bone sites were increased in OVX rats relative to control rats, but decreased cancellous bone volume was found only in the PTM. At 1 year postovariectomy, OVX rats exhibited severe cancellous osteopenia in the PTM and moderate cancellous osteopenia in the LV. In contrast, cancellous osteopenia did not develop in the DTM and CV even at 1 year postovariectomy, despite the fact that OVX rats still exhibited a trend for increased bone turnover at these yellow marrow sites. Conclusions: The results indicate that unlike skeletal sites with red marrow, estrogen depletion does not induce cancellous osteopenia at skeletal sites with yellow marrow in rats. Since increased bone turnover occurred at the various skeletal sites in OVX rats regardless of marrow composition, this skeletal alteration does not by itself induce cancellous bone loss. An imbalance between bone resorption and formation appears to be the major factor that determines the magnitude of bone loss at a given skeletal site in OVX rats. Differences in the anatomical characteristics of red and yellow marrow that may form a basis for these findings are discussed.