Postmenopausal bone loss is associated with estrogen deficiency, increased bone remodeling, and altered osteocyte viability. Osteocytes are mechanosensory cells that may alter their surroundings in response to mechanical or environmental changes. To better understand the effects of estrogen loss on bone degradation, osteocyte viability, and bone remodeling that may alter the osteocyte mechanical environment, studies were designed. The ovariectomized (OVX) rat was used as a model for postmenopausal osteoporosis. Firstly, changes were assessed in the osteocyte lacunar-canalicular network using high-resolution microscopy techniques by quantifying several aspects of the osteocyte microenvironment. Confocal microscopy analyses showed that OVX rats have a larger effective lacunar-canalicular porosity surrounding osteocytes from proximal tibial metaphysis, due to increased effective canalicular size. Electron microscopy demonstrated nanostructural matrix-mineral level differences surrounding the osteocyte in OVX rats. Nanostructural changes in the osteocyte microenvironment suggest that lacunar-canalicular walls are becoming more permeable in estrogen-deficient rats, which could affect interstitial fluid flow around osteocytes during mechanical loading. The second study determined effects of estrogen loss on osteocyte apoptosis and tested two potential candidates of bone degradation, matrix metalloproteinases MMP-2 and -3. A temporal increase in osteocyte apoptosis was seen in OVX rats. The MMP analysis demonstrated that significant differences were not found in MMP-2 and MMP-3 presence between SHAM and OVX. These results indicate that MMP-2 and MMP-3 are not primary candidates of bone degradation that may create the nanostructural matrix changes observed in the osteocyte lacunar-canalicular environment in estrogen-deficient rats. Finally newly formed bone and differences in mineralization of the OVX tissue were assessed using fluorescent bone labels and nanoindentation. Mineral apposition and bone formation rates increased in OVX rats at endocortical surface, but no changes were seen in mineralizing surface on periosteal surface. A non-significant trend of increasing percent mineralizing vascular pores was also seen in OVX rats. The nanoindentation analysis showed that elastic modulus and hardness were unaltered due to estrogen deficiency. These results suggest that nanostructural matrix-mineral level changes in the estrogen-deficient state are alterations occurring locally on the osteocyte lacunar-canalicular surfaces. These results provide evidence that osteocytes may be modulating the lacunar-canalicular spaces during estrogen deficiency