Effects of Goserelin Acetate and Voluntary Wheel Running on Bone Morphology in Female Rats

Abstract

The luteinizing hormone-releasing hormone (LHRH) agonist, goserelin acetate, is used in the clinical setting to treat hormone-sensitive cancers in pre- and perimenopausal women. With prolonged use, this treatment has been shown to decrease bone mineral density due to a reduction in estrogen release by the ovaries. Regular physical activity, in contrast, has been shown to provide a number of beneficial effects on bone health. PURPOSE: To determine whether voluntary wheel running attenuates the negative effects of goserelin acetate on proximal and diaphyseal tibial bone structure in female rats. METHODS: Female Sprague-Dawley rats (n=40) were randomly assigned to one of four groups: sedentary control, SED+C; sedentary goserelin acetate, SED+GA; voluntary wheel run control, WR+C; and voluntary wheel run goserelin acetate, WR+GA. Animals treated with GA received implants on day 1 and 29 while control animals received sham implants. During the 56 day experimental protocol, SED animals did not exercise while animals in WR groups were allowed free access to cage-mounted running wheels. Upon completion of the 56 day drug and exercise regimens, animals were sacrificed and the tibia was excised and assessed for bone architecture via Micro Computed Tomography. RESULTS: Treatment with GA had no effect on tibial diaphyseal total bone volume, cortical volume, cortical volume/total volume ratio, marrow volume, or cortical thickness. GA treatment did, however, significantly lower bone volume (-79%, p < 0.001), bone volume/total volume ratio (-78%, p < 0.001), trabecular number (-62%, p < 0.001), trabecular thickness (-8%, p < 0.05), and significantly increased trabecular spacing (+182%, p < 0.001). Voluntary wheel running did not protect against the degenerative tibial bone effects of GA on bone volume, bone volume/total volume ratio, or trabecular thickness. Voluntary running attenuated the decline in trabecular spacing and trabecular number (p<0.05), yet even with this attenuation, trabecular spacing was still 50% lower than SED+C and trabecular number was still 115% higher than SED+C. CONCLUSION: Goserelin acetate had a degenerative effect on cancellous bone while demonstrating little effect on cortical bone. Voluntary wheel running provided minimal benefits on bone morphology in female rats during GA treatment.