The purpose of the present study was to examine the effects of vitamin K(2) and risedronate on bone formation and resorption, the osteocyte lacunar system, and porosity in the cortical bone of glucocorticoid (GC)-treated rats. Forty-nine female Sprague-Dawley rats, 3 months of age, were randomized into five groups according to the following treatment schedule: age-matched control, GC administration, and GC administration with concomitant administration of vitamin K(2), risedronate, or vitamin K(2) + risedronate. At the end of the 8-week experiment, classical bone histomorphometric analysis was performed, and the osteocyte lacunar system and porosity were evaluated on the cortical bone of the tibial diaphysis. GC administration decreased percent cortical bone area and increased percent marrow area as a result of decreased periosteal bone formation, and increased endocortical bone erosion, and increased cortical porosity. Vitamin K(2) prevented a reduction in periosteal bone formation but did not affect percent cortical bone and marrow areas. Risedronate prevented a reduction in periosteal bone formation and an increase in endocortical bone erosion, resulting in prevention of alterations in percent cortical bone and marrow areas. Both vitamin K(2) and risedronate increased osteocyte density and lacunar occupancy and prevented a GC-induced increase in cortical porosity. Vitamin K(2) and risedronate had additive effects on osteocyte density and lacunar occupancy and a synergistic effect on cortical porosity. The present study showed the efficacy of vitamin K(2) and risedronate for bone formation and resorption, the osteocyte lacunar system, and porosity in the cortical bone of GC-treated rats.