The effect of daidzein (D), 4-methylbenzylidene camphor (4-MBC) or estradiol-17b-benzoate (E 2 ) on muscle of osteoporotic rats during fracture healing was studied. After performing a metaphyseal tibia osteotomy in 96 osteoporotic 5-month-old female Sprague-Dawley rats, they received daily 50 mg D, 200 mg 4-MBC or 0 . 4 mg E 2 per kg body weight, or soy free (SF) diet up to 36 and 72 days. Mitochondrial activity, fiber area, and capillary density were analyzed in M. gastrocnemius. Osseous callus bridging of fracture was observed in half of the rats after 36 days. By day 72, fracture was healed in most of the animals. State 3 mitochondrial respiration significantly enhanced in E 2 , 4-MBC and D groups versus SF after 36 days (30, 32 and 32 vs 23 pmol O 2 /s per mg). It declined after 72 days, however, in E 2 group it was still at a higher level versus SF (25, 23 and 21 vs 20 pmol O 2 /s per mg). Size of fast oxidative glycolytic (FOG) and fast glycolytic (FG) fibers, capillary density did not differ significantly between the groups, however, at day 36 an increase in D and 4-MBC groups was detectable. FOG diameter was 64, 66, 68, and 58 mm and FG diameter was 88, 98, 95, and 89 mm in SF, D, 4-MBC, and E 2 groups. The ratio of capillaries to muscle fiber was 1 . 1, 1 . 4, 1 . 3, and 1 . 1 in SF, D, 4-MBC and E 2 groups by day 36. D and 4-MBC react similar to estrogen thereby improving oxidative cell metabolism in severe osteoporotic rats. The level of mitochondrial activity was higher, though no significant morphological differences could be shown.