Influence of treadmill running on femoral bone in young orchidectomized rats M.-N. HORCAJADA, 1 V. COXAM, 1 M.-J. DAVICCO, 1 N. GAUMET, 1 P. PASTOUREAU, 2 C. LETERRIER, 3 J. CULIOLI, 1 AND J.-P. BARLET 1 1 Institut National de la Recherche Agronomique Clermont-Theix, F-63122 Ceyrat; 2 Laboratoires Servier, F-92150 Suresnes; and 3 Institut National de la Recherche Agronomique Nouzilly, F-37380 Nouzilly, France Horcajada, M.-N., V. Coxam, M.-J. Davicco, N. Gau- met, P. Pastoureau, C. Leterrier, J. Culioli, and J.-P. Barlet. Influence of treadmill running on femoral bone in young orchidectomized rats. J. Appl. Physiol. 83(1): 129–133, 1997.—Forty 6-wk-old male Wistar rats weighing 308 6 24 g were divided into two groups. On day 0, the 20 animals in one group were surgically castrated and the other group was sham operated. Within each group, 10 rats were selected for treadmill running (60% maximal O 2 consumption, 1 h/day, 6 days/wk for 15 wk). The 20 sedentary rats were used as controls. At the time the rats were killed (day 105), running had no significant effect on femoral mechanical properties either in castrated or in sham-operated rats. Femoral bone density was lower in orchidectomized than in sham-operated rats. Nevertheless, it was higher in exercised than in seden- tary rats. Femoral Ca content paralleled changes in bone density. Treadmill running had no significant effect on plasma osteocalcin concentration but inhibited the increase in uri- nary deoxypyridinoline excretion observed in castrated rats. Image analysis (measured at the distal femoral diaphysis) revealed that these effects mainly resulted from decreased trabecular bone resorption in castrated exercised rats. osteoporosis; exercise; osteocalcin; deoxypyridinoline IN GROWING AS WELL AS IN ADULT RATS, orchidectomy decreases cortical and trabecular femoral bone density. Castrated animals have a lower trabecular bone mass but no decrease in biomechanical properties of the femoral shaft. Testosterone replacement prevents the decrease in both cancellous and cortical bone densities and also the age-related thinning of the femoral cortex (28, 37, 40). The mechanism whereby androgens exert their positive action on bone mass is unclear. Specific androgen receptors are present in human osteoblasts (5). Androgens directly stimulate primary osteoblastic cell populations in vitro to proliferate and differentiate (17). They also exert their osteoanabolic action by stimulating differentiated osteoblastic functions and enhancing growth factor-mediated osteoblastic prolif- eration (16). Bone remodeling is controlled by both mechanical and hormonal factors (7, 9). Moderate physical exercise such as voluntary and/or endurance run training (8, 27, 31, 42), wheel running (19, 20, 35), swimming (32), and jump training (36) has been shown to increase bone mass in rats. However, intensive [80% of maximal O 2 consumption (V ˙ O 2 max ), 1 h/day, 5 days/wk for 11 wk] swimming (3) or treadmill running (2) leads to retarded longitudinal bone growth, architectural alteration, and osteoblastic impairment in the tibia of 3-wk-old male rats. In rats, bone remodeling imbalance spontaneously occurs with aging and after castration, because bone resorption then exceeds bone formation (4, 9). In 6-wk- old female rats, immobilization for 6 wk results in an increase in bone resorption and a rapid fall in bone formation, whereas treadmill running (20 m/min for 60 min/day for 3 wk) is associated with an initial increase and then a decrease in bone resorption, with a sus- tained bone formation (42). The purpose of the present experiment was to study the influence of treadmill running on bone metabolism in young castrated male rats. METHODS Treatment of Animals The animal protocol for this study was reviewed and approved by the Animal Care and Use Committee of Institut National de la Recherche Agronomique Clermont-Theix. Thus 40 male Wistar rats weighing 308 6 24 (SE) g were used at 6 wk of age. The animals were randomized by body weight in two groups. On day 0, under chloral anesthesia (8 g chloral hydrate/100 ml saline; 0.4 ml/100 g body wt ip) the animals (n 5 20) from the first group were surgically castrated (CX). The 20 other rats were sham operated (SH). Seventy-two hours after surgery, 10 rats within each group were selected according to their willingness for treadmill running. These exercised [sham-operated exercised (SHE) and castrated exer- cised (CXE)] rats were then trained daily to run on a flatbed treadmill. During the first 2 wk, the speed of the treadmill and the duration of each running session were gradually increased from 15 m/min for 15 min to 20 m/min for 60 min, to reach 30 m/min for 60 min at the end of the experiment (day 105). Thus, during the experimental period, the running speed corresponded to ,60% of V ˙ O 2 max for these animals (13, 18, 39). Control resting (SHR and CXR) rats were handled twice daily at 1-h intervals to mimic the stress induced by handling before and after running. Each rat was housed individually in a 22 3 22 3 18-cm plastic metabolic cage allowing separation and collection of feces and urine (Etablissements Pajon, Fleury les Aubrais, France), at 21°C, with a 12:12-h light-dark cycle. The animals were fed a laboratory chow (Usine d’Alimentation Rationnell, Villemoisson/Orge, France) containing 0.84% calcium and 0.78% phosphorus. To prevent hyperphagia induced by castra- tion, the daily consumption of each rat was measured and each animal received the mean quantity of the chow con- sumed by sham-operated rats (SHE and SHR) during the previous day. Each rat was weighed every Tuesday before running. Every 2 wk, immediately after the running session, urine from each animal was collected during a 24-h period to measure the excretion of deoxypyridinoline (DPD), a marker of bone resorption (23). On day 105, rats were killed by cervical dislocation. Blood was collected by cardiac puncture. 0161-7567/97 $5.00 Copyright r 1997 the American Physiological Society 129 http://www.jap.org Downloaded from journals.physiology.org/journal/jappl (054.237.236.131) on January 26, 2023.