Physical activity in the growing period has been shown to be effective for increasing bone mass because immature bones are more sensitive than mature adult bones to the stimulation with mechanical stress. However, bone growth is not uniform and changes markedly at puberty. Therefore, the response of bone to exercise may differ according to the growth process. The purpose of the present study was to investigate the process of the bone response to running training, and the relationship between the bone response and serum insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) levels in female rats. Thirty-three female Wistar-Imamichi rats 4 weeks of age were divided randomly into control (CON) and running training (RUN) groups for 6 and 12 weeks. Training consisted of running on a flatbed treadmill at 30 m/min for 60 min/day, 5 days/week. The bone mineral content (BMC) and bone mineral density (BMD) in the whole and five parts of the tibia were measured by a dual-energy X-ray absorptiometer (DXA) . Simultaneously, we measured serum concentrations of IGF-I, IGFBP-3, osteocalcin and 17β-estradiol. The whole tibial BMD was significantly higher in the RUN groups than in the age-matched CON groups. When BMD was analyzed at five different studied parts within the same tibia, the increase of BMD. was noted in the proximal and distal cancellous bone in the 6-week RUN group, and in the diaphysial, cortical bone, in the 12-week RUN group. Serum concentrations of osteocalcin, a marker of bone formation, were not altered by training, whereas they decreased with aging. Serum IGF-I levels in the training groups were not changed, but IGFBP-3 levels were increased significantly only in 6-week RUN rats. As a complex between IGFBP-3 and IGF-I may be more improve than free IGF-I in the bone formation, the high levels of IGFBP-3 in the 6-week RUN group may induce an increase in the activity of IGF-I. There was a significant positive relationship between serum IGF-I concentration and BMD of the whole tibia in the 6-week study, and between the IGFBP-3 level and BMD in both the 6 and 12-week studies.
In conclusion, 1) the process of the skeletal response to running training is site-specific within the same bone, and 2) the increment of the IGFBP-3 level with training in the growth period may reflect the increment of tibial BMD through training.

Bone (tibia, femur, and lumbar spine) and blood samples were obtained from 100 (50 males and 50 females) Wistar-Imamichi rats in groups aged 3, 5, 7, 9, 12, 15 and 20 weeks old to investigate the changes in bone mass during puberty in relation to insulin-like growth factor 1 (IGF-1), IGF binding protein (IGFBP) -3, osteocalcin (OC) and sex steroids in normal rats.
Sharp increases in BMD (bone mineral density) in the tibia, femur and lumbar appeared earlier in female than in male rats, and the BMD in females tended to be higher than in males between 5 and 9 weeks old. After 9 weeks old, BMD in males was higher than that in females, as BMD in males continued to increase whereas that in females tended to remain in a steady state after this stage. This sex-related difference in changes in BMD pattern is probably related to the serum concentrations of IGF-1, IGFBP-3, testosterone, and 17β-estradiol with maturation. In males, marked increases in serum IGF-1 and IGFBP-3 concentrations appeared earlier than that in serum testosterone level. IGF-1 and testosterone peaked at 9 weeks of age, and thereafter remarked in a steady state, whereas IGFBP-3 reached a peak at 7 weeks of age, and then declined gradually. In females, the changes in patterns of serum 17β-estradiol, IGF-1, and IGFBP-3 levels were very similar. The levels increased gradually from 3-5 weeks old, peaked at 9 weeks, and then decreased slowly thereafter. In contrast, serum OC concentrations remain relatively high from 3 to 9 and from 3 to 7 weeks old in males and females, respectively, although OC in both sexes declined gradually with aging.
These observations suggest that BMD development occurs earlier in female than in male rats. This sex-related difference in changes in the BMD pattern may result from the earlier onset of puberty in females, and from the sex-specific differences in concentrations of IGF-1, IGFBP-3 and sex steroids with maturation.