Increase of medicine technology and health service will increase quality of life and will be followed with increasing the number of menopausal women. Thus make osteoporosis disease increase which will give impact in increasing morbidity and mortality caused by osteoporosis. This study is done to detect osteoporosis early in menopausal women. The objective of this study is to analyze differentiation, correlation, risk factor between serum estradiol, IL-6, IGF-1 level to bone density in menopausal women with and without regular exercise and to analyze role of regular exercise. The method used was cross sectional that conducted on 56 menopausal women first decade who chosen randomly and divided into two groups, with and without regular exercise. Data were analyzed with T-test for normal and Mann-Whitney test for abnormal data distribution, Pearson correlative test, multiple linier regression test, multiple logistic regression test, and count risk factor used RP (Prevalence Ratio) risk and 95% CI (Confident Interval). The results showed that menopausal women with regular exercise had increased estradiol level significantly (22.94 (6.09) vs 14.23 (3.54)) (p<0.05), decreased IL-6 level significantly (1.69 (0.95) vs 3.198 (2.82)) (p<0.05) and increased IGF-1 level non significantly (89.36 (39.33) vs 79.57 (32.37)) (p=0.243) compare with menopausal women without regular exercise, although non significantly, there was tendency increasing IGF-1. Menopausal women with regular exercise showed higher bone mass density significantly compare with menopausal women without regular exercise (p<0.001). Menopausal women with regular exercise had positive correlation between IGF-1 with bone mass density (BMD-T) significantly (r=0.648; p<0.05). Menopausal women with and without regular exercise had positive correlation between estradiol with IL-6 significantly (p<0.05). Base on multiple linier regression test in menopausal women with regular exercise, there was significant correlation (p<0.001) between IGF-1 and BMD-T, but there was no correlation between estradiol, IL-6 and BMD-T. Based on ROC curve, estradiol cut off point ≤16.38, IL-6 ≤ 1.661, IGF-1 ≤ 69. If estradiol level ≤16.38, IL-6 > 1.661, IGF-1 ≤ 69 possibility for osteoporosis 28.2% among menopausal women with regular exercise and 64.7% among menopausal women without regular exercise. In conclusion, menopausal women with regular exercise have estradiol level higher, IL-6 level lower, and IGF-1 level higher and bone mass density higher vs. menopausal woman without regular exercise. There are correlation between serum IGF-1 level and bone mass density among menopausal women with regular exercise. The value of serum estradiol, serum IL-6, and serum IGF-1 can become risk factors of osteoporosis and sensitive measurement for the diagnostic test.