Background: Postmenopausal osteoporosis is a significant health concern, leading to increased risk of fractures and decreased quality of life among affected women. Various preventive strategies, including exercise, calcium supplementation, and hormone-replacement therapy (HRT), have been proposed. This study aims to compare the effectiveness of these interventions in preventing bone density loss among postmenopausal women. Materials and Methods: A total of 150 postmenopausal women aged 50-65 years were enrolled in this study. Participants were randomly assigned to one of three groups: Group A (n=50) received a structured exercise program, Group B (n=50) was given daily calcium supplementation (1000 mg), and Group C (n=50) underwent hormone-replacement therapy. Bone Mineral Density (BMD) was measured at baseline and after 12 months using dual-energy X-ray absorptiometry (DEXA). The primary outcome was the percentage change in BMD at the lumbar spine and hip regions. Results: After 12 months, Group A (exercise) showed a mean increase in BMD of 1.5% at the lumbar spine and 1.2% at the hip. Group B (calcium supplementation) demonstrated a mean increase of 1.0% at the lumbar spine and 0.8% at the hip. Group C (HRT) exhibited the most significant improvement, with a mean increase in BMD of 3.2% at the lumbar spine and 2.9% at the hip. Statistical analysis revealed that the improvements in BMD in Group C were significantly greater than those in Groups A and B (p < 0.05). Conclusion: Hormone-replacement therapy is more effective in preventing bone density loss in postmenopausal women compared to exercise and calcium supplementation. However, all three interventions positively impact bone health, suggesting that a combined approach may offer the best protection against postmenopausal osteoporosis.