Background/Objectives: Osteopenia predisposes to osteoporosis and fracture, especially at the femoral neck and spine. Conventional calcium supplements offer modest benefit with tolerability limits. CalGo®, a salmon bone complex (calcium hydroxyapatite, colla-gen, trace minerals), may support skeletal health. We evaluated its efficacy and safety in postmenopausal women with osteopenia. Methods: In a 24-month, randomized, dou-ble-blind, placebo-controlled trial, 80 women aged 50–80 years with DXA-confirmed fem-oral-neck osteopenia were assigned to daily CalGo® (n=40) or placebo (n=40). The prima-ry endpoint was 24-month change in femoral-neck BMD (g/cm²) analyzed by base-line-adjusted linear regression; secondary outcomes were lumbar spine and distal radius BMD, serum bone turnover markers (β-CTX-I, P1NP), health-related quality of life, and safety. Results: The primary analysis included participants with 24-month DXA (CalGo® n=29; placebo n=30). Femoral-neck BMD was maintained with CalGo® (+0.003 g/cm²; +0.4%) but declined with placebo (–0.017 g/cm²; –2.4%), yielding a significant base-line-adjusted between-group difference of +0.019 g/cm² (95% CI 0.001–0.038; p=0.044). Lumbar-spine loss was attenuated with CalGo® (–0.005 g/cm²; –0.3%) versus placebo (–0.028 g/cm²; –3.4%); the adjusted difference favored CalGo® (+0.026 g/cm²; p=0.058), and ≥1% spine gain was more likely with CalGo® (32.5% vs 11.4%; OR 3.61; p=0.043). No treatment effects were seen at the distal radius, in bone turnover markers, or in EQ-5D/EQ-VAS. CalGo® was well tolerated, with low adverse-event rates and no hepatic or renal safety signals. Conclusions: Over 24 months, CalGo® preserved femoral-neck BMD and attenuated lumbar-spine loss in osteopenic postmenopausal women, with a favorable safety profile.