OBJECTIVES: This is an open labeled and retrospective cohort study which compared the effectiveness and safety of ibandronate (IBN) and minodronate (MIN) combined with eldecalcitol (ELD) in primary osteoporosis of women. METHODS: One hundred and forty-eight primary osteoporotic women were classified into 3 groups; 1) intravenous IBN combined with oral ELD (IBN + ELD group, N = 50; 81.8 ± 6.2 years), 2) oral MIN combined with oral ELD (MIN + ELD group, N = 50; 77.2 ± 6.9 years) and 3) oral ELD alone (ELD group, N = 48; 75.0 ± 8.3 years). For statistical analysis, lumbar spine bone mineral density (L-BMD), hip total bone mineral density (H-BMD), serum corrected calcium (Ca), serum inorganic phosphorus (iP), intact-parathyroid hormone (PTH), tartrate-resistant acid phosphatase 5b (TRACP-5b), bone alkaline phosphatase (BAP), serum homocysteine (Hcy), estimated glomerular filtration rate (eGFR) and urine calcium / creatinine (Ca/Cr) ratio were measured until 12 months after the start of therapy. RESULTS: L-BMD values increased significantly in both IBN + ELD and MIN + ELD group, however, H-BMD increased significantly in the IBN + ELD group only. TRACP-5b values decreased rapidly during the first 6 months in both IBN + ELD and MIN + ELD group. However, BAP value in the IBN + ELD group decreased more gradually compared with that in the MIN + ELD group. Both serum Ca value and urine Ca/Cr ratio tended to increase, and the eGFR value decreased significantly in each group. CONCLUSIONS: IBN combined with ELD administration can act more effectively to increase BMD compared with MIN combined with ELD administration. Differences of decreasing rate in TRACP-5b and BAP value may lead to differences of increased rate of BMD in the IBN + ELD and MIN + ELD group. Because many cases of osteoporosis are elderly persons associated with chronic kidney disease, monitoring of kidney function and concentration of Ca in blood and urine is essential.