Evidence regarding the clinical benefits of combination therapy with romosozumab and active vitamin D analogs in the treatment of osteoporosis is lacking. The aim of the present study was to evaluate the outcome of romosozumab (ROMO) as well as ROMO + eldecalcitol (ELD) treatment in patients with osteoporosis with and without chronic kidney disease (CKD). Data from 146 patients who were administered ROMO was retrospectively investigated. Patients were classified into two groups based on estimated glomerular filtration rate (eGFR): CKD (eGFR <60 ml/min/1.73 m; N=64) and non-CKD (eGFR ≥60 ml/min/1.73 m; N=82) groups. A total of 15 patients in the CKD and 18 in the non-CKD group received ROMO + ELD treatment. The primary outcomes were bone mineral density (BMD) responses in the lumbar spine (LS) and femoral neck (FN). The combined impact of ROMO + ELD treatment was also assessed. The LS BMD was significantly increased in the both groups after 12 months of treatment compared with that at baseline. The FN BMD value was not significantly altered from baseline in both groups, and there were no significant differences in the LS and FN BMD increases between the groups. In the CKD group, the percentage changes in the FN BMD and serum procollagen type I N-terminal propeptide levels observed with ROMO + ELD treatment were greater than those with ROMO monotherapy. ROMO demonstrated efficacy in the treatment of osteoporosis, irrespective of renal function. ROMO + ELD treatment may be beneficial for patients with CKD.