Abstract Background and Aims The treatment of osteoporosis in patients undergoing hemodialysis (HD) has not been established, as there is insufficient evidence regarding the treatment of osteoporosis. The Kidney Disease: Improving Global Outcomes (KDIGO) 2017 guidelines suggest that determining the bone marrow density (BMD) of HD patients is useful. In 2011, we began treating HD patients' osteoporosis with alendronate. Herein, we describe the effects of the treatment based on our 10-year experience. Method This was a single-center prospective observational study of 85 HD patients (age 67.8 ± 11.0 yrs; 47 females, 38 males) treated for osteoporosis with alendronate at our hospital during the 10 years 2011–2021. The average observational period was 3.9 ± 2.9 years. The patients' BMD values including those at the lumbar spine, femoral neck, and total hip were determined by dual-energy X-ray absorptiometry. The patients whose first T-score was ≤ −2.5 were treated with alendronate. We evaluated the patients' yearly BMD measurements and their yearly values of bone metabolism markers, i.e., parathyroid hormone (PTH), bone alkaline phosphatase (BAP), and tartrate-resistant acid phosphatase 5b (TRACP-5b). Results We compared the data before and after the start of alendronate treatment by dividing the patients into a responder group (the patients whose T-score had improved at 1 year after treatment started; n=44) and a non-responder group (the patients whose T-score had not improved; n=32). The mean observational period of the responder group was significantly longer than that of the non-responder group (p<0.01). In a multiple regression analysis, a longer observational period was significantly associated with the improvement of T-scores (p=0.02). Only the mean T-score of the lumbar spine gradually improved during the study period; those of the femoral neck and total hip did not. Conclusion A long-term use of alendronate for the treatment of osteoporosis may be effective in hemodialysis patients, especially for the lumbar spine. Decisions regarding the effect of alendronate treatment for osteoporosis patients undergoing HD should not be made within only a year after the treatment initiation; rather, a longer observation period is necessary.