〔Abstract〕 Objective To explore the effect of zoledronic acid combined with calcitriol in the treatment of osteoporosis on bone metabolism indexes, bone mineral density and quality of life. Methods A selection of 68 patients with osteoporosis admitted to the hospital from July 2017 to July 2019 were divided into observation group (34 cases) and control group (34 cases) according to different treatment methods. The control group was treated with calcitriol and calcium, and the observation group was treated with zoledronic acid injection on the basis of the control group. Compare the bone metabolism indexes and bone mineral density levels of the two groups before and after treatment. The safety of medication during treatment was compared between the two groups of patients. The quality of life (QUALEFFO–41) scores before and after treatment were compared between the two groups. The safety of medication during treatment was compared between the two groups of patients. Results After treatment, the level of bone– specific alkaline phosphatase (BLAP) in the observation group was higher than that in the control group. Type I collagen cross–linked C–terminal peptide (β–CTX), osteocalcin N–terminal mid–molecular fragment (N–MID) and anti–tartaric acid The level of hydrochloric phosphatase isoform–5b (TRACP–5b) was lower than that of the control group (P < 0.05). After treatment, the bone mineral density levels of the lumbar spine, femoral neck and hip of the observation group were higher than those of the control group (P < 0.05). In the QUALEFFO–41 score of the observation group, the scores of pain degree, social function, mental state, physical health status, self–evaluation, activity, daily and housework activities were lower than those of the control group (P < 0.05). No serious adverse reactions occurred during the treatment of the two groups. Conclusions The treatment of osteoporosis patients with zoledronic acid combined with calcitriol can improve the bone metabolism index and bone density of the patients, and improve the quality of life, with good curative effect and good safety.