Objective To review the patients diagnosed with bone marrow edema syndrome who had been treated with one single dose of zoledronic acid. Methods The data of 54 patients with bone marrow edema syndrome treated with a single dose of intravenous zoledronic acid and partial weight-bearing were included in the study. The diagnosis was based on clinical examination, the existence of prolonged pain, the presence of bone marrow edema on magnetic resonance imaging, and the patient's medical history. The efficacy was assessed using changes in symptoms, visual analogue scale, and changes in magnetic resonance imaging. Results Overall, 54 patients (35.2% male) were included with bone marrow edema syndrome, with a mean age of 52.7 ± 9.77 years (range: 35-74 years). The most commonly affected joint was the knee in 32 patients (59.2%), followed by the foot/ankle in 13 patients (24.1%), and the hip in nine patients (16.7%). Improved mobility was reported by 29 patients (53.7%) among the total number of the patients at the six-month follow-up visit. The mean visual analogue scale was 6.77 ± 0.83, 7.25 ± 1.19, and 7.46 ± 0.96 at baseline and 5.11 ± 2.14, 4.25 ± 1.84 and 5.15 ± 2.03 at the six-month follow-up for the hip, knee and foot/ankle, respectively (p = 0.098, p < 0.001, p = 0.002). At the six-month follow-up, the MRI showed resolution of the edema in 20 out of 54 patients (approximately 37%). Only 7.4% of the patients reported minor adverse events which were resolved through a single administration of paracetamol. Conclusion Our data show that the combination treatment of a single dose of zoledronic acid and partial weight-bearing for one month improves mobility and reduces edema in patients with bone marrow edema syndrome in the primary weight-bearing joints.