Summary The receptor activator of nuclear factor-kappa B ligand (RANKL)/RANK/osteoprotegerin system is dysregulated in hyperparathyroid bone diseases. The introduction of denosumab preceding elective surgery as an alternative option when surgery is not possible immediately. Introduction The effects of denosumab on vascular calcification in patients with chronic renal failure and low bone mass have been a subject of interest. Therefore, this investigation aimed to determine the short-term changes in vascular calcification after denosumab treatment using a serial electrocardiography-gated computed tomography (CT) to measure coronary artery calcification (CAC) in patients with secondary hyperparathyroidism (SHPT) and low bone mass. Methods This 6-month study enrolled patients with SHPT and low bone mass (T-score < − 2.5) owing to dialysis. The 2 groups administered denosumab at a dose of 60 mg (denosumab group), and conventional treatment (control group) had 21 patients each. All patients underwent CT scans at baseline and at the follow-up examination at 6 months to determine the bone mineral density and CAC. Results The control group demonstrated a significant increase in Agatston scores (187.79 ± 72.27) ( P  = 0.004). However, no significant change was noted in the denosumab group ( P  = 0.41). In the denosumab group, only the baseline serum alkaline phosphatase levels correlated negatively with changes in the CAC score ( P =  0.01); the baseline alkaline phosphatase levels were the deciding biomarkers for non-responsive CAC scores by Berry Criteria after denosumab treatment ( P  = 0.02). The denosumab group demonstrated significantly increased bone mineral density in the femoral neck and lumbar spine ( P  < 0.01). Conclusion The findings provide evidence that denosumab may suppress the progression of CAC and also regress osseous calcification in severe cases of high bone turnover.