Objectives We aimed to investigate the safety of zoledronic acid (ZOL) combined with acetaminophen (APAP) regarding both the adverse events and the efficacy of ZOL combined with an eldecalcitol (ELD) in a randomized clinical trial conducted in patients with primary osteoporosis. Methods A total of 109 patients were administered ZOL 5 mg and then were randomly assigned to the following groups (3:2:1): those treated with ZOL, those treated with ZOL combined with APAP and ELD, and those treated with ZOL combined with ELD. For the analyses, the groups were classified into four treatment groups: patients treated with APAP (APAP group) and without APAP (non-APAP group), and those treated with ELD (ELD group) and without ELD (non-ELD group). The incidence rates of symptomatic adverse events were compared between the APAP and non-APAP groups, and the efficacy was compared between the ELD and non-ELD groups. Results In the APAP and non-APAP groups, the incidence rates of symptomatic adverse events were 20.6% and 44.6% (p=0.009), respectively. Age and APAP use were found to be significant factors associated with adverse events. The percent changes in the bone mineral density values from baseline (ΔBMD) in the ELD and non-ELD groups at 12 months were 8.2% and 6.2% for the lumbar spine, 4.2% and 4.0% for the total hip, and 3.9% and 2.2% for the femoral neck, respectively. The ΔBMD of all sites did not differ significantly between the ELD and non-ELD groups. Conclusion In ZOL treatment, the co-administration of APAP should thus be considered as a therapeutic option to reduce the occurrence of symptomatic adverse events stemming from ZOL treatment in Japanese patients with primary osteoporosis, particularly in younger patients.
Keywords: acetaminophen; adverse event; eldecalcitol; osteoporosis; zoledronic acid.