The numbers of deaths, trial discontinuations, and treatment interruptions due to AEs were similar between the two groups as well. Deaths (9 [10.6%] 15-minute group vs 6 [7.1%] 30-minute group) were not suspected to be related to zoledronic acid. Eight patients in each treatment group discontinued therapy because of an AE; events leading to treatment discontinuation that were suspected to be related to zoledronic acid occurred in two patients in the 15-minute group (skeletal pain and ONJ) and one patient in the 30-minute group (jaw pain). AEs that required treatment interruption occurred in eight and nine patients in the 15-minute and 30-minute groups, respectively.
AEs of special interest included those related to kidney dysfunction, cardiac arrhythmias, SREs, and ONJ. The number of patients reporting overall kidney and urinary disorders was the same in the two treatment groups (14 patients in each group); however, acute renal failure was reported more frequently in patients receiving the 15-minute infusion compared with the 30-minute infusion (four patients [5%] vs one patient [1%] in 30-minute group). Details of these five patients are presented in Table 4. AEs related to cardiac rhythm occurred in 20 patients while on study; however, only one case of bradycardia was suspected to be related to zoledronic acid therapy (in the 30-minute group). The incidence of SREs at 2 years was comparable in the two groups (19% in 15-minute group vs 21% in 30-minute group). The time to onset of SREs was longer in the 15-minute group (222 vs 158 days), but this was not statistically significant. A total of 10 patients with suspected ONJ were identified, with three patients in the 15-minute group (all moderate) and seven patients in the 30-minute group (mild [n = 5], moderate [n = 1], severe [n = 1]). Six of these patients received bisphosphonates before entering the study (four patients received no prior bisphosphonates), but the length of previous bisphosphonate therapy varied (0–30 months). Patients with suspected ONJ were assessed by clinicians and referred to dental professionals for further evaluation.