Systematic review and meta-analysis comparing zoledronic acid administered at 12-week and 4-week intervals in patients with bone metastasis

Abstract

Zoledronic acid is used to treat patients with bone metastasis, but the optimal dosing interval remains controversial. We therefore performed a systematic review and meta-analysis to compare the efficacy and safety of a 12-week interval of zoledronic acid with the standard 4-week interval. Three randomized controlled trials comprising 2650 patients were analyzed. Using a random-effects model, pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated. No differences in the occurrence of skeletal-related events (SREs: RR = 0.98; 95% CI = 0.86–1.12; P = 0.80) or grade 3/4 adverse events (RR = 0.91; 95% CI = 0.69–1.20; P = 0.52) were observed between the 12-week and 4-week groups. The 12-week group tended to have lower incidences of osteonecrosis of the jaw [13 (0.98%) vs. 23 (1.73%)] and kidney dysfunction [21 (1.68%) vs. 31 (2.45%)] than the 4-week group, though the difference did not reach statistical significance (RR = 0.58, 95% CI: 0.30–1.12; P = 0.11); (RR = 0.67, 95% CI: 0.39–1.15, P = 0.15). These data show that zoledronic acid administered at 12-week intervals instead of 4-week intervals does not increase the risk of SREs, and may reduce the incidence of osteonecrosis of the jaw and kidney dysfunction. This suggests the 12-week interval with zoledronic acid may be an acceptable treatment option.

Bone metastases from differentiated thyroid carcinoma: current knowledge and open issues

“…Among breast cancer patients, ZA therapy every 12 week—rather than every 4 week—has been proposed and might be considered an acceptable treatment schedule. Indeed, no difference in terms of SREs occurrence has been observed, while incidence of ONJ and kidney dysfunction resulted lower in the 12-week population, even if statistical significance was not reached [ 111 ] . In DTC population, randomized trial data to clarify this issue have not yet been published.…”

How do skeletal morbidity rate and special toxicities affect 12-week versus 4-week schedule zoledronic acid efficacy? A systematic review and a meta-analysis of randomized trials

“…Therefore, longer follow-up updates are warranted to investigate if the SRE events will change in the two compared schedules. Despite these evident limits, the present study, as suggested by the previous meta-analysis by Ling Cao (Cao et al, 2017), suggests that compared with the standard 4-week intervals, the administration of zoledronic acid at 12-week intervals do not significantly increase SREs and time to SREs and may reduce the occurrence of jaw osteonecrosis, hypocalcaemia and kidney dysfunction. Additionally, for the first time our results assessed the equivalence of the two different schedules of zoledronic acid in term of SMR.…”

Development of Zoledronic Acid-Based Nanoassemblies for Bone-Targeted Anticancer Therapy

“…Conventional nanoparticle-based formulations follow a passive targeting mechanism i.e., the enhanced permeation and retention effect may not be suitable due to the lack of leaky vasculature at the metastases bone sites. , Zoledronic acid is a third-generation bisphosphonate drug molecule widely used clinically to minimize pain and skeletal related events in patients with bone metastases . This molecule comprises bisphosphonate, which has strong binding potential with hydroxyapatite of the bone, thus it is a bone-directing molecule. , Upon reaching the bone, ZA forms strong bonds with calcium, which are stable in bone for about a year. Therefore, purpose of the current study was to develop a structurally well-defined nanoparticle system for effective targeting of bone and treat bone metastasis.…”