Increased antiresorptive activity of zoledronic acid (Z) administered in the night as compared to morning administration in breast cancer (BC) patients with bone metastases.

Background: Z is an effective bisphosphonate in preventing skeletal related events (SREs) in bone metastatic patients. Decrease in bone resorption markers during Z therapy is a potential surrogate of drug efficacy. Bone resorption markers maintain a circadian rhythmicity in metastatic BC patients (Generali et al ASCO 2005), suggesting that Z may be more active if administered in a chronomodulated way. Raised PTH after Z could impair the drug efficacy (Berruti et al ASCO 2006). Methods: Forty-four BC patients with bone metastases were randomised to receive Z, 4 mg i.v. at 11.00 p.m or 11 a.m every 28 days for 4 times. Serum cross laps (CTX), urinary n-telopeptide (NTX) and serum parathyroid hormone (PTH) levels were measured at baseline and after 4, 7, 14, 28, 56 and 84 days, respectively. Results: Z administration in the night resulted in a greater decrease of either serum CTX or urinary NTX and lower increase in serum PTH (Table) than morning administration. Conclusions: Z administration in the night might be more efficacious than morning administration.