A case series of six women with postmenopausal osteoporosis who had received continuous denosumab for 7 years and were then given a single infusion of zoledronate (5 mg) is reported. During denosumab treatment, bone mineral density (BMD) in the spine increased 18.5% (P = 0.006), and total hip BMD by 6.9% (P = 0.03). Post-zoledronate BMDs were measured 18–23 months after treatment, and there were significant declines at each site (P_spine = 0.043, P_hip = 0.005). Spine BMD remained significantly above the pre-denosumab baseline (+9.3%, P = 0.003), but hip BMD was not significantly different from baseline (−2.9%). At the time of post-zoledronate BMD measurements, serum PINP levels were between 39 and 60 μg/L (mean 52 μg/L), suggesting that the zoledronate treatment had not adequately inhibited bone turnover. It is concluded that this regimen of zoledronate administration is not adequate to preserve the BMD gains that result from long-term denosumab treatment.