Abstract Background Denosumab is a commonly used to treat osteoporosis though should not be stopped without transitioning to bisphosphonates to reduce the risk of rebound bone loss and fracture. Recent NOGG guidelines recommend IV zoledronic acid (ZA) six months after the last denosumab injection with further infusions based on bone turnover markers (BTM). Methods We collated data (over the past 5 years) on the first follow up BTM measured after zoledronic acid treatment given to patients where denosumab was stopped. ZA was administered between 6-7 months after the last denosumab injection. The bone resorption marker (C-Telopeptide type I collagen, CTX ng/ml) was measured at different time points: 4 months, 4-6 months, and between 6-12 months. A subtherapeutic CTX was defined as > 0.300 ng/ml. Results There were 95 patients, 93% female, mean age 67.8 years and duration of denosumab therapy 4.6 years. Bone markers were significantly elevated from baseline at all timepoints. Mean CTX at 4 months was 0.450, 6 months 0.470 and 6-12 months 0.65. Overall, 45% had a subtherapeutic CTX at 4 months, 45% at 6 months and 70% between 6-12 (mean 9 months) and this was predicted by time from first ZA infusion (P=0.03). Conclusion Nearly half of patients had subtherapeutic BTM at 4-6 months and the majority at 6-12 months after receiving ZA. For patients on denosumab therapy for a similar duration (4-5 years), our results support the routine administration of a second ZA six months after their first ZA. Delays in administering a second infusion may result in a substantial rise in bone resorption markers and significant bone loss. This highlights the need for timely access to ZA for such patients transitioning off denosumab therapy.