239 Predictors of raised bone turnover markers after transitioning to Zoledronic acid from denosumab

Abstract

Abstract Background Denosumab is a commonly used to treat osteoporosis though if stopped there is a rebound increase in bone turnover and vertebral fracture risk. Treatment with Zoledronic Acid (ZA) after denosumab discontinuation is recommended to reduce this risk, though in some patients a second ZA infusion may be required six months later to maintain adequate suppression of Bone Turnover Markers (BTM). We aimed to assess the proportion of patients with a sub-therapeutically suppressed BTM after a single dose of ZA post denosumab cessation and explore for predictors of this. Methods We identified patients at our bone health clinic who received ZA 6 to 9 months after the last and final denosumab injection. BTM measured was cross linked C-Telopeptide type I collagen (CTX). Sub-therapeutic BTM response was defined as a CTX >0.300 ng/ml. Logistic regression was used to explore for prectiors of CTX >0.300 including age, body mass index (BMI), denosumab duration and lumbar spine bone mineral density (BMD). Results There were 88 patients, 93% female with a mean age of 67 years. Median duration of denosumab therapy was 5.0 years and 44% had osteoporosis prior to transitioning to ZA. Mean CTX after ZA (median 127 days post ZA) was 0.252. However, 45% had a CTX >0.300 and in these patients the median value was 0.412. Older age (p = 0.045), longer denosumab duration (p = 0.010) and lower BMD at the spine (p = 0.008) were associated with a CTX >0.30. Conclusion A large proportion (45%) had subtherapeutic BTM suppression 3 to 6 months after receiving ZA post stopping denosumab and this was predicted by older age, lower spine BMD and longer denosumab duration. Guidelines suggest a second ZA infusion at 6 months in such patients. If transitioning to ZA, findings highlight the importance of optimising BMD first, especially in older adults with longer denosumab therapy.