Maintenance of bone resorption markers in the low premenopausal range during the year following denosumab discontinuation is associated to bone density preservation. The ReoLaus study.

Abstract

Denosumab discontinuation (DD) is associated with serum C-terminal X-linked telopeptides (sCTX) increase, bone mineral density (BMD) loss and vertebral fractures (VFs) risk increase. We compared clinical characteristics of women losing or not lumbar spine (LS) BMD one-year after DD, and their sCTX values at different time-points. We included women from the ReoLaus cohort having received ≥2 denosumab 60mg injections, with three BMD measurements on the same device (before (DXA1), at the end of denosumab treatment (DXA2), and one-year after (DXA3)) and sCTX measured at different time-points. Losers (LS DXA3-DXA2>2.8%) and stable groups were compared. 63 postmenopausal women were included (mean age 64.2±9.1years, 7.9±2.7 denosumab injections). 19months after last denosumab injection, 65% had lost LS BMD. Losers were younger, had lower BMD and higher sCTX before denosumab, received more injections and gained more BMD under denosumab, and had higher sCTX after DD. Same proportion of patients received bisphosphonates in both groups, but 11 (all in losers group) received ≥1 zoledronate infusion. Three women developed VFs in the losers group (none in the stable). Mean sCTX at 10 and 19months were 590±372 versus 221±101, and 598±324 versus 293±157ng/l, respectively (premenopausal range<573ng/l, p<0.01 for both). LS BMD loss and sCTX levels measured at 10 and 19months were correlated (r2=0.29, p=0.01, and r2=0.16, p<0.005). Maintenance of BMD gained with denosumab is associated with sCTX in the low premenopausal range after DD. Whether this could be achieved by regular sCTX monitoring and adjustment of bisphosphonates doses or frequency administration needs to be confirmed by further studies.