Keeping bone resorption markers very low for 1 year after denosumab prevents bone loss at 2 years: the ReoLaus study

BMD loss is common after denosumab discontinuation, and longer treatment is associated with greater BMD loss. Serum crosslaps (sCTX) can predict BMD loss at the lumbar spine after discontinuation. Keeping sCTX below the lower half of the ULN during the first year is needed to avoid BMD loss at 2 years.

After denosumab discontinuation (DD), elevated serum crosslaps (sCTX) is associated with bone mineral density (BMD) loss over 2 years. Bisphosphonates reduce but do not always prevent this loss.

To define an sCTX threshold below which BMD is maintained after DD.

Postmenopausal women receiving ≥ 2 denosumab doses and followed ≥ 2 years after DD with regular BMD and sCTX measurements were included retrospectively. Linear regression analysis and ROC curves were performed to define sCTX threshold (%ULN, upper limit of the norm in premenopausal women) preventing 1- and 2-year lumbar spine (LS) BMD loss.

From 161 women who had received 8.0 ± 2.9 injections, 50% lost BMD after 2 years. BMD at DD were similar at all sites in non-losers and losers' groups but losers had received more injections. Their T-score decreased after 1 and 2 years (p < 0.001). BMD loss was highly correlated with increased sCTX during both periods. After DD, first-year sCTX levels predicted 1- and 2-year LS BMD loss. The optimal sCTX thresholds during the first year to avoid LS BMD loss at 1 and 2 years were 69% and 49% ULN; for 100% sensitivity, they were 32% and 23% ULN, respectively. Losers received more often ≥ 3 zoledronate infusions and were less treated with alendronate only.

sCTX level during the first year after DD predict 1- and 2-year LS BMD loss. Keeping sCTX below the lower half of the ULN during the first year is needed to avoid BMD loss. Despite high bisphosphonates doses, it is not always possible to reach this target.