Background Denosumab discontinuation (DD) induces bone turnover markers (BTMs) increase, bone mineral density (BMD) decrease, and increased risk of spontaneous vertebral fractures. Prescribing a bisphosphonate after DD could avoid this rebound effect.
Objectives The objective of the ReoLaus (Rebound Effect Observatory in Lausanne) Bone Project is to follow bone parameters after DD. We report the determinants associated to BMD loss 1 year after DD.
Methods 170 patients are followed in ReoLaus. Patients with a BMD follow-up > 1 year after DD with a standardized management were included. We defined as significant a lumbar spine BMD loss (Loosers group) over 3.96% at one year after DD as compared with values at the end of the denosumab treatment 18 months after last injection.
Results 71 post-menopausal women stopped denosumab after 7.7±2.2 injections: age 63.8±8.1 years, BMI 23.8±4.5, 0.96 prevalent fractures/patient, 8.45% previously exposed to corticoids, 22.54% to anti-aromatases. 17.25 months after last denosumab injection 30 patients were classified as Loosers and 41 as Stable.
At denosumab introduction Loosers were younger (61.4±7.3 vs 65.5±8.2 years, p=0.034) with higher sCTX level (644.7 vs. 474.1 ng/ml, p=0.005). The rate of BP given less than 2 years before denosumab was not different, but none of the Loosers had received zoledronate vs. 12% of the Stable (p=0.047). Other pre-denosumab characteristics were not different. Number of denosumab injections, BTMs and BMD values were comparable in both groups during denosumab treatment. First BTMs values measured 7.5 months (median) after last denosumab injection and before bisphosphonates were not different (sCTX: Loosers, 592 ng/ml; Stable, 379 ng/ml, p=0.06). At DD 59% received zoledronate, 24% alendronate, 3% others, and 14% nothing (p=0.39 between groups). BTMs 12.8 months post-BP were higher in Loosers as compared to Stable (sCTX 537 vs. 336 ng/ml, p=0.009). Incidence of new fractures was low (0.18/patient) without between group’s difference.
Conclusion In our sub-cohort, being younger, having high BMTs and not having received zoledronate before denosumab introduction increases the risk of a BMD loss, even if a bisphosphonate is prescribed at DD. Our results support the use of denosumab after a bisphosphonate to restrain the BMD loss at its discontinuation.
Disclosure of Interests Bérengère Aubry-Rozier Speakers bureau: Lilly Pfizer Amgen Novartis, Giovanni Liebich: None declared, Delphine Stoll: None declared, Elena Gonzalez-Rodriguez: None declared, Didier Hans Shareholder of: co owner of TBS, medimaps group, Speakers bureau: Amgen Lilly, Olivier Lamy Speakers bureau: Amgen Lilly
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