J Bone Miner Res. 2021 Apr 4.doi: 10.1002/jbmr.4305.
Background: Increased bone turnover and rapid bone loss follow discontinuation of denosumab. We investigated the long-term efficacy of zoledronate (ZOL) in maintaining BMD after discontinuation of denosumab.
Methods: In this randomized, open label, interventional study we included 61 postmenopausal women and men above 50 years discontinuing denosumab after 4.6±1.6 years. We administered ZOL 6 months (6M) or 9 months (9M) after the last denosumab or when bone turnover had increased (OBS). ZOL was re-administrated if p-crosslinked C-terminal telopeptide (p-CTX) increased ≥1.26 μg/L or BMD decreased ≥5%. The results after 12 months have previously been published, here we report the outcome after 24 months. Clinicaltrials NCT03087851.
Results: Fifty-eight patients completed the study. From 12 to 24 months after the initial ZOL, lumbar spine (LS) BMD was maintained; 0.9±0.9%, 0.4±0.8%, 0.3±0.7% in the 6M, 9M, and OBS groups, respectively (p>0.05, no between group differences). Similarly, total hip (TH) and femoral neck (FN) BMD did not change in any group during year 2. From baseline to 24 months after ZOL LS BMD decreased by 4.0±0.8%, 4.1±0.8%, 4.3±1.5% in the 6M, 9M, and OBS groups, respectively (p<0.001, no between group differences). Significant bone loss (LS, TH or FN) was seen in all groups 24 months after ZOL; 6M group: n=12 (60%), 9M group: n=7 (37%), OBS group: n=10 (53%). P-CTX did not change significantly during the second year (p>0.05, no between group differences). No patient fulfilled the CTX or fracture criteria for retreatment during year 2, however, 9 patients were retreated at M24 due to BMD loss ≥5%. Two patients sustained a non-vertebral fracture during year 2.
Conclusion: Treatment with ZOL subsequent to long-term denosumab, did not fully prevent increased bone turnover and bone loss during the first year, however, CTX remained with the reference range and BMD was maintained during the second year.