Objective: The discontinuation of denosumab for the treatment ofosteoporosis can result in a rebound effect, characterized by a significant loss of bone mineral density (BMD) and an increased risk of vertebral fractures. This prospective multi-institutional randomized controlled trial aims to investigate whether zoledronate can prevent BMD loss after denosumab discontinuation in patients who have been receiving denosumab treatment for two or more years. Materials and methods: A total of 101 patients, including 95 females and 6 males with an average age of 70.9 years, were recruited for the study. Participants were stratified into 4 groups and received either regular denosumab therapy (group 1) or zoledronate treatment in the first year followed by on-time denosumab (group 2), on-time zoledronate (group 3), or drug holiday (group 4) in the second year. BMD and bone turnover markers (BTMs) were measured at baseline and annually thereafter. To facilitate the analysis of first-year results, we combined groups 2, 3, and 4 since all of them received zoledronate treatment in the first year, and compared them with group 1. Results: After one year, patients receiving continuous denosumab therapy had a significant increase in vertebral BMD compared to those receiving zoledronate treatment in the first year (2.07 ± 0.80% vs 0.64 ± 0.58%, p = 0.02). The difference in BMD loss was more pronounced in patients who had received denosumab for C 3 years compared to those treated for B 2.5 years (- 3.94 ± 1.60% vs. 0.45 ± 1.87%, p = 0.03). Low body weight was also identified as a risk factor for decreased BMD. Changes in P1NP were more sensitive to changes in bone metabolism indicators than CTX. Conclusions: The study results suggest that the duration of deno-sumab treatment affects the efficacy of sequential treatment with zoledronate, with significantly greater BMD loss observed in patients receiving denosumab for C 3 years compared to those treated for B 2.5 years. P1NP may be a leading indicator for deciding to add another zoledronate when monitoring BTMs. These findings align with the recommendation of the European Calcified Tissue Society.
Date:
2023-07-21
Relation:
Aging Clinical and Experimental Research. 2023 Jul 21;35:S72.
