No overshoot of bone turnover after withdrawal of denosumab treatment of adults with Langerhans cell histiocytosis: a prospective clinical trial
- 26.05.2025
- Original Article
Erschienen in:
- Verfasst von
- Polyzois Makras
- Maria P. Yavropoulou
- Athanasios D. Anastasilakis
- Athanasios Papatheodorou
- Socrates E. Papapoulos
- Erschienen in
- Osteoporosis International | Ausgabe 7/2025
Abstract
Summary
Denosumab (Dmab) discontinuation in osteoporosis leads to overshoot (rebound) of bone turnover, but its cause remains largely unclear. In a prospective trial, Dmab-treated Langerhans cell histiocytosis (LCH) patients showed no overshoot of bone turnover markers despite high short-term dosing. Findings suggest that total Dmab dose does not drive the overshoot of bone turnover markers.
Purpose
In patients with osteoporosis, the length of treatment with denosumab (Dmab) is an important risk factor for the overshoot (rebound) of bone turnover markers following its discontinuation. Whether this is due to the higher total Dmab dose given and/or the severity of the disease is unknown. To address this question, long-term follow-up of changes in bone metabolism after stopping Dmab with doses higher than those used in osteoporosis is essential.
Methods
In a prospective, single-arm, open label, phase 2b clinical trial, ten adult patients with Langerhans cell histiocytosis (LCH), eight with bone lesions (four single, four multiple) and two without, were treated with Dmab sc injections 120 mg/2 months for 6 months (total 480 mg) and were followed for 24 months after the last injection.
Results
Treatment reduced bone turnover markers to about 10% of pretreatment values, which increased after treatment arrest to a peak that did not exceed pretreatment levels; mean (± SD) peak serum CTX 0.522 ± 0.366 ng/mL and P1NP 72.2 ± 35.9 ng/mL were not significantly different from baseline (p = 0.11 and 0.65, respectively). Moreover, pretreatment and peak serum CTX values were significantly correlated (rs = 0.818, p = 0.007). No vertebral fractures, bone loss, or hypercalcemia were observed.
Conclusion
Dmab withdrawal in patients with LCH was not followed by an overshoot of bone turnover markers or bone loss despite the administration in 6 months of a total dose equal to that given in osteoporosis for 4 years. Total Dmab dose is, thus, not an important determinant of the bone turnover overshoot after treatment withdrawal.
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- Titel
- No overshoot of bone turnover after withdrawal of denosumab treatment of adults with Langerhans cell histiocytosis: a prospective clinical trial
- Verfasst von
-
Polyzois Makras
Maria P. Yavropoulou
Athanasios D. Anastasilakis
Athanasios Papatheodorou
Socrates E. Papapoulos
- Publikationsdatum
- 26.05.2025
- Verlag
- Springer London
- Erschienen in
-
Osteoporosis International / Ausgabe 7/2025
Print ISSN: 0937-941X
Elektronische ISSN: 1433-2965 - DOI
- https://doi.org/10.1007/s00198-025-07538-6
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