Pretreatment bone turnover status and long-term bone mineral density response to denosumab
- 1Duke University
Abstract
SummaryPretreatment low-turnover status identified patients with attenuated total hip BMD gain after denosumab. Integrated assessment of bone resorption and formation markers may help stratify long-term hip response.
IntroductionDenosumab increases bone mineral density (BMD) and reduces fracture risk, but BMD response varies among patients. Given its potent antiresorptive action, denosumab may produce greater BMD gains in patients with higher pretreatment bone turnover; however, its relationship with long-term BMD response remains unclear. We developed a turnover index (TI) integrating bone resorption and formation markers and evaluated its association with BMD response trajectories up to 5 years after denosumab initiation.
MethodsThis retrospective observational study included 230 patients with primary osteoporosis who initiated denosumab between January 2014 and January 2025. TI was calculated as the mean of standardized log-transformed TRACP-5b and total P1NP values. Patients were classified into high-, intermediate-, and low-turnover groups according to TI quartiles. Lumbar spine and total hip BMD changes were analyzed using mixed-effects models.
ResultsThe cohort included 52 high-turnover, 114 intermediate-turnover, and 64 low-turnover patients. In both unadjusted and multivariable-adjusted models, BMD gain trajectories differed significantly among TI groups at the lumbar spine and total hip (all p < 0.001). Adjusted BMD gains showed a stepwise gradient across TI groups. Five-year adjusted lumbar spine BMD gains were 20.31%, 17.01%, and 12.16% in the high-, intermediate-, and low-turnover groups, respectively. Corresponding total hip BMD gains were 10.56%, 6.76%, and 2.49%, with significantly lower gains in the low-turnover group compared to the other two groups.
ConclusionsBaseline bone turnover status was associated with long-term BMD response to denosumab. Low pretreatment turnover may identify patients at risk for attenuated BMD gain during denosumab treatment.
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BibTeX
@misc{asada2026pretreatment,
title = {{Pretreatment bone turnover status and long-term bone mineral density response to denosumab}},
author = {T. Asada and W. Richardson and S. Tani and M. Ishikawa and P. Varnadore and T. Towatari and P. Passias and Y. Kudo and B. Alman and K. Ishikawa},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.20.26366058},
url = {https://www.medrxiv.org/content/10.64898/2026.10.20.26366058v1},
note = {CC BY-ND},
}
RIS
TY - UNPB
TI - Pretreatment bone turnover status and long-term bone mineral density response to denosumab
AU - T. Asada
AU - W. Richardson
AU - S. Tani
AU - M. Ishikawa
AU - P. Varnadore
AU - T. Towatari
AU - P. Passias
AU - Y. Kudo
AU - B. Alman
AU - K. Ishikawa
PY - 2026
DA - 2026/10/20
PB - medRxiv
DO - 10.64898/2026.10.20.26366058
UR - https://www.medrxiv.org/content/10.64898/2026.10.20.26366058v1
AB - SummaryPretreatment low-turnover status identified patients with attenuated total hip BMD gain after denosumab. Integrated assessment of bone resorption and formation markers may help stratify long-term hip response. IntroductionDenosumab increases bone mineral density (BMD) and reduces fracture risk, but BMD response varies among patients. Given its potent antiresorptive action, denosumab may produce greater BMD gains in patients with higher pretreatment bone turnover; however, its relationship with long-term BMD response remains unclear. We developed a turnover index (TI) integrating bone resorption and formation markers and evaluated its association with BMD response trajectories up to 5 years after denosumab initiation. MethodsThis retrospective observational study included 230 patients with primary osteoporosis who initiated denosumab between January 2014 and January 2025. TI was calculated as the mean of standardized log-transformed TRACP-5b and total P1NP values. Patients were classified into high-, intermediate-, and low-turnover groups according to TI quartiles. Lumbar spine and total hip BMD changes were analyzed using mixed-effects models. ResultsThe cohort included 52 high-turnover, 114 intermediate-turnover, and 64 low-turnover patients. In both unadjusted and multivariable-adjusted models, BMD gain trajectories differed significantly among TI groups at the lumbar spine and total hip (all p < 0.001). Adjusted BMD gains showed a stepwise gradient across TI groups. Five-year adjusted lumbar spine BMD gains were 20.31%, 17.01%, and 12.16% in the high-, intermediate-, and low-turnover groups, respectively. Corresponding total hip BMD gains were 10.56%, 6.76%, and 2.49%, with significantly lower gains in the low-turnover group compared to the other two groups. ConclusionsBaseline bone turnover status was associated with long-term BMD response to denosumab. Low pretreatment turnover may identify patients at risk for attenuated BMD gain during denosumab treatment.
ER -