Objective:
This retrospective analysis applied updated built-in tissue thickness–adjusted TBS algorithm to investigate the long-term effect of denosumab on bone microarchitecture in FREEDOM and OLE.
Material and Methods:
This analysis included 279 postmenopausal women with LS or total hip BMD T-score <−2.5 and ≥−4.0 who completed the FREEDOM DXA substudy and continued in the OLE study: 150 women received denosumab 60 mg SC Q6M for 3 years and open-label denosumab for 7 years (long-term group); 129 women received placebo for 3 years and open-label denosumab for 7 years (crossover group). BMD and TBS were assessed on LS DXA scans.
Results:
Baseline characteristics were similar between groups. Long-term denosumab led to significant and progressive increases in TBS over 10 years of treatment (Figure). A similar trend was observed in the crossover group during 7 years of denosumab therapy. In the long-term denosumab group, % of patients with normal microarchitecture (TBS >1.074) increased from 26.1% at baseline to 53.2% up to Year 10, and % of patients with degraded (TBS ≤1.027) or partially degraded (1.027<TBS≤1.074) microarchitecture decreased from 48.6% to 29.1% and from 25.4% to 17.7%, respectively (P < 0.0001; TBS thresholds equivalent to 1.230 and 1.310 for the classical TBS algorithm corrected for body mass index). A similar improvement in bone microarchitecture was observed in the crossover group from OLE baseline up to OLE Year 7 (P < 0.0001). Over the course of long-term denosumab treatment, TBS changes were largely unrelated to LS BMD changes: r2was 0.05 from baseline to Year 10 in the long-term group and 0.28 from OLE baseline to OLE Year 7 in the crossover group.
Conclusion:
Up to 10 years of denosumab treatment significantly and progressively improved TBS assessment of bone microarchitecture independently of BMD in postmenopausal women with osteoporosis.