Updated trabecular bone score accounting for the soft tissue thickness (TBS(TT)) demonstrated significantly improved bone microstructure with denosumab in the FREEDOM TBS post hoc analysis

SUMMARY: TBS algorithm has been updated to account for regional soft tissue noise. In postmenopausal women with osteoporosis, denosumab improved tissue thickness–adjusted TBS vs placebo independently of bone mineral density over 3 years, with the magnitude of changes from baseline or placebo numerically greater than body mass index–adjusted TBS. INTRODUCTION: To evaluate the effect of denosumab on bone microarchitecture assessed by trabecular bone score (TBS) in the FREEDOM study using the updated algorithm that accounts for regional soft tissue thickness (TBS(TT)) in dual-energy X-ray absorptiometry (DXA) images and to compare percent changes from baseline and placebo with classical body mass index (BMI)–adjusted TBS (TBS(BMI)). METHODS: Postmenopausal women with lumbar spine or total hip bone mineral density (BMD) T score < − 2.5 and ≥ − 4.0 received placebo or denosumab 60 mg subcutaneously every 6 months. TBS(BMI) and TBS(TT) were assessed on lumbar spine DXA scans at baseline and months 1, 12, 24, and 36 in a subset of 279 women (129 placebo, 150 denosumab) who completed the 3-year FREEDOM DXA substudy and rolled over to open-label extension study. RESULTS: Baseline characteristics were similar between groups. TBS(TT) in the denosumab group showed numerically greater changes from both baseline and placebo than TBS(BMI) at months 12, 24, and 36. Denosumab led to progressive increases in BMD (1.2, 5.6, 8.1, and 10.5%) and TBS(TT) (0.4, 2.3, 2.6, and 3.3%) from baseline to months 1, 12, 24, and 36, respectively. Both TBS changes were significant vs baseline and placebo from months 12 to 36 (p < 0.0001). As expected, BMD and TBS(TT) were poorly correlated both at baseline and for changes during treatment. CONCLUSION: In postmenopausal women with osteoporosis, denosumab significantly improved bone microstructure assessed by TBS(TT) over 3 years. TBS(TT) seemed more responsive to denosumab treatment than TBS(BMI) and was independent of BMD. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00198-022-06549-x.