Objective: Evidence for further reduction of nonvertebral fracture (NVFX) beyond 3 years of antiresorptive therapy is limited. Since long-term denosumab (DMAb) treatment is associated with continuous increases in BMD and sustained fracture reduction, we analyzed the influence of femoral neck (FN) BMD after 3 years on NVFX rates.
Methods: Long-term subjects received 7 continuous years of DMAb; cross-over subjects received 3 years of placebo (FREEDOM) and 4 years of DMAb (extension). NVFX rates for years 13 vs the 4th year of DMAb were compared in each group separately and combined, and for subgroups defined by FN BMD T-score after 3 years of DMAb treatment. Adjusted rate ratios (RR) (95% CIs) between observational periods were computed by GEE Poisson regression.
Results: For long-term subjects, the NVFX rate was 1.98/100 subject-years during years 13 of DMAb treatment vs 1.43 (RR(95%CI)=0.73(0.501.06)) during year 4 and 1.45 (RR(95%CI)=0.74(0.590.95)) during years 47. For cross-over subjects, the NVFX rate was 2.20 during years 13 of DMAb vs 1.03 (RR(95%CI)=0.48(0.290.79)) in year 4. In the combined groups (n=4073) the rate was 2.08 during years 13 of DMAb and 1.27(RR(95%CI)=0.62(0.460.83)) in year 4. Compared with the first 3 years of treatment, the greatest reduction in NVFX in year 4 was observed in subjects with FN T-scores ≤−2.5 (n=778; RR(95%CI)=0.39(0.190.80)). A further reduction in NVFX was also present, but less pronounced, in subjects with T-scores >−2.5 and <−1.0 (n=2407; RR(95%CI)=0.69(0.471.01)), but not in subjects with T-scores ≧−1.0.
Conclusion: Continued DMAb treatment beyond 3 years was associated with further reductions in NVFX rates, particularly in women whose BMD remained low after 3 years of treatment. These data suggest it may be possible to identify a BMD value below which ongoing treatment will have maximum fracture reduction benefit.
17 May 2014 - 20 May 2014