Purpose: The relationship between BMD T-score and fracture risk has not been established in patients on therapy. We previously reported that denosumab (DMAb) treatment over 8 years enables a substantial proportion of women with osteoporosis to achieve non-osteoporotic BMD T‑scores. Further improvement in T-score would only be meaningful if it were associated with fracture reductions; thus, we investigated the relationship between total hip BMD T-score and the incidence of nonvertebral fracture through 8 years of DMAb therapy.
Methods: Women who were randomized to DMAb in FREEDOM and had an observed total hip BMD T-score at FREEDOM baseline and at least one observed total hip BMD T-score during FREEDOM or the Extension (N=3612), were analysed. A repeated-measures model was used to estimate each subject’s BMD T-scores during the entire follow-up, specifically at each unique nonvertebral fracture time among all subjects at risk at the time of each fracture. Cox’s proportional-hazards model was fitted with time to nonvertebral fracture as the response and total hip BMD T‑score time course as a time‑dependent covariate.
Results: The incidence of nonvertebral fracture was lower with higher total hip BMD T‑score throughout a wide and clinically relevant T-score interval (Figure). The relationship flattened at a T-score between –2.0 and –1.0, similar to what occurs in untreated subjects. This inverse relationship between total hip BMD T-score and nonvertebral fracture incidence was maintained regardless of age or prior fracture (data not shown).
Conclusions: Higher total hip BMD T-scores during DMAb treatment were associated with a lower incidence of nonvertebral fractures, similar to the relationship previously established in treatment-naïve patients. Improvements of similar magnitude in BMD would result in different reductions in fracture risk depending on the baseline BMD value. Our findings highlight the importance of BMD measurement in patients on osteoporosis treatment as a predictor of fracture risk and support the concept that specific T‑scores should be evaluated as practical goals for therapy.