Underestimation of Vertebral Fractures After Denosumab Discontinuation

We have read with interest the article on vertebral fractures after stopping Denosumab by Cummings SR et al. (1). Denosumab discontinuation is followed by a rebound effect with an increase of CTX above baseline values for two years and a decrease of BMD to baseline value after one year (2). Spontaneous clinical vertebral fractures, most often multiple, occur in the 8 to 16 months (median 11.2 months) following the last Denosumab injection (3). The risk of clinical vertebral fractures in the 12 months following the last Denosumab injection was evaluated at 7.3% (4). This risk is certainly higher with a follow-up of 16 months and the inclusion of non clinical fractures. Cummings SR et al. calculate an exposure-adjusted participant incidence of vertebral fractures (radiological and clinical) of 7.1 per 100 participant-years, from which only 39.3% where clinical fractures. We think that the difference between the previously published data and the actual study is due to the fact that the duration of the follow-up was not sufficient to capture all the vertebral fractures. Moreover, we found that this study has methodological caveats.