We would like to thank Dr. Daly and colleagues for their interest in our article [1] in which we outlined the beneficial effects of denosumab on muscle performance in patients with low BMD. Indeed, there were considerable individual changes in measures of grip force and chair rising test in some patients. Recommendation for regular exercise was part of the usual treatment in all patients studied, although this could not be standardized due to the retrospective study design. Patients with recent fractures had been excluded from the study.

Regarding the annual changes in grip force, there was one patient (male, 76 years) who improved by 148%. In this patient, we did not detect any abnormalities in terms of recent fractures or general changes in physical activity. After exclusion of this patient, the denosumab group still showed a higher increase in grip force compared to the basic therapy group (mean difference, 7.5%; 95% confidence interval [CI], 2.0 to 13.0% per year, p = 0.002). In the correlation analysis, inclusion or exclusion of the outlier did not change the lack of significant associations between changes in grip strength and DXA or laboratory results. We performed propensity-score matching to ensure that the groups did not differ in important baseline variables (such as sex, age, and BMI). Regarding the influence of vitamin D (25-OH-D) levels, we acknowledge that this may be a possible confounding factor [2]. However, both baseline values and annual percentage changes in 25-OH-D levels showed no differences between groups (all p > 0.05). All patients received moderate-dose vitamin D supplementation (1000 to 3000 IU daily), resulting in 25-OH-D levels in the reference range (> 30 µg/L) in most patients. Therefore, it appears unlikely that the differences in changes in muscle performance were related to 25-OH-D levels. Finally, although no precision measurements in terms of inter- or intra-rater reliability could be performed in the context of the present study, both grip force and chair rising test measurements were performed by the same investigators under strict standardization and in compliance with current standards.

Taken together, a positive effect of denosumab on muscle performance has also been reported by other authors [3, 4], but further methodologically robust studies should be performed before definitive conclusions or clinical recommendations can be made.