We thank Ho et al. for their interest in our study and fully agree with their insightful comments.

As stated by Ho, there is no clear protocol for routine monitoring of calcium levels before or during treatment with denosumab. This was our incentive to assess the incidence of denosumab-associated hypocalcemia (DAH) in a large community-based cohort of patients. Most of these patients were treated in primary care clinics. This probably contributes to the major difference in the rate of hypocalcemia observed in our study versus that observed by Ho et al. In our study, the large variability in timing of calcium tests after the start of denosumab therapy suggests that these were random checks rather than tests aimed at detection of treatment-associated adverse events. Moreover, 32 of the patients with hypocalcemia at baseline received denosumab and were excluded from our study. This suggests that awareness to DAH should be increased. In the study by Ho et al., patients were closely monitored. Their results support the notion that vitamin D repletion, adequate calcium and vitamin D supplementation, and regular follow-up of serum calcium are the key to safe treatment with denosumab in high-risk patients.

Previous studies observed a high rate of DAH in patients with end-stage renal disease [1]. Therapeutic options are limited for these patients who have complex metabolic bone disease. We eagerly await the results by Ho et al. in patients with progressive kidney dysfunction treated with vitamin D versus calcitriol.

Gloria Tsvetov, MD

And Talia Diker-Cohen, MD PhD

Department of Endocrinology, Diabetes & Metabolism

Rabin Medical Center - Beilinson Hospital

39 Jabotinski St., 4941492, Petach Tikva, Israel