Does the Osteoporosis Dose of Denosumab Really Cause Clinically Significant Hypocalcaemia in CKD 4 and 5

Abstract

Denosumab is a potent novel antiresorptive agent for treatment of osteoporosis with unique mechanism of action . It is a fully human monoclonal antibody to the receptor activator of nuclear factor-κB ligand (RANKL) that blocks its binding to RANK, inhibiting the development and activity of osteoclasts, decreasing bone resorption, and increasing bone density. Initially denosumab appeared particularly promising for patients with advanced stages of renal failure but over the past two years several publications questioned that, reporting adverse effects and especially severe hypocalcaemia. Aim of the Study: to investigate further the effect of the osteoporosis dose of denosumab on serum calcium levels in patients with CKD 4 and CKD 5. Methods: This retrospective outpatient study included 17 females with CKD 4 and 5 who received a single or a multiple (at 6 months intervals) 60-mg subcutaneous dose of denosumab. Adjusted serum Calcium was measured prior to the dose and at various points of time after that. Results: Only two of the subjects developed clinically significant hypocalcaemia. Both of them were clearly inadequately supplemented with calcium and vitamin D. Conclusion: The results from the current study along with a critical analysis of the previous publications reveal that the vast majority of the previous reports were based on inadequately supplemented with calcium and vitamin D patients and that severe hypocalcaemia is unlikely in appropriately supplemented subjects, especially in the CKD 4 subgroup. However, due to the scarcity of data further research is warranted, especially in the CKD 5 subgroup. In the mean time more cautious approach rather than a blanket ban on denosumab appears to be the most appropriate policy in these two populations.