Background/Purpose: Denosumab is an antiresorptive drug used for the treatement of postmenopausal osteoporosis. One of the major and critical adverse events of denosumab injection is hypocalcemia, which is most often observed in the one-week period following administration. Examination of albumin-adjusted calcium (Ca) level after one week is recommended to exclude the presence of hypocalcemia. Although hypophosphatemia has been reported to be an adverse event with a frequency of more than 1% in patients subcutaneously administered 120mg of denosumab for tumor treatment, there have been no reported data regarding its frequency in patients administered 60mg for osteoporosis. The purpose of the present study was to evaluate the occurrence of denosumab adverse events, focusing on serum electrolyte levels soon after administration, as well as to confirm its efficacy.

Methods: Forty-three women between the ages of 55 and 91 years with postmenopausal osteoporosis were enrolled and treated with a 60mg subcutaneous injection of denosumab and an oral calcium tablet combined with native vitamin D and magnesium (Mg).Serum Ca and phosphorus (P) were measured at baseline and at 1,2,3,and 4 weeks after administration. Serum Mg, bone formation marker intact serum procollagen type 1 N-terminal propeptide (P1NP), and bone resorption marker tartrate-resistant acid phosphatase-5b (TRACP-5b) were also evaluated at baseline and 4 weeks after administration. Laboratory investigations after a second injection were performed in 33 patients in the same manner. Bone mineral density (BMD) was measured at baseline and 6 months after administration.

Results: Both serum Ca and P electrolyte levels significantly decreased soon after administration. Hypocalcemia was detected in 3 patients: 2 patients 1 week after administration, and 1 patient 2 weeks after. Hypophosphatemia was observed in 10 patients: 8 patients 1 week after administration and 2 patients after 2 weeks. Hypocalcemia was observed 1 week after the second administration in 1 of the 33 patients. Hypophosphatemia was detected in 1 patient 1 week after. Serum Mg levels were within normal limits on all examinations. There were no patients who discontinued the treatment due to adverse events in the present study. All serum electrolyte levels recovered within 4 weeks of each administration. At 4 weeks, P1NP level was decreased by 24.0% and TRACP-5b was decreased by 66.9 %. At 6 months, BMD of the lumbar spine was increased by 2.5%, the femur by 1.5%, and the distal radius by 0.6%.

Conclusion: Adverse events were not observed clinically throughout the duration of the study period. However,hypocalcemia and hypophosphatemia were observed within 1 or 2 weeks after the first and/or second administration of denosumab. Therefore, measuring serum electrolyte levels of Ca and P within in 1 or 2 weeks is strongly recommended for the detection of hypocalcemia and hypophosphatemia. Furthermore, denosumab administration resulted in a low bone remodeling ratio reflected by decreases in both P1NP and TRACP-5b levels, and increase in BMD, which may reduce fracture risk.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-study-of-serum-electrolyte-levels-after-denosumab-administration/