Background Denosumab is a fully human monoclonal antibody that targets the receptor activator of nuclear factor kappa B ligand (RANKL) and blocks its binding to RANK, preventing osteoclasts from resorbing bone mass and significantly reducing the risk of vertebral, non-vertebral, and proximal femoral fractures. 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.
Objectives Thirty-one 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.
Methods Serum Ca and phosphorus (P) were measured at baseline and at 1,2,3,and 4 weeks after administration. The bone resorption marker intact serum procollagen type 1 N-terminal propeptide (P1NP) and bone formation marker tartrate-resistant acid phosphatase-5b (TRAP-5b) were also evaluated at baseline and 4 weeks after administration. Laboratory investigations after a second injection were performed in three 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 2 patients: one patient 1 week after administration, and the other 2 weeks after. Hypophosphatemia was observed in 7 patients: 5 patients 1 week after administration and 2 patients after 2 weeks. Hypocalcemia was observed 1 week after the second administration in 1 of the 3 patients. Patients with hypocalcemia and/or hypophosphatemia tended to have a body mass index (BMI) of less than 22.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 31.7% and TRAP-5b was decreased by 71.3%. At 6 months, BMD of the lumbar spine was increased by 2.0%, the femur by 1.5%, and the distal radius by 0.6%.
Conclusions 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. Adverse events were not observed clinically throughout the duration of the study period. However, denosumab administration to individuals with a BMI less than 22 may carry a risk of hypocalcemia and /or hypophosphatemia. Furthermore, denosumab administration resulted in a low bone remodeling ratio reflected by decreases in both P1NP and TRAP5b levels, and increase in BMD, which may reduce fracture risk.
Disclosure of Interest None declared