Rikako Hiramatsu1,2, Yoshifumi Ubara1, Naoki Sawa1, Akinori Sakai2. 1. Nephrology Centre, Toranomon Hospital, Tokyo, Japan. 2. Department of Orthopedic Surgery, University of Occupational and Environmental Health, Japan.
Abstract
BACKGROUND: Increases in bone mineral density (BMD) following a single dose of denosumab and increased incidence of denosumab-associated acute hypocalcemia (DAAH) have been reported in chronic kidney disease (CKD) patients. Little is known about clinical risk factors related to DAAH and the long-term effect of denosumab on BMD in hemodialysis patients. METHODS: An observational non-controlled study involving 47 hemodialysis patients was conducted to determine the independent risk factors related to percent changes in serum Ca levels associated with denosumab using multivariate regression analysis. Optimal predictive markers for DAAH were explored by receiver operating characteristic (ROC) analysis. Percent changes of BMD at the lumbar spine (LS) and femoral neck (FN) over 24 months were investigated. RESULTS: The incidence of DAAH (serum corrected Ca (cCa) ≤ 8 mg/dL) following denosumab was 25.5%. Multivariate regression analysis showed baseline bone alkaline phosphatase (BAP) was independently related to percent changes in cCa levels (β = -0.407, P = 0.008). Tartrate-resistant acid phosphatase (TRACP-5b) was found to be the most accurate marker to predict DAAH with AUC of 0.750 (95% CI; 0.546-0.954, P = 0.02) and the optimal cut-off level was 670 mU/mL with sensitivity; 0.727 and specificity; 0.733. BMD significantly increased by 5.9 ± 1.7% (P = 0.01) at LS and 4.2 ± 1.5% (P = 0.04) at FN at 24 months. CONCLUSION: In hemodialysis patients, high bone turnover was an independent risk factor for the Ca declines induced by denosumab. Denosumab significantly increased BMD at LS and FN over 24 months.
BACKGROUND: Increases in bone mineral density (BMD) following a single dose of denosumab and increased incidence of denosumab-associated acute hypocalcemia (DAAH) have been reported in chronic kidney disease (CKD) patients. Little is known about clinical risk factors related to DAAH and the long-term effect of denosumab on BMD in hemodialysis patients. METHODS: An observational non-controlled study involving 47 hemodialysis patients was conducted to determine the independent risk factors related to percent changes in serum Ca levels associated with denosumab using multivariate regression analysis. Optimal predictive markers for DAAH were explored by receiver operating characteristic (ROC) analysis. Percent changes of BMD at the lumbar spine (LS) and femoral neck (FN) over 24 months were investigated. RESULTS: The incidence of DAAH (serum corrected Ca (cCa) ≤ 8 mg/dL) following denosumab was 25.5%. Multivariate regression analysis showed baseline bone alkaline phosphatase (BAP) was independently related to percent changes in cCa levels (β = -0.407, P = 0.008). Tartrate-resistant acid phosphatase (TRACP-5b) was found to be the most accurate marker to predict DAAH with AUC of 0.750 (95% CI; 0.546-0.954, P = 0.02) and the optimal cut-off level was 670 mU/mL with sensitivity; 0.727 and specificity; 0.733. BMD significantly increased by 5.9 ± 1.7% (P = 0.01) at LS and 4.2 ± 1.5% (P = 0.04) at FN at 24 months. CONCLUSION: In hemodialysis patients, high bone turnover was an independent risk factor for the Ca declines induced by denosumab. Denosumab significantly increased BMD at LS and FN over 24 months.