SaO030
Hypocalcemia and bone mineral changes following denosumab treatment in end-stage renal disease patients with low bone mineral density: A 2-year observational study Free

INTRODUCTION: Denosumab-associated hypocalcemia is a major safety concern in end-stage renal disease (ESRD) patients and its incidence and factors related to hypocalcemia remain elusive. Furthermore, limited data are available on the long-term effect of denosumab on bone mineral density (BMD) changes in ESRD. The aims of this study were to (1) investigate the incidence of denosumab-associated acute hypocalcemia, (2) identify risk factors related to reductions in serum calcium concentrations, and (3) assess the effects of denosumab on BMD over 24 months in ESRD patients with low BMD.

METHODS: We conducted an observational, retrospective, single-centre study on 47 hemodialysis patients with low BMD treated with denosumab (60 mg) between May 2013 and May 2018. All patients were ≥20 years old and were without skeletal malignancies. Low BMD was defined either as BMD T-score ≤ -2.5 at the lumbar spine (LS), femoral neck (FN), and distal one-third radius (RS) analyzed by dual-X-ray absorptiometry, or BMD T-score of -2.5 to -1.0 with history of fragility fractures. The incidence of acute hypocalcemia—defined as serum-corrected Ca [= serum Ca (mg/dl)-albumin (g/dl)+4.0] ≤ 8.0 mg/dl on day 7 (cCa7) after the first denosumab injection—and risk factors related to cCa decrement were investigated. Correlation between the absolute value of clinical parameters and the percent change of cCa on day 7 (⊿cCa7) from baseline cCa (cCa0) [(cCa7-cCa0)/cCa0*100 (%)] following the first denosumab injection were determined by univariate and multivariate linear regression analyses. Within-individual percent change of BMD and bone turnover markers (bone alkaline phosphatase [BAP] and tartrate-resistant acid phosphatase 5b [TRACP-5b]) at 6, 12, and 24 months (mo) were evaluated.

RESULTS: Data from a total of 47 patients (mean age: 66.1±11.1 years; mean dialysis time: 16.1±11.1 years) were reviewed. No patients were prescribed osteoporosis pretreatments in the 1 year prior to the study. Laboratory data at baseline were intact PTH (iPTH): 165.9±137.5 pg/ml; cCa: 9.79±0.4 mg/dl; BAP: 35.6±72.5 µg/l; and TRACP-5b: 699.9±499.7 mU/dl. The respective baseline BMD T-scores were -1.90±1.50, -2.31±1.06, and -3.01±2.04 at LS, FN, and RS. Mean cCa7 was 8.77±1.08 mg/dl (P < 0.001 vs. baseline) and the incidence of acute hypocalcemia was 12 out of 47 (25.5%).⊿cCa7 had a significant negative correlation with baseline BAP (r = -0.405, P < 0.001), TRACP-5b (r = -0.362, P = 0.02), and iPTH (r = -0.347, P = 0.017). Multivariate linear regression analyses showed that elevated baseline TRACP-5b was a significant independent risk factor associated with ⊿cCa7 (β = -0.414, P = 0.005), even after adjusting for baseline cCa. The LS-BMD and FN-BMD changes at 24 mo from baseline were 6.2±7.8% and 4.6±7.6%, respectively, and statistically significant (P < 0.001). There were significant decreases in BAP and TRACP-5b at 6 mo of -39.2±36.6% and -27.2±30.0%, respectively, which persisted during the period up until 24 mo.

CONCLUSIONS: High bone turnover, particularly greater bone absorption status, was a risk factor related to denosumab-associated hypocalcemia in ESRD patients. Denosumab significantly increased LS and FN-BMD, and decreased bone turnover markers over 2 years. Further study is needed to assess denosumab’s safety and potentiality to reduce fracture risk in ESRD.