Impaired residual renal function predicts denosumab-induced serum calcium decrement as well as increment of bone mineral density in non-severe renal insufficiency
Denosumab treatment of osteoporotic patients, except those with severe renal insufficiency, reduced cCa levels. Low baseline cCa, low estimated glomerular filtration rate, and high bone turnover increased the risk of lower cCa, while increasing bone mineral density. Pretreatment with antiresorptive agents was beneficial in reducing the risk of hypocalcemia.
Although denosumab-induced hypocalcemia has been frequently observed in patients with chronic kidney disease (CKD) stages 4–5D being treated with denosumab for osteoporosis, few studies have assessed the risk factors for serum-corrected calcium (cCa) reductions in patients with non-severe renal insufficiency. This study assessed the risk factors for reduced cCa concentration following denosumab administration and analyzed factors predictive of changes in bone mineral density (BMD).
Seventy-seven osteoporotic patients, not including those with CKD stages 4–5D, were treated with 60 mg denosumab once every 6 months. Biochemical parameters and BMD were analyzed from prior to the initial dose until 1 month after the second dose.
Following the first administration of denosumab, cCa levels decreased, reaching a minimum on day 7. Multiple linear regression analyses showed that baseline cCa, estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2, tartrate-resistant acid phosphatase-5b (TRACP-5b), and bone alkaline phosphatase (BAP) or pretreatment with antiresorptive agents were significant factors independently associated with the absolute reduction in cCa from baseline to day 7 (ΔcCa0–7 days). ΔcCa0–7 days after the second dose of denosumab was significantly lower than that after the first dose. After 6 months of denosumab treatment, both LS-BMD and FN-BMD significantly increased from baseline. LS-BMD and FN-BMD correlated significantly with baseline TRACP-5b or BAP and eGFR, respectively.
Both low eGFR and high bone turnover were independent risk factors for denosumab-induced cCa decrement, and for increases in BMD. Pretreatment with antiresorptive agents may reduce the risk of hypocalcemia.
KeywordsAntiresorptive agent Bone turnover Chronic kidney disease Denosumab Hypocalcemia Osteoporosis
DM contributed to the acquisition, analysis, and interpretation of the data. YI, ME, and MI contributed to the conception and design of the study. MO, NH, YN, SY, and KM contributed to the acquisition of the data. DM took responsibility for the integrity of the data analysis. All authors participated in drafting or revising the manuscript and approved the final version of the manuscript for submission.
Compliance with ethical standards
Conflicts of interest
MI received grant support and lecture fees from Daiichi Sankyo Co., Limited. YI, KM, EM, and MI received lecture fees from Daiichi Sankyo Co., Limited. DM, MO, NH, YN, and SY have no conflicts of interest to report.
Human and animal rights and informed consent
All participants provided written informed consent. The study protocol was approved by the institutional ethics committee of Osaka City University Graduate School of Medicine. This study was conducted in accordance with the principles of the Declaration of Helsinki.
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