Hypocalcaemia in patients with metastatic bone disease treated with denosumab

AbstractBackgroundThis analysis was performed to further characterise treatment-emergent hypocalcaemia in patients with bone metastases receiving denosumab.MethodsLaboratory abnormalities and adverse events of hypocalcaemia in patients with metastatic bone disease were analysed using data from three identically designed phase 3 trials of subcutaneous denosumab 120mg (n=2841) versus intravenous zoledronic acid 4mg (n=2836).ResultsThe overall incidence of laboratory events of hypocalcaemia grade ⩾2 was higher with denosumab (12.4%) than with zoledronic acid (5.3%). Hypocalcaemia events were primarily grade 2 in severity and usually occurred within the first 6months of treatment. Patients who reported taking calcium and/or vitamin D supplements had a lower incidence of hypocalcaemia. Prostate cancer or small-cell lung cancer, reduced creatinine clearance and higher baseline bone turnover markers of urinary N-telopeptide of type I collagen (uNTx; >50 versus ⩽50nmol/mmol) and bone-specific alkaline phosphatase (BSAP; >20.77μg/L [median] versus ⩽20.77μg/L) values were important risk factors for developing hypocalcaemia. The risk associated with increased baseline BSAP levels was greater among patients who had >2 bone metastases at baseline versus those with ⩽2 bone metastases at baseline.ConclusionHypocalcaemia was more frequent with denosumab versus zoledronic acid, consistent with denosumab’s greater antiresorptive effect. Low serum calcium levels and potential vitamin D deficiency should be corrected before initiating treatment with a potent osteoclast inhibitor, and corrected serum calcium levels should be monitored during treatment. Adequate calcium and vitamin D intake appears to substantially reduce the risk of hypocalcaemia