Effects of denosumab on bone mineral density and bone metabolism in patients with end‐stage renal disease: A systematic review and meta‐analysis

Abstract Introduction The effects of denosumab on bone mineral density (BMD) and metabolism in patients with end‐stage renal disease (ESRD) remain controversial. Hence, we performed a systematic review and meta‐analysis of observational studies. Methods The MEDLINE, EMBASE, and Cochrane Library databases were searched in June 2022 to identify studies that evaluated the risk of denosumab‐associated hypocalcemia and changes in bone metabolism, changes in BMD from baseline to post‐treatment in patients with ESRD. Findings Twelve studies with 348 participants were included. The pooled incidence of hypocalcemia during denosumab treatment was 35.0% (95% confidence interval [CI], 25%–46%; I 2 = 63.6%). There were no significant changes in either the serum calcium or phosphate levels from the baseline to post‐treatment period; the mean differences were 0.04 mg/dL (95% CI, −0.12 to 0.20 mg/dL) and −0.39 mg/dL (95% CI, −0.89 to 0.12 mg/dL). We found significant changes in the alkaline phosphatase and parathyroid hormone levels; the standardized mean differences were −2.98 (95% CI, −5.36 to –0.59) and −3.12 (95% CI: –4.94 to –1.29), respectively. Denosumab may increase BMD, with mean differences of 9.10% (95% CI: 4.07%–14.13%) and 9.00% (95% CI: 5.93%–12.07%) for the femoral neck and lumbar spine, respectively. Discussion Denosumab increased the BMDs of the lumbar spine and femoral neck in patients with ESRD. The onset of hypocalcemia must be carefully monitored during denosumab administration.