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Hypocalcemia and bone mineral density changes following denosumab treatment in end-stage renal disease patients: a meta-analysis of observational studies

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Abstract

The incidence of hypocalcemia and bone mineral density (BMD) changes in end-stage renal disease (ESRD) patients on denosumab remains unclear. We performed this meta-analysis to assess the incidence of denosumab-associated hypocalcemia and effects of denosumab on BMD in ESRD patients. A literature search was conducted using MEDLINE, EMBASE, and Cochrane Database from inception through November 2017 to identify studies evaluating incidence of denosumab-associated hypocalcemia and changes in serum calcium, phosphate, alkaline phosphatase (ALP), parathyroid hormone (PTH), and BMD from baseline to post-treatment course of denosumab in ESRD patients. Study results were pooled and analyzed using a random-effect model. The protocol for this meta-analysis is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42017081074). Six observational studies with a total of 84 ESRD patients were enrolled. The pooled estimated incidence of hypocalcemia during denosumab treatment was 42% (95% CI 29–55%, I2 = 0%). Hypocalcemia occurred approximately 7 to 20 days after the first dose and reached nadir of low calcium levels in the first 2 weeks up to 2 months. However, there were no significant changes in serum calcium or phosphate from baseline to post-treatment course (≥ 3 months after treatment) with mean differences [MDs] of 0.20 mg/dL (95% CI, − 0.30 to 0.69 mg/dL) and − 0.10 mg/dL (95% CI, − 0.70 to 0.49 mg/dL). There were significant reductions in ALP and PTH levels with standardized mean differences (SMDs) of − 0.65 (95% CI − 1.13 to − 0.16) and − 1.89 (95% CI − 3.44 to − 0.34), respectively. There were significant increases in T-scores with MDs of 0.39 (95% CI 0.10 to 0.69) and 0.79 (95% CI 0.60 to 0.98) for lumbar spine and femoral neck, respectively. Our study demonstrates the estimated incidence of denosumab-associated hypocalcemia in dialysis patients of 42%. From baseline to post-treatment course, although there are no differences in serum calcium and phosphate, our findings suggest significant reductions in ALP and PTH and a significant increase in BMD. Currently, denosumab should not be considered as the treatment of choice in ESRD patients until more safety and efficacy data are available.

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Authors and Affiliations

  1. Department of Internal Medicine, Bassett Medical Center, Cooperstown, NY, USA

    C. Thongprayoon, T. Bathini, K. Sharma & K. Wijarnpreecha

  2. Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, Mississippi, 2500 N. State St., Jackson, MS, 39216, USA

    P. Acharya, C. Acharya, M.L. Gonzalez Suarez & W. Cheungpasitporn

  3. Department of Internal Medicine, Metrowest Medical Center, Framingham, MA, USA

    J. Chenbhanich

  4. Department of Internal Medicine, East Tennessee State University, Johnson City, TN, USA

    B. Boonpheng

  5. Clinical Epidemiology Unit, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand

    P. Ungprasert

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  1. C. Thongprayoon
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Charat Thongprayoon and Prakrati Acharya are co-first authors.

Maria Lourdes Gonzalez Suarez and Wisit Cheungpasitporn are co-senior authors.

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Thongprayoon, C., Acharya, P., Acharya, C. et al. Hypocalcemia and bone mineral density changes following denosumab treatment in end-stage renal disease patients: a meta-analysis of observational studies. Osteoporos Int 29, 1737–1745 (2018). https://doi.org/10.1007/s00198-018-4533-6

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