Advertisement

Denosumab-Associated Severe Hypocalcemia in a Patient With Chronic Kidney Disease

Published:October 10, 2017DOI:https://doi.org/10.1016/j.amjms.2017.09.008

      Abstract

      Denosumab is a monoclonal antibody directed against the receptor activator of nuclear factor kappa B ligand (RANKL). Denosumab has been shown to reduce the risk of skeletal-related events, including spinal cord compression, pathologic fracture and hypercalcemia of malignancy in patients with bone metastases. Hypocalcemia is a known side effect of denosumab, occurring in an estimated 8-14% of the patients. Here, we present an asymptomatic patient with stage-5 chronic kidney disease and severe hypocalcemia who had received denosumab 1 month earlier.

      Key Indexing Terms

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to The American Journal of the Medical Sciences
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Chen C.-L.
        • Chen N.-C.
        • Liang H.-L.
        • et al.
        Effects of denosumab and calcitriol on severe secondary hyperparathyroidism in dialysis patients with low bone mass.
        J Clin Endocrin Metab. 2015; 100: 2784-2792
        • Body J.-J.
        • Facon T.
        • Coleman R.E.
        • et al.
        A study of the biological receptor activator of nuclear factor-kappaB ligand inhibitor, denosumab, in patients with multiple myeloma or bone metastases from breast cancer.
        Clin Cancer Res. 2006; 12: 1221-1228
        • McCormick B.B.
        • Davis J.
        • Burns K.D.
        Severe hypocalcemia following denosumab injection in a hemodialysis patient.
        Am J Kidney Dis. 2012; 60: 626-628
        • Chennuru S.
        • Koduri J.
        • Baumann M.
        Risk factors for symptomatic hypocalcaemia complicating treatment with zoledronic acid.
        Int Med J. 2008; 38: 635-637
        • Huynh A.L.H.
        • Baker S.T.
        • Stewardson A.J.
        • et al.
        Denosumab‐associated hypocalcaemia: incidence, severity and patient characteristics in a tertiary hospital setting.
        Pharmacoepidemiol Drug Safety. 2016; 25: 1274-1278
      1. Amgen. Prolia general package insert Thousand Oaks, CA. Amgen2011.

      2. Xgeva. Package Insert Thousand Oaks, CA: Amgen Inc. 2010.

        • Narayanan P.
        Denosumab: A comprehensive review.
        South Asian J Cancer. 2013; 2: 272
        • Pierroz D.D.
        • Bonnet N.
        • Baldock P.A.
        • et al.
        Are osteoclasts needed for the bone anabolic response to parathyroid hormone? A study of intermittent parathyroid hormone with denosumab or alendronate in knock-in mice expressing humanized RANKL.
        J Biol Chem. 2010; 285: 28164-28173
        • Fizazi K.
        • Yang J.
        • Peleg S.
        • et al.
        Prostate cancer cells-osteoblast interaction shifts expression of growth/survival-related genes in prostate cancer and reduces expression of osteoprotegerin in osteoblasts.
        Clin Cancer Res. 2003; 9: 2587-2597
        • Agarwal M.
        • Csongrádi É.
        • Koch C.A.
        • et al.
        Severe symptomatic hypocalcemia after denosumab administration in an end-stage renal disease patient on peritoneal dialysis with controlled secondary hyperparathyroidism.
        Br J Med Medical Res. 2013; 3: 1398-1406
        • Jamal S.A.
        • Ljunggren Ö.
        • Stehman‐Breen C.
        • et al.
        Effects of denosumab on fracture and bone mineral density by level of kidney function.
        J Bone Mineral Res. 2011; 26: 1829-1835
        • Body J.-J.
        • Bone H.G.
        • De Boer R.H.
        • et al.
        Hypocalcaemia in patients with metastatic bone disease treated with denosumab.
        Eu J Cancer. 2015; 51: 1812-1821
        • Muqeet Adnan M.
        • Bhutta U.
        • Iqbal T.
        • et al.
        Severe hypocalcemia due to denosumab in metastatic prostate cancer.
        Case Reports Nephrol. 2014;
        • Spiegel M.C.
        • et al.
        Denosumab-Induced Severe Hypocalcemia in a Patient with Crohn′s Disease.
        J Academic Hosp Med. 2014; 6
        • Body J.J.
        • Greipp P.
        • Coleman R.E.
        • et al.
        A phase I study of AMGN‐0007, a recombinant osteoprotegerin construct, in patients with multiple myeloma or breast carcinoma related bone metastases.
        Cancer. 2003; 97: 887-892
        • Dave V.
        • Chiang C.Y.
        • Booth J.
        • et al.
        Hypocalcemia post denosumab in patients with chronic kidney disease stage 4-5.
        Am J Nephrol. 2015; 41: 129-137
        • Wolf M.
        Update on fibroblast growth factor 23 in chronic kidney disease.
        Kidney Int. 2012; 82: 737-747
        • Afshan S.
        • Musa A.R.F.
        • Echols V.
        • et al.
        Persisting Hypocalcemia After Surgical Parathyroidectomy: The Differential Effectiveness of Calcium Citrate Versus Calcium Carbonate With Acid Suppression.
        Am J Med Sci. 2017; 353: 82-86
        • Aguilar E.A.
        • Barry S.D.
        • Cefalu C.A.
        • et al.
        Osteoporosis Diagnosis and Management in Long-Term Care Facility.
        Am J Med Sci. 2015; 350: 357-363
      3. Group KDIGOC-MW. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl. 2009(113):S1.

        • Miller P.D.
        Fragility fractures in chronic kidney disease: an opinion-based approach.
        Clev Clinic J Med. 2009; 76: 715-723