Skip to main content


Log in

Severe hypocalcemia after denosumab in a patient with acquired Fanconi syndrome

  • Case Report
  • Published:
Osteoporosis International Aims and scope Submit manuscript


We report the case of a 48-year-old man with acquired Fanconi syndrome due to IgG-kappa monoclonal gammopathy, who received a single dose of denosumab 60 mg for secondary prevention of skeletal fractures, in conjunction with oral calcium and vitamin D supplementation. The treatment was complicated with a severe, symptomatic hypocalcemia occurring 1 month after the injection and necessitating 4 weeks of intravenous calcium gluconate therapy. Similarly to bisphosphonates, inhibitors of the receptor activator of nuclear factor kappa-B ligand may not be appropriate for the treatment of acquired Fanconi syndrome and other forms of osteomalacia regardless of the degree of renal insufficiency and vitamin D levels. Clinicians should carefully interpret the radiographic and bone densitometry results in light of diverse mechanisms of bone demineralization and potential dependence of calcium homeostasis on high bone turnover.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2


  1. Ma CX, Lacy MQ, Rompala JF, Dispenzieri A, Rajkumar SV, Greipp PR, Fonseca R, Kyle RA, Gertz MA (2004) Acquired Fanconi syndrome is an indolent disorder in the absence of overt multiple myeloma. Blood 104:40–42. doi:10.1182/blood-2003-10-3400

    Article  CAS  PubMed  Google Scholar 

  2. Clarke BL, Wynne AG, Wilson DM, Fitzpatrick LA (1995) Osteomalacia associated with adult Fanconi's syndrome: clinical and diagnostic features. Clin Endocrinol (Oxf) 43:479–490

    Article  CAS  Google Scholar 

  3. Dore RK (2011) The RANKL pathway and denosumab. Rheum Dis Clin N Am 37:433–452. doi:10.1016/j.rdc.2011.07.004, vi-vii

    Article  Google Scholar 

  4. Kostenuik PJ (2005) Osteoprotegerin and RANKL regulate bone resorption, density, geometry and strength. Curr Opin Pharmacol 5:618–625. doi:10.1016/j.coph.2005.06.005

    Article  CAS  PubMed  Google Scholar 

  5. Boyle WJ, Simonet WS, Lacey DL (2003) Osteoclast differentiation and activation. Nature 423:337–342. doi:10.1038/nature01658

    Article  CAS  PubMed  Google Scholar 

  6. Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki S, Tomoyasu A, Yano K, Goto M, Murakami A, Tsuda E, Morinaga T, Higashio K, Udagawa N, Takahashi N, Suda T (1998) Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci U S A 95:3597–3602

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, Delmas P, Zoog HB, Austin M, Wang A, Kutilek S, Adami S, Zanchetta J, Libanati C, Siddhanti S, Christiansen C, Trial F (2009) Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 361:756–765. doi:10.1056/NEJMoa0809493

    Article  CAS  PubMed  Google Scholar 

  8. Lipton A, Fizazi K, Stopeck AT, Henry DH, Brown JE, Yardley DA, Richardson GE, Siena S, Maroto P, Clemens M, Bilynskyy B, Charu V, Beuzeboc P, Rader M, Viniegra M, Saad F, Ke C, Braun A, Jun S (2012) Superiority of denosumab to zoledronic acid for prevention of skeletal-related events: a combined analysis of 3 pivotal, randomised, phase 3 trials. Eur J Cancer 48:3082–3092. doi:10.1016/j.ejca.2012.08.002

    Article  CAS  PubMed  Google Scholar 

  9. Jamal SA, Ljunggren O, Stehman-Breen C, Cummings SR, McClung MR, Goemaere S, Ebeling PR, Franek E, Yang YC, Egbuna OI, Boonen S, Miller PD (2011) Effects of denosumab on fracture and bone mineral density by level of kidney function. J Bone Miner Res 26:1829–1835. doi:10.1002/jbmr.403

    Article  CAS  PubMed  Google Scholar 

  10. Block GA, Bone HG, Fang L, Lee E, Padhi D (2012) A single-dose study of denosumab in patients with various degrees of renal impairment. J Bone Miner Res 27:1471–1479. doi:10.1002/jbmr.1613

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Levey AS, Coresh J, Greene T, Stevens LA, Zhang YL, Hendriksen S, Kusek JW, Van Lente F, Chronic Kidney Disease Epidemiology C (2006) Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med 145:247–254

    Article  CAS  PubMed  Google Scholar 

  12. Eastell R, Christiansen C, Grauer A, Kutilek S, Libanati C, McClung MR, Reid IR, Resch H, Siris E, Uebelhart D, Wang A, Weryha G, Cummings SR (2011) Effects of denosumab on bone turnover markers in postmenopausal osteoporosis. J Bone Miner Res 26:530–537. doi:10.1002/jbmr.251

    Article  CAS  PubMed  Google Scholar 

  13. McCormick BB, Davis J, Burns KD (2012) Severe hypocalcemia following denosumab injection in a hemodialysis patient. Am J Kidney Dis 60:626–628. doi:10.1053/j.ajkd.2012.06.019

    Article  PubMed  Google Scholar 

  14. Ungprasert P, Cheungpasitporn W, Srivali N, Kittanamongkolchai W, Bischof EF (2013) Life-threatening hypocalcemia associated with denosumab in a patient with moderate renal insufficiency. Am J Emerg Med 31(756):e751–e752. doi:10.1016/j.ajem.2012.11.011

    Google Scholar 

  15. Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group (2009) KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl 113:S1–S130. doi:10.1038/ki.2009.188

    Google Scholar 

  16. Rosen CJ, Brown S (2003) Severe hypocalcemia after intravenous bisphosphonate therapy in occult vitamin D deficiency. N Engl J Med 348:1503–1504. doi:10.1056/NEJM200304103481521

    Article  PubMed  Google Scholar 

  17. Witteveen JE, van Thiel S, Romijn JA, Hamdy NA (2013) Hungry bone syndrome: still a challenge in the post-operative management of primary hyperparathyroidism: a systematic review of the literature. Eur J Endocrinol 168:R45–R53. doi:10.1530/EJE-12-0528

    Article  CAS  PubMed  Google Scholar 

  18. Milat F, Goh S, Gani LU, Suriadi C, Gillespie MT, Fuller PJ, Teede HJ, Strickland AH, Allan CA (2013) Prolonged hypocalcemia following denosumab therapy in metastatic hormone refractory prostate cancer. Bone 55:305–308. doi:10.1016/j.bone.2013.04.012

    Article  CAS  PubMed  Google Scholar 

  19. Wald H, Popovtzer MM (1984) Renal refractoriness to PTH in experimental Fanconi syndrome: evidence for intact adenylate cyclase activation. Pflugers Arch 402:116–119

    Article  CAS  PubMed  Google Scholar 

  20. Jüppner H (2011) Phosphate and FGF-23. Kidney Int Suppl 121:S24–S27. doi:10.1038/ki.2011.27

    Article  PubMed  Google Scholar 

  21. Stewart I, Roddie C, Gill A, Clarkson A, Mirams M, Coyle L, Ward C, Clifton-Bligh P, Robinson BG, Mason RS, Clifton-Bligh RJ (2006) Elevated serum FGF23 concentrations in plasma cell dyscrasias. Bone 39:369–376. doi:10.1016/j.bone.2006.01.163

    Article  CAS  PubMed  Google Scholar 

  22. Kitaoka T, Namba N, Miura K, Kubota T, Ohata Y, Fujiwara M, Hirai H, Yamamoto T, Ozono K (2011) Decrease in serum FGF23 levels after intravenous infusion of pamidronate in patients with osteogenesis imperfecta. J Bone Miner Metab 29:598–605. doi:10.1007/s00774-011-0262-z

    Article  CAS  PubMed  Google Scholar 

  23. Henry DH, Costa L, Goldwasser F, Hirsh V, Hungria V, Prausova J, Scagliotti GV, Sleeboom H, Spencer A, Vadhan-Raj S, von Moos R, Willenbacher W, Woll PJ, Wang J, Jiang Q, Jun S, Dansey R, Yeh H (2011) Randomized, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma. J Clin Oncol 29:1125–1132. doi:10.1200/JCO.2010.31.3304

    Article  CAS  PubMed  Google Scholar 

  24. Terpos E, Roodman GD, Dimopoulos MA (2013) Optimal use of bisphosphonates in patients with multiple myeloma. Blood 121:3325–3328. doi:10.1182/blood-2012-10-435750

    Article  CAS  PubMed  Google Scholar 

Download references

Conflicts of interest


Author information

Authors and Affiliations


Corresponding author

Correspondence to A. J. Olszewski.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shafqat, H., Alquadan, K.F. & Olszewski, A.J. Severe hypocalcemia after denosumab in a patient with acquired Fanconi syndrome. Osteoporos Int 25, 1187–1190 (2014).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: