Correspondence
Severe Hypocalcemia after Intravenous Bisphosphonate Therapy in Occult Vitamin D Deficiency
N Engl J Med 2003; 348:1503-1504April 10, 2003
- Article
To the Editor:
Oral bisphosphonates are effective for the prevention and treatment of osteoporosis. Powerful second- and third-generation parenteral bisphosphonates, including pamidronate and zoledronate, are also available for off-label use. Although rarely observed, mild hypocalcemia has been reported with this class of agents.1 On the other hand, osteomalacia, as a result of vitamin D deficiency, is common, especially in elderly persons and those with malabsorptive states such as those due to gastric bypass, nontropical sprue, and cystic fibrosis.2 A recent case illustrates a serious complication of bisphosphonate use in a patient with coexisting but occult osteomalacia.
A 52-year-old woman presented with rib and foot pain. Menopause had occurred at the age of 50. The patient had undergone gastric stapling in 1987 and a Roux-en-Y procedure in 2001 for morbid obesity. Serum calcium and phosphorus levels were normal. The T score for bone mineral density at the hip was –1.7. A bone scan showed multiple areas of uptake in the ribs and feet but no fractures. Pamidronate (60 mg) was administered intravenously over a period of four hours. Three weeks later, the patient presented with tetany and rapid atrial fibrillation. The serum calcium level was 4.8 mg per deciliter (normal range, 8.5 to 10.0). The serum 25-hydroxyvitamin D level was 7 ng per milliliter (normal range, 9 to 55); the parathyroid hormone level was more than 300 pg per milliliter (normal range, 10 to 65), and the alkaline phosphatase level was four times the normal value. Intravenous and oral calcium, as well as dihydrotachysterol (0.4 mg twice daily), was administered for seven days. One month after admission, the serum calcium level was 7.0 mg per deciliter; four months after admission, the serum calcium level was 7.9 mg per deciliter; the serum 25-hydroxyvitamin D level was 15 ng per milliliter. Discontinuation of dihydrotachysterol and the addition of ergocalciferol (50,000 units three times per week) for two months and 4 g of oral calcium per day increased the serum calcium level to 8.6 mg per deciliter and increased the serum 25-hydroxyvitamin D level to 27 ng per milliliter. The patient's symptoms resolved completely.
In this patient, subclinical osteomalacia due to vitamin D deficiency, coupled with the administration of a potent intravenous bisphosphonate, resulted in severe, life-threatening hypocalcemia. Pamidronate is a potent inhibitor of bone resorption; as such, it slows calcium efflux from the skeleton. In the face of inadequate vitamin D due to gastrointestinal malabsorption and concurrent pamidronate use, the serum calcium level cannot be maintained in the normal range. Patients with osteoporosis should be prescreened for vitamin D deficiency, and those with such a deficiency should receive vitamin D–replacement therapy before intravenous bisphosphonate therapy is considered.
2 ReferencesClifford J. Rosen, M.D.
St. Joseph Hospital, Bangor, ME 04401
rofe@aol.com Sue Brown, M.D.
University of North Carolina, Chapel Hill, NC 27599-71721
Papapoulos SE. Bisphosphonates. In: Rosen CJ, Glowacki J, Bilezikian JP, eds. The aging skeleton. San Diego, Calif.: Academic Press, 1999:541-9.
2
Gloth FM III ,Tobin JD . Vitamin D deficiency in older people. J Am Geriatr Soc 1995;43:822-828
Web of Science | Medline
- Citing Articles (37)
Citing Articles
1
J. D. Adachi, K. W. Lyles, C. S. Colón-Emeric, S. Boonen, C. F. Pieper, C. Mautalen, L. Hyldstrup, C. Recknor, L. Nordsletten, K. A. Moore, C. Bucci-Rechtweg, G. Su, E. F. Eriksen, J. S. Magaziner. (2011) Zoledronic acid results in better health-related quality of life following hip fracture: the HORIZON–Recurrent Fracture Trial. Osteoporosis International 22:9, 2539-2549
CrossRef2
Virginia Ruiz-Esquide, Pilar Peris, Laia Gifre, Nuria Guañabens. (2011) Alteraciones del metabolismo óseo en la cirugía bariátrica. Medicina Clínica 136:5, 215-221
CrossRef3
Patricia A. Howard, Brian J. Barnes, James L. Vacek, Warren Chen, Sue-Min Lai. (2010) Impact of Bisphosphonates on the Risk of Atrial Fibrillation. American Journal Cardiovascular Drugs 10:6, 359-367
CrossRef4
E. M. Lewiecki, C. Cooper, E. Thompson, F. Hartl, D. Mehta, S. E. Papapoulos. (2010) Ibandronate does not increase risk of atrial fibrillation in analysis of pivotal clinical trials. International Journal of Clinical Practice 64:6, 821-826
CrossRef5
George Liamis, Haralampos J. Milionis, Moses Elisaf. (2009) A review of drug-induced hypocalcemia. Journal of Bone and Mineral Metabolism 27:6, 635-642
CrossRef6
C. J. Bacon, G. D. Gamble, A. M. Horne, M. A. Scott, I. R. Reid. (2009) High-dose oral vitamin D3 supplementation in the elderly. Osteoporosis International 20:8, 1407-1415
CrossRef7
Meral Sayın, Gozde Yazici. (2009) Hyperparathyroidism secondary to zoledronic acid infusion: case report. Supportive Care in Cancer 17:5, 469-470
CrossRef8
Jeffrey I. Mechanick, Robert F. Kushner, Harvey J. Sugerman, J. Michael Gonzalez-Campoy, Maria L. Collazo-Clavell, Adam F. Spitz, Caroline M. Apovian, Edward H. Livingston, Robert Brolin, David B. Sarwer, Wendy A. Anderson, John Dixon. (2009) AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS, THE OBESITY SOCIETY, AND AMERICAN SOCIETY FOR METABOLIC & BARIATRIC SURGERY MEDICAL GUIDELINES FOR CLINICAL PRACTICE FOR THE PERIOPERATIVE NUTRITIONAL, METABOLIC, AND NONSURGICAL SUPPORT OF THE BARIATRIC SURGERY PATIENT. Obesity 17, S3-S72
CrossRef9
N. A. Andrews. (2009) Postoperative Management of Hip Fractures: Recent inaugural IBMS BoneKEy Online Forum focused on pharmacological and non-pharmacological approaches to managing patients post-hip fracture. IBMS BoneKEy 6:2, 55-62
CrossRef10
K. Poole, . (2008) Comment on: Hypovitaminosis D among rheumatology outpatients in clinical practice: reply. Rheumatology 48:2, 204-204
CrossRef11
Cathleen S Colón-Emeric. (2008) Fracture prevention in frail older adults: Why, when and how. IBMS BoneKEy 5:11, 426-435
CrossRef12
Jeffrey I. Mechanick, Robert F. Kushner, Harvey J. Sugerman, J. Michael Gonzalez-Campoy, Maria L. Collazo-Clavell, Safak Guven, Adam F. Spitz, Caroline M. Apovian, Edward H. Livingston, Robert Brolin, David B. Sarwer, Wendy A. Anderson, John Dixon. (2008) American Association of Clinical Endocrinologists, The Obesity Society, and American Society for Metabolic & Bariatric Surgery Medical Guidelines for Clinical Practice for the Perioperative Nutritional, Metabolic, and Nonsurgical Support of the Bariatric Surgery Patient. Surgery for Obesity and Related Diseases 4:5, S109-S184
CrossRef13
P Lee, S Milliken, J R Center. (2008) Hypocalcaemic cardiac failure post BMT secondary to unrecognized vitamin D deficiency. Bone Marrow Transplantation 42:5, 363-364
CrossRef14
D Generali, A Dovio, M Tampellini, M Tucci, S Tedoldi, M Torta, S Bonardi, G Allevi, S Aguggini, M Milani, A L Harris, A Bottini, L Dogliotti, A Angeli, A Berruti. (2008) Changes of bone turnover markers and serum PTH after night or morning administration of zoledronic acid in breast cancer patients with bone metastases. British Journal of Cancer 98:11, 1753-1758
CrossRef15
Ian R Reid. (2008) Once-yearly zoledronate—an effective preventative therapy for new fractures after hip fracture?. Nature Clinical Practice Endocrinology & Metabolism
CrossRef16
Yuka Kinoshita, Kazuhiro Masuoka, Shigesaburo Miyakoshi, Shuichi Taniguchi, Yasuhiro Takeuchi. (2008) Vitamin D insufficiency underlies unexpected hypocalcemia following high dose glucocorticoid therapy. Bone 42:1, 226-228
CrossRef17
Miguel Navarro, Rafael López, Monica Alaña, Alberto Ocaña, Ruben Leno, Feliciano Sánchez, Emilio Fonseca, Juan J. Cruz. (2007) Tonic–Clonic Seizure as the Presentation Symptom of Severe Hypocalcemia Secondary to Zoledronic Acid Administration. Journal of Palliative Medicine 10:6, 1226-1227
CrossRef18
Kenneth W. Lyles. (2007) Bisphosphonates in Paget’s Disease of Bone. Clinical Reviews in Bone and Mineral Metabolism 5:3, 165-171
CrossRef19
(2007) Yearly Zoledronic Acid in Postmenopausal Osteoporosis. New England Journal of Medicine 357:7, 711-715
Full Text20
Sue A Brown, Theresa A Guise. (2007) Drug Insight: the use of bisphosphonates for the prevention and treatment of osteoporosis in men. Nature Clinical Practice Urology 4:6, 310-320
CrossRef21
Marianne S. Elston, Inge J. Stewart, Roderick Clifton-Bligh, John V. Conaglen. (2007) A case of oncogenic osteomalacia with preoperative secondary hyperparathyroidism: Description of the biochemical response of FGF23 to octreotide therapy and surgery. Bone 40:1, 236-241
CrossRef22
Ronald C W Ma, Alice P S Kong, Norman Chan, Peter C Y Tong, Juliana C N Chan. (2007) Drug-Induced Endocrine and Metabolic Disorders. Drug Safety 30:3, 215-245
CrossRef23
Daniele Santini, Maria Elisabetta Fratto, Bruno Vincenzi, Sara Galluzzo, Giuseppe Tonini. (2006) Zoledronic acid in the management of metastatic bone disease. Expert Opinion on Biological Therapy 6:12, 1333-1348
CrossRef24
Maria Luisa Brandi, Alberto Falchetti. (2006) What Is the Relationship Between Paget's Disease of Bone and Hyperparathyroidism?. Journal of Bone and Mineral Research 21:S2, P69-P74
CrossRef25
Heather E. Whitson, Bruce Lobaugh, Kenneth W. Lyles. (2006) Severe hypocalcemia following bisphosphonate treatment in a patient with Paget's disease of bone. Bone 39:4, 954-958
CrossRef26
Horacio Plotkin, Susan Coughlin, Rose Kreikemeier, Kathryn Heldt, Matias Bruzoni, Gary Lerner. (2006) Low doses of pamidronate to treat osteopenia in children with severe cerebral palsy: a pilot study. Developmental Medicine & Child Neurology 48:9, 709-712
CrossRef27
C. Cormier, J.-C. Souberbielle. (2006) Nouvelles définitions de l'insuffisance vitaminique D, retentissement sur les normes de PTH. La Revue de Médecine Interne 27:9, 684-689
CrossRef28
Whyte, Michael P., . (2006) Paget's Disease of Bone. New England Journal of Medicine 355:6, 593-600
Full Text29
Cathleen S. Colón-Emeric, Kenneth G. Saag. (2006) Osteoporotic fractures in older adults. Best Practice & Research Clinical Rheumatology 20:4, 695-706
CrossRef30
Jean-Claude Souberbielle, Gérard Friedlander, André Kahan, Catherine Cormier. (2006) Evaluating vitamin D status. Implications for preventing and managing osteoporosis and other chronic diseases. Joint Bone Spine 73:3, 249-253
CrossRef31
Paul J. Drinka. (2006) The Importance of Parathyroid Hormone and Vitamin D Status in the Treatment of Osteoporosis and Renal Insufficiency. Journal of the American Medical Directors Association 7:3, S5-S9
CrossRef32
Reid, Ian R., Miller, Paul, Lyles, Kenneth, Fraser, William, Brown, Jacques P., Saidi, Youssef, Mesenbrink, Peter, Su, Guoqin, Pak, Judy, Zelenakas, Ken, Luchi, Monica, Richardson, Peter, Hosking, David, . (2005) Comparison of a Single Infusion of Zoledronic Acid with Risedronate for Paget's Disease. New England Journal of Medicine 353:9, 898-908
Full Text33
Rosen, Clifford J., . (2005) Postmenopausal Osteoporosis. New England Journal of Medicine 353:6, 595-603
Full Text34
Paul J. Drinka. (2004) The Importance of Parathyroid Hormone and Vitamin D Status in the Treatment of Osteoporosis and Renal Insufficiency. Journal of the American Medical Directors Association 5:6, 382-386
CrossRef35
Lockley, Steven W., Cronin, John W., Evans, Erin E., Cade, Brian E., Lee, Clark J., Landrigan, Christopher P., Rothschild, Jeffrey M., Katz, Joel T., Lilly, Craig M., Stone, Peter H., Aeschbach, Daniel, Czeisler, Charles A., . (2004) Effect of Reducing Interns' Weekly Work Hours on Sleep and Attentional Failures. New England Journal of Medicine 351:18, 1829-1837
Full Text36
Robert P Heaney. (2003) How does bone support calcium homeostasis?. Bone 33:3, 264-268
CrossRef37
&NA;. (2003) Pamidronic acid. Reactions Weekly &NA;:947/48, 10
CrossRef
