|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
Journal of Clinical Oncology, Vol 22, No 8 (April 15), 2004: pp. 1531-1532 © 2004 American Society of Clinical Oncology. DOI: 10.1200/JCO.2004.99.013
Prolonged Hypocalcemia After Treatment With Zoledronic Acid in a Patient With Prostate Cancer and Vitamin D DeficiencyDepartment of Medicine, College of Physicians & Surgeons, Columbia University, New York, NY To the Editor: Zoledronate (Zometa) is a new long-acting and highly potent bisphosphonate that has been shown to reduce bone pain as well as decrease the number of skeletal complications in patients with prostate cancer metastatic to bone.1 We report a patient with metastatic prostate cancer who presented with symptomatic hypocalcemia (requiring 17 days of continuous intravenous calcium supplementation) after receiving zoledronate for pain related to bony metastases. The patient is a 63-year-old Hispanic man who was diagnosed with prostate cancer in 1998. He initially underwent a transurethral resection of the prostate and bilateral orchiectomy. One year later he was found to have metastatic disease in the retroperitoneum, vertebrae, femurs, and skull that was refractory to treatment with bicalutamide and leuprolide. He had recently begun treatment with estramustine and taxotere. His past history is significant for hypertension, gastric cancer treated with partial gastrectomy two years before admission, and a partial right nephrectomy secondary to a stab wound. His outpatient medications included morphine sulfate, hydromorphone, celecoxib, erythropoietin, metoclopramide, warfarin, and the proton pump inhibitor, pantoprazole. Seven days after receiving a single intravenous dose of zoledronate 4 mg for bony pain related to metastatic prostate cancer, the patient presented to our emergency room with complaints of nausea and dysphagia. On admission, his physical examination was remarkable for a positive Trousseau sign and laryngeal spasm. The ECG showed a prolonged QT interval (QTc = 559 ms). Laboratory studies revealed profound hypocalcemia, with an albumin-corrected serum calcium of 5.4 mg/dL (normal, 8.5 to 9.8 mg/dL). His admission laboratory data confirmed the hypocalcemia and were also notable for hypophosphatemia (2.2 mg/dL; normal, 2.5 to 4.5 mg/dL), a serum magnesium of 1.6 mg/dL (normal, 1.5 to 2.3 mg/dL), and a serum creatinine level of 1.2 mg/dL (normal, 0.8 to 1.2 mg/dL). Serum 25-hydroxyvitamin D (25-OHD) and parathyroid hormone (PTH) levels were sent and therapy was initiated with intravenous calcium gluconate. During the first 24 hours after admission, the patient received a total of 18 ampules of intravenous calcium gluconate (1,620 mg of elemental calcium) with resolution of his tetany and normalization of his ECG. He was started on oral calcium (Oscal + D 500 mg qid) and 1,25 dihydroxyvitamin D (calcitriol 0.5 g po qd). The proton pump inhibitor was stopped to increase gastric acidity and improve intestinal calcium absorption. Despite these measures, the patient required continuous slow infusion of calcium gluconate (one ampule/h or approximately 2,200 mg/d of elemental calcium) for an additional 16 days in order to maintain serum calcium levels above 7.0 mg/dL. The admission serum 25-OHD concentration (9 ng/dL; normal, 10 to 68 ng/dL) was consistent with severe vitamin D deficiency. The markedly elevated serum PTH concentration (174 pg/dL; normal, 12 to 72 pg/dL), indicated secondary hyperparathyroidism, likely related both to profound hypocalcemia and vitamin D deficiency. Review of the patient's past laboratory data revealed declining serum calcium values during the previous year (9.3 to 7.5 mg/dL) and no prior assessment of serum 25-OHD levels. The patient was discharged on oral parent vitamin D (ergocalciferol 50,000 U weekly) and Citracal plus D (2 tablets qid), which provided approximately 2,500 mg of elemental calcium daily. One month later, his serum calcium was 8.2 mg/dL. In healthy individuals, osteoclast-mediated bone resorption constitutes a major defense against hypocalcemia of diverse etiologies. Zoledronate exerts its effects on the skeleton by inhibiting osteoclast-mediated bone resorption and lowers serum calcium both in normocalcemic and hypercalcemic individuals. Individuals would be less able to counteract hypocalcemic stimuli after treatment with zoledronate. This patient had several risk factors for developing severe hypocalcemia after therapy with zoledronate. In addition to severe vitamin D deficiency, achlorhydria, secondary to gastric surgery, and proton pump inhibitor use may also have limited intestinal calcium absorption, as optimal absorption of calcium requires gastric acid. He also had extensive osteoblastic metastases and may have been depositing calcium into these lesions. All of these factors may have limited his ability to mobilize skeletal calcium into the serum, a situation that would have been greatly exacerbated by the zoledronate. Zoledronate, which is being increasingly used in patients with malignancies, appears to be more potent than pamidronate in treating hypercalcemia of malignancy,2 and in reducing bony pain in metastatic prostate cancer.3 It is also long-acting. A group of osteoporotic women who received a single dose of zoledronate (4 mg) demonstrated suppression of biochemical markers of bone resorption one year later.4 Most studies using zoledronate have reported a low incidence of asymptomatic hypocalcemia.5,6 There are, however, reports in the literature of older bisphoshonates causing symptomatic hypocalcemia.7-9 This report highlights the importance of diagnosing and treating vitamin D deficiency before initiating zoledronate therapy. Vitamin D deficiency has been well documented in elderly and inpatient populations and may have an incidence as high as 60%.10,11 In addition, proton pump inhibitors, which are being increasingly prescribed, limit the absorption of dietary calcium. As more patients with osteoporosis, skeletal metastases and hypercalcemia of malignancy are treated with intravenous bisphosphonates, the incidence of symptomatic hypocalcemia will likely increase, particularly in patients with underlying disorders of calcium and bone metabolism. This is particularly true in the case of zoledronate, which appears to be more potent and longer acting than older bisphosphonates. Authors' Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest. REFERENCES 1. Saad F: Treatment of bone complications in advanced prostate cancer: Rationale for bisphosphonate use and results of a phase III trial with zoledronic acid. Semin Oncol 29:19-27, 2002 2. Wellington K, Goa KL: Zoledronic acid: A review of its use in the management of bone metastases and hypercalcaemia of malignancy. Drugs 63:417-437, 2003[CrossRef][Medline] 3. Lipton A, Small E, Saad F, et al: The new bisphosphonate, Zometa (zoledronic acid), decreases skeletal complications in both osteolytic and osteoblastic lesions: A comparison to pamidronate. Cancer Invest 20:45-54, 2002 (suppl 2)
4. Reid IR, Brown JP, Burckhardt P, et al: Intravenous zoledronic acid in postmenopausal women with low bone mineral density. N Engl J Med 346:653-661, 2002 5. Body JJ, Lortholary A, Romieu G, et al: A dose-finding study of zoledronate in hypercalcemic cancer patients. J Bone Miner Res 14:1557-1561, 1999[CrossRef][Medline] 6. Major PP, Coleman RE: Zoledronic acid in the treatment of hypercalcemia of malignancy: Results of the international clinical development program. Semin Oncol 28:17-24, 2001[CrossRef]
7. Schussheim DH, Jacobs TP, Silverberg SJ: Hypocalcemia associated with alendronate. Ann Intern Med 130:329, 1999 8. Champallou C, Basuyau JP, Veyret C, et al: Hypocalcemia following pamidronate administration for bone metastases of solid tumor: Three clinical case reports. J Pain Symptom Manage 25:185-190, 2003[CrossRef][Medline]
9. Rosen CJ, Brown S: Severe hypocalcemia after intravenous bisphosphonate therapy in occult vitamin D deficiency. N Engl J Med 348:1503-1504, 2003
10. Harris SS, Soteriades E, Coolidge JA, et al: Vitamin D insufficiency and hyperparathyroidism in a low income, multiracial, elderly population. J Clin Endocrinol Metab 85:4125-4130, 2000
11. Thomas MK, Lloyd-Jones DM, Thadhani RI, et al: Hypovitaminosis D in medical inpatients. N Engl J Med 338:777-783, 1998
This article has been cited by other articles:
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||||||
|
|||||||||||
|
|
Copyright © 2004 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|
