BERKELEY, CA (UroToday.com) - Many physicians are aware of well-publicized side effects of intravenous bisphosphonates such as renal dysfunction and osteonecrosis of the jaw. Hypocalcemia associated with bisphosphonate therapy is relatively rare but is severe in about 2% of cases¹. Bisphosphonates such as zoledronate lower serum calcium by inhibiting osteoclast-mediated bone resorption. Fluctuations in serum calcium, phosphate and magnesium during bisphosphonate therapy are usually mild, but may cause vague symptoms such as weakness and tingling, classic symptoms of perioral paresthesia, carpopedal spasm, and QT prolongation, or more serious symptoms such as tetany, seizure, or cardiac arrhythmia.

In healthy individuals, normal serum calcium is largely maintained by a balance of osteoblast-mediated bone formation (calcium deposition) and osteoclast-mediated bone resorption (calcium release). It is possible that in some patients with a large burden of osteoblastic metastases that relative hypocalcemia due to the osteoblast excesses can be exacerbated by bisphosphonate therapy.

This case highlights the importance of diagnosing and treating mild hypocalcemia before initiating bisphosphonate therapy. As more patients with skeletal metastases and osteoporosis are treated with intravenous bisphosphonates, incidence of severe hypocalcemia may increase, particularly in patients with underlying calcium metabolism disorders. Vitamin D and calcium supplements are strongly recommended to minimize the incidence of hypocalcemia during bisphosphonate therapy, and to decrease or prevent the incidence of bisphosphonate-associated secondary hyperparathyroidism. Serum magnesium, calcium, and phosphate should be monitored periodically. Treatment with either oral or intravenous calcium is dictated by the severity of hypocalcemia.

1. 1. Saad F, Gleason DM, Murray R, et al. A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. J Natl Cancer Inst 2002;94(19):1458-68.

Written by
James L. Gulley, M.D., Ph.D., F.A.C.P., Director, Clinical Immunotherapy Group, Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.

Persistent Hypocalcemia Induced by Zoledronic Acid in a Patient with Androgen-Independent Prostate Cancer and Extensive Bone Metastases - Abstract

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