This Article Full Text (PDF) All Versions of this Article: theoncologist.2008-0227v1 14/5/548    most recent eLetters: Submit a response to this article Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services E-mail this article link to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Zuradelli, M. Articles by Santoro, A. Search for Related Content PubMed PubMed Citation Articles by Zuradelli, M. Articles by Santoro, A.

High Incidence of Hypocalcemia and Serum Creatinine Increase in Patients with Bone Metastases Treated with Zoledronic Acid

^aDepartment of Medical Oncology and Hematology, ^bRadiotherapy Unit, ^cNeurosurgery Unit, ^dTrauma Unit, and ^eStatistics Unit, Istituto Clinico Humanitas, Rozzano, Milan, Italy

Key Words. Bisphosphonates • Laboratory abnormalities • Bone metastasis • Zoledronic acid

Correspondence: Correspondence: Monica Zuradelli, M.D., Dipartimento di Oncologia Medica ed Ematologia, Istituto Clinico Humanitas, Via Manzoni 56, 20089 Rozzano (Milano), Italy. Telephone: 39-02-8224-3518; Fax: 39-02-8224-6297; e-mail: monica.zuradelli{at}humanitas.it

Received October 15, 2008; accepted for publication April 8, 2009.

Disclosure: Monica Zuradelli: None; Giovanna Masci: None; Giuseppe Biancofiore: None; Giuseppe Gullo: None; Marta Scorsetti: None; Pierina Navarria: None; Flavio Tancioni: None; Marco Berlusconi: None; Laura Giordano: None; Armando Santoro: None. The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the authors or independent peer reviewers.

Background. Zoledronic acid belongs to the new generation of bisphosphonates with demonstrated clinical benefit for the treatment of bone metastases from different kinds of neoplasms. Hypocalcemia and serum creatinine elevation are expected adverse events during this therapy. The monitoring of serum calcium and creatinine is therefore recommended. The primary aim of this study was to establish the actual incidence of hypocalcemia and serum creatinine elevation during treatment with zoledronic acid. Skeletal-related events and side effects were also assessed.

Methods. Serum creatinine and calcium levels were evaluated in 240 consecutive patients (83 males, 157 females; mean age, 62 years) with metastatic bone lesions from different solid tumors treated with zoledronic acid.

Results. Overall, 93 of 240 patients (38.8%) developed hypocalcemia, which was grade (G)1 in 45 patients (48.4%), G2 in 37 patients (39.8%), G3 in 10 patients (10.8%), and G4 in one patient (1.1%). The median time to occurrence of hypocalcemia (any grade) was 2.3 months after the beginning of the treatment (range, 0–34.9 months).

Increased serum creatinine was observed in 33 of 240 patients (13.7%), of whom 19 had G1 (57.6%), 11 had G2 (33.3%), and three had G3 (9.1%). The median time to serum creatinine increase (for any grade) was 4.7 months (range, 0–29.2 months).

Conclusions. Our analysis shows a high incidence of hypocalcemia and increased serum creatinine level during treatment with zoledronic acid. These results strongly support the need for accurate monitoring of plasma calcium and creatinine levels.