title: Cytotoxic effect of zoledronic acid-loaded bone cement on giant cell tumor, multiple myeloma, and renal cell carcinoma cell lines.
abstract: BACKGROUND
  Local recurrence with subsequent osteolysis is a problem after intralesional curettage of giant cell tumor of bone, myeloma, and metastatic carcinoma. The bisphosphonate zoledronic acid (zoledronate) has been shown to reduce osteoclast activity, and its local administration is a potentially attractive therapy, especially for the osteoclast-rich giant cell tumor. The aim of this study was to analyze the elution dynamics of zoledronic acid release from acrylic bone cement and its in vitro antitumor efficacy.
  
  
  METHODS
  Various concentrations of zoledronic acid were mixed with bone cement and placed in distilled water. The concentration in the water was measured daily for fourteen days. The cytotoxic effects of the dissolved zoledronic acid on cultures of multiple myeloma, giant cell tumor, and renal cell carcinoma cells were tested with use of the MTT assay (tetrazolium [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] dye) and analyzed according to the zoledronic acid concentration and the elapsed time.
  
  
  RESULTS
  The release of zoledronic acid was greatest during the first twenty-four hours for all concentrations and decreased rapidly during the next forty-eight hours to reach a plateau after four days. The proliferation assay (MTT) showed zoledronic acid to have significant cytotoxicity in cultures of stromal giant cell tumor, multiple myeloma, and renal cell carcinoma cells. In addition, zoledronic acid decreased the number of viable tumor cells in a dose-dependent manner. Renal cell carcinoma from bone (RBM1-IT4) and stromal giant cell tumor of bone were more susceptible to zoledronic acid than was multiple myeloma.
  
  
  CONCLUSIONS
  The method presented in our study is a reproducible technique for evaluating zoledronic acid elution from bone cement and determining its impact on tumor growth. Zoledronic acid is released from bone cement, remains biologically active despite the polymerization of cement, and inhibits the in vitro growth of cell lines from giant cell tumor of bone, myeloma, and renal cell carcinoma.
authors.affiliation: Department of Orthopaedic Surgery, University of Minnesota Medical School and Masonic Cancer Center, 2450 Riverside Avenue, R200, Minneapolis, MN 55454, USA.
authors.forename: Pawel
authors.initials: P
authors.lastname: Zwolak
authors.forename: J Carlos
authors.initials: JC
authors.lastname: Manivel
authors.forename: Piotr
authors.initials: P
authors.lastname: Jasinski
authors.forename: Mark N
authors.initials: MN
authors.lastname: Kirstein
authors.forename: Arkadiusz Z
authors.initials: AZ
authors.lastname: Dudek
authors.forename: James
authors.initials: J
authors.lastname: Fisher
authors.forename: Edward Y
authors.initials: EY
authors.lastname: Cheng
mesh_terms: D001843:Bone Cements / Q000009:adverse effects / Q000494:pharmacology; D050071:Bone Density Conservation Agents / Q000009:adverse effects* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004164:Diphosphonates / Q000009:adverse effects* / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects* / Q000494:pharmacology; D000077211:Zoledronic Acid
chemical_list: D001843:Bone Cements; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid