Cytotoxic effects of zoledronic acid-loaded hydroxyapatite and bone cement in malignant tumors

Metastatic and primary bone tumors are malignant tumors affecting the skeleton. Although the prognosis of patients with these tumors has improved with the development of effective chemotherapy, the challenges of local recurrence, subsequent osteolysis, degradation of bone strength and unresectable t...

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Bibliographic Details
Published in:Oncology letters 2017-08, Vol.14 (2), p.1648-1656
Main Authors: Koto, Kazutaka, Murata, Hiroaki, Sawai, Yasushi, Ashihara, Eishi, Horii, Motoyuki, Kubo, Toshikazu
Format: Article
Language:English
Subjects:
Antibiotics
Apoptosis
Bone cancer
Bone surgery
Bone tumors
Cancer metastasis
Cancer therapies
Care and treatment
Cement
Complications and side effects
Drug delivery systems
Drug dosages
Health aspects
Heat
Hydroxyapatite
Hydroxyapatites
Joint surgery
Kidney cancer
Metastasis
Oncology
Orthopedics
Polymerization
Polymethyl methacrylate
Product development
Prostate
Prostate cancer
Sarcoma
Solvents
Studies
Transplants & implants
Tumors
Zoledronic acid
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Summary:Metastatic and primary bone tumors are malignant tumors affecting the skeleton. Although the prognosis of patients with these tumors has improved with the development of effective chemotherapy, the challenges of local recurrence, subsequent osteolysis, degradation of bone strength and unresectable tumors persist. Local control of these tumors is therefore a key strategy to address these limitations. The third-generation bisphosphonate (BP), zoledronic acid (ZOL), has been demonstrated to reduce osteoclasts and exhibited potent antitumor effects in a number of malignancies. Hydroxyapatite (HA) and polymethyl methacrylate (PMMA) bone cement are used in orthopedic surgery as bone graft substitutes, for implant arthroplasty and bone strengthening, and as a sustained-release system for drugs such as antibiotics. At present, the antitumor effects of ZOL-loaded HA or or of ZOL-loaded bone cement have not been described. Therefore, the present study assessed the effects of ZOL-loaded HA and bone cement in malignant tumor cells. The two materials exerted strong antitumor effects against osteosarcoma, fibrosarcoma, synovial sarcoma, renal cancer, prostate cancer and lung cancer cells upon releasing ZOL. The antitumor effects of ZOL-loaded HA were less potent compared with those of ZOL-loaded bone cement, possibly as BPs exhibit higher affinity to HA. ZOL-loaded bone cement also exerted antitumor effects against pulmonary metastases and primary lesions, without exhibiting systemic toxicity . These results demonstrate that these materials may be beneficial for the treatment of malignant bone tumors, including metastatic bone tumors. In addition, as these materials are already in clinical use, such applications may be easily implemented.
ISSN:1792-1074
1792-1082
DOI:10.3892/ol.2017.6355