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

Abstract

Abstract. 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 in vitro or in vivo or of ZOL-loaded bone cement in vivo 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 in vivo. 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.

Low-dose zoledronate for the treatment of bone metastasis secondary to prostate cancer

“…Indeed, the use of an intradermal catheter to deliver chemotherapeutics/antiresorptives in cancer patients is not only subject to infections [48], but could also be incapacitating to patients during the treatment period. Progress has clearly been made in vitro and in vivo of material-based systems for local release of zol and/or other drugs such as the use zol-impregnated magnetic [49] or poly lactide-glycolide acid (PLGA) [50] nanoparticles, zol-loaded hydroxyapatite [51], calcium phosphate bone cement delivering zol [51–53] and nanohydroxyapatite/zol scaffolds [54]. Establishing a novel zol-loaded carrier as a new therapy strategy is therefore of important clinical significance since it would allow for effective and sustained local delivery of zol at the site of bone metastasis tumors following resection.…”

Anti-Tumor Effects of Low Dose Zoledronate on Lung Cancer-Induced Spine Metastasis

“…Local delivery exposure could therefore present an exciting potential to sustainably release low doses of pharmaceutical compounds with anti-tumor properties directly at the tumor site. Our previous work and that of others have provided promising therapeutic approaches for local drug delivery including the use of subcutaneous catheterization [33], nanoparticles carriers [57,58], bone cement [59] and nanohydroxyapatite scaffolds [60]. Our team recently developed 3D-printed nanoporous PORO Lay scaffolds that uptake and deliver low doses of doxorubucin [61] or Zol [34], which at the same time inhibited the proliferation of prostate cancer-induced bone metastasis cells in vitro.…”

Release Characteristics of Enoxaparin Sodium Loaded Polymethylmethacrylate Bone Cement

“…PMMA bone cement has been widely used in clinical practice, such as total hip replacement, half hip replacement, total knee replacement or single patella replacement, vertebroplasty, bone tumors, pathological fractures, spacers with PMMA bead chain during infection, or placeholders for soft tissue defect in open fracture, etc. [20][21][22][23][24] . As the drug carrier, the most mature and largest scale commercial application of PMMA bone cement is antibiotic loaded PMMA bone cement [25][26][27][28] .…”