Polyethylene glycol improves elution properties of polymethyl methacrylate bone cements.

BACKGROUND: Bone cements are used as adjuncts to fracture fixation methods and can also function as a local drug delivery system. The ability to elute drugs makes bone cement a promising and powerful chemotherapy treatment modality for osseous tumors. However, because of poor elution rates, the clinical application of this drug delivery mode remains challenging. Soluble fillers, such as sugars, salts, or biocompatible polymers, offer a solution to improve elution rates. This study quantified the effect of polyethylene glycol (PEG) on the elution properties of three commercially available bone cements. METHODS: Two grams of Vertebroplastic, Palacos, and Confidence bone cement powder containing three concentrations (0%, 20%, or 50%) of PEG filler were hand mixed with 10 mg of methotrexate. This powder mixture was then polymerized with 1.0 mL of the cement specific liquid monomer. The cylindrical elution samples were placed in saline solution and methotrexate elution was recorded for 720 h. RESULTS: The cumulative and daily elution rate increased as the concentration of PEG increased for each bone cement. However, the percent of increase depended on the bone cement used. Cumulative methotrexate elution increased by 40%-54% in case of the highest PEG filler concentration when compared with controls. CONCLUSIONS: PEG soluble filler offers a promising method for improving methotrexate drug elution in bone cement. Future studies need to optimize the PEG and bone cement ratio that produces the greatest drug elution profile without sacrificing the biomechanical properties of bone cement.

Creation of rabbit bone and soft tissue tumor using cultured VX2 cells.

BACKGROUND: To create rabbit VX2 bone tumors, it is surgically less demanding to implant VX2 cell suspensions than minced tumor fragments. A VX2 cell line that can be expanded using standard cell culture techniques might provide an unlimited supply of cells needed to create these bone tumors. Therefore, the aim of the present study was to establish a VX2 cell line and verify its tumorigenicity in an athymic mouse and rabbit animal model. MATERIALS AND METHODS: Minced VX2 tumor fragments were allowed to grow as a monolayer in 10 mL Dulbecco's modified Eagle medium/nutrient mixture F-12 (1:1) supplemented with 10% fetal calf serum and passaged multiple times. The tumorigenecity of the cultured VX2 cells were tested in athymic mice (intradermal tumor development) and in New Zealand white rabbits (bone and soft tissue tumor model). RESULTS: The VX2 cells proliferated rapidly in tissue culture flasks containing Dulbecco's modified Eagle medium/nutrient mixture F-12 medium supplemented with 10% fetal bovine serum. After reaching confluence, the VX2 cells can only be subcultured when plated at a greater density (e.g., at a dilution of 1:1). All 6 athymic mice developed tumors within 15 d of VX2 cell suspension implantation. In the rabbits, the VX2 cells were able to produce tumors in muscle tissue and in the distal femurs but not in the proximal tibia. CONCLUSIONS: VX2 cell lines can be successfully created from VX2 tumor fragments and passaged multiple times. In contrast to previous reports, the VX2 cells grown in vitro are capable of maintaining their tumorigenecity. However, successful tumor growth might depend on the initial number of cells implanted and the use of extracellular matrices for tumor proliferation.

Evaluation of elution and mechanical properties of two injectable chemotherapeutic bone cements.

Chemotherapeutic bone cements can both stabilize the bone fractures as well as deliver chemotherapy agents directly to the bone metastatic site and adjacent soft tissue tumors. This study evaluated the in vitro elution and flexural properties of Vertebroplastic™ and Confidence Ultra™ bone cements (Depuy Spine Inc., Raynham, Mass., USA) containing methotrexate. In vitro elution was measured by placing bone cement specimens containing 4 different methotrexate amounts in 20 ml saline, and the methotrexate elution was measured at regular intervals for 672 h. The flexural properties of bone cement containing 2 different initial methotrexate amounts after storage in physiological saline were measured using a 3-point bending test. The drug elution rate depended on the initial methotrexate amount added and the type of bone cement used. The relationship between the initial drug amount added and the drug elution rate was not linear. Methotrexate elution decreased the flexural modulus and strength of specimens; this decrease was not proportional to the initial amount of methotrexate added. The results show that bone cements are well suited for use with chemotherapy agents. However, the elution and mechanical properties of each bone cement-drug amount combination should be thoroughly quantified in vitro before using such a combination in a clinical setting.

Effect of atorvastatin on the cortical bones of corticosteroid treated rabbits.

Osteoporosis ("secondary" osteoporosis) and avascular necrosis (AVN) of the femoral head are well-known adverse effects of corticosteroid therapy. Statins have been reputed to increase bone strength and bone density. In this study, we evaluated the effect of atorvastatin calcium on the flexural properties (3-point bending strength and modulus) of corticosteroid (methylprednisolone acetate) treated rabbit femurs and tibias. Our study hypothesis was that the use of statins would counteract the loss of bone strength caused by corticosteroid treatment. The 40 rabbits were divided into 5 groups: control, corticosteroid alone and corticosteroid combined with oral doses of atorvastatin calcium (2, 10, or 20 mg/day). A daily oral dose of atorvastatin calcium treatment for 70 days weakened the long bones of methylprednisolone acetate treated rabbits irrespective of the dosage (2, 10, or 20 mg). Cortical bone strength was assessed using the 3-point bending test at the end of the study period. A daily oral dose of atorvastatin calcium did not attenuate the loss of cortical bone strength caused by corticosteroid treatment in rabbits. It appeared to decrease that bone strength. If these results hold true in humans, they would have wide applicability given the frequent combined use of corticosteroids and statins in many patients.

Method for the physical analysis of drug-bone cement composite.

Skeletal metastases are often complicated by progression to impending or pathologic fracture and fixation with polymethylmethacrylate (PMMA) bone cement is used for stabilization and pain relief. Adjuvant therapy involving the delivery of PMMA composites mixed with antibiotic or chemotherapeutic agents requires an understanding of the rate of drug diffusion from the cement in addition to measurement of its mechanical properties pre- and postelution of drug. We have developed a method for the analysis of drug diffusion rate and mechanical properties of drug-cement composites using PMMA/methotrexate as a model system. The analysis method revealed the addition of methotrexate to PMMA in concentrations of 1.8 g methotrexate per 40 g PMMA did not change the compression modulus of the cement pre- or postelution of drug. The PMMA/methotrexate composites displayed an average diffusion rate of 50 ng/(mm2)(hour) during the first 6 hours, which decreased to 10 ng/(mm2)(hour) by 36 hours. Diffusion modeling predicts the 20 x 13-mm cylindrical PMMA/methotrexate samples used by the method deliver 10% of the total methotrexate content within 80 hours and 25% of the total within 133 days.