Locally enhanced early bone formation of zoledronic acid incorporated into a bone cement plug in vivo.

OBJECTIVES: The aim of the study was to gain experience about the short-term effects of zoledronic acid (ZOL) on bone-implant contact (BIC), bone regeneration and bone area (BA). METHODS: In this in-vivo study, ZOL was released locally from a drug-loaded pre-shaped calcium phosphate bone cement plug which was implanted into a bone defect in the proximal tibia of rats. At 1 and 3 weeks post implantation, tissue reactions as well as bone regeneration capabilities at the implant site were investigated. Furthermore, tissue samples, harvested at placebo and verum plug sites were used to analyse the gene expression of selected bone-specific markers by using quantitative polymerase chain reaction. Data were normalized against ribosomal RNA (Rn18s) subunits. KEY FINDINGS: In the placebo interface a higher amount of cells could be detected as indicated by higher expression of small subunit Rn18s. Nevertheless, comparing the normalized data of the selected gene expression levels, no significant differences were detected. The histomorphometric results showed a significant higher BIC and BA for ZOL-loaded plugs at 3 weeks after implantation. CONCLUSIONS: In this model, ZOL was demonstrated to be effective in impacting the bone regeneration process towards reduction of early bone resorption and enhanced bone formation.

Bone substitute materials delivering zoledronic acid: physicochemical characterization, drug load, and release properties.

Calcium phosphate-like bone substitute materials have a long history of successful orthopedic applications such as bone void filling and augmentation. Based on the clinical indications, these materials may be loaded with active agents by adsorption offering a perspective for providing innovative drug-delivery systems. The highly effective bisphosphonate zoledronic acid (ZOL) demonstrated a strong affinity to biominerals and is known to significantly reduce osteoclastic activity. Support of early bone formation and reduction of bone resorption can be promoted after implantation of bioceramics releasing ZOL. The aim of this study was to develop an easy to handle approach to combine ZOL with bone substitutes by use of a dipping technique. The properties of three different materials were investigated by using a number of physicochemical methods such as light microscopy, scanning electron microscopy (SEM), dynamic vapor sorption (DVS), true density, and surface area measurement to evaluate the feasibility of being potential drug carriers. Besides physicochemical characterization, the bone substitutes were evaluated by their ZOL-loading capacity in a time- and concentration-dependent manner. Additionally, the materials were assessed as release systems in an in vitro study. A controlled ZOL load in a range of 0.04-1.86 µg/mg material and a release of 0.02-0.18 µg/mg within 30 min is demonstrated. The findings support using the investigated bioceramics as carrier systems to release ZOL. Overall, the results create the base for further development of drug-delivery systems with controlled drug loading and prolonged release and need to be further analyzed in an in vivo study.

In vivo tissue response to ultrasound assisted application of biodegradable pins into cortical and cancellous bone structures: a histological and densitometric analysis in rabbits.

In orthopaedic traumatology biodegradable pins are increasingly used for fixation of small bone fragments. In the present study, the ultrasound-assisted anchoring technique (SonicFusion technique), a osteosynthesis method being recently introduced in cranial applications, in which ultrasonic energy is used to insert and anchor polymer pins in bone, was compared with the conventional pin application procedure. The aim of the present study was to assess the short and long term thermal impact of two different ultrasonic energy levels on different bone structures in the distal medial femur of rabbits. The treatment groups consisted of customized polylactide pins applied at a low and a high energy level, the Reference Control and a Negative Control. The thermal effect on bone tissues was evaluated by means of qualitative and semi-quantitative histology and micro-computerized tomography. Five days following surgery, all implant sites showed no tissue damage but normal signs of early ongoing tissue repair. Enhancing the energy level by about 30% had no significant impact on the tissue response. At 4 weeks after surgery test sites covered by ultrasound-aided implantation showed a significantly enhanced bone/implant contact as compared to pins applied by conventional application. In conclusion, the ultrasound assisted anchoring technique not only did not impair bone regeneration, but even improved implant integration.

Antimicrobial efficacy of surface-coated external fixation pins.

In clinical applications, colonization of metal implants by adhesive and biofilm-forming bacteria not only prolong healing but create additional healthcare costs for implant revision and antimicrobial treatment. An in vitro assay was established investigating the antimicrobial surface activity of external fixation pins intended for use in bone fractures and deformities. Test articles made out of stainless steel and coated with a polymer-containing nanoparticulate silver were compared to non-coated reference controls out of stainless steel, copper and titanium. Staphylococcus epidermidis, known as a predominant cause for implant-related infections was used as test organism. Test pins and bacteria were incubated for a period of 20 h found to be sufficient for initiating biofilm formation. After removing non- and low-adherent bacteria by rinsing, two methods were used to isolate high-adherent (sessile) bacteria from the implant surfaces. Besides shaking the implants in a solution containing small glass beads, a cytobrush technique was used to mechanically harvest viable bacteria. Finally, the amount of detached bacteria was determined by plate counts. Several parameters identified to be critical within the different removal procedures such as the inoculum concentration and the shaking time in the presence of glass beads as well as time of the cytobrush treatment were analysed. The final test scheme resulted in the use of an inoculum of 10(5) colony forming units (CFU) per millilitre, ten rinsing steps for the removal of low adherent bacteria and 5 min of shaking in the presence of glass beads, detaching the high-adherent bacteria. Due to subjective variations impacting the outcome of the procedure, the cytobrush technique was not favoured and finally rejected. Using the in vitro assay developed, it could be demonstrated that fixation pins coated with silver show a 3 log step reduction in the number of biofilm-forming bacteria compared to a non-coated stainless steel or titanium implant. Pins made out of copper showed the highest antimicrobial efficacy, as the number of detached bacteria was found to be below the detection limit, they served as a positive control within this test.

User's guide to the orthopaedic literature: how to use an article about a randomized trial?

Randomized trials, when well conducted, sit atop the hierachy of evidence. By limiting bias through randomization, concealment and blinding, surgeons can conduct high quality trials in orthopaedic surgery. The current article provides an easy, practical approach to critical appraisal of a randomized trial in orthopaedic surgery.