A clinical investigation into a new bone void filler is giving
first data on systemic and local exposure to the anti-infective
substance after implantation. A total of 20 patients with post-traumatic/post-operative bone
infections were enrolled in this open-label, prospective study.
After radical surgical debridement, the bone cavity was filled with
this material. The 21-day hospitalisation phase included determination
of gentamicin concentrations in plasma, urine and wound exudate, assessment
of wound healing, infection parameters, implant resorption, laboratory
parameters, and adverse event monitoring. The follow-up period was
six months. Objective
Method
Shock wave treatment has been shown to induce new bone formation both under physiologic conditions and during fracture repair. Whereas various underlying molecular working mechanisms have been shown in recent studies, no study has assessed the influence of varying energy flux densities (EFD) on the amount of new bone formation in vivo. Therefore, the aim of this study was to investigate whether the effect of shock waves on bone is dependent on the applied EFD and if so, to identify the minimal dose necessary to induce new bone formation in vivo to avoid unwanted side effects of high-energy shock waves. To this end, 30 New Zealand white rabbits were randomly divided in 5 groups and treated with extracorporeal shock waves at the distal femoral region (1,500 pulses at 1 Hz frequency each):
(a) control (sham treatment), (b) EFD 0.35 mJ/mm2, (c) EFD 0.5 mJ/mm2, (d) EFD 0.9 mJ/mm2 and (e) EFD 1.2 mJ/mm2. To investigate new bone formation, animals were injected with oxytetracycline at the days 5 to 9 after shock wave application and sacrificed on day 10. Histological sections of treated and untreated femora of all animals were examined using broad-band epifluorescent illumination and contact microradiography. The amount of new periosteal and endosteal bone was measured and signs of periosteal detachment, cortical fractures, and fragmented trabecular bone with callus were recorded. Application of shock waves showed new bone formation beginning with 0.5 mJ/mm2 EFD and increasing with 0.9 mJ/mm2 and 1.2 mJ/mm2. The latter EFD resulted in new bone formation also on the opposite cortical bone and cortical fractures and periosteal detachment occurred. EFD of 0.35 mJ/mm2 did not lead to any new bone formation. Here for the first time a threshold level is presented for new bone formation after applying shock waves to intact bone in vivo. We conclude that the results presented here have significant impact on further clinical applications of shock waves on bone tissue. In the present study, it is clearly demonstrated that the amount of new bone formation is directly dependent on the applied EFD. If the applied EFD is to low, no significant new bone formation will occur. If it is too high, unwanted side effects, like the formation of bone spurs in the shoulder or nerve entrapment syndromes in the elbow or feet by bony overgrowth may result.
The fluorescent microsphere (FM) method is considered the best technique to determine regional bone blood flow (RBBF) in acute experiments. In this study we verified the accuracy and validitiy of this technique for measurement of RBBF in a long-term experiment and examined RBBF after meniscectomy. 24 anesthetized female New Zealand rabbits (3 groups, each n=8) received consecutive left ventricular injections of FM in defined time intervals after meniscectomy. Group 1 from preoperatively to 3 wks postoperatively, group 2 from 3 wks to 7 wks, and group 3 from 7 wks to 11 wks postoperatively. To test the precision of the FM-method in long-term experiments two FM-species were injected simultaneously at the first and last measurement. After the experiment both humeri, femora, and tibiae and reference organs (kidney, lung, brain) were removed and dissected according to standardized protocol. Fluorescence was determined in each reference blood and tissue sample and blood flow values were calculated. Blood flow in kidney, lung, and brain revealed no significant difference between right and left side and remained unchanged during the observation period excluding errors due to shunting and dislodging of spheres in our experiments. Comparison of relative bone blood flow values obtained by simultaneously injected FM showed an excellent correlation at the first and last injection indicating valid RBBF measurements in long-term experiment. We found a significant increase of RBBF 3 wks after meniscectomy in the right tibial condyles compared to the non-operated left side. Similar changes were found in the femoral condyles. RBBF in other regions of tibia, femur, and humerus revealed no significant difference between right and left bone samples of the same region. Our results demonstrate that the FM method is also valid for measuring regional bone blood flow in long-term experiments. In addition we could demonstrate that meniscectomy leads to an increase of RBBF in the tibial condyles very early. This increase might be caused by stress-induced alterations of the subchondral bone.
