Masataka Uchino

Growth factor expression in the osteophytes of the human femoral head in osteoarthritis.

Osteoarthritis is characterized by marked osteophyte formation consisting of new cartilage and bone. Because several growth factors are known to be involved in chondrogenesis and osteogenesis, the expression of transforming growth factor-β1 and basic fibroblast growth factor in the osteophytes of the human femoral heads in osteoarthritis were examined. Transforming growth factor-β1 messenger ribonucleic acid was detected in the osteophytes by reverse transcription-polymerase chain reaction. All of the nine examined osteophytes expressed transforming growth factor-β1 messenger ribonucleic acid, whereas one of four osteoarthritic femoral heads and none of four osteonecrotic femoral heads expressed transforming growth factor-β1 messenger ribonucleic acid. The extent of transforming growth factor-β1 messenger ribonucleic acid expression varied among the osteophytes. Transforming growth factor-β1 or basic fibroblast growth factor was analyzed in osteophytes immunohistochemically. Transforming growth factor-β1 was localized in the superficial cells in the osteophyte cartilage, but it was scarcely detected in the superficial cells in the degenerative articular cartilage. Basic fibroblast growth factor was detected in the cells in the whole layer of osteophyte cartilage and in the articular cartilage. There was a difference in the localization, which suggests the different roles of transforming growth factor-β1 and basic fibroblast growth factor in bone and cartilage metabolism in osteophyte formation.

Immediate versus delayed intramedullary nailing for open fractures of the tibial shaft: A multivariate analysis of factors affecting deep infection and fracture healing

Background: The purpose of this study was to evaluate contributing factors affecting deep infection and fracture healing of open tibia fractures treated with locked intramedullary nailing (IMN) by multivariate analysis. Materials and Methods: We examined 99 open tibial fractures (98 patients) treated with immediate or delayed locked IMN in static fashion from 1991 to 2002. Multivariate analyses following univariate analyses were derived to determine predictors of deep infection, nonunion, and healing time to union. The following predictive variables of deep infection were selected for analysis: age, sex, Gustilo type, fracture grade by AO type, fracture location, timing or method of IMN, reamed or unreamed nailing, debridement time (≤6 h or >6 h), method of soft-tissue management, skin closure time (≤1 week or >1 week), existence of polytrauma (ISS< 18 or ISS≥18), existence of floating knee injury, and existence of superficial/pin site infection. The predictive variables of nonunion selected for analysis was the same as those for deep infection, with the addition of deep infection for exchange of pin site infection. The predictive variables of union time selected for analysis was the same as those for nonunion, excluding of location, debridement time, and existence of floating knee and superficial infection. Results: Six (6.1%; type II Gustilo n=1, type IIIB Gustilo n=5) of the 99 open tibial fractures developed deep infections. Multivariate analysis revealed that timing or method of IMN, debridement time, method of soft-tissue management, and existence of superficial or pin site infection significantly correlated with the occurrence of deep infection (P< 0.0001). In the immediate nailing group alone, the deep infection rate in type IIIB + IIIC was significantly higher than those in type I + II and IIIA (P = 0.016). Nonunion occurred in 17 fractures (20.3%, 17/84). Multivariate analysis revealed that Gustilo type, skin closure time, and existence of deep infection significantly correlated with occurrence of nonunion (P < 0.05). Gustilo type and existence of deep infection were significantly correlated with healing time to union on multivariate analysis (r2 = 0.263, P = 0.0001). Conclusion: Multivariate analyses for open tibial fractures treated with IMN showed that IMN after EF (especially in existence of pin site infection) was at high risk of deep infection, and that debridement within 6 h and appropriate soft-tissue managements were also important factor in preventing deep infections. These analyses postulated that both the Gustilo type and the existence of deep infection is related with fracture healing in open fractures treated with IMN. In addition, immediate IMN for type IIIB and IIIC is potentially risky, and canal reaming did not increase the risk of complication for open tibial fractures treated with IMN.

Immediate interlocking nailing versus external fixation followed by delayed interlocking nailing for Gustilo type IIIB open tibial fractures

Purpose. To compare immediate interlocking nailing with external fixation followed by delayed interlocking nailing, for Gustilo type IIIB open tibial fractures. Methods. 23 patients with Gustilo IIIB open tibial fractures were treated with either immediate unreamed interlocking nailing (n=9) or external fixation followed by delayed unreamed interlocking nailing (n=14). Patient age, sex ratio, fracture site, fracture type, and severity were similar in both groups. The time to union, deep infection rate, and nonunion rate in the 2 groups were compared. Results. In the immediate and delayed nailing groups, respective mean times to union were 21 (standard deviation [SD], 14) months and 14 (SD, 8) months; nonunion rates were 44% (4/9) and 36% (5/14), and deep infection rates were 22% (2/9) and 7% (1/14). All corresponding differences were not statistically significant. Conclusion. Prospective, randomised, multicentre studies are needed to assess whether there are significant differences between the 2 treatment methods.

The expense for one implantation of a banked bone allograft from a cadaveric donor and the issues affecting current advanced medical treatment in the Japanese orthopaedic field

Demand for banked bone allografts is increasing in Japan; however, there are too few bone banks and the bone bank network is not well-established. One reason for this was lack of funding for banks. Bone banks had to bear all material expenses of banked bone allografts themselves because this was not designated a covered expense. In December 2004, the Japanese government started a new “Advanced Medical Treatment” administration system which allowed an approved institution to charge the expense of authorized advanced medical treatments directly to patients. The treatment named “Cryopreserved allogenic bone and ligamentous tissue retrieved from cadaveric donor” was approved as an advanced medical treatment in March 2007. We present the calculation method and the expense per implantation of a banked bone allograft from a cadaveric donor under this treatment and raise issues which affect this advanced medical treatment and remain to be resolved in the Japanese orthopaedic field.

Tibial fractures associated with crush injuries to the soft tissues of the dorsal foot in children

We retrospectively studied 15 children with tibial fractures associated with crush injuries to the soft tissues of the dorsal foot. The fractures, including six open fractures, were united with no complications within an average of 11.1 weeks. Wound closure to treat crush injuries of the dorsal foot was achieved using split- or full-thickness skin grafts in most patients. The outcomes of these grafts were acceptable, and all skin coverage was successful and remained viable with no breakdown. Extensor tendon injuries of the foot sustained by eight patients could not be sutured or repaired due to the nature of the injuries. However, the functional abilities of those injured tendons that could be sutured to surrounding tissues in a neutral position were acceptable, even though two patients had contracture of the toes that was problematic when wearing shoes. To manage crush skin injuries of the dorsal foot, split- or full-thickness skin grafts appear to provide a simple and convenient treatment strategy. In cases associated with extensor tendon injuries, suturing damaged extensor tendons to surrounding tissues represents another useful strategy with acceptable outcomes.

Influence of hooks and a lag screw on internal fixation plates for lateral malleolar fracture: a biomechanical and ergonomic study

BackgroundFor internal fixation of AO classification Type B lateral malleolar fracture, insertion of lag screws into the fracture plane and fixation with a one-third tubular plate as a neutralization plate are the standard treatment procedures. The one-third tubular plate is processed to a hook shape and hung on the distal end of the fibula. In this study, to compare the function of the hook and lag screws of a one-third tubular plate and LCP for osteosynthesis of lateral malleolar fracture, mechanical indices of internal fixation were compared among the one-third tubular plates with lag screws with and without the hook and a locking compression plate.MethodsAs mechanical tests, a compression test was performed in which compression in the bone axis direction produced by supporting the body weight was simulated, and a torsion test was performed in which external rotation of the bone axis caused by plantar flexion of the ankle joint was simulated. Muscle strength during walking and the force and torque acting on the ankle and knee joints were determined using inverse dynamic analysis. Finite element analysis was performed to analyze the function of hooks and lag screws. The joint reaction force determined by inverse dynamic analysis was adopted as the loading condition of finite element analysis.ResultsA stiffness equivalent to that of healthy bone could be achieved by all three internal fixations. It was clarified that the presence of the hook does not make a difference in stiffness. Displacement of the one-third tubular plate was small regardless of the presence or absence of the hook compared with those of locking compression plates.ConclusionsThe presence of the hook did not make any difference in stiffness, suggesting that active preparation of the hook is unnecessary. We also clarified that lag screws inhibit displacement.

4. The Low-Intensity Pulsed Ultrasound (LIPUS) Mechanism and the Effect of Teriparatide on Fracture Healing.

Low-Intensity Pulsed Ultrasound (LIPUS) provided a mechanical stimulus, and was thought to promote fracture healing by signal transduction through integrin, a cytoskeletal protein. Meanwhile, teriparatide, a drug for osteoporosis treatment, showed efficacy in promoting bone metabolism. This drug also appeared to prevent fractures in patients with serious osteoporosis by improving bone mineral density and bone quality, which in turn resulted from promoting action for bone metabolism. Further, clinical trials and fundamental research reported that teriparatide demonstrated the effect of promoting fracture healing. Mechanical stimulus by LIPUS had a topical effect on fractures; on the other hand, teriparatide (peptide hormone) had both topical and systemic effects. Both LIPUS and teriparatide had the effect of fracture healing, but it was supposed that the characteristics of each effect were different because of the different mechanism of action. Moreover, the combination therapy of LIPUS and teriparatide was expected to produce synergies. We used elderly rats as models for the femoral fracture to examine the effects of LIPUS and teriparatide on promoting fracture healing for treatment delay by aging. We observed the fracture healing process in 40-week-old rats as an elderly model using simple radiographs, and recognized a delay in fracture healing compared with that of 8-week-old rats. As discussed in histomorphology, it was demonstrated that the period of endochondral ossification, from chondrogenesis to teleost cross-linked callus, was prolonged and the fracture healing process was delayed by aging. Next, we treated the elderly fracture models with LIPUS for 20 minutes a day from the first day after the fracture, and compared them with non-treated models. The bone unions of the treated models were observed earlier than those of non-treated models in the simple radiographs. LIPUS shortened the period of endochondral ossification. Further, we gave the elderly fracture models teriparatide subcutaneously 5 &mgr;g/kg three times a week from the first day after the fracture. Bone unions of the treated models were observed earlier than those of non-treated models in simple radiographs as well. In micro CT analysis, it was demonstrated that lamellar bone transforming and bone remodeling of the trabecular structure of external callus were especially accelerated. The results of these trials showed that both LIPUS and teriparatide demonstrated the effect of promoting fracture healing, and each had unique characteristics.

Elution Characteristics of Vancomycin, Gentamicin, and Vancomycin/Gentamicin Combination from Calcium Phosphate Cement

The antibiotic elution profiles from calcium phosphate cement (CPC) used for treating infection sites after total joint arthroplasty vary depending on the type and number of impregnated antibiotics. The purpose of this study was to develop a method for efficiently eluting vancomycin hydrochloride (VCM) and gentamicin sulfate (GM) from CPC. Examination of the antibiotic elution profiles of CPC impregnated with either VCM (CPC/V) or GM (CPC/G) or both (CPC/VG) revealed that the early elution of VCM from CPC/VG was impaired compared to CPC/V. However, the elution of GM from CPC/VG was similar or higher compared to CPC/G. Scanning electron microscopy showed that the pore structure of CPC markedly differed depending on the type and number of antibiotics present. The pore size of CPC/VG was smaller compared to CPC/V but was larger compared to CPC/G. Thus, the inhibition of the early elution of VCM, which is a larger molecule than GM, was attributed to the decreased pore size of CPC/VG. These findings suggest that when dual treatment with VCM and GM is required for infection following total joint arthroplasty, each antibiotic should be individually impregnated into CPC to maximize the elution efficiency of VCM.

Study on the Angiogenic Effect of Low-Intensity Pulsed Ultrasound

Objectives: We examined the angiogenic effects of low-intensity pulsed ultrasound (LIPUS) on immunohistological outcomes in a rat femoral fracture model, vascular endothelial cell migration, and allogeneic bone tissue transplant in a rat model. Subjects and Methods: Experiment 1: We exposed the fracture site in the femur of the Wister rat model to LIPUS every day. We collected the femur on the 14th day after bone fracture and prepared decalcified tissue sections. We performed immunostaining with anti-VEGF antibody in serial sections for comparison with the non-treated group. Experiment 2: We performed a scratch test 12 hours after plating 1 × 106 human vascular endothelial cells in a 6-well culture plate. To examine the effect of LIPUS on cell migration, we exposed cells to LIPUS via the bottom face of the culture plate for comparison with the non-treated group. Experiment 3: We transplanted a delipidized frozen dry bone to the anterior surface of a Wister rat femur, and exposed the site to LIPUS every day. We collected the femur 3 weeks after transplantation for histological examination. Results: Experiment 1: The LIPUS radiation group exhibited an anti-VEGF positive region surrounding the callus, and robust new vascularization was confirmed in the region. Experiment 2: Vascular endothelial cell migration was promoted in the LIPUS treated group. Experiment 3: The LIPUS treatment group exhibited significant formation of new vascularization around the grafted bone, compared with the non-treated group, in addition to significant formation of TRAP-positive cells. Discussions: It was suggested that LIPUS would promote the formation of new vascularization and accelerate cell migration.

12. Influence of Wound Dressing on the Fracture Healing Effect of Low-Intensity Pulsed Ultrasound (LIPUS).

Objective: We have conducted a basic study on the influences on ultrasonic properties when LIPUS is applied through wound dressing. According to the results of ex vivo experiments conducted to date, LIPUS showed ultrasonic properties such as transmittance, coefficient of transmission, and a non-uniformity ratio through film wound dressing better than other wound dressing, and it was considered that LIPUSs effect for fracture healing was not influenced by film wound dressing. Then, we discussed the influence on the effect of LIPUS through film wound dressing. Methods: Thirty male 8-week-old Sprague-Dawley rats were used for the trial. After creating close transverse femoral fractures on the right legs of these 30 rats, they were divided into 3 groups of 10; LIPUS through wound dressing (Group A), LIPUS without wound dressing (Group B), and No LIPUS treatment (Group C). OPSITE Wound, which was thought to have the least influence on ultrasound properties, was used for this trial. Group A and B received LIPUS for 20 minutes a day from the first day after the fractures. LIPUS was generated from Teijin Pharmas device for a basic experiment. When treating Group A, the wound dressing was pasted on the ultrasound terminal in order to apply LIPUS through the dressing. We assessed the time-oriented morphological change of each group in anesthetized condition using simple radiographs on the 8th, 16th, and 24th day after the fractures. Results: Six rats in Group A, 2 in Group B, and 1 in Group C died in anesthesia, and we discussed the remaining 4 rats in Group A, 8 in Group B, and 9 in Group C. We defined more than one teleost callus bridging as bone-union. We also counted a bone remodeling when we recognized the absorption of existing cortical bone and the transformation of new bone to cortical bone in simple radiographs. As a result, compared with Group C, we recognized that both bone union and remodeling accelerated remarkably in Group B, but not in Group A. Discussion: It suggested that LIPUS through wound dressing had negative influences on both period shorting of fracture healing and bone remodeling. When LIPUS was conducted through film wound dressing, transmittance and coefficient of transmission were unchanged; however, the non-uniformity ratio changed slightly. The non-uniformity ratio of the ultrasound transducer had a significant influence on the effect of LIPUS on fracture healing.