Alendronate does not prevent long bone fragility in an inactive rat model.

The lack of estrogen and inactivity are both important in the pathogenesis of osteoporosis in elderly women, and there have been no appropriate rodent studies to examine the effects of common bisphosphonates on these two components separately. We compared the efficacy of alendronate (ALN) on the long bones of aged female rats, which were sedentary, estrogen deficient, or both. The rats were either forced to remain in a sitting position or allowed to walk in standard cages with or without ALN administration. The 8-week experimental period began 5 weeks after ovariectomy or sham surgery. Parameters of the hindlimb bones were determined by a three-point bending test, peripheral quantitative computed tomography, microfocus computed tomography, confocal laser Raman microspectroscopy, and dynamic histomorphometry. Regardless of ovariectomy, ALN was ineffective against the deterioration of breaking stress caused by sitting even though the trabecular bone mineral density was significantly higher in the sitting-ALN groups. Toughness was significantly deficient in the ovariectomy sitting-ALN group. This was in agreement with the bone geometry with a greater marrow space. Sitting also increased the mineral-to-matrix ratio and the carbonate-to-phosphate ratio, both indicative of aged bone. A greater loss of proteinaceous amide intensity compared with mineral intensity resulted in an increased mineral-to-matrix ratio in the presence of ALN. Sitting resulted in deficits in the quality and the geometry of cortical bone, resulting in fragility. The use of bisphosphonates, such as ALN, may provide a therapy best suited for osteoporotic individuals whose daily activity is not limited.

Morphologic differences of the distal femur between Caucasian and Japanese women.

PURPOSE: To compare the morphology of the distal femur between Caucasian and Japanese women. METHODS: 30 Caucasian women aged 41 to 84 (mean, 67) years and 70 Japanese women aged 54 to 86 (mean, 70) years who underwent total knee arthroplasty for osteoarthritis were randomly selected. Morphologic measurements of the distal femur were compared using lateral radiographs. Both race and height influenced the morphology. To adjust for the influence of height on morphology, each measurement was divided by the patient's height and the ratios were compared. RESULTS: Caucasian women were generally taller and heavier (p<0.001) and had higher body mass index (p=0.03) than the Japanese women. Each morphologic measurement of the distal femur was significantly longer in the Caucasian women. In both groups, anteroposterior width of the condyle correlated more with height than weight. In women of equal height, the anteroposterior and metaphyseal widths of the femur and the anterior and resected condyles were longer in Caucasian women, but the posterior condyle was longer in Japanese women. CONCLUSION: Both the size of the femur and the anterior and posterior condyles are significantly larger in Caucasian than Japanese women.

Anatomic study for pubic medullary screw insertion.

PURPOSE: To study the anatomy of the pubic ramus and adjacent structures in 160 Japanese to establish a safer pubic screw fixation technique. METHODS: 80 male and 80 female Japanese aged 16 to 89 (mean, 50) years (10 persons in each decade of age) underwent 3-dimensional computed tomographic scanning of their pelvises. The angle at which the screw should be targeted, the appropriate length of the screw, the size of the canal for screw insertion, and the proximity to the bladder, iliac artery, and iliac vein were determined. Correlations between the canal diameters (of the acetabular, base, and parasymphyseal areas) and body features (age, height, and weight) were analysed. RESULTS: In men and women respectively, the appropriate mean screw length was 124.6 and 123.8 mm; the guide wire should be targeted at a mean of 66 degrees and 67 degrees cephalad and 54.1 degrees and 55.9 degrees laterally for insertion of a retrograde pubic screw; the minimum distances from the pubis to the bladder/iliac artery/ iliac vein were 0 and 0 mm/4.9 and 4.6 mm/0.8 and 0.2 mm. In both men and women, the canal diameters at the base were positively correlated to weight. In women, the canal diameters at the parasymphyseal area were correlated to height and weight. Canal diameters at the acetabulum were not correlated to height and weight. CONCLUSION: Pubic screw fixation may be potentially disastrous (owing to joint penetration and iliac vein injury) and should be performed with caution. When the canal diameter at the acetabulum is extremely narrow, plate fixation, computer-assisted surgery, or changing to a smaller-diameter screw is recommended.

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.

Attenuation of monosodium urate crystal-induced arthritis in rabbits by a neutralizing antibody against interleukin-8.

Accumulating evidence implicates interleukin-8 (IL-8) as an essential mediator in neutrophil-mediated acute inflammation. Neutrophils have also been shown to have a crucial role in the pathogenesis of acute gouty arthritis. Thus, we investigate the pathophysiological role of IL-8 in an experimental model of acute gout, monosodium urate (MSU) crystal-induced arthritis in rabbits. The injection of MSU crystals into knee joints caused a marked swelling of joints. Concomitantly, the infiltration ofleukocytes, mostly neutrophils, was observed in synovial membrane and synovial fluids. The injection of MSU crystals also induced an elevation in synovial fluid IL-8 levels preceding neutrophil infiltration into synovial fluids, without an accompanying increase in plasma IL-8 levels. Immunoreactive IL-8 protein was detected in synovial lining cells at 12-24 h after the injection. IL-8 protein was also observed in infiltrated leukocytes in synovium as early as 3-24 h after the injection. Finally, the intraarticular injection of a neutralizing anti-IL-8 antibody significantly attenuated the crystal-induced joint swelling that occurred at 12 h, and neutrophil infiltration into arthritic joints at 12 and 24 h after the induction. These results provide evidence on the pathogenic roles of locally produced IL-8 in MSU crystal-induced gouty arthritis.

Rat whole-limb viability after cold immersion using University of Wisconsin and Euro-Collins solutions.

The purpose of this study was to compare University of Wisconsin (UW) solution with Euro-Collins (EC) solution in their cold preservation effects on rat limbs. Thirty-six Lewis rat limbs were preserved in EC solution (n=18) or UW solution (n=18) at 4 degrees C for 72 hr, and grafted orthotopically to a syngeneic rat using microsurgical techniques. The surgeon was blinded to the solution used. We evaluated the vascular patency rate and death rate of both groups at day 7 after surgery and performed histological evaluations of bone, muscle, growth plate, and articular cartilage for each specimen of successful grafts in both groups. The vascular patency rates of the EC and UW groups were 27.7% (5/18) and 11% (2/18), respectively, and showed no significant difference. The death rates of the EC and UW groups were 50% (9/18) and 60% (10/18), which were not significantly different. There were no clear differences in histological viability between both groups, in all tissues exclusive of bone marrow and muscle tissue. Our results showed that in comparing EC and UW solutions, one was not significantly superior to the other as a cold immersion storage medium after a 72 hr ischemia-induced reperfusion injury.

Isolated paralysis of the infraspinatus muscle.

We report six patients with isolated paralysis of the infraspinatus and discuss the diagnosis, pathology, treatment, and outcome over a mean follow-up period of 33 months. Four patients were shown to have space-occupying lesions at the spinoglenoid notch by MRI or ultrasonography or both, and ganglia were confirmed and removed surgically in three, with good results. Ganglia at this site are not uncommon and should be included in the differential diagnosis of patients presenting with shoulder pain and weakness.

Protective effects of coenzyme Q10 on ischemia-induced reperfusion injury in ischemic limb models.

We examined simple cold preservation of rat limbs in Euro-Collins' solution to elucidate the protective effect of coenzyme Q10 (CoQ10) on the ischemia-induced reperfusion injury in an ischemic extremity replant model. A total of 126 Lewis rat limb replants were performed. Limbs were amputated from donor rats and preserved at 4 degrees C in Euro-Collins' solution and were orthotopically grafted to isogeneic rats by microsurgical technique. In the experimental groups (n = 42), coenzyme Q10 (10 mg/kg) was injected intraperitoneally into the recipients about 1 hour before reperfusion. In the control groups (n = 84), the same dose of solvent was given by the same route. We evaluated vascular patency of anastomoses by direct observation or microangiogram and performed histologic examinations 7 days after replantation. In the control groups, the ischemic limit was 96 hours. Ischemic limbs treated with coenzyme Q10 showed a statistically significant (p < 0.05) improvement in vascular patency after 72 and 96 hours of ischemia. Histologically, bone viability with osteoblastic activity was maintained in coenzyme Q10-treated animals of the 72-hour ischemic group. We conclude that the protective effect of coenzyme Q10 on reperfusion injury is suggested in this replant model.

Technique for removing a bent intramedullary femoral nail: a case report.

The authors present a case in which an interlocked intramedullary nail placed to secure a left femoral shaft fracture was deformed twelve months after surgery because of secondary trauma. The nail was straightened by sectioning through half of its diameter with a drill for metal under minimal soft tissue dissection, then removed and replaced with another nail. The femur subsequently healed without complications.

Functional outcomes of "floating elbow" injuries in adult patients.

OBJECTIVES: To assess elbow function, complications, and problems of floating elbow fractures in adults receiving surgical treatment. DESIGN: Retrospective clinical review. SETTING: Level I trauma center in Kanagawa, Japan. PATIENTS: Fourteen patients with fifteen floating elbow injuries, excluding one immediate amputation, seen at the Kitasato University Hospital from January 1, 1984, to April 30, 1995. INTERVENTION: All fractures were managed surgically by various methods. In ten cases, the humeral and forearm fractures were treated simultaneously with immediate fixation. In three cases, both the humeral and forearm fractures were treated with delayed fixation on Day 1, 4, or 7. In the remaining two cases, the open forearm fracture was managed with immediate fixation and the humerus fracture with delayed fixation on Day 10 or 25. MAIN OUTCOME MEASUREMENTS: All subjects underwent standardized elbow evaluations, and results were compared with an elbow score based on a 100-point scale. The parameters evaluated were pain, motion, elbow and grip strength, and function during daily activities. Complications such as infections, nonunions, malunions, and refractures were investigated. RESULTS: Mean follow-up was forty-three months (range 13 to 112 months). At final follow-up, the mean elbow function score was 79 points, with 67 percent (ten of fifteen) of the subjects having good or excellent results. The functional outcome did not correlate with the Injury Severity Score of the individual patients, the existence of open injuries or neurovascular injuries, or the timing of surgery. There were one deep infection, two nonunions of the humerus, two nonunions of the forearm, one varus deformity of the humerus, and one forearm refracture. CONCLUSION: Based on the present data, we could not clarify the factors influencing the final functional outcome after floating elbow injury. These injuries, however, potentially have many complications, such as infection or nonunion, especially when there is associated brachial plexus injury. We consider that floating elbow injuries are severe injuries and that surgical stabilization is needed; beyond that, there are no specific forms of surgical treatment to reliably guarantee excellent results.

Chondrocyte transplantation for osteochondral defects with the use of suspension culture.

Cartilage graft is considered to be useful in repairing chondral or osteochondral defects. One method of the cartilage graft is achieved by autologous chondrocyte transplantation following cell culture. However, chondrocytes change their phenotype during culture. We used costal chondrocytes cultured over agarose (suspension culture) as a source of graft materials. The suspension-cultured chondrocytes formed aggregate in culture. We first examined the expressions of cartilage-specific matrices of cultured chondrocytes after two weeks in culture. The chondrocytes cultured over agarose expressed more type II collagen mRNA than those cultured on plastic dishes did after two weeks in culture. Safranin O staining showed the presence of glycosaminoglycans in the chondrocyte culture over agarose, while glycosaminoglycans were not observed in the culture on plastic dishes. We then examined the changes of rat articular osteochondral defects after transplantation of suspension-cultured chondrocytes. The aggregate of suspension-cultured chondrocytes was easily picked up with forceps and transplanted in the osteochondral defects. The defects were filled with safranin O-stained hyaline cartilage tissue two weeks after chondrocyte transplantation. On the contrary, the fibrous materials, which were not stained with safranin O, were observed in the control defects. These results suggest that the suspension-cultured chondrocytes are useful for autologous cartilage grafts by preserving chondrocyte phenotype.

Problems of various fixation methods for open tibia fractures: experience in a Japanese level I trauma center.

Two hundred thirty-seven patients with open tibial fractures (245 fractures) were treated as follows: nonoperative stabilization alone (Nonop group, n = 54); immediate open reduction and internal fixation (ORIF group, n = 47); delayed ORIF (D-ORIF group, n = 109); or external fixation (EF group, n = 35). The D-ORIF group was further divided into ORIF after nonoperative treatment (Nonop/ORIF, n = 86), and ORIF after external fixation (EF/ORIF, n = 23). The open tibial fractures were classified as follows: 42 type I (no infections), 107 type II (4 infections), 43 type IIIA (3 infections), 42 type IIIB (12 infections), and 11 type IIIC (2 infections), with significant differences in infection rate between type IIIB and type I, type II, or type IIIA. The deep infection rates in Nonop, ORIF, Nonop/ORIF, EF/ORIF, and EF groups were 3.7%, 12.8%, 5.8%, 30.4%, and 2.9%, respectively. There were significant differences in deep infection rates between the EF/ORIF and Nonop/ORIF, and the EF group. The mean period of fracture healing for type IIIB fractures was delayed. The mean time to union of the EF/ORIF was significantly longer than that of the ORIF, Nonop/ORIF, and EF groups, respectively. Complete and consecutive debridement procedures and early soft-tissue coverage should be done to avoid wound infection, especially in type IIIB fractures. Delayed internal fixation after external fixation had the highest risk of infection, mandating meticulous wound management in such patients.

Contributing factors influencing the functional outcome of floating knee injuries.

The purpose of the present study was to retrospectively review the floating knee injuries treated at our institute and to determine various factors, such as severity of soft-tissue or skeletal injuries, site of fractures, and treatment methods that may significantly influence the final functional result in these injuries. Between 1986 and 1996, 65 patients with 66 floating knee injuries were treated in our institution. Among 66 fractures of the femur, 19 (29%) were open. There were 43 open tibial fractures. Fifty cases were Fraser type I floating knee fractures, 7 were type IIa, 2 were type IIb, and 7 were type IIc. In 63 cases (95%), both bones had been surgically stabilized with interlocked nails, Ender pins, plates, screws with/without pinning, or external fixations. Final functional results were evaluated according to Karlström and Olerud's criteria. Satisfactory results were rated as cases with excellent or good results. The mean follow-up time was 16.6 months range, (12-50 months). We assessed various factors influencing functional results, including Fraser type, severity of open injury grade (Gustilo) in both fractures, combination of open/closed injuries, fracture types (AO/ASIF type), existence of multiple trauma, neurovascular injuries, polyskeletal trauma, and stabilizing method or operation timing of both fractures. Satisfactory rates in Fraser type I and type II were 64% and 25%, respectively (P= .02). The satisfactory rate in closed, grade I+II, and grade III injuries of the femoral fractures was 53.2%, 81.8%, and 25%, respectively (grade I+II vs. grade III: P < .03). There were no significant correlations between the functional result and the following factors: soft-tissue injuries of the tibia; the fracture pattern of both fractures; the combination of open/closed injuries in each fracture; injury severity score; the existence of neurovascular injuries and double femoral fractures; treatment methods; and operation timing. Severity of damage to the knee joint and open injuries in the thigh were found to be significant factors contributing to the functional outcome in floating knee injuries.

Deep infection and fracture healing in immediate and delayed locked intramedullary nailing for open femoral fractures.

Fifty-nine patients with 61 open femoral fractures were treated with immediate locked intramedullary (IM) nailing (group 1; n=15), delayed IM nailing following nonoperative treatment (group 2; n=42), and delayed IM nailing following external fixation (group 3; n=7). Sixteen fractures were Gustilo type I, 28 were type II, 7 were type IIIA, 6 were type IIIB, and 4 were type IIIC open fractures. Four (6.6%) deep infections occurred. Significant differences existed in the deep infection rate (DIR) between types I and II and all type III fractures (2.3% for types I and II versus 17.6% for type III). The deep infection rate did not differ significantly among the nailing groups (13.3%, 2.6%, and 15.3% for groups 1, 2, and 3, respectively), nor did the deep infection rate correlate with the degree of fracture comminution, the existence of polytrauma or polyskeletal trauma, or preexistence of superficial or pin-site infections. Seven (11.7%) of these fractures resulted in nonunion, excluding one secondary amputation; the nonunion rate correlated with fracture location. There were no significant differences in the mean fracture healing times between any of the nailing groups. These results suggest that IM nailing for the treatment of type III open femoral fractures should be considered carefully, regardless of whether it is performed immediately or delayed.

Changes in nitric oxide, superoxide, and blood circulation in muscles over time after warm ischaemic reperfusion in rabbit rectus femoris muscle.

We present the sequence of changes in nitric oxide (NO) and superoxide (O2-) over time in reperfusion injuries. We examined both the changes in NO and O2- over time and the blood flow in an isolated ischaemia-reperfusion muscle model in rabbits. The ischaemic group comprised 8 animals which had had vascular pedicles clamped on the their rectus femoris muscles for 4 hours. The control group (n = 6) had a sham operation. Blood samples from the femoral vein proximal to the clamping point were collected before the operation, before clamping, before reperfusion, immediately after reperfusion, and 5, 15, 30, 60, and 120 minutes after reperfusion. NO was measured by Griess' method, and O2- by chemiluminescence. Blood flow was measured with a laser Doppler flowmeter. The amount of NO increased significantly immediately after reperfusion, and 15 and 30 minutes after reperfusion in the ischaemic group, compared with the control group (p < 0.05). O2- increased significantly at 5, 15, 60, 90 and 120 minutes after reperfusion, compared with the control group (p < 0.05). The blood flow volume curve increased by 1.4 times about four minutes after reperfusion compared with previously. After this it gradually decreased. The adverse effects of O2- became apparent when NO was extinguished by O2-.

Effect of coenzyme Q10 on superoxide production in rats with reperfusion injuries.

We examined the effect of coenzyme Q10 (Co Q10) on superoxide radical (O2-) production in a model of rat reperfusion injury. The chemiluminescence method using a derivative of luciferin was used to quantify O2- production by erythrocytes in the reperfused limb after a period of ischaemia. A total of 20 limbs from Lewis rats were preserved at 4 degrees C in Euro-Collins solution for 72 hours, and were grafted orthotopically to syngeneic rats by a microsurgical technique. In the treated group (n = 10), Co Q10 (10 mg/kg) was injected intraperitoneally into the recipients one hour before reperfusion. In the control group (n = 10), the same dose of solvent was given. To measure the extent of oxidative stress, heparinised blood from the treated and control recipients was collected before, and at 15, 30, and 60 minutes after reperfusion for the measurement of chemiluminescence. O2- production in the Co Q10-treated group was significantly lower than in the control group (p < 0.05). Although these findings suggest that Co Q10 scavenged O2- that was produced in the replanted limbs as a result of ischaemia-reperfusion injury, we should consider other possible mechanisms by which this agent may protect against ischaemia-induced reperfusion injury.

Discrepancy between anatomical axis and stem position of various femoral components in Japanese.

PURPOSE: To evaluate the discrepancy between the anatomical axis of the distal femur of Japanese patients and the stem position of 5 types of femoral components. METHODS: Lateral radiographs of 12 men and 88 women aged 31 to 83 (mean, 59) years with rheumatoid arthritis were evaluated. The discrepancy between the anatomical axis of the distal femur and the stem position of 5 types of femoral components (Nexgen LCCK, Press-Fit Condylar, Scorpio, Total Stabilizer, and Rotating Hinge) was determined by superimposing the template of each model over each lateral radiograph. RESULTS: The anatomical axis varied widely among our patients, as did the stem position of the 5 femoral components. Stems of all 5 femoral components tended to be more posterior than the anatomical axis. The discrepancy was smallest in the Nexgen LCCK, followed by the Press-Fit Condylar components. It was >3 mm in the other 3 models. In 35% of the patients, none of the prosthesis could be placed in an appropriate position. Smaller-size prostheses appear necessary for the Japanese. CONCLUSION: The stem position should be an important factor guiding selection of the appropriate model. The currently available femoral components may not be appropriate for the Japanese. Prostheses with appropriately positioned stems for Japanese patients with rheumatoid arthritis should be developed.

Comparison of the cytokine-induced migratory response between primary and subcultured populations of rat mesenchymal bone marrow cells.

BACKGROUND: The aim of this study was to investigate the phenotypic differences of primary rat mesenchymal bone marrow cells (MBMCs) and subcultured cells, the influence of subculture and cell density on the cellular phenotypes, and the difference in the migratory responses of these cells to cytokines. METHODS: MBMCs were isolated from 8-week-old Wistar rats, and the cells were cultured for 1 week (passage 0, P0) or 3 weeks (P0-3W). P0 cells were subcultured for 1 week (P1). P1 cells were subcultured at several cell densities for 1 week (P2). Cell size and granularity were analyzed by flow cytometry. The gene expression characteristics of these cells were analyzed by reverse transcription polymerase chain reaction. Cell migration to bone morphogenetic protein-2 (BMP-2), fibroblast growth factor-2 (FGF-2), and platelet-derived growth factor-bb (PDGF-bb) was evaluated using a Boyden chamber. RESULTS: Three morphologically distinct populations in P0 and two in P2 were detected. The levels of human rapidly self-renewing cell-related marker genes in P0 were more highly expressed than in P2. Mesenchymal stem cell-associated markers were expressed at the same level in P0 and P2. The gene expression levels of immature oligodendrocyte precursor cell markers in P0 were higher than those in P2, whereas those of smooth muscle cell markers and osteoblastic cell markers in P0 were lower than those in P2. Subculture decreased the gene expression levels of human rapidly self-renewing cell-associated markers. Cell migration of P0 cells was stimulated by PDGF-bb but not by BMP-2 or FGF-2. In contrast, PDGF-bb, BMP-2, and FGF-2 all stimulated cell migration of P2. CONCLUSION: The types of cells in populations of primary and subcultured rat MBMCs were different, and the distribution of each cell population appeared to be changed by the culture conditions. The cell migration effect by PDGF-bb, BMP-2, and FGF-2 differed between the primary and subcultured MBMCs.

Experimental study on allogenic bone grafts.

The effects of various processing techniques on the biomechanical properties and the histological incorporation of bone grafts were investigated in a rat model over a 6 month period. The stiffness of bone increased after freezing to -80 degrees C and freeze-drying. Decalcified bone was very soft. Visco-elasticity was pronounced at 4 to 12 weeks and the stiffness of the graft increased at 16 weeks. This progressive rise in stiffness was in line with the progressive incorporation of the graft. The bone incorporation ratio is proposed as a histological indicator of osteo-inductive properties. It was found to be best in fresh autografts, followed by processed allografts (frozen, freeze-dried and decalcified) and fresh allografts. The values of these 3 groups showed a statistically significant difference.

Aseptic necrosis of the femoral head supervening on systemic lupus erythematosus in identical twins--case report.

Identical twins who grew up in different environments from 100 days after birth developed systemic lupus erythematosus (SLE), followed later by aseptic necrosis of the femoral head (ANFH). Diagnosis of SLE was made in the younger sister (case 1) at age 14 and the elder (case 2) at 21 years of age. ANFH developed in these cases 5.9 and 1.2 years after the onset of SLE respectively. From some ovular identifications, they were diagnosed as being completely identical. These cases are of particular interest, since they suggest that hereditary factors are concerned with the development of ANFH to some degree.