Preoperative abaloparatide plus zoledronate treatment accelerates femoral bone healing in rats following osteotomy.

Purpose: We investigated the potential efficacy of abaloparatide (Abalo) and zoledronate (ZA) combination therapy for accelerating femoral union in a rat osteotomy model. Methods: Nine-week-old male Sprague-Dawley rats were randomly divided into four groups (n = 14 per group): control, abaloparatide (Abalo, 30 µg/kg via subcutaneous injection [s.c.] 5 times per week for 6 weeks), zoledronate (ZA; 0.1 mg/kg via s.c., single dose), and Abalo + ZA. Rats were then subjected to unilateral osteotomy of the femoral shaft, followed by osteosynthesis with intramedullary nailing to establish bone healing models. At 2 and 4 weeks after osteotomy, both femurs were removed from seven rats per group for soft X-ray imaging to evaluate bone union and microcomputed tomography (micro-CT) for bone morphometric evaluation. Blood samples were collected from all rats every 2 week starting 6 weeks pre- to 4 weeks postosteotomy. Toluidine blue staining was used for histopathological evaluation of the undecalcified specimens. Results: Soft X-ray imaging revealed accelerated callus formation, callus maturation, and fracture line closure in Abalo and Abalo + ZA groups compared to ZA and control groups. Micro-CT demonstrated greater cortical bone and trabecular bone to total volume ratios in contralateral (left) femurs of the Abalo + ZA group compared to the Abalo group. Both trabecular and cortical bone mineral densities were also greater in contralateral femurs of the Abalo + ZA group compared to Abalo and ZA groups. Conclusion: These findings suggest substantial additive or synergistic efficacy of abaloparatide plus zoledronate combination therapy for accelerating bone healing following osteotomy and for maintaining normal bone health.

Gait analysis of a patient after femoral nerve and malignant soft tissue tumor resections: a case report.

BACKGROUND: Malignant femoral soft tissue tumors are occasionally resected together with the femoral nerves, but this can cause loss of knee extensor muscle activity. To the best of our knowledge, no previous reports have detailed the gait analysis of such cases in combination with electromyography. Herein, we report the gait analysis of a patient who underwent left groin synovial sarcoma and left femoral nerve resection 12 years ago. CASE PRESENTATION: We analyzed the gait of a 38-year-old man who was able to walk unaided after the resection of a synovial sarcoma in the left groin together with the ipsilateral femoral nerve. The muscle activities of the affected medial (MH) and lateral hamstrings (LH), and lateral heads of the gastrocnemius (GL) were increased during 50-75% of the stance phase. The hip flexion angle of the affected limb was smaller, and the ankle plantar flexion angle of the affected limb was larger than that of the non-affected limb. This means that in the affected limb, the hip and ankle angles were adjusted to prevent knee collapse, and the MH, LH, and GL muscles contributed in the mid- and late-stance phases. Moreover, we found that the hamstring and gastrocnemius of the affected limb worked together to keep the ipsilateral knee extended in the mid-stance phase and slightly flexed in the late-stance phase. CONCLUSIONS: Patients capable of walking after femoral nerve resection may control their hamstrings and gastrocnemius muscles collaboratively to prevent ipsilateral knee collapse in the mid- and late-stance phases.

The effects of romosozumab combined with active vitamin D3 on fracture healing in ovariectomized rats.

BACKGROUND: In this study, we investigated the potential acceleration of fracture healing and bone mineral density-increasing effects of romosozumab and active vitamin D3 combination therapy for fractures in ovariectomized rats. METHODS: Ovariectomy was performed on 40 24-week-old female Sprague-Dawley rats. After 8 weeks, the rats were subjected to periosteum removal and osteotomy of the femoral shaft followed by osteosynthesis with intramedullary nailing to create fracture models. The rats were then divided into four groups: C group (control), R group (receiving romosozumab at 25 mg/kg once a month via subcutaneous injection), VD group (receiving active vitamin D3 at 0.2 µg/kg twice a week via subcutaneous injection), and R + VD group. Further, 10 rats were included in a sham group. At 10 weeks after the intervention, both femurs were removed and blood samples were collected from all rats. Soft X-ray imaging was used to evaluate bone union, and microcomputed tomography (micro-CT) was used for bone morphometric evaluation. Toluidine blue staining was used for the histopathological evaluation of the undecalcified specimens, and bone turnover marker levels were measured using enzyme-linked immunosorbent assay. RESULTS: Bone morphometry analysis via micro-CT revealed increased mineral density of the trabecular bone in the R + VD group femurs, demonstrating the effectiveness of romosozumab plus active vitamin D3 combination therapy. However, there were no differences in bone union evaluated using soft X-ray imaging, indicating no acceleration of fracture healing. CONCLUSIONS: Although romosozumab and active vitamin D3 combination therapy increased trabecular bone volume, there was no evidence on its ability to accelerate fracture healing.

Analysis of the risk factors for increasing cervical sagittal vertical axis after cervical laminoplasty for cervical spondylotic myelopathy.

INTRODUCTION: The cervical sagittal vertical axis (cSVA) as another aspect of cervical alignment been recognized as one of the important factors affecting the pain and disability outcomes of cervical spine surgery. The purpose of the present study was to analyze the risk factors for increasing cSVA after cervical laminoplasty for cervical spondylotic myelopathy (CSM). MATERIALS AND METHODS: This retrospective study included 110 consecutive patients (68 males and 42 females, average age 72.6 years) who underwent laminoplasty for CSM between January 2007 and June 2018. We recorded the operative time, blood loss, Japanese Orthopaedic Association (JOA) score and the recovery rate. Radiological measurements were performed to analyze the following parameters: pre- and 1-year postoperative McGregor's slope (McGS), occiput to C2 Cobb angle (O-C2 angle), C2-C7 Cobb angle (C2-7 angle), T1-slope (T1S), C2-7 SVA (cSVA) and calculated the change (Δ). Patients were divided into two groups according to whether ΔcSVA was positive or negative. We also used Spearman's correlation coefficient and multiple regression analysis. RESULTS: ΔC2-7 angle, ΔT1S-preoperative C2-7 angle, ΔO-C2 angle were different between the two groups significantly. Correlation analysis between the ΔcSVA and the various sagittal parameters showed some independent explanatory factors including the ΔC2-7 angle (r = - 0.25, p = 0.010), T1S-preoperative C2-7 angle (r = - 0.28, p = 0.004), postoperative O-C2 angle (r = 0.26, p = 0.007), ΔO-C2 angle (r = 0.37, p = 0.001). Multiple regression analysis revealed that ΔcSVA was associated with the T1S-preoperative C2-7 angle (ß = - 0.25, p = 0.034) and ΔO-C2 angle (ß = 0.32, p = 0.001). CONCLUSIONS: The imbalance between T1S and preoperative C2-7 angle influences the change of cSVA after cervical laminoplasty. If cSVA increases postoperatively, the O-C2 angle increases to compensate and maintain the horizontal gaze.

Gait analysis of a patient who underwent complete resection of the patella and quadriceps femoris for soft tissue sarcoma.

The knee extension mechanism including the quadriceps femoris muscles and patella plays a crucial role in the stance phase of a normal gait cycle. We performed gait analysis of a patient who had undergone complete resection of the knee extension mechanism. An 8-month-old boy developed infantile fibrosarcoma of the right knee and underwent resection of the quadriceps femoris muscles, patella, and patellar tendon. The gait analysis performed at 8 years of age demonstrated that he could maintain the knee joint extension position during the stance phase. Increased muscle activities in the hamstring and gastrocnemius were observed. The results suggest that the hamstring and gastrocnemius muscles might play a role in maintaining the knee extension position during the stance phase. We suggest the importance of reinforcing these muscles in rehabilitation for patients who lost the knee extension mechanism.

Analysis of reciprocal changes in upper cervical profiles after posterior spinal fusion with the simultaneous double rod rotation technique for adolescent idiopathic scoliosis.

BACKGROUND: The relationship between postoperative change of cervical lordotic alignment and restoration of thoracic kyphosis with adolescent idiopathic scoliosis (AIS) is still controversial. We investigated reciprocal changes in the sagittal profiles of the upper and middle-lower cervical spinal segments after posterior spinal fusion with the simultaneous double rod rotation technique (SDRRT) for AIS. HYPOTHESIS: Occiput-C2 and C2-C7 sagittal profiles of patients with AIS could change significantly after surgical adequate increase of thoracic kyphosis with SDRRT. PATIENTS AND METHODS: Twenty-seven consecutive patients with AIS treated with the SDRRT were retrospectively reviewed. We investigated the following parameters preoperatively, postoperatively, and at the 2-year follow-up: the Cobb angles of main thoracic curves; C7 sagittal vertical axis; thoracic kyphosis (TK) from T5 to T12; lumbar lordosis from L1 to S1; chin-brow vertical angle; McGregor's slope; occiput to C2 Cobb angle (O-C2angle); C2-C7 Cobb angle (C2-C7angle); T1-slope; and C2-C7 sagittal vertical axis. Additionally, the Scoliosis Research Society questionnaire was completed preoperatively and at the 2-year follow-up. Patients were categorized according to preoperative TK (T5-T12) into hypokyphotic (TK<20°) and normo-hyperkyphotic (TK≧20°) groups. To assess the effect of corrective surgery on sagittal profiles, we investigated correlations among the changes in sagittal parameters. RESULTS: The mean preoperative TK was 6.1±3.7° in the Hypokyphotic group and 23.5±4.7° in the Normo-hyperkyphotic group (p<0.001), which was significantly improved postoperatively (22.3±4.4° and 26.1±2.6°, respectively; p=0.02) and at the 2-year follow-up (23.0±6.3° and 26.8±5.0°, respectively; p=0.04). The mean preoperative C2-C7angle reflected kyphosis (7.4±9.8°) in the Hypokyphotic group, and, in contrast, lordosis (-8.8±6.8°) in the Normo-hyperkyphotic group (p<0.001), which improved toward greater lordosis postoperatively (-3.7±5.8° and -14.8±5.1°, respectively; p<0.001) and at the 2-year follow-up (-5.1±4.4° and -15.3±6.4°, respectively; p<0.001). On the other hand, the mean preoperative O-C2angle was -20.5±6.5° in the Hypokyphotic group and -13.1±2.8° in the Normo-hyperkyphotic group (p=0.002), which was significantly changed postoperatively (-12.6±6.4° and -7.7±4.3°, respectively; p=0.04) and at the 2-year follow-up (-13.1±6.3° and -7.9±4.3°, respectively; p=0.04). ΔC2-C7 was negatively correlated with ΔT5-T12 (r=-0.298) and ΔO-C2angle (r=-0.332). DISCUSSION: Lordotic reciprocal alignment changes in the C2-C7angle can occur after adequate restoration of TK. The O-C2angle compensates the C2-C7angle for a maintained horizontal gaze. O-C2 and C2-C7 sagittal profiles of patients with AIS changed significantly after corrective surgery with SDRRT. LEVEL OF EVIDENCE: IV, Case-series.

Cervical alignment after single-level anterior cervical corpectomy and fusion using autologous bone graft without spinal instrumentation for cervical pyogenic spondylitis.

BACKGROUND: Subsidence in anterior cervical corpectomy and fusion (ACCF) for cervical degenerative disease (CDD) are constantly observed during the postoperative course. Although kyphotic change of cervical alignment occurred frequently in cervical pyogenic spondylitis (CPS) postoperatively, studies on the postoperative change in segmental angle for CPS are limited. This study aimed to analyze cervical alignment after single-level ACCF using autologous bone graft without spinal instrumentation for CPS compared with that for CDD. METHODS: Six patients underwent single-level ACCF using autologous bone graft without spinal instrumentation for CPS. The control group included 18 age-matched patients who underwent single-level ACCF using autologous bone graft for CDD without spinal instrumentation for the same duration. Cervical and lateral plain radiographs and computed tomography scans were taken. The Frankel classification was used to assess the neurological status preoperatively, postoperatively, and at 2-year follow-up for CPS. RESULTS: At 2-year follow-up, the average segmental angle at the fusion level was - 12.2° ± 6.9° for CPS and - 5.2° ± 7.6° for CDD (p = 0.04). Changes in segmental angle at the fusion level were - 7.2 ± 9.0° for CPS and - 1.1° ± 7.1° for CDD (p = 0.02). At 2-year follow-up, the average anterior segmental fusion height was 23.4 ± 1.7 mm for CPS and 29.1 ± 5.1 mm for CDD (p < 0.001). At 2-year follow-up, bone fusion in the CPS group was classified as grade 5 (complete fusion) in 4 patients (66.7%) and grade 4 (probable fusion) in 2 (33.3%). In the CDD group, it was grade 5 in 13 patients (72.2%) and grade 4 in 5 patients (27.8%). Overall, both groups achieved 100% bone fusion rate. The Frankel classification in all CPS cases improved or leveled off. CONCLUSION: Progression of segmental kyphosis angle and subsidence of graft bone were observed postoperatively on all CPS cases. However, the neurological recovery and bone union were satisfactory.

Analysis of computed tomography-based infra-acetabular morphometry to assess the feasibility of infra-acetabular screws.

INTRODUCTION: The number of pelvic fractures based on osteoporosis has been increasing. The infra-acetabular screw (IAS), which connected both osseous columns, is a safe method of screw placement going through the infra-acetabular corridor (IAC). However, the specifics of the anatomy of IAC have been far from completely understood, especially in the Asian population. The purpose of our study was to reveal the details of the IAC using computed tomography (CT) data. MATERIALS AND METHODS: Traumatized in-patients having pelvic CT scans from 2014 to 2016 were enrolled. Pediatric and adult patients with pelvic fractures and hip prostheses were excluded. The male/female ratio and distribution of patients' age were equalized manually; 40 male and 40 female patients were included. The IAC was measured on the plane of the inlet view (25° caudal) in multi-planar reconstructed CT images. MEASUREMENTS: infra-acetabular diameter (IAD), anterior-posterior length of the IAC (APL), length from the starting point of the IAC to the medial edge of the pelvis (LME), length from the starting point of the IAC to the top of the pubic symphysis (LPS), and tilting on inlet plate (TIP). RESULTS: Age was 59 ± 22 (mean ± SD). Height was 159 ± 11 cm, and body mass index (BMI) was 22.9 ± 4.1. IAD, APL, LME, LPS, and TIP was 4.0 ± 1.3 mm, 89.5 ± 7.1 mm, 8.7 ± 3.6 mm, 57.8 ± 4.8 mm, and 4.7 ± 5.2°, respectively. Over 20% of corridors (35 of 160) were not feasible for IAS placement, because of inadequate width (less than 3.0 mm). Nine corridors (5.6%) had curvature in IAC, which meant technically demanding to insert IAS. There was no difference in IAD between male and female patients, while APL, LME, LPS, and TIP had sex-related differences. CONCLUSIONS: Surgeons should pay attention to the fact that over 20% of IACs are not feasible for infra-acetabular screw placement even with the perfect reduction of fragments when treating acetabular fractures.

Enhancement of the effects of intermittent parathyroid hormone (1-34) by bone morphogenetic protein in a rat femoral open fracture model.

BACKGROUND: Nonunion in cases of open fracture is common. Both bone morphogenetic protein 2 (BMP-2) and parathyroid hormone (PTH) have been used to enhance bone healing. We investigated the combination of BMP-2 and PTH and examined the effects on a rat model of open femoral fractures. METHODS: Group I (n = 11) was implanted with control carrier. Group II (n = 12) was implanted with carrier containing 1 µg of recombinant human BMP-2 (rhBMP-2). Group III (n = 12) was implanted with carrier alone, followed by injections of PTH 1-34. Group IV (n = 11) was implanted with carrier containing 1 µg of rhBMP-2, followed by injections of PTH 1-34. Group V (n = 11) was implanted with carrier containing 10 µg of rhBMP-2. Group VI (n = 11) was implanted with carrier containing 10 µg of rhBMP-2, followed by injections of PTH 1-34. Rats were euthanized after 8 weeks, and their fractured femurs were explanted and assessed by manual palpation, radiographs, micro-computerized tomography, and histological analysis. RESULTS: Manual palpation tests showed that the fusion rates of groups III (66.7%), IV (63.6%), V (81.8%), and VI (81.8%) were considerably higher than those of group I. Groups V and VI had higher radiographic scores compared to group I. Micro-CT analysis revealed enhanced bone marrow density expressed as bone volume/tissue volume in groups V (61.88 ± 3.16%) and VI (71.14 ± 3.89%) versus group I (58.26 ± 1.86%). A histological analysis indicated that group VI had enhanced remodeling. CONCLUSION: The combination of abundant rhBMP-2 and PTH enhanced bone healing and remodeling of newly formed bone in a rat femoral open fracture model.

Effect of intraoperative position in single-level transforaminal lumbar interbody fusion at the L4/5 level on segmental and overall lumbar lordosis in patients with lumbar degenerative disease.

The purpose of this study was to investigate the effect of intraoperative positions in single-level (L4-5) transforaminal lumbar interbody fusion (TLIF) on segmental and overall lumbar lordosis (LL) in patients with lumbar degenerative disease. Thirty-eight consecutive patients who had undergone single-segment (L4-5) TLIF with 0° polyetheretherketone (PEEK) cage and pedicle screw fixation were evaluated. Twenty patients underwent surgery on the four-poster type frame with hip flexion at 30° (Group I) and 18 patients were operated on a Jackson spinal table to adjust their hip flexion to 0° (Group II). Preoperative standing, intraoperative prone, and postoperative standing lateral radiographs were obtained in each patient. The overall and segmental LL were analyzed according to the position in which the patients were placed for their operation and results compared between Groups I and II. Intraoperative intervertebral segmental LL at L4-5 and L5-S1 was increased in Group II than in Group I, whereas postoperative intervertebral segmental LL at L4-5 (fused level) was increased LL. In Group I intraoperative intervertebral segmental LL at L4-5 did not achieve sufficient lordosis, whereas postoperative intervertebral segmental LL at L3-4 was increased. The overall spinal alignment was unaffected by the decreased segmental LL in the fused level owing to the compensation of the upper adjacent segments. The more the hip was extended intraoperatively, the more the segmental lordosis increased in the lower lumbar spine. Thus, selecting the appropriate surgical table and hip position are very important. Underachievement of segmental lordosis leads to the acceleration of upper adjacent segment load.

Isolated acetabular revision with femoral stem retention using computed tomography-based navigation.

BACKGROUND: In isolated acetabular revision surgery, surgeons must place the cup at an appropriate angle with various retained stem anteversion angles to prevent postoperative dislocation. For accurate acetabular cup position, various navigation systems have been used. Nevertheless, no publications have reported combined cup and stem anteversion and dislocation rates after isolated acetabular revision, especially comparing the use of navigation with manual implantation. Therefore we performed a retrospective comparative study to answer the following questions: (1) What is the combined anteversion after isolated acetabular revision with computed tomography-based navigation? (2) Does navigation improve the accuracy of cup angle and combined anteversion, (3) reduce dislocation rate, and (4) reduce operative time? HYPOTHESIS: A navigation system makes combined anteversion near the target angle in isolated acetabular revision. PATIENTS AND METHODS: We conducted a retrospective study of 32 hips in 24 patients who underwent isolated acetabular revision total hip arthroplasty using computed tomography-based navigation system. The control group comprised 8 hips in 8 patients who underwent the same procedure without navigation. RESULTS: In the navigation group, average Widmer's combined anteversion was 39.0°±8.7° (range, 25.3°-56.6°). Cup positions were 40.3°±2.9° (range, 29.0°-49.0°) for radiographic abduction angle, 24.3°±8.0° (range, 4.6°-42.6°) for radiographic anteversion. In the control group, Widmer's combined anteversion was 47.2°±15.1° (range, 27.0°-74.3°, p=0.048). The average cup positions for radiographic abduction angle and anteversion were 36.7°±8.9° (range, 24.5°-54.9°) and 29.1°±7.3° (range, 17.2°-38.8°), respectively (p>0.05). Widmer's combined anteversion deviated from the target angle by a smaller amount in the navigation group than in the control group: errors in measurement of Widmer's combined anteversion were 7.2°±5.1° (range, 0.74°-19.6°) in the navigation group and 13.9°±11.1° (range, 3.6°-37.3°) in the control group (p=0.135). Postoperative dislocation occurred in none of the 32 hips (0%) in the navigation group and in one of the 8 hips (12.5%) in the control group (p=0.2). DISCUSSION: Using the navigation system, combined anteversion is made near the target angle in isolated acetabular revision surgery and more accurately than manual implantation. These results should be considered as preliminary since this is a limited cohort, but it brings new knowledge in navigation considering the very limited number of series using of navigation in isolated cup revision of total hip arthroplasty. In addition this is the first study to investigate combined cup and stem anteversion in isolated acetabular revision. The use of CT-scan is helpful to diagnose error in stem anteversion and to adapt the orientation of the new cup. LEVEL OF EVIDENCE: III, Retrospective case control study.

Spinal epidural lipomatosis is associated with liver fat deposition and dysfunction.

OBJECTIVE: This study examined the association of spinal epidural lipomatosis (SEL) with liver fat deposition and any other liver dysfunction, except steroid involvement. PATIENTS AND METHODS: We analyzed 102 patients (62 men and 40 women; mean age 73.3 years) who underwent spinal magnetic resonance imaging (MRI), computed tomography (CT), and myelography for the diagnosis of lumbar spinal canal stenosis between January 2014 and June 2018. Additional data collected included height, weight, body mass index, blood test results (C-reactive protein, albumin, total bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase [γ-GTP], total cholesterol, neutral fat, amylase, urea nitrogen, creatinine, estimated glomerular filtration rate, uric acid, platelets), the epidural fat-occupying ratio in each vertebra from L1/2 to L5/S1 on MRI, and liver CT values. RESULTS: In 30 cases, the average occupying ratio of epidural fat was ≥40% (SEL), and in 45 cases, liver CT values were <40 HU (fatty liver). Correlation analysis between average occupying ratio of epidural fat and various measurements showed liver CT value (r = -0.574, P <  0.001), body weight (r = 0.304, P =  0.002), γ-GTP (r = 0.370, P =  0.01), and uric acid (r = 0.201, P =  0.04) to be independent explanatory factors. Multivariate analysis revealed that SEL was associated with liver CT value (odds ratio 0.774, 95% confidence interval [CI] 0.689-0.871) and body weight (odds ratio 1.063, 95% CI 1.016-1.135). CONCLUSION: There was a strong correlation between epidural fat and liver fat deposits suggesting an association between SEL and systemic fat deposition.

Minimally invasive triangular osteosynthesis for highly unstable sacral fractures: Technical notes and preliminary clinical outcomes.

Triangular osteosynthesis involves unilateral L5 iliac posterior instrumentation combined with an iliosacral screw fixation. The aim of this study was to describe this procedure and report the preliminary clinical results in patients with unstable sacral fractures treated with minimally invasive triangular osteosynthesis (MITO). Between 2012 and 2017, 10 patients (6 men and 3 women, mean age, 50 ±â€Š23 years) with sacral fractures were treated with MITO and were followed up for a mean of 15.0 ±â€Š8.5 months in our institution. Classification of sacral fracture, operative time, intraoperative bleeding, timing of full weight bearing, bone union, complications, and clinical outcomes were investigated. Two cases were classified as Denis zone 1, 2 cases as zone 2, and 6 as zone 3. Four patients had Roy-Camille type 1 fracture and 2 patients had type 2. All patients underwent MITO, which involved bilateral lumbopelvic fixation and a uni/bilateral iliosacral screw with stab incisions for percutaneous fixation or central longitudinal incision. The operative time was a mean of 182 ±â€Š64 minutes, and the amount of intraoperative bleeding was a mean of 63 ±â€Š74 g. Full-weight bearing was initiated at a mean of 8.2 ±â€Š2.4 weeks. Eight fractures healed; 1 patient had pulmonary embolism and 1 had implant loosening. Based on Majeed score, 8 patients had "excellent" clinical outcomes, 1 patient had a "good" clinical outcome, and the other had a "fair" clinical outcome. MITO could be less invasive on the soft tissues and be a reliable procedure for bony union. It might provide sufficient stability to accelerate the commencement of post-operative rehabilitation, even in patients with highly unstable sacral fractures.

Combination therapy with low-dose teriparatide and zoledronate contributes to fracture healing on rat femoral fracture model.

BACKGROUND: Delay in fracture healing or non-union can be devastating complication. Recent studies have reported that teriparatide (TP) demonstrated effectively on callus formation and mechanical strength and zoledronate (ZA) increased the callus size and resistance at the fracture site in rat fracture model. In this study, the effects of combination therapy with low dose TP and ZA on fracture healing was evaluated. METHODS: From 1 week post-operation, TP (5 times a week administration) and ZA (0.1 mg/kg single administration) were administered by dividing the rats into the following five groups: TP 1 µg group {T(1): TP 1 µg/kg}, ZA group (ZA:0.1 mg/kg), TP1 µg+ZA group {T(1)+ZA: TP 1 µg/kg+ZA}, TP 10 µg+ZA group {T(10)+ZA: TP 10 µg/kg + ZA}, and control group (C: administered saline). Rt femurs were excised 7 weeks after the surgery; bone fusions were evaluated with soft X-ray images on a 4-point scale. And the histopathological examination was performed in demineralized and non-demineralized specimens. Furthermore, the Radiographic Union Scale was conducted in all specimens. RESULTS: About the bone fusions rates, C, T(1), ZA, T(1)+ZA, and T(10)+ZA groups demonstrated 20.0%, 55.6%, 70.0%, 70.0%, and 80.0%, respectively, and with 4-point scale, each group was 0.50, 1.56, 2.00, 2.60, and 2.80 points, respectively. The callus volume was significantly increased to 16.66 mm2 and 17.75 mm2 in the T(1)+ZA and T(10)+ZA groups, respectively, while 10.65 mm2 (p < 0.05) in the C group. Furthermore, the callus area in the T(10)+ZA group was also observed to have significantly increased to 78.78%, compared with 54.63% and 44.11% in the C and T(1)+ZA groups, respectively (p < 0.01). Histopathologically, cartilage tissue and immature callus formation were observed at the bone junction in the C group; however, the osseous bridge formation of mature callus was observed in the ZA, T(1)+ZA, and T(10)+ZA groups. CONCLUSION: It is suggested that administration of low dose TP and ZA in combination may lead to the treatment of delayed union of fracture. We hope the combination treatment may become one of new therapeutic strategy.

Manipulation of the anabolic and catabolic responses with BMP-2 and zoledronic acid in a rat femoral fracture model.

Bone repair involves a complex set of regulated signaling pathways that control the formation of new bone matrix and the resorption of damaged bone matrix at the fracture site. It has been reported that the optimal time point for single-dose zoledronic acid (ZA) administration systemically increased the strength of bone morphogenetic protein (BMP)-7-mediated callus. However, its repair mechanism during bone fracture healing remains unknown. We aimed to investigate the synergic effect of recombinant human (rh) BMP-2 and ZA in a rat femoral fracture model. Fifty-eight rats were divided into 4 groups. Group I (n=14) animals were implanted with a carrier alone. Group II (n=15) animals were implanted with a carrier containing 1-µg rhBMP-2. Group III (n=14) animals were implanted with a carrier and a subcutaneous systemic ZA injection 2 weeks after surgery. Group IV (n=15) animals were implanted with a carrier containing 1-µg rhBMP-2 and ZA subcutaneous injection 2 weeks after surgery. The rats were euthanized after 6 weeks and their fractured femurs were explanted and assessed by manual palpation, radiographs, and high-resolution micro-computerized tomography (micro-CT) and were subjected to biomechanical and histological analysis. The fusion rates in Group IV (93.3%) were considerably higher than those in Groups I (28.6%), II (53.3%), and III (57.1%). Additionally, the radiographic scores of Group IV were higher than those in Groups I, II, and III. In micro-CT analysis, the tissue volume (TV) of the callus was higher in Group IV than in Groups I and II (p<0.05). New bone volume (BV) and trabecular spacing (Tb.Sp) also showed essentially the same trend as that of TV. The ratio of BV to TV (BV/TV), the trabecular number (Tb.N), and the trabecular thickness (Tb.Th) was higher in Groups III and IV than in Groups I and II (p<0.05). In biomechanical analysis, the ultimate loads at failure and stiffness in Groups III and IV were on average higher than those in Groups I and II (p<0.05), while the energy absorption of Group IV was higher than those of Groups I and II (p<0.05). The synergic effect of rhBMP-2 and ZA given systemically as a single dose at the optimal time was efficacious for fracture repair and significantly enhanced bone fusion. Our results suggest that this combination facilitates bone healing and has potential clinical application.

Involvement of CD14 in lipopolysaccharide- induced liver injury in mice pretreated with Propionibacterium acnes.

OBJECTIVE: The aim of this study was to elucidate the role of CD14 in the Propionibacterium acnes-lipopolysaccharide (LPS) system. METHODS AND RESULTS: CD14 transgenic mice (M14M), which expressed heterotopic CD14 and showed decreased responses to LPS in vivo, were used. Seven days after priming, the size of granulomas induced by an intraperitoneal administration of P. acnes in the M14M mice was smaller than that in the nontransgenic mice. The number of CD14-positive cells in granulomas was also decreased in the M14M mice compared to the nontransgenic mice. An LPS challenge induced apoptotic and necrotic changes in hepatocytes in the nontransgenic mice but not in the M14M mice. Seven days after priming, tumor necrosis factor-alpha expression was found in monocytic cells in granulomas and Kupffer cells in the nontransgenic mice and was significantly upregulated after LPS injection, whereas the expression was very weak in these cells in the M14M mice. CONCLUSIONS: CD14 plays a role in the P. acnes-LPS system in both priming and induction phases.

Subchondral cyst of the tibia secondary to Wilson disease.

We present the case of a 40-year-old male patient who had been suffering from Wilson disease for over 20 years, whose knee was diagnosed as osteoarthritis combined with subchondral cyst of the tibia. Preoperative examinations (X-ray, CT and MRI) confirmed the diagnosis. The microscopic examination detected thickening of the synovial membrane, and histopathological findings revealed that lymphoid cells and plasma cells were infiltrated at the synovial membrane. On copper-specific staining, no copper pigmentation was identified. However, the energy-dispersive X-ray (EDX) microanalysis revealed copper pigmentation in high concentration. These findings may contribute to our better comprehension of the development process of the arthropathy in patients with Wilson disease. The combination of subchondral cyst with Wilson disease is extremely rare, as only about 16 such cases have been reported in the English literature.

Roles of CD14 in LPS-induced liver injury and lethality in mice pretreated with Propionibacterium acnes.

The mechanism of the liver damage and lethality in Propionibacterium acnes (P. acnes)-LPS system remains obscure. To examine the role of CD14 in the system, M14M mice, in which CD14 was expressed heterotopically under the control of the metallothionein promoter were used. The production of soluble CD14 (sCD14) was increased by both P. acnes - priming and LPS challenge (1 microg per mouse) in both nontransgenic and M14M mice, although the plasma level was much higher in M14M nontransgenic than mice. The size of granulomas induced by an intraperitoneal administration of P. acnes in M14M mice 7 days after priming was smaller than that in nontransgenic mice. An LPS challenge induced apoptotic and necrotic changes in hepatocytes in nontransgenic mice but not in M14M mice. The challenge dose resulted in almost 90% lethality in nontransgenic mice but not in M14M mice 24h after challenge. TNF-alpha, IFN-gamma, IL-12, IL-18 and inducible nitric oxide synthase (iNOS) mRNA expressions produced by LPS challenge in M14M mice were low compared with those in nontransgenic mice. IL-18 mRNA expression was upregulated in P. acnes-primed nontransgenic mice but not in M14M mice. These results suggest that the high sCD14 concentration may account for less marked liver damage in M14M mice. Increase in the challenge dose of LPS (2 microg per mouse) resulted in increased lethality of M14M mice without liver damage. The levels of endothelial cell leukocyte adhesion molecule (ELAM)-1 mRNA expression in several organs in M14M mice 1-3h after LPS challenge were, however, lower than those in nontransgenic mice. The high sCD14 concentration may stimulate endothelial cell activation, which may account for lethality without liver damage in M14M mice. Thus, CD14 is involved in both the priming and induction phases as well as lethality in P. acnes-LPS system.

Influence of aeration, storage, and rinsing conditions on residual ethylene oxide in freeze-dried bone allograft.

Bone allografts sterilized with ethylene oxide gas (EO) are used in the field of orthopedic surgery, and the reduction of the EO residual concentration is an urgent clinical matter. We therefore investigated the efficacy of aeration and the effects of varied preservation periods and rinsing conditions on the reduction of EO residuals in freeze-dried bone allografts in the present study. Before aeration, the EO residual level was 12.6 ppm, and, after the repeating of aeration at 60 degrees C once, two times, and three times, the level decreased to 10.9 ppm, 3.1 ppm, and 0.47 ppm, respectively. Regarding the duration of preservation at room temperature, the mean EO residual level was 10.5 ppm, 4.9 ppm, and 4.6 ppm, 1, 2, and 3 weeks after EO sterilization, respectively. By rinsing with physiological salt solution, the level was decreased to 6.9 ppm by 5-min rinsing with 100 ml. Rinsing with 500 ml of this solution decreased the levels to 3.9 ppm, 2.8 ppm, and 2.0 ppm when done for 1, 5, and 10 min, respectively. Rinsing with 2000 ml of this solution decreased the levels to 3.6 ppm, 2.6 ppm, and 1.7 ppm when done for 1, 5, and 10 min, respectively. These experimental results with chip bone allografts lead us to recommend repeated preoperative aeration and more than 2 weeks' preservation before use for reducing the residual EO concentration. It was also evident that intraoperative rinsing with 500 ml of physiological saline for 10 min reduced the EO residual level.