Shoulder ultrasonography performed by orthopedic surgeons increases efficiency in diagnosis of rotator cuff tears.

BACKGROUND: Rotator cuff tears are very common and their incidence increases with age. Shoulder ultrasonography has recently gained popularity in detecting rotator cuff tears because of its efficiency, cost-effectiveness, time-saving, and real-time nature of the procedure. Well-trained orthopedic surgeons may utilize shoulder ultrasonography to diagnose rotator cuff tears. The wait time of patients planned to have shoulder MRI (magnetic resonance imaging) to rule in rotator cuff tears may decrease after orthopedic surgeon start doing shoulder ultrasonography as a screening tool for that. Patients with rotator cuff tears may be detected earlier by ultrasonography and have expedited surgical repair. The efficacy in determination of rotator cuff tears will also increase. METHODS: Patients were retrospectively reviewed from January 2007 to December 2012. They were divided into 2 groups: Ultrasound (-) group and the Ultrasound (+) group. Age, gender, wait time from outpatient department (OPD) visit to MRI exam, MRI exam to operation (OP), and OPD visit to OP, patient number for MRI exam, and number of patients who finally had rotator cuff repair within two groups were compared. RESULTS: The wait time of OPD visit to OP and MRI to OP in patients who received shoulder ultrasonography was significantly less than that in patients did not receive shoulder ultrasonography screening. Only 23.8% of the patients with a suspected rotator cuff injury undergone arthroscopic rotator cuff repair before ultrasonography was applied as a screening tool. The percentage increased to 53.6% after orthopedic surgeon started using ultrasonography as a screening tool for rotator cuff tears. CONCLUSIONS: Office-based shoulder ultrasound examination can reduce the wait time for a shoulder MRI. The efficacy of determination of rotator cuff tears will also increase after the introduction of shoulder ultrasonography.

Tapentadol immediate-release for acute postbunionectomy pain: a phase 3, randomized, double-blind, placebo-controlled, parallel-group study in Taiwan.

OBJECTIVE: To evaluate the efficacy and safety of tapentadol immediate-release (IR) for treating acute pain following orthopedic bunionectomy surgery in a Taiwanese population. METHODS: This was a phase 3, randomized, double-blind, placebo-controlled, parallel-group bridging study in which Taiwanese patients (N = 60) with moderate-to-severe pain following bunionectomy were randomized (1:1:1) to receive tapentadol IR 50 or 75 mg or placebo orally every 4-6 hours over a 72 hour period. The primary endpoint was the sum of pain intensity difference over 48 hours (SPID48), analyzed using analysis of variance. RESULTS: Out of 60 patients randomized (mainly women [96.7%]; median age 44 years), 41 (68.3%) completed the treatment. Mean SPID48 values were significantly higher for tapentadol IR (p ≤ 0.006: 50 mg, p ≤ 0.004: 75 mg) compared with placebo. Between-group differences in LS means of SPID48 (vs. placebo) were tapentadol IR 50 mg: 105.6 (95% CI: 32.0; 179.2); tapentadol IR 75 mg: 126.6 (95% CI: 49.5; 203.7). Secondary endpoints including SPID at 12, 24, and 72 hours, time to first use of rescue medication, cumulative distribution of responder rates, total pain relief and sum of total pain relief and sum of pain intensity difference at 12, 24, 48, and 72 hours, and patient global impression of change showed numerically better results supporting that tapentadol IR (50 and 75 mg) was more efficacious than placebo in relieving acute pain. The most frequent treatment emergent adverse events reported in ≥ 10% patients in either group were dizziness, nausea, and vomiting. A limitation of this study may possibly include more controlled patient monitoring through 4-6 hour dosing intervals, which reflects optimal conditions and thus may not approximate real-world clinical practice. However, all treatment groups would be equally affected by such bias of frequent monitoring, if any, since it was a randomized and double-blind study. CONCLUSIONS: Tapentadol IR treatment significantly relieved acute postoperative pain and was well tolerated in a Taiwanese population. ClinicalTrials.gov identifier: NCT01813890.

Arthroscopy-assisted reduction of posteromedial tibial plateau fractures with buttress plate and cannulated screw construct.

PURPOSE: To present the radiologic and clinical results of posteromedial fractures treated with arthroscopy-assisted reduction and buttress plate and cannulated screw fixation. METHODS: Twenty-five patients with posteromedial tibial plateau fractures treated by the described technique were included in this study. According to the Schatzker classification, there were 5 type IV fractures (20%), 2 type V fractures (8%), and 18 type VI fractures (72%). The mean age at operation was 46 years (range, 21 to 79 years). The mean follow-up period was 86 months (range, 60 to 108 months). Clinical and radiologic outcomes were scored by the Rasmussen system. Subjective data were collected to assess swelling, difficulty climbing stairs, joint stability, ability to work and participate in sports, and overall patient satisfaction with recovery. Secondary osteoarthritis was diagnosed when radiographs showed a narrowed joint space in the injured knee at follow-up in comparison with the films taken at the time of injury. RESULTS: The mean postoperative Rasmussen clinical score was 25.9 (range, 18 to 29), and the mean radiologic score was 15.8 (range, 10 to 18). All 25 fractures achieved successful union, and 92% had good or excellent clinical and radiologic results. The 3 fracture types did not significantly differ in Rasmussen scores or rates of satisfactory results (P > .05). Secondary osteoarthritis was noted in 6 injured knees (24%). CONCLUSIONS: Arthroscopy-assisted reduction with buttress plate and cannulated screw fixation can restore posteromedial tibial plateau fractures of the knee with well-documented radiographic healing, good clinical outcomes, and low complication rates. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Pretension effects of the Dynesys cord on the tissue responses and screw-spacer behaviors of the lumbosacral construct with hybrid fixation.

STUDY DESIGN: The pretension of the Dynesys cord was varied to evaluate its effects on both tissue responses and screw-spacer behaviors by the finite-element method. OBJECTIVE: This study aimed to provide detailed information about the motion-preserving and load-shielding mechanisms of the Dynesys screw-spacer joint. SUMMARY OF BACKGROUND DATA: Intuitively, higher cord pretension aims to ensure the occurrence of screw-spacer contact, thus making the spacer the transmitter of the vertebral loads. However, detailed investigations of the cord-pretension effects have not yet been carried out. METHODS.: Using a validated lumbosacral model, the moderately degenerative L4-L5 segment was instrumented by a static fixator and the Dynesys fixator was further used to bridge a mildly degenerative L3-L4 segment. The pre-tended cord was modeled as an elastic spring with 0- and 300-N pretensions. The disc range-of-motion, disc stress, facet force, bone-screw stress, and screw-spacer force were chosen as comparison indices. RESULTS.: At the transition and adjacent segments, the range-of-motion differences between the 2 pretensions were 7.7% and 2.0% on average, respectively. The mechanical differences at the transition and adjacent segments were 9.0% and 5.2% (disc stress) and 9.4% and 9.1% (facet force), respectively. The results indicated that the cord pretension has a minor effect on the adjacent segments in comparison with the transition segment. However, the stress at the screw hub and force of the screw-spacer contact of the 300-N pretension were increased by 33.7% and 316.5% on average than without pretension, respectively. CONCLUSION: The moment arm from the screw-cord center to the fulcrum is significantly less than that of vertebral loads. This leads to the minor effect of increasing the cord pretension on the responses of the adjacent segments. However, the cord pretension can significantly affect both screw-spacer force and bone-screw stress. LEVEL OF EVIDENCE: 4.

Comparison among load-, ROM-, and displacement-controlled methods used in the lumbosacral nonlinear finite-element analysis.

STUDY DESIGN: For lumbosacral nonlinear analysis, the characteristics and differences between the load- and range-of-motion (ROM)-controlled methods (LCM and RCM) were compared using the numerical approach. OBJECTIVE: This study aimed to discuss the LCM and RCM problems inherent in the method assumption and calculation procedure. A displacement-controlled method (DCM) based on the nodal movement at the lumbosacral top was proposed to offer a more efficient and equivalent comparison between the evaluated models. SUMMARY OF BACKGROUND DATA: Both LCM and RCM have been extensively used to evaluate the biomechanical performance of lumbosacral implants. The LCM models were subject to the same loads as the intact model. The ROMs of the RCM models were controlled in the same way by iteratively adjusting some of the applied loads. However, the different strategies for adjusting lumbar loads might affect the predicted results and the execution might be inefficient. To the best of the authors' knowledge, the kinematic, mechanical, and computational comparisons between the 2 methods have still not been extensively investigated. METHODS: An intact lumbosacral model was developed and validated with the cadaveric and numerical data from the literature studies. The intact model was then modified as a degenerative model, in which the moderately dehydrated L4-L5 segment was instrumented with transpedicular fixation. Lumbosacral flexion was simulated by ligament interconnection, muscular contraction, and weight compression. One LCM, 3 RCM, and 1 DCM models were developed to evaluate their effects on biomechanical results and the computational efficiency of the lumbosacral nonlinear analysis. RESULTS: Both solution feasibility and calculation time were closely related to the loading sequence that was defined as the time curves of the load-incremental control. The calculation of the RCM models was the most time-consuming. The calculation time of the DCM model was about 17 times faster than that of the RCM counterparts. Apart from the LCM model, the total ROM of the other models could be consistently controlled with the same value as that of the intact model. The intersegmental ROMs of all models were quite comparable. However, the LCM model predicted the least value of the screw stress and averaged 15.6% and 19.9% less than the RCM and DCM models. In general, the computational efficiency between the models was the most different, followed by the mechanical stress; the kinematic results were the most comparable. CONCLUSION: The superiority of the computational efficiency of the DCM compared with its counterparts makes it the improved strategy for executing lumbosacral nonlinear analysis.

Biomechanical influence of pin placement and elbow angle on joint distraction and hinge alignment for an arthrodiatasis elbow-pin-fixator construct.

Stiffness and contracture of the periarticular tissues are common complications of a post-traumatic elbow. Arthrodiatasis is a surgical technique that uses an external fixator for initial immobilization and subsequent distraction. The two prerequisites for an ideal arthrodiatasis are concentric distraction (avoiding bony contact) and hinge alignment (reducing internal stress). This study used the finite element (FE) method to clarify the relationship between these two prerequisites and the initial conditions (pin placement, elbow angle, and distraction mode). A total of 12 variations of the initial conditions were symmetrically arranged to evaluate their biomechanical influence on concentric distraction and hinge alignment. The humeroulnar surface was hypothesized to be ideally distracted orthogonal to the line joining the tips of the olecranon and the coronoid. The eccentric separation of the humeroulnar surfaces is a response to the non-orthogonality of the distracting force and joining line. Pin placement significantly affects the effective moment arm of the fixing pins to distract the bridged elbow. Both elbow angle and distraction mode directly alter the direction of the distracting force at the elbow center. In general, the hinges misalignment occurs in a direction opposite to the distraction-activated site. After joint distraction, the elastic deflection of the fixing pins inevitably makes both elbow and fixator hinges to misalign. This indicates that both joint distraction and hinge alignment are the interactive mechanisms. The humeroulnar separation is more concentric in the situation of the 120 degrees humeral distraction by using stiffer pins with convergent placement. Even so, the eccentric displacement of the elbow hinge is a crucial consideration in the initial placement of the guiding pin to compensate for hinge misalignment.

Biomechanical effects of disc degeneration and hybrid fixation on the transition and adjacent lumbar segments: trade-off between junctional problem, motion preservation, and load protection.

STUDY DESIGN: The biomechanical effects of disc degeneration and hybrid fixation on the transition and adjacent segments were evaluated using a numerical approach. OBJECTIVE: This study aimed to evaluate the rigidity-rising effects of the dehydrated disc and bridged fixator on the kinematic and mechanical redistribution of the transition and adjacent segments. SUMMARY OF BACKGROUND DATA: After static fixation, a dynamic fixator can be used to preserve motion and share loads for the transition segments. However, the hybrid use of both static and dynamic fixators and its effects on the biomechanical behavior of the transition and adjacent segments were not investigated extensively. METHODS: A nonlinear and osseoligamentous lumbar model from L1 vertebra to S1 vertebrae was developed. Ligament interconnection, muscular contraction, and weight compression were all used to simulate lumbar flexion. The static fixator was instrumented at the degenerative L4-L5 segment and the dynamic fixators (Dynesys system) with different stiffness were subsequently applied to the degenerative or healthy L3-L4 segment. A healthy lumbar model was used as a reference point for further comparison and evaluation. The predicted results were validated with the cadaveric and numerical values of the literature studies. Among the 21 models, the junctional problem at the adjacent (L2/L3 and L5/S1) discs as well as the motion preservation and stress distribution at the transition (L3/L4) disc were compared. RESULTS: Static fixation and the degenerative disc deteriorated the junctional problem at adjacent segments. On average, the hybrid fixation of the original Dynesys cord constrained the range of motion (ROM) by 65%. Furthermore, it shared 43% of the stress on the transition disc. However, this resulted in the adjacent discs increasing about 50% ROM and 40% stress. The term "trade-off stiffness" was used to express the concept that the decreased stiffness of the original cord could balance the junctional problem, motion preservation, and load protection of the transition and adjacent segments. The trade-off stiffness of the degenerative transition disc was higher than that of the healthy disc. Compared with the original design, the increased ROM and stress of the adjacent segments can be reduced by about 43% using the trade-off stiffness. CONCLUSION: The use of the hybrid fixator should involve a certain trade-off between the protection of the transition segment and the deterioration of the adjacent segments. This trade-off stiffness, which largely depends on both fixator design and disc degeneration, provides the improved rigidity and flexibility of the transition and adjacent segments.

Closed reduction and internal fixation for acute midshaft clavicular fractures using cannulated screws.

BACKGROUND: Although most acute midshaft clavicular fractures can be successfully treated nonsurgically, surgery is more appropriate for cases with severe displaced fractures, skin tenting, initial shortening of fracture ends, and associated with multiple injuries. However, methods of surgical treatment for such fractures remain controversial. This study discusses a closed reduction and internal fixation technique for midshaft clavicular fracture. METHODS: Between 2000 through 2003, 34 acute midshaft clavicular fractures were operatively treated with cannulated screws using closed reduction technique by one surgeon. The follow-up and clinical evaluation was performed by another surgeon. RESULTS: Thirty-one patients were followed for an average of 27.4 months (range, 24-37 months). Thirty (96.8%) fractures healed within 12 weeks, and one fracture healed at 18 weeks. No major surgical complications occurred, although superficial wound infection occurred in one patient. No implants needed to be removed. The final union rate was 100%. CONCLUSIONS: Closed reduction and internal fixation with cannulated screw is an alternative choice for treating acute midshaft clavicular fracture in selected cases where surgery is indicated and should be done cautiously.

Enalapril increases ischemia-induced endothelial progenitor cell mobilization through manipulation of the CD26 system.

Enalapril, an angiotensin-converting enzyme (ACE) inhibitor, reduces cardiovascular events in patients with acute myocardial infarction. However, whether the beneficial effect of enalapril is mediated in part through endothelial progenitor cells (EPCs) has yet to be elucidated. This study investigated the role of the CD26/dipeptidylpeptidase IV (DPP IV) system in enalapril-modulated EPC mobilization. C57 BL/6 mice were divided into control and enalapril-treated groups. Peripheral EPCs were enumerated before and after ischemic stress. CD26/DPP IV activity and stroma-derived factor-1alpha (SDF-1alpha) levels were measured in the blood and the bone marrow. In response to ischemic stress, the enalapril group displayed a significant increase in circulating EPCs (with a 3.6-fold increase of sca-1+KDR+ cells and a 2.2-fold increase of c-kit+CD31+ cells versus controls at 12 h). Enalapril also caused a sixfold increase in the contribution of bone marrow-derived EPCs to the ischemia-induced neovascularization. In the bone marrow, enalapril did not alter CD26+ cell numbers; however, it did amplify DPP IV activity. In the blood, through the anti-inflammatory effect, enalapril significantly decreased CD26+ cell numbers, leading to a decrease in total DPP IV activity. These phenomena were associated with a lower SDF-1alpha concentration in the bone marrow but higher in the blood in the enalapril group, compared to the controls. All these findings were not demonstrated without ischemic stress. The effect of enalapril on EPC mobilization could be substantially blocked by Diprotin-A, a DDP IV antagonist. This study demonstrates that one of the pleiotropic effects of enalapril on the cardiovascular system involves the modulation of circulating EPC numbers via the CD26/DPP IV system, which may serve as a potential target for mobilizing EPCs for therapeutic purposes.

One-stage posterior cruciate ligament inlay reconstruction combining anterior cruciate ligament reconstruction following knee dislocation.

Knee dislocation is a rare but severe injury that involves damage to the anterior cruciate ligament (ACL), posterior cruciate ligament (PCL), lateral or medial ligamentous structures, and other soft tissues or bony structures surrounding the knee joint. No consensus exists regarding the best treatment method. This work presents a method of 1-stage ACL and PCL reconstruction in which a contralateral quadriceps tendon-bone autograft with tibial inlay technique is used for the PCL and contralateral hamstring tendon autograft with suspension fixation is used for the ACL. After harvesting grafts, the patient is put in the lateral decubitus position. Under arthroscopy, the femoral tunnel for the anterolateral bundle of the PCL is created using an 8-mm reamer via a prepositioned guide pin. Next, the tibial tunnel of the ACL is created with an appropriate diameter cannulated reamer. Directed by the femoral guide instrument with a 7-mm offset, a guide pin is positioned retrograde through the tibial tunnel. A reamer is then used to create a 35-mm long closed-ended femoral tunnel for the ACL. A posterior arthrotomy for the PCL inlay technique is performed. After capsulotomy, a unicortical window is created at the footprint of the PCL and the inlay graft is fixed using a 3.5mm-cancellous screw and washer. The PCL graft is then passed into the femoral tunnel. The ACL graft is passed in a retrograde fashion using the Beath pin. The ACL graft is fixed by tying with a washer on the femoral side and by tying with a screw on the tibial side. The PCL graft is then fixed on the femoral side.

Secreted frizzled-related protein 1 modulates glucocorticoid attenuation of osteogenic activities and bone mass.

Prolonged glucocorticoid treatment is known to cause osteoporosis or aseptic necrosis. Secreted frizzled-related proteins 1 (SFRP1) and low-density lipoprotein-related protein 5 (LRP5), a Wnt protein antagonist and a coreceptor, have been found to regulate skeletogenesis. Whereas recent studies have reported that excess glucocorticoid promotes bone loss, the biological role of SFRP1 and LRP5 in regulating glucocorticoid attenuation of bone formation is not fully understood. We showed that a supraphysiological level of glucocorticoid enhanced SFRP1 but not LRP5 expression of primary mesenchymal cell cultures in vitro and osteoblasts at metaphyseal trabecular endosteum and chondrocytes at calcified cartilage in vivo. Glucocorticoid augmentation of SFRP1 expression was transcriptionally mediated. The inhibitory action of glucocorticoid on osteogenic differentiation appeared to be regulated by SFRP1 mediation of beta-catenin destabilization because knocking down SFRP1 by RNA interference abrogated the supraphysiological level of glucocorticoid attenuation of osteogenesis. Recombinant human SFRP1 reduced the promoting effect of physiological level of glucocorticoid on cytosolic beta-catenin accumulation, runt-related transcription factor-2 activation, and osteogenic activities. Glucocorticoid and recombinant human SFRP1 significantly increased osteochondral cell apoptosis associated with reduced mineral density, biomechanical properties, trabecular bone volume, and midshaft cortical bone areas in rat femurs. These findings suggest that SFRP1 modulates glucocorticoid-induced bone loss. Regulation of Wnt/SFRP signal transduction can be used in the future as an alternative strategy for the prevention of glucocorticoid-induced osteoporosis.

Extracorporeal shock waves promote healing of collagenase-induced Achilles tendinitis and increase TGF-beta1 and IGF-I expression.

Extracorporeal shock waves (ESW) have recently been used in resolving tendinitis. However, mechanisms by which ESW promote tendon repair is not fully understood. In this study, we reported that an optimal ESW treatment promoted healing of Achilles tendintis by inducing TGF-beta1 and IGF-I. Rats with the collagenease-induced Achilles tendinitis were given a single ESW treatment (0.16 mJ/mm(2) energy flux density) with 0, 200, 500 and 1000 impulses. Achilles tendons were subjected to biomechanical (load to failure and stiffness), biochemical properties (DNA, glycosaminoglycan and hydroxyproline content) and histological assessment. ESW with 200 impulses restored biomechanical and biochemical characteristics of healing tendons 12 weeks after treatment. However, ESW treatments with 500 and 1000 impulses elicited inhibitory effects on tendinitis repair. Histological observation demonstrated that ESW treatment resolved edema, swelling, and inflammatory cell infiltration in injured tendons. Lesion site underwent intensive tenocyte proliferation, neovascularization and progressive tendon tissue regeneration. Tenocytes at the hypertrophied cellular tissue and newly developed tendon tissue expressed strong proliferating cell nuclear antigen (PCNA) after ESW treatment, suggesting that physical ESW could increase the mitogenic responses of tendons. Moreover, the proliferation of tenocytes adjunct to hypertrophied cell aggregate and newly formed tendon tissue coincided with intensive TGF-beta1 and IGF-I expression. Increasing TGF-beta1 expression was noted in the early stage of tendon repair, and elevated IGF-I expression was persisted throughout the healing period. Together, low-energy shock wave effectively promoted tendon healing. TGF-beta1 and IGF-I played important roles in mediating ESW-stimulated cell proliferation and tissue regeneration of tendon.

Nitric oxide mediates ultrasound-induced hypoxia-inducible factor-1alpha activation and vascular endothelial growth factor-A expression in human osteoblasts.

Vascular endothelial growth factor (VEGF) is an important regulator for angiogenesis and endochondral bone formation. Although low-intensity pulsed ultrasound (US) has been recently used for accelerating fracture healing, the effect of US stimulation on angiogenic factor production by osteoblasts remains undetermined. Here, we found that US elevation of VEGF-A expression in human osteoblasts to be mediated by nitric oxide (NO) and hypoxia-inducible factor-1alpha (HIF-1alpha). Human osteoblasts were treated with or without US stimulation (200 micros pulse, 1 kHz at 30 mW/cm2) for 20 min. Cells were subjected to assessment of VEGF-A expression, NO production, nitric oxide synthase (NOS) catalytic activities, and HIF-1alpha transactivation. Results showed that US significantly increased VEGF-A mRNA and protein levels in 6 h. US augmentation of VEGF level was transcriptionally mediated. Early inhibition of NO production, but not calcium or prostaglandin E2, significantly reduced US-enhanced VEGF-A levels. Osteoblasts responded to US treatment by increasing NO production, NOS catalytic activities, iNOS immunoexpression, nuclear HIF-1alpha activation, and binding to the VEGF-A promoter. Inhibition of NOS activity by N-nitro-L-arginine methyl ester (L-NAME) or blockade of guanylate cyclase activity by ODQ reduced US-augmented HIF-1alpha transactivation and VEGF-A levels. Conditioned medium harvested from US-treated osteoblasts promoted tube formation of human umbilical vein endothelial cells (HUVEC). Monoclonal VEGF-A antibody neutralization or L-NAME pretreatment reduced the promoting effect of conditioned medium on angiogenesis of HUVEC. Together, these findings show that NO plays an important role in mediating extracellular stimuli released by US and triggering intracellular response of osteoblasts to produce angiogenic factor after US treatment.

Serious pyogenic spondylitis following vertebroplasty--a case report.

STUDY DESIGN: The aim of this case report is to examine the problem of serious pyogenic spondylitis that may follow vertebroplasty. OBJECTIVES: To report 1 case of serious pyogenic spondylitis caused by percutaneous vertebroplasty with polymethyl methacrylate. SUMMARY OF BACKGROUND DATA: Serious pyogenic spondylitis caused by percutaneous vertebroplasty with polymethyl methacrylate is a rare complication. We herein report a case of pyogenic spondylitis that occurred after the patient had undergone vertebroplasty. METHODS: A 78-year-old woman with a T12 osteoporotic compression fracture, and without a magnetic resonance imaging sign of infection, underwent percutaneous vertebroplasty using polymethyl methacrylate without complication. RESULTS.: About 1 month after the operation, the patient was readmitted because of severe backache, and the diagnosis of pyogenic spondylitis was made using radiograph and magnetic resonance imaging. Anterior inter-body fusion with a strut bone graft after debridement and posterior instrumentation were then performed. CONCLUSIONS: Vertebroplasty should proceed under sterile conditions. Excluding the possibility of spinal infection before surgery and a detailed evaluation assuring that the patient is without systemic infectious disease before the vertebroplasty procedure is crucial.

Vertebroplasty for the treatment of osteoporotic compression spinal fracture: comparison of remedial action at different stages of injury.

BACKGROUND: Outstanding results have been achieved using vertebroplasty for the treatment of osteoporotic compression spinal fractures, and a number of studies have reported the results from the application of this procedure. This study compared the results of vertebroplasty used at the different stages of injury. METHODS: A retrospective study reviewing the period between January 2001 and July 2001 investigated 68 patients who underwent single-level vertebroplasty: 22 patients within 2 weeks of the injury, 22 patients 2 weeks to 2 months after the injury, and 24 patients more than 2 months after the injury. Clinical evaluations compared the results of treatment at different injury stages during a mean follow-up period of 13 months. RESULTS: Although all the patients undergoing vertebroplasty in the acute and subacute stages reported satisfaction within 1 week of the operation, only 72.7% of the acute-stage group reported satisfaction with 24 hours of surgery. Moreover, evidence of cement leakage after vertebroplasty was detected for 27.3% of the acute-stage patients. This percentage significantly higher than for the patients in the subacute and chronic stages. Radiographic examination showed that new, adjacent compression fracture had occurred for 10.3% of the patients, with anterior interbody restabilization occurring for 11.8%. CONCLUSIONS: The results for vertebroplasty treatment of osteoporotic compression fractures appear to be injury stage dependent, with patients in the acute-injury stage needing longer recovery times, and with cement leakage quite common. These findings lead to the conclusion that the subacute stage is optimal for vertebroplasty. Furthermore, it is suggested that the use of spinal orthoses and postsurgical supplementation for the bone matrix reduces the risk of new, adjacent compression fractures and increases anterior interbody restabilization. Importantly, the findings suggest that a presurgical magnetic resonance imaging evaluation is an absolute necessity.

Recruitment of mesenchymal stem cells and expression of TGF-beta 1 and VEGF in the early stage of shock wave-promoted bone regeneration of segmental defect in rats.

Extracorporeal shock wave (ESW) treatment has recently been established as a method to enhance bone repair. Here, we reported that ESW-promoted healing of segmental defect via stimulation of mesenchymal stem cell recruitment and differentiation into bone forming cells. Rats with a segmental femoral defect were exposed to a single ESW treatment (0.16 mJ/mm(2), 1 Hz, 500 impulses). Cell morphology and histological changes in the defect region were assessed 3, 7, 14, and 28 days post-treatment. Presence of mesenchymal stem cell was assayed by immuno-staining for RP59, a recently discovered marker, and also production of TGF-beta 1 and VEGF was monitored. ESW treatment increased total cell density and the proportion of RP59 positive cells in the defect region. High numbers of round- and cuboidal-shaped cells strongly expressing RP59 were initially found. Later, the predominant cell type was spindle-shaped fibroblastic cells, subsequently, aggregates of osteogenic and chondrogenic cells were observed. Histological observation suggested that bone marrow stem cells were progressively differentiated into osteoblasts and chondrocytes. RP59 staining was initially intense and decreased with the appearance of expression depended on the differentiation states of osteogenic and chondrogenic cells during the regeneration phase. Mature chondrocytes and osteoblasts exhibited only slight RP59 immuno-reactivity. Expression of TGF-beta 1 and VEGF-A mRNA in the defect tissues was also significantly increased (P<0.05) after ESW treatment as determined by RT-PCR. Intensive TGF-beta 1 immuno-reactivity was induced immediately, whereas a lag period was observed for VEGF-A. Chondrocytes and osteoblasts at the junction of ossified cartilage clearly exhibited VEGF-A expression. Our findings suggest that recruitment of meseoblasts at the junction of ossified cartilage clearly exhibited mesenchymal stem cells is a critical step in bone reparation that is enhanced by ESW treatment. TGF-beta 1 and VEGF-A are proposed to play a chemotactic and mitogenic role in recruitment and differentiation of mesenchymal stem cells.

Tibial inlay technique with quadriceps tendon-bone autograft for posterior cruciate ligament reconstruction.

Surgical reconstruction of the posterior cruciate ligament (PCL) is indicated in a PCL-deficient knee with symptomatic instability and injury to other ligaments. However, the choice of graft tissues remains controversial. The tibial inlay method has the benefit of preventing the acute turn associated with transtibial reconstruction and permitting accurate anatomic placement of the graft. This study describes an arthroscopic-assisted inlay technique for PCL reconstruction using quadriceps tendon-patellar bone autograft. This technique is a reasonable alternative for PCL reconstruction.

Activation of extracellular signal-regulated kinase (ERK) and p38 kinase in shock wave-promoted bone formation of segmental defect in rats.

Extracorporeal shock waves (ESW) have recently been used in bone repair. Extracellular signal-regulated kinase (ERK) and p38 kinase are found to act as important mediators for osteogenic factor and mechanical-stimulated proliferation and differentiation of bone-forming cells. A previous study reported that ESW promoted healing of segmental defects in rats by inducing bone morphogenetic proteins (Bone 32 (2003) 387-396) and stimulating osteogenic differentiation of mesenchymal stem cells. In this study, we found that ERK and p38 activation was involved in ESW-augmented bone regeneration of segmental defects. ESW treatment (0.16 mJ/mm2, 1 Hz, 500 impulses) rapidly promoted [3H]-thymidine uptake in 1 day and progressively increased alkaline phosphatase activity, collagen I, II, and osteocalcin synthesis in callus organ culture within 14 days after treatment. Results of [gamma-32P]-phosphotransferase activity assay showed that ERK and p38 in calluses were rapidly activated 1 day and 7 days after ESW treatment, respectively. Histological observation showed that segmental defects subjected to ESW treatment underwent typical bone formation (mesenchymal cell aggregation, hypertrophic cartilage, and endochondral/intramembrane ossification). Intensive bone formation coincided with evident expression of phosphorylated ERK and p38. Moreover, expression of phosphorylated ERK persisted in mesenchymal, chondral, and osteoblastic cells at newly developed bone and cartilage, and the expression of activated p38 was evident on chondral cells located at hypertrophic cartilage. Our findings suggest that mitogen-activated protein kinases (MAPK) regulate the stimulation of biophysical ESW, triggering mitogenic and osteogenic responses in the defects. ERK phosphorylation is active throughout the period of ESW-induced bone regeneration. p38 activation most likely plays an important role in signaling cartilage formation in callus.

Nitric oxide donor increases osteoprotegerin production and osteoclastogenesis inhibitory activity in bone marrow stromal cells from ovariectomized rats.

Nitric oxide (NO) has emerged as a potent regulator useful in alleviating estrogen deficiency bone loss. Osteoprotegerin (OPG) and receptor activator of nuclear factor-kappaB ligand (RANKL) play important roles in regulating osteoclastogenesis. Although recent studies have reported NO donor attenuation of bone loss, the effect of NO donor on OPG and RANKL expression of osteogenic stromal cells and bone microenvironment in ovariectomized rats is not fully understood. Here, we showed that optimal NO donor treatment [2,2'-(hydroxynitrosohydrazino)bis-ethanamine; 15 microm] increased OPG, but not RANKL, levels in bone marrow stromal cells from ovariectomized rats. NO donor augmentation of OPG synthesis was transcriptionally mediated. The stimulatory action of NO donor on OPG expression appeared to be regulated by tyrosine kinase-dependent activation of Cbfa1/Runx2 binding to the OPG promoter, because cell cultures pretreated with tyrosine kinase inhibitor (herbimycin A), but not with protein kinase A inhibitor (calphostain C) or protein kinase C inhibitor [(Rp)-cAMP] significantly reduced NO-augmented Runx2 activation and OPG levels. Conditioned medium from NO donor-treated cells inhibited macrophage-colony-stimulating factor and RANKL-induced osteoclast formation of macrophage-colony-stimulating factor-dependent bone marrow macrophages. Neutralization with anti-OPG antibodies abolished the inhibitory effect of conditioned medium on osteoclastogenesis. Immunohistochemical observation also showed that 2,2'-(hydroxynitrosohydrazino)bis-ethanamine increased OPG expression of osteochondral cells located at metaphyseal endosteum and calcified cartilage of proximal femurs in ovariectomized rats. These findings suggest that NO donor can be an alternative pharmacological strategy for regulating bone resorption.

Ras induction of superoxide activates ERK-dependent angiogenic transcription factor HIF-1alpha and VEGF-A expression in shock wave-stimulated osteoblasts.

Vascular endothelial growth factor (VEGF) released by osteoblasts plays an important role in angiogenesis and endochondral ossification during bone formation. In animal studies, we have reported that shock waves (SW) can promote osteogenic differentiation of mesenchymal stem cells through superoxide-mediated signal transduction (Wang, F. S., Wang, C. J., Sheen-Chen, S. M., Kuo, Y. R., Chen, R. F., and Yang, K. D. (2002) J. Biol. Chem. 277, 10931-10937) and vascularization of the bone-tendon junction. Here, we found that SW elevation of VEGF-A expression in human osteoblasts to be mediated by Ras-induced superoxide and ERK-dependent HIF-1alpha activation. SW treatment (0.16 mJ/mm(2), 1 Hz, 500 impulses) rapidly activated Ras protein (15 min) and Rac1 protein (30 min) and increased superoxide production in 30 min and VEGF mRNA expression in 6 h. Early scavenging of superoxide, but not nitric oxide, peroxide hydrogen, or prostaglandin E(2), reduced SW-augmented VEGF-A levels. Inhibition of superoxide production by diphenyliodonium, an NADPH oxidase inhibitor, was found to suppress VEGF-A expression. Transfection of osteoblasts with a dominant negative (S17N) Ras mutant abrogated the SW enhancement of Rac1 activation, superoxide synthesis, and VEGF expression. Further studies demonstrated that SW significantly promoted ERK activation in 1 h and HIF-1alpha phosphorylation and HIF-1alpha binding to VEGF promoter in 3 h. In support of the observation that superoxide mediated the SW-induced ERK activation and HIF-1alpha transactivation, we further demonstrated that scavenging of superoxide by superoxide dismutase and inhibition of ERK activity by PD98059 decreased HIF-1alpha activation and VEGF-A levels. Moreover, culture medium harvested from SW-treated osteoblasts increased vessel number of chick chorioallantoic membrane. Superoxide dismutase pretreatment and anti-VEGF-A antibody neutralization reduced the promoting effect of conditioned medium on angiogenesis. Thus, modulation of redox reaction by SW may have some positive effect on angiogenesis during bone regeneration.