Branched-chain amino acids plus vitamin D supplementation promote increased muscle strength following lumbar surgery for lumbar spinal stenosis: a randomized trial.

BACKGROUND CONTEXT: Adequate nutrition is essential to address the surgical stress response and mitigate loss of muscle mass, strength, and functionality in older adults with lumbar spinal stenosis (LSS). However, it is unknown whether amino acids and/or vitamin D are beneficial in older adults following lumbar surgery for LSS. PURPOSE: To evaluate whether branched-chain amino acids (BCAA) plus vitamin D supplementation could attenuate the loss of muscle mass and strength, accelerate the return of functional mobility, and improve clinical outcomes following lumbar surgery for LSS. STUDY DESIGN/SETTING: A single-center, single-blind randomized controlled trial. PATIENT SAMPLE: Eighty patients who received lumbar surgery for LSS. OUTCOME MEASURES: The primary outcome was the Zurich claudication questionnaire (ZCQ), and secondary outcomes included knee muscle strength, muscle mass measured by bioelectrical impedance analysis, gait speed and a timed up-and-go test (TUG) at 12 weeks postoperatively. Follow-up assessment was performed for the ZCQ at 52 weeks postoperatively. METHODS: Patients ingested the supplementation (BCAA group: BCAA plus vitamin D, Nonamino acid group: nonamino acid) twice daily for 3 weeks from the day after surgery, and received two hours of postoperative inpatient rehabilitation 5 times a week. RESULTS: No significant differences were observed in the mean changes on the ZCQ between the two groups at 12 weeks and 52 weeks. At 2 weeks postoperatively, the nonamino acid group showed significant deterioration compared with the BCAA group for strengths of knee extensor and knee flexor (p < .01). At 12 weeks, the BCAA group showed significant improvements in knee extensor strength and knee flexor strength compared with the nonamino acid group (p <.01). There were no significant differences in mean changes of muscle mass, maximum gait speed, and TUG at 12 weeks between two groups. CONCLUSIONS: BCAA plus vitamin D supplementation did not improve LSS-related clinical outcomes after lumbar surgery for LSS, even though muscle strength increased. Future studies should focus on long-term outcomes for muscle mass and physical function, including development of sarcopenia and frailty.

MRI grading of spinal stenosis is not associated with the severity of low back pain in patients with lumbar spinal stenosis.

BACKGROUND: Although lumbar spinal stenosis (LSS) often coexists with other degenerative conditions, few studies have fully assessed possible contributing factors for low back pain (LBP) in patients with LSS. The purpose of this study was to identify factors associated with the severity of LBP in patients with LSS. METHODS: The patients with neurogenic claudication caused by LSS, which was confirmed by magnetic resonance imaging (MRI) were included in this cross-sectional study. Data included ratings of LBP, buttock and leg pain, and numbness on a numerical rating scale (NRS), 36-item Short-Form Survey (SF-36) scores, muscle mass measured by bioelectrical impedance analysis, and radiographic measurements including lumbopelvic alignment and slippage. The severity of LSS, endplate defects, Modic endplate changes, intervertebral disc degeneration, and facet joint osteoarthritis were evaluated on MRI. Spearman correlation and multivariate linear regression analyses were used to examine the factors associated with the severity of LBP (NRS score). RESULTS: A total of 293 patients (135 male and 158 female, average age 72.6 years) were analyzed. LBP was moderately correlated with buttock and leg pain, and buttock and leg numbness. Significant but weak correlations were observed between LBP and body mass index, appendicular and trunk muscle mass, all domains of SF-36, pelvic tilt, total number of endplate defects and Modic endplate changes, and summary score of disc degeneration grading, but not severity or number of spinal stenoses. In the multivariate regression analysis, age, female sex, trunk muscle mass, diabetes, NRS buttock and leg pain, NRS buttock and leg numbness, SF-36 vitality, pelvic tilt, and total number of endplate defects were associated with the severity of LBP. CONCLUSIONS: Trunk muscle mass, lumbopelvic alignment, and endplate defects, but not severity of stenosis are partly associated with severity of LBP, but buttock and leg pain and buttock and leg numbness have strongest relationships with LBP in patients with LSS.

Supervised physical therapy versus surgery for patients with lumbar spinal stenosis: a propensity score-matched analysis.

BACKGROUND: Previous studies comparing surgical with nonsurgical treatment for lumbar spinal stenosis (LSS) reported that surgery is superior to nonsurgical treatments, but intensive and adequate volume of physical therapy were rarely performed. The purpose of this study was to compare the 1-year follow-up outcomes of patients with LSS treated with supervised physical therapy or surgery using propensity score-matched analysis. METHODS: A total of 224 patients with LSS who received supervised physical therapy (n = 38) or surgery (n = 186) were included, of which 66 were matched on baseline demographics, radiological findings, and patient-reported outcomes. The physical therapy group received supervised physical therapy twice weekly for 6 weeks. The physical therapy sessions included manual therapy, individually tailored exercises, cycling, and body-weight supported treadmill walking. The surgery group underwent decompression surgery with or without spinal fusion. A propensity score analysis was performed using a one-to-one nearest neighbor approach. RESULTS: The surgery group showed greater improvements in Zurich claudication questionnaire symptom severity and physical function, SF-36 physical functioning, bodily pain, and mental health, but had more severe stenosis and symptoms and mental health problems than the physical therapy group at baseline (P <  0.05). After propensity score matching, there were no significant differences in baseline characteristics, and all clinical outcomes at 1 year, except for a higher percentage of responders achieving minimum clinically important difference in the role-emotional subscale of SF-36 in the surgery group (P <  0.05). CONCLUSIONS: When baseline characteristics were considered, supervised physical therapy yielded similar effects to lumbar surgery. These results suggest that supervised physical therapy is preferred over surgery as first-choice treatment, to prevent complications and to minimize health care costs, especially in mild to moderate cases of LSS.

Mortality and complications in elderly patients with cervical spine injuries.

PURPOSE: To assess the complications and mortality in elderly individuals with cervical spine injuries. METHODS: This retrospective observational study was conducted in a tertiary care hospital in a rural area in Japan. Data sets from the trauma registry (January 2011 to March 2018) were analyzed. Patients with cervical spine injury were divided into those aged ≥ 65 years (group Y) and > 65 years (group E). We then analyzed age, sex, 30-day mortality, hospital stay, level of cervical spine injury, presence of cervical vertebral fracture, perioperative complications (pneumonia, urinary tract infection, and severe bedsore), neurological deficit (Frankel classification), Abbreviated Injury Scale (AIS) score, and Injury Severity Score (ISS). RESULTS: We evaluated a total of 398 patients; among them, 177 were included in group Y and 221 in group E. The assessed parameters were as follows: age (group Y/E; 48.7/75.9 years), men (78.0/72.3%), 30-day mortality (8.5/10.0%, p = 0.159), hospital stay (17.2/19.1 days, p = 0.36), level of cervical spine injury (C1 [5.7/4.5%], C2 [12.4/15.8%], C3 [10.2/17.2%], C4 [14.1/16.3%], C5 [26.6/22.2%], C6 [22.0/12.2%], and C7 [11.3/10.9%]), vertebral fracture (56.6/61.9%), central cord syndrome (36.2/33%), operation (18.6/13.1%), pneumonia (6.8/11.8%, p = 0.077), urinary tract infection (4.0/6.3%, p = 0.26), severe bedsore (0/1.8%, p = 0.068), Frankel classification (grade A [5.7/6.3%], grade B [6.8/7.7%], grade C [24.9/28.5%], grade D [17.5/11.8%], and grade E [34.5/33.9%]), mean AIS score in the cervical spine (3.3/3.5, p = 0.04), and mean ISS (23.2/22.2, p = 0.38). C3 injuries tended to be higher in group E. CONCLUSION: Mortality and morbidity associated with cervical spine injuries did not differ between younger and older patients. Nevertheless, vigilance is required for the detection of C3 injury in elderly individuals.

Endplate Deficits and Posterior Wall Injury Are Predictive of Prolonged Back Pain after Osteoporotic Vertebral Body Fracture.

Introduction: Osteoporotic vertebral compression fracture (OVCF) in the elderly is a major public health concern. This retrospective case-control study aimed to determine the difference in interobserver reliability between radiography, magnetic resonance imaging (MRI), and computed tomography (CT), respectively, and whether CT radiological findings can predict prolonged back pain at 2 weeks after OVCFs. Methods: Patients were divided into the prolonged back pain group or the recovered back pain group depending on the numerical rating scale at 2 weeks after admission. Radiography, MRI, and CT images were classified on the basis of conventions described by previous classifications. Interobserver reliability was calculated on images rated by two board-certified spine surgeons. Multivariate logistic regression models were used to evaluate whether the presence or absence of anterior wall injury, endplate deficit, posterior wall injury, lateral wall injury, or intervertebral disc deficit on CT was predictive of prolonged back pain. Results: Of the 130 patients, 89 cases (68.5%) involved prolonged back pain at 2 weeks after admission. Neither average age (79.8 vs. 80.1 years, respectively) nor duration to initial consultation (9.4 vs. 6.4 days, respectively) differed significantly between the prolonged and recovered back pain groups. Interobserver reliability was 0.51, 0.77 (0.67-0.86), and 0.82 (0.72-0.92) for radiography, MRI, and CT, respectively. After adjusting for confounding factors such as age, sex, duration to initial consultation, and extent of OVCF, the multivariate analysis showed that the presence of endplate deficit and posterior wall injury was a significant predictive factor for prolonged back pain (odds ratio [OR] 8.5, area under the curve (AUC); 0.79 and OR 2.5, AUC 0.72), respectively. Conclusions: Good reliability assessments of CT-based evaluations were noted. After a detailed novel CT evaluation at initial presentation, the presence of an endplate deficit and posterior wall injury was the significant risk factor for prolonged back pain at 2 weeks after an OVCF.

Microendoscopic Decompression for Lumbar Spinal Stenosis With Degenerative Spondylolisthesis: The Influence of Spondylolisthesis Stage (Disc Height and Static and Dynamic Translation) on Clinical Outcomes.

STUDY DESIGN: This study was a retrospective subgroup analysis of prospective cohort data. OBJECTIVE: The main objectives of this study were to develop a classification of degenerative spondylolisthesis (DS) and concurrent lumbar spinal stenosis (LSS) based on pathologic stage, and to determine how these subtypes of DS affect outcomes for minimally invasive (MIS) decompression SUMMARY OF BACKGROUND DATA:: DS with LSS is a common clinical scenario, yet there is no consensus on optimal treatment. Natural history of DS is described as early degenerative damage, followed by instability, and eventual restabilization via spondylotic changes. MIS decompression surgery has become increasingly popular, but the effect of DS subtypes on clinical outcomes after MIS decompression is unknown. PATIENTS AND METHODS: From 2008 to 2013, all patients who underwent microendoscopic laminotomy for single-level LSS with DS were included. In total, 218 patients (91 male, 127 female individuals) were reviewed. DS pathologic staging was defined as early, advanced, or end stage, based on percent slippage (10% slippage), degree of dynamic instability (3 mm), and disc height. The following variables were evaluated preoperatively and >2 years postoperatively and compared among groups: Japanese Orthopaedic Association (JOA) score, JOA recovery rate, and Visual Analog Scale low back pain. RESULTS: In total, 173 patients were included in final analysis. Final follow-up period was 2.3 years. Average JOA recovery rate was 63.8%. There were no significant differences in JOA recovery and Visual Analog Scale among 3 DS stages (P>0.05). In total, 9.8% of patients required additional spine surgery, with 5% requiring subsequent fusion. All patients who required subsequent fusion were in the advanced stage DS group. CONCLUSIONS: Microendoscopic decompression is an effective treatment for patients with DS and concurrent LSS, with only 5% of patients requiring subsequent fusion at over 2-year follow-up, and another 5% requiring revision or adjacent segment decompression. The advanced stage DS group, indicating a >10% anterolisthesis and/or >3 mm of dynamic instability, was more likely to require additional surgery.

Early versus delayed kyphoplasty for thoracolumbar osteoporotic vertebral fractures: The effect of timing on clinical and radiographic outcomes and subsequent compression fractures.

OBJECTIVE: Osteoporotic vertebral body fractures (OVFs) represent a significant medical and socioeconomic burden. There is ongoing debate concerning the role of cement augmentation versus conservative management, but we are increasingly recognizing the longer-term effects of kyphotic vertebral alignment on functional outcomes, pain, and subsequent fracture rates. The purpose of this study was to determine the effect of timing of intervention with percutaneous balloon kyphoplasty (BKP) for OVF on clinical and radiographic outcomes. PATIENTS AND METHODS: 51 patients (mean age, 75.5 years) who underwent BKP for OVF were analyzed. Patients were divided into two groups based on timing of BKP: early (<4 weeks) or late (>4 weeks). Multiple factors were assessed preoperatively and throughout follow up and compared between groups using bivariate testing, including: focal kyphosis, subsequent vertebral fracture, and low back pain. RESULTS: This was a retrospective sub-group analysis. There were 32 patients in the early group and 19 patients in the late group. There was no significant difference in preoperative bone density between groups. Mean follow-up was 1.2 years. Local kyphosis at final follow-up was significantly greater in the late group (-28.4°) than in the early group (-9.5°; p < 0.001). There was no significant difference in local kyphosis between preoperative measurement and final follow-up in the early (p = 0.741) or late cohort (p = 0.794). Patients treated with early BKP demonstrated significantly better LBP scores (p < 0.05) and a lower rate of subsequent vertebral fracture (p < 0.05). CONCLUSION: BKP is able to prevent progressive collapse and kyphosis after OVF, but not effectively restore alignment, and as a result, patients who undergo early BKP (<4 weeks) demonstrate better alignment, better LBP scores, and reduced rates of subsequent fracture at an average of 1.2 years following treatment.

Noncontiguous double-level unstable spinal injuries.

PURPOSE: Noncontiguous double-level unstable spinal injuries (NDUSI) are uncommon and have not been well described. In this study, we aimed to better understand the patterns of NDUSI, in order to recommend proper diagnostic and treatment methods, as well as to raise awareness among traumatologists about the possibility of these uncommon injuries. METHODS: A total of 710 consecutive patients with spine fractures were treated for >9 years since 2007 at a single regional trauma center. Of them, 18 patients with NDUSI were reviewed retrospectively. RESULTS: The incidence of NDUSI was 2.5 % of all spine fractures. In 17 of 18 patients (94.7 %), NDUSI was caused by a high-energy trauma. Nine patients (50.0 %) exhibited complete neurological deficit. Spinal cord injury occurred in the cranial injured region in all American Spinal Injury Association grade A cases. In one case, a second fracture was overlooked at the initial examination. CONCLUSION: NDUSI are common in cases of high-energy trauma and should be taken into consideration at the initial examination. A second fracture may be easily overlooked because of the high frequency of concomitant severe spinal cord injury in the cranial injured region and/or loss of consciousness due to associated injuries. To avoid overlooking injuries, full spine computed tomography is useful at the initial examination. Operative reduction and internal fixation with instrumentation through a posterior approach is recommendable for cases of NDUSI. In elderly patients, a very rapid stabilizing surgery should be planned before aspiration pneumonia occurs or the pulmonary condition worsens.

Radiographic natural course of lumbar degenerative spondylolisthesis and its risk factors related to the progression and onset in a 15-year community-based cohort study: the Miyama study.

BACKGROUND: The natural history and risk factors for lumbar degenerative spondylolisthesis (DS) remain unclear. Because it is important for physicians to take these factors into account to ensure accurate decisions regarding surgical methods, this study aimed to elucidate the natural course and risk factors for the progression of DS. METHODS: This is a prospective observation and case control study of 15-year follow-up in a rural mountainous cohort in Wakayama, Japan. In 1990 and 2005, a total of 200 participants (baseline age, range 40-75) were subjected to anteroposterior and lateral radiographs of the lumbar spine, which were acquired with patients in a standing position. The prevalence of DS (slip ≥3 mm) at baseline and the incidence of DS at 15-year follow-up were recorded. Risk factors at baseline for progression of L4 slip (≥3 mm) over the 15-year period were determined by multiple logistic regression analysis. RESULTS: The overall prevalence of DS in 1990 was 10 % (20/200), and by spinal level was as follows: one case at L3, 14 cases at L4, and five at L5. In 2005, the overall prevalence of DS had risen to 22.5 % (45/200). Thus the incidence of de novo DS during the 15-year period was estimated at 14 % (25/180). Progression of the L4 slip (≥3 mm), regardless of baseline condition, was observed in 23 participants after 15 years. In multiple regression analysis, significant risk factors for L4 slip progression were identified as age less than 60 years, female sex, lumbar axis sacral distance, facet sagittalization, and existence of slip at baseline. CONCLUSIONS: We successfully elucidated the risk factors for the progression of DS in a general population. Moreover, the results of this study identified preventive factors as well as risk factors for slip progression. This study provides useful information for physicians treating DS.

A biomechanical comparison of 360° stabilizations for corpectomy and total spondylectomy: a cadaveric study in the thoracolumbar spine.

BACKGROUND: To date, there has been no adequate biomechanical model that would allow a quantitative comparison in terms of stability/stiffness between a corpectomy with the posterior column preserved and a total spondylectomy with the posterior column sacrificed. The objective of this study was to perform a biomechanical comparison of 360° stabilizations for corpectomy and total spondylectomy, using the human thoracolumbar spine. METHODS: Five human cadaveric thoracolumbar spines (T8-L2) were tested according to the following loading protocol: axial compression, flexion, extension, lateral bending to the right and left, and axial rotation to the right and left. This loading protocol was applied three times. Each specimen was tested intact, after corpectomy, and after total spondylectomy. The relative stiffness of each motion segment was determined for each test. RESULTS: There was no significant difference in stiffness after reconstruction of total spondylectomy versus corpectomy in our thoracolumbar model. Our construct consisted of an anterior cage and four-level pedicle screw instrumentation (two above and two below) and provided similar stiffness in both models. Despite the additional bone resection in a total spondylectomy versus corpectomy, the constructs did not differ biomechanically. Additionally, there was no significant difference in stiffness between the intact specimen and either reconstruction model. CONCLUSIONS: A classic corpectomy, which leaves the posterior column intact, is no better in terms of stability/stiffness than a total spondylectomy carried out using a shorter cage, followed by compression using posterior instrumentation.

Do CT scans overestimate the fusion rate after anterior cervical discectomy and fusion?

DESIGN: This study is a radiographic analysis. OBJECTIVE: To compare the fusion rates after anterior cervical discectomy and fusion (ACDF) using x-rays versus computerized tomography (CT). BACKGROUND: Although fusion status may be obvious when evaluating ACDFs performed in the remote past, determining the presence of a solid fusion at earlier time points after ACDF is often ambiguous but a necessary part of practice. Commonly used tools include radiographs and CT scans. Currently, there is no gold standard imaging modality to determine fusion status. METHODS: Twenty-two patients status post-ACDF (cortical allograft with anterior plates) at 34 levels with CT scans and dynamic x-rays obtained at 3, 6, and 12 months postoperatively were included. Four spine surgeons blinded to the time point independently determined fusion status according to the criteria. RESULTS: On the basis of the x-ray criteria, the fusion rates were 26%, 41%, and 65% at 3, 6, and 12 months, respectively, postoperatively. On the basis of CT criteria, the fusion rates were 79%, 79%, and 91% at 3, 6, and 12 months, respectively. There was a significant difference in the predicted fusion rate at each time point comparing x-ray versus CT criteria. In addition, at 3 months, 41% of the levels (11/27) thought to be fused by CT criteria demonstrated >1 mm motion on dynamic x-rays. At 6 months, 33% (9/27) of the levels thought to be fused by CT demonstrated persistent motion of ≥1 mm. At 12 months, 23% (7/31) of the levels considered fused by CT still had persistent motion. DISCUSSION: X-ray criteria for fusion, which incorporate both static and dynamic factors, predicted lower fusion rates at each time point when compared with CT scans, which evaluate only static factors. Depending on the time point, anywhere from 23% to 41% of levels thought to be fused by CT criteria demonstrated persistent motion on dynamic x-rays. Although <1 mm motion is not a sufficient criteria for fusion by itself, levels demonstrating >1 mm motion are less likely to be solidly fused. Thus, we conclude that CT scans may overestimate the fusion rate during the early stages of ACDF healing with cortical allograft, and that CT scans alone may not accurately determine fusion status. Reliable determination of fusion may thus require dynamic information obtained from flexion-extension x-ray in association with high-resolution static information from CT.

Prevalence of diffuse idiopathic skeletal hyperostosis (DISH) of the whole spine and its association with lumbar spondylosis and knee osteoarthritis: the ROAD study.

We aimed to assess the prevalence of diffuse idiopathic skeletal hyperostosis (DISH) and its association with lumbar spondylosis (LS) and knee osteoarthritis (KOA) using a population-based cohort study entitled Research on Osteoarthritis/osteoporosis Against Disability (ROAD). In the baseline ROAD study, which was performed between 2005 and 2007, 1,690 participants in mountainous and coastal areas underwent anthropometric measurements and radiographic examinations of the whole spine (cervical, thoracic, and lumbar) and both knees. They also completed an interviewer-administered questionnaire. Presence of DISH was diagnosed according to Resnick criteria, and LS and KOA were defined as Kellgren-Lawrence (KL) grade ≥3. Among the 1,690 participants, whole-spine radiographs of 1,647 individuals (97.5%; 573 men, 1,074 women; mean age, 65.3 years) were evaluated. Prevalence of DISH was 10.8% (men 22.0%, women 4.8%), and was significantly higher in older participants (presence of DISH 72.3 years, absence of DISH 64.4 years) and mainly distributed at the thoracic spine (88.7%). Logistic regression analysis revealed that presence of DISH was significantly associated with older age [+1 year, odds ratio (OR): 1.06, 95% confidence interval (CI): 1.03-1.14], male sex (OR: 5.55, 95% CI: 3.57-8.63), higher body mass index (+1 kg/m(2), OR: 1.08, 95% CI: 1.02-1.14), presence of LS (KL2 vs KL0: 1, OR: 5.50, 95% CI: 2.81-10.8) (KL ≥3 vs KL0: 1, OR: 4.09, 95% CI: 2.08-8.03), and presence of KOA (KL ≥3 vs KL0: 1, OR: 1.89, 95% CI: 1.14-3.10) after adjusting for smoking, alcohol consumption, and residential area (mountainous vs coastal). This cross-sectional population-based study clarified the prevalence of DISH in general inhabitants and its significant association with LS and severe KOA.

Microendoscopic lateral decompression for lumbar foraminal stenosis: a biomechanical study.

STUDY DESIGN: A biomechanical study. OBJECTIVE: How much of the facet joint and the pars interarticularis (PI) can be removed in microendoscopic lateral decompression (MELD) for lumbar foraminal stenosis (LFS)? SUMMARY OF BACKGROUND DATA: MELD is a surgical modality for patients with LFS. In severe degenerative cases, unilateral facet joint resection or unilateral removal of the lateral part of the PI are sometimes needed to decompress the nerve root adequately. METHODS: Twelve human lumbar motion segments were tested according to the following loading protocol: axial compression, flexion, extension, lateral bending to the right and left, and axial rotation to the right and left. This loading protocol was applied to each motion segment after MELD in 2 experiments: (1) unilateral graded facetectomy was performed in stages of 25%, 50%, 75%, and 100% using 3 segments of L3/L4 and 3 segments of L5/S1; (2) unilateral removal of the lateral part of the PI was performed in stages of 25%, 50%, 75%, and 100% using 3 segments of L3/L4 and 3 segments of L5/S1. The relative stiffness of each motion segments was determined each time. RESULTS: (1) Unilateral facet joint resection of >75% can lead to a significant reduction in stiffness in axial rotation at both L3/L4 and L5/S1. (2) Unilateral removal of 75% of the lateral part of the PI can lead to significant reduction in stiffness in right and left rotation at L3/L4 and in left rotation at L5/S1. (3) Unilateral removal of 100% of the lateral part of the PI can lead to a significant reduction in stiffness in right axial rotation at L5/S1. CONCLUSIONS: It would seem judicious to remove no >50% of the facet joint or the lateral part of the PI in order to prevent postoperative instability when using MELD for LFS.

Characterization of a unique motif in LIM mineralization protein-1 that interacts with jun activation-domain-binding protein 1.

Development and repair of the skeletal system and other organs are highly dependent on precise regulation of the bone morphogenetic protein (BMP) pathway. The use of BMPs clinically to induce bone formation has been limited in part by the requirement of much higher doses of recombinant proteins in primates than were needed in cell culture or rodents. Therefore, increasing cellular responsiveness to BMPs has become our focus. We determined that an osteogenic LIM mineralization protein, LMP-1 interacts with Smurf1 (Smad ubiquitin regulatory factor 1) and prevents ubiquitination of Smads resulting in potentiation of BMP activity. In the region of LMP-1 responsible for bone formation, there is a motif that directly interacts with the Smurf1 WW2 domain and thus effectively competes for binding with Smad1 and Smad5, key signaling proteins in the BMP pathway. Here we show that the same region also contains a motif that interacts with Jun activation-domain-binding protein 1 (Jab1) which targets a common Smad, Smad4, shared by both the BMP and transforming growth factor-ß (TGF-ß) pathways, for proteasomal degradation. Jab1 was first identified as a coactivator of the transcription factor c-Jun. Jab1 binds to Smad4, Smad5, and Smad7, key intracellular signaling molecules of the TGF-ß superfamily, and causes ubiquitination and/or degradation of these Smads. We confirmed a direct interaction of Jab1 with LMP-1 using recombinantly expressed wild-type and mutant proteins in slot-blot-binding assays. We hypothesized that LMP-1 binding to Jab1 prevents the binding and subsequent degradation of these Smads causing increased accumulation of osteogenic Smads in cells. We identified a sequence motif in LMP-1 that was predicted to interact with Jab1 based on the MAME/MAST sequence analysis of several cellular signaling molecules that are known to interact with Jab-1. We further mutated the potential key interacting residues in LMP-1 and showed loss of binding to Jab1 in binding assays in vitro. The activities of various wild-type and mutant LMP-1 proteins were evaluated using a BMP-responsive luciferase reporter and alkaline phosphatase assay in mouse myoblastic cells that were differentiated toward the osteoblastic phenotype. Finally, to strengthen physiological relevance of LMP-1 and Jab1 interaction, we showed that overexpression of LMP-1 caused nuclear accumulation of Smad4 upon BMP treatment which is reflective of increased Smad signaling in cells.

Risk Factors and Natural History of De Novo Degenerative Lumbar Scoliosis in a Community-Based Cohort: The Miyama Study.

STUDY DESIGN: A prospective study of de novo degenerative lumbar scoliosis in a community-based cohort. OBJECTIVES: To investigate risk factors and natural history of de novo scoliosis in the elderly. SUMMARY OF BACKGROUND DATA: Most previous studies have focused on the risk of progression with greater curve magnitude, which often manifests with serious clinical symptoms. There have only been a few reports regarding the etiology of de novo scoliosis. METHODS: Subjects (n = 400) were selected by sex and age from a list of 1,543 district residents, born from 1910 to 1949; 50 men and 50 women were selected from each age decade. Radiographic examinations of the lumbar spine in anteroposterior and lateral views were performed in 1990 and repeated in 2005 and 2008. De novo scoliosis was defined as newly developed scoliosis (a Cobb angle of 10° or greater and an increase in Cobb angle 5° or greater) in 2005 or 2008. RESULTS: Evaluation of radiographic surveys was completed for 200 of the 400 participants in 2005 and for 154 in 2008. De novo scoliosis was found in 33 inhabitants in 2005 and 24 in 2008. The scoliotic angles were less than 30°. During the follow-up period, significant asymmetric intervertebral disc degeneration developed, especially in the upper lumbar spine (p < .03), and lumbar coronal imbalance was significantly increased (p = .016). Logistic regression analysis, which was performed with the occurrence of scoliosis as an objective factor, identified L3 rotation as a significant risk factor (odds ratio, 13.95; 95% confidence interval, 4.05-52.34; p < .0001). CONCLUSIONS: This epidemiological study using radiography of the lumbar spine suggests that patients with asymmetric intervertebral disc degeneration and rotation of L3 in initial radiography without scoliosis should be closely followed up to observe the occurrence of scoliosis. Although the incidence of de novo scoliosis increases with age, scoliosis is usually benign.

Electrophysiological diagnosis using sensory nerve action potential for the intraforaminal and extraforaminal L5 nerve root entrapment.

BACKGROUND: The diagnosis of lumbar intraforaminal and extraforaminal stenosis (lumbar foraminal stenosis) is sometimes difficult. However, sensory nerve action potential (SNAP) decreases in amplitude when the lesion is at or distal to the dorsal root ganglion. Therefore, the amplitude of SNAP with lumbar foraminal stenosis should be decreased. In this cohort study, the usefulness of SNAP for the preoperative diagnosis of L5/S foraminal stenosis was assessed. METHODS: In 63 patients undergoing unilateral L5 radiculopathy, bilateral SNAPs were recorded for the superficial peroneal nerve (L5 origin). The patients were divided into two groups according to the results of imaging examinations. Group A (37 patients) included patients whose lesion was located only at the intraspinal canal. In group B (26 patients), the lesion was located only at the intra- or extraforaminal area. All patients received surgery and the symptoms were diminished. The ratios of the amplitudes of SNAPs on the affected side to that on the unaffected side were compared between groups A and B. RESULTS: SNAPs could not be elicited bilaterally in four patients. The amplitude ratio for group B (median 0.42, max 1.17, min 0) was significantly lower than that in group A (median 0.85, max 1.43, min 0) (p < 0.001 by Mann-Whitney U test). Using a cut-off value of 0.5 for the amplitude ratio, the sensitivity for the diagnosis of lumbar foraminal stenosis was 91.3 % with a specificity of 85.7 %. CONCLUSIONS: Measurement of SNAP could be useful to diagnose a unilateral L5/S foraminal stenosis.

Safety of epidural administration of Osteogenic Protein-1 (OP-1/BMP-7): behavioral and macroscopic observation.

STUDY DESIGN: To assess the safety of epidural administration of Osteogenic Protein-1 (OP-1). OBJECTIVES: To examine if epidural administration of OP-1 or administration into the nucleus pulposus (NP) resulted in ectopic bone formation and/or pain-related behavior. SUMMARY OF BACKGROUND DATA: OP-1 has the potential for treatment of degenerative disc disease. However, OP-1's safety, when it is applied into the epidural space or herniated nucleus pulposus, is not well established. METHODS: Forty rats were divided into 5 groups. Sham group: Left L4 and L5 nerve roots were exposed. NP group: The NP obtained from the tail was relocated onto the exposed nerve roots. NP+OP group: The NP obtained from the tail and injected with 0.2 microg of OP-1 in 1 microL of 5% lactose-buffered solution was placed on the nerve roots. GS group: A gelatin sponge was applied on the nerve roots. GS+OP group: A gelatin sponge soaked with 0.2 microg of OP-1 in 1 microL of 5% lactose-buffered solution was placed onto the nerve roots. Motor function and reflex responses to mechanical noxious stimuli were measured in all rats up to 3 weeks after surgery. Three weeks after surgery, all rats were killed for analysis of ectopic bone formation and magnitude of neural compression. RESULTS: Motor paresis was not observed in any groups. Only rats in the NP group showed evidence of irreversible mechanical hyperalgesia after surgery. There were no differences in the mechanical stimuli response among all groups except the NP group. Macroscopic examination revealed no ectopic bone formation or differences in neural compression among the groups. CONCLUSION: OP-1 application in the epidural space is safe based on behavioral measures and macroscopic observation on ectopic bone formation at 21 days after surgery.

The effects of bone morphogenetic protein and basic fibroblast growth factor on cultured mesenchymal stem cells for spine fusion.

STUDY DESIGN: Posterolateral lumbar transverse process fusion was carried out using cultured mesenchymal stem cells with or without bone morphogenetic protein (BMP) and basic fibroblast growth factor (FGF). OBJECTIVES: To determine the ability of BMP and basic FGF to enhance the efficacy of bone marrow-derived mesenchymal stem cells in lumbar arthrodesis. SUMMARY OF BACKGROUND DATA: Our previous study hypothesized that it would be important to differentiate into osteogenic cells and to implant a large number of cells for achieving solid spinal fusions. METHODS: Thirty-six adult rabbits underwent single-level bilateral posterolateral intertransverse process fusions at L4-L5. Animals were divided into 5 groups, each according to the material implanted: (1) autologous bone (autograft; n = 8); (2) mesenchymal stem cells (n = 7); (3) mesenchymal stem cells with recombinant human bone morphogenetic protein (rhBMP)-2 (mesenchymal stem cell-BMP; n = 7); (4) mesenchymal stem cells with basic FGF (mesenchymal stem cell-FGF; n = 7); and (5) mesenchymal stem cells with rhBMP-2 and basic FGF (mesenchymal stem cell-BMP-FGF; n = 7). Fresh bone marrow cells from the iliac crest of each animal were cultured in a standard medium for 2 weeks. For an additional week, the mesenchymal stem cells (1 x 10(6) cells/mL) were cultured in 10(-8) M dexamethasone, type I collagen gel and porous hydroxyapatite particles with or without rhBMP-2 (2 microg/mL) and basic FGF (5 microg/mL). Animals were killed 6 weeks after surgery. Radiograph, manual palpation, and histology were used to evaluate spinal fusions. RESULTS: Fusion rates were 5/7 in the autograft group, 0/7 in the mesenchymal stem cell group, 2/7 in the mesenchymal stem cell-BMP group, 3/7 in the mesenchymal stem cell-FGF group, and 6/7 in the mesenchymal stem cell-BMP-FGF group. The histology in some of both mesenchymal stem cell-BMP and mesenchymal stem cell-FGF groups demonstrated that fibrous tissues and cartilages remained in grafted areas. In the mesenchymal stem cell-BMP-FGF group, each grafted fragment was connected with new bone ingrowths. CONCLUSIONS: This study showed that bone marrow-derived mesenchymal stem cells cultured with rhBMP-2 and basic FGF act as a substitute for autograft in lumbar arthrodesis. This technique may yield a more consistent quality of fusion bone as compared to that with autograft.

Sarpogrelate hydrochloride, a 5-HT2A receptor antagonist, attenuates neurogenic pain induced by nucleus pulposus in rats.

STUDY DESIGN: An in vivo study using a rat lumbar disc herniation model. OBJECTIVES: To evaluate the effects of sarpogrelate hydrochloride on neurogenic pain induced by nucleus pulposus translocation and to elucidate its mechanism. SUMMARY OF BACKGROUND DATA: Sarpogrelate, an antiplatelet agent with selective 5-hydroxytryptamine (5-HT) receptor 2A antagonist activity, has been reported to improve low back pain, sciatica, and numbness of lower extremities in patients with lumbar disc herniation. However, the efficacy of sarpogrelate for pain relief in this situation has not been established by clinical studies and its mechanism remains unknown. METHODS: The autologous nucleus pulposus was placed onto the left L4 and L5 nerve roots of 30 Sprague-Dawley rats allotted to sarpogrelate (100 mg/kg, n = 15) and control (vehicle, n = 15) treatment groups. Sarpogrelate or vehicle was administered orally once daily between days 7 and 14 after surgery. Mechanical allodynia was measured before and after treatment. The right and left nerve roots and dorsal root ganglions were isolated from 5 animals in each group to assay 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), and norepinephrine on day 5 of administration (= day 11 after surgery). RESULTS: Sarpogrelate treatment significantly reduced mechanical allodynia on days 5 and 8 of administration. The placement of the nucleus pulposus onto nerve roots increased norepinephrine but not 5-HT and 5-HIAA contents in inflamed nerve roots or dorsal root ganglions. Sarpogrelate did not affect these levels. CONCLUSIONS: Sarpogrelate attenuated pain-related behavior induced by the nucleus pulposus in the animal model. Although further investigation is needed concerning the mechanism of action, this study supported the hypothesis that sarpogrelate is efficacious for treating the pain of lumbar disc herniation.

True aneurysm of a thumb digital artery in a radiographer: a case report.

True aneurysms of the digital artery are very rare. We report a case of true aneurysm of a proper digital artery of the right thumb in a radiographer. Treatment by ligation and excision resulted in complete relief of symptoms.