Quantitative evaluation of the lumbar ligamentum flavum using MRI T2-mapping: Efficacy of its clinical application in patients with lumbar spinal stenosis.

OBEJECTIVE: To perform a magnetic resonance imaging T2-mapping of the ligamentum flavum in healthy individuals and patients with lumbar spinal stenosis scheduled for surgery and compare the T2 relaxation times. SUBJECTS AND METHODS: The T2 relaxation time of the ligamentum flavum was compared among 3 groups, healthy young individuals (H group (age< 50)), healthy middle-aged and older individuals (H group (age≥50)), and patients with lumbar spinal stenosis (L group). Additionally, the thickness of the ligament was measured in the axial image plane, and the occupied area ratio of each fiber was measured by staining the surgically obtained ligament, and each was correlated with the T2 relaxation time. We also evaluated the adhesion of the ligamentum flavum with the dura mater during the surgery. RESULTS: The T2 relaxation times were significantly prolonged in H group (age ≥50) and L group (P < 0.001) compared to H group (age<50). The relationship between collagen fiber and T2 relaxation times was significantly positive (r = 0.720, P < 0.001). Moreover, the relaxation times were significantly prolonged in those with adhesion of the ligamentum flavum with the dura mater (P < 0.05). The cut-off for the relaxation time was 50 ms (sensitivity: 62.50%, false positive rate: 10.8%). CONCLUSION: Healthy middle-aged and older individuals and patients with lumbar spinal stenosis and adhesion of the ligamentum flavum with the dura mater have prolonged T2 relaxation times. Hence, the adhesion between the ligamentum flavum and dura mater should be considered in cases with a relaxation time ≥50 ms.

Characteristics and comparative study of thoracolumbar spine injury and dislocation fracture due to tertiary trauma.

PURPOSE: Thoracolumbar spine injury is frequently seen with high-energy trauma but dislocation fractures are relatively rare in spinal trauma, which is often neurologically severe and requires urgent treatment. Therefore, it is essential to understand other concomitant injuries when treating dislocation fractures. The purpose of this study is to determine the differences in clinical features between thoracolumbar spine injury without dislocation and thoracolumbar dislocation fracture. METHODS: We conducted an observational study using the Japan Trauma Data Bank (2004-2019). A total of 734 dislocation fractures (Type C) and 32,382 thoracolumbar spine injuries without dislocation (Non-type C) were included in the study. The patient background, injury mechanism, and major complications in both groups were compared. In addition, multivariate analysis of predictors of the diagnosis of dislocation fracture using logistic regression analysis were performed. RESULTS: Items significantly more frequent in Type C than in Non-type C were males, hypotension, bradycardia, percentage of complete paralysis, falling objects, pincer pressure, accidents during sports, and thoracic artery injury (P < 0.001); items significantly more frequent in Non-type C than in Type C were falls and traffic accidents, head injury, and pelvic trauma (P < 0.001). Logistic regression analysis showed that younger age, male, complete paralysis, bradycardia, and hypotension were associated with dislocation fracture. CONCLUSION: Five associated factors were identified in the development of thoracolumbar dislocation fractures. LEVEL OF EVIDENCE: III.

MRI T2-mapping of lumbar facet joints is effective for quantitative evaluation of lumbar instability in patients with degenerative lumbar disorders.

PURPOSES: To analyze T2 relaxation times of the facet joint by MRI T2-mapping in patients with degenerative lumbar disorders (DLD), and to determine the correlation with lumbar instability in radiographs. METHODS: We conducted a T2-mapping of the lumbar facet joint using a 1.5 T MRI system. We classified patients with degenerative lumbar disorders scheduled to undergo decompression surgery into groups with stability and instability using radiographs, and compared the T2 relaxation times of the lumbar facet. Lumbar instability was defined as the presence of anterior translation ratio > 5% or disk range of motion (ROM) > 5° in the sagittal plane of SLFE radiographs. RESULTS: Inclusion criteria were met by 22 patients (45 levels, mean age 64.3 years). Facet effusions had high sensitivity (90%) but had low specificity (28%) for diagnosis of lumbar instability. Mean T2 relaxation times of right and left facet joints are significantly longer (98.4 ms) in the instability group than they are (87.6 ms) in the stability group (p < 0.001). Anterior translation ratio was positively correlated with mean T2 relaxation times of facet joint (R2 = 0.493, p < 0.05). From a ROC analysis, the cutoff value of T2 relaxation times for lumbar instability was 98.65 ms (sensitivity 60.0%, specificity 95.7%, AUC 0.763). CONCLUSIONS: The T2 relaxation times were positively correlated with lumbar instability. This new quantitative evaluation of lumbar facet joint using MRI T2-mapping might be useful to determine lumbar instability.

Assessment of locomotive syndrome in patients with visceral cancer, the comparison with non-cancer patients using propensity score matching.

BACKGROUND: When treating cancer patients, the progression of symptoms is accompanied by the deterioration of systemic conditions and motor function. From a risk-benefit perspective, a certain level of physical function must be maintained to continue cancer treatment. Recently, outpatient cancer treatment has become more common. Motor function is important to determine the feasibility of continuing cancer treatment. The study aimed to evaluate the motor function of patients with visceral cancer using locomo tests established by Japanese Orthopaedic Association. METHODS: Locomo tests were performed, and the results were compared with data from non-cancer individuals. Background data were matched by propensity score matching. Data from 53 cancer patients (group C) were compared with that of 75 non-cancer patients (group N). RESULTS: The average score in the two-step test of group C was lower than that of group N (1.27: 1.37, p = 0.004). The average function in the stand-up test of group C was worse than that of group N (p = 0.001). The average score in the 25-question geriatric locomotive function scale (GLFS) of group C was significantly higher than that of group N (19.92: 5.29, SE 2.21, p < 0.001). Higher 25-question GLFS scores indicate reduced mobility. The proportion of the locomo stage 2 in group C was significantly higher than in group N (51%: 13%, p < 0.001). The results of the two field tests revealed a clinically minimal difference between the two groups, but a statistically significant difference. Locomo tests may be detect potential motor dysfunction in outpatient cancer patients with apparently maintained motor function. CONCLUSIONS: Even in cancer patients who attend outpatient clinics, their motor functions could be potentially impaired. Therapeutic interventions to maintain and enhance motor function for cancer patients could be useful for continuing cancer treatment, and furthermore, improving prognosis.

Good clinical outcomes in nonunion cases after facet fusion with a percutaneous pedicle screw system for degenerative lumbar spondylolisthesis.

There are many satisfactory long-term outcomes after posterolateral fusion (PLF) for degenerative lumbar spondylolisthesis (DLS); nonunion cases have also achieved good clinical outcomes. Facet fusion (FF), a minimally invasive evolution of PLF, also resulted in good clinical outcomes. We aimed to assess the course of nonunion cases after FF and determine whether the nonunion cases achieved good clinical outcomes. We retrospectively reviewed the records of 136 patients who underwent FF for DLS. Range of motion (ROM) at the fused level was measured using a flexion-extension lateral radiograph preoperatively and 1 year postoperatively. Patients were classified into the Fusion or Unconfirmed Fusion group by computed tomography (CT) 1 year postoperatively. Furthermore, patients in the Unconfirmed Fusion group were classified into the Delayed Union or Nonunion group depending on the confirmation status of FF upon the following CT. The average preoperative ROM and clinical outcomes were compared between the three groups. The Fusion, Delayed Union, and Nonunion groups had 109, 14, and 13 patients, respectively. In the Nonunion group, the average ROM significantly decreased from 13.0° preoperatively to 4.9° postoperatively. There was a significant difference in the average preoperative ROM between the groups. The larger the preoperative ROM, the fewer facets fused. There was no significant difference in clinical outcomes between the groups. Five patients (3.7%) required revision surgery for adjacent segment disease 1-5.5 years after FF. Even nonunion cases after FF achieved good clinical outcomes, likely because the unstable spondylolisthesis was stabilized. FF did not require revision surgery for nonunion itself.

Pedicle screw shift without loosening following instrumented posterior fusion: limitations of pedicle screw fixation.

The disc angle at the fused segment is extended in operative prone position, but eventually returns to preoperative neutral position within 6 months to 1 year. This study aimed to assess pedicle screw (PS) shift without loosening to identify the mechanism of the change in disc angle after posterior fusion for degenerative lumbar spondylolisthesis (DLS). Sixty-three consecutive patients who underwent facet fusion for L4 single-level DLS were retrospectively reviewed using computed tomography (CT) immediately after surgery and 6 months postoperatively. Twenty-two patients (88 PSs) in whom the disc angle had decreased by more than 4° at 6-month postoperative radiographic follow-up were selected to more readily identify and quantify PS shift. Six patients with PS loosening and/or nonunion were excluded. We reconstructed a CT plane, vertical to the cranial endplate of the vertebrae and passing through the cannula used for percutaneous PSs. Angle α, which is formed by the cranial endplate and the cannula on this plane, was measured. A change in angle α of more than 2° between the immediate postoperative period and the 6-month follow-up was defined as a PS shift. Angle α did not change by more than 2° in any of the 44 PSs in the upper vertebrae of the fused segment. In the lower vertebrae, angle α changed by more than 2° in 22 of 44 PSs. The change in angle α in the lower vertebrae (average, 2.3°) was significantly greater than that in the upper vertebrae (average, 0.2°) (P < 0.0001). The change in the disc angle was not relevant to clinical outcomes assessed by the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire, the Roland-Morris Disability Questionnaire, and the visual analogue scale. The disc angle at the fused segment returned to preoperative neutral position due to PS shift without loosening, mainly in the lower vertebrae. PS shift is caused by bone remodeling in response to biomechanical load, similar to that in orthodontic tooth movement. As PS has limited ability to maintain a lordotic disc angle, even with the insertion of a cage, lumbar alignment will return to preoperative neutral position owing to cage subsidence or adjacent segment disease. These findings might indicate that it is not necessary to correct the spinal alignment for DLS.

A simple formula for predicting diameter of safely inserted cortical bone trajectory screws for fixation of the lower lumbar spine.

BACKGROUND: Cortical bone trajectory (CBT) screws are popular for spinal fixation, but their ideal diameter has not been determined. Studies using postoperative computed tomography (CT) have revealed ample bone marrow space around 5.5-mm screws, which are commonly used. However, evidence indicates that a larger screw diameter provides a greater fixation strength. This study aimed to develop a generalizable formula for computing the diameter of CBT screws that could be inserted safely for fixation of the lower lumbar spine. METHODS: Records of 44 consecutive patients who had undergone posterior fusion with CBT screws for single-level degenerative lumbar spondylolisthesis were retrospectively reviewed. We estimated the maximum diameter for conventional pedicle screws by the minimum diameter of the pedicle using preoperative CT (PSD). We measured the minimum endosteal diameter of the pedicle on the reconstructed plane of the postoperative CT which passed through the cannula used for the screw and estimated the maximum diameter for the CBT screws that could be inserted within the bone marrow space of the pedicle (CBTD). RESULTS: Among the 176 pedicles measured, there were 151 (85.8%) with a PSD of 8.5 mm and 13, 7.5 mm. Because of a slight pedicle wall breach, 13 screws were excluded from the sample. There were 64 (39.3%) screws with a CBTD of 8.5 mm; 45, 7.5 mm; and 40, 6.5 mm. Of 163 screws, 156 (95.7%) had PSD minus CBTD ≤2 mm for each pedicle. PSD minus the minimum outer cortical diameter was ≤1 mm for each pedicle in 155 (95.1%) screws. CONCLUSION: Our results show that CBT screws with a diameter 1 mm smaller than the endosteal diameter of the pedicle were inserted safely. STUDY: Design: Clinical study.

Negative pressure wound therapy and skin grafting for necrotizing fasciitis in a patient with rheumatoid arthritis treated with abatacept: A case report.

Herein, we present a case of necrotizing fasciitis (NF) in a patient with rheumatoid arthritis (RA) treated with abatacept. Cultures of the patient's leg effusion revealed group A Streptococcus. Treatment included antibiological drugs, repeat debridement, negative pressure wound therapy (NPWT), and skin grafting. This case highlights the need for suspicion of severe bacterial infection for early diagnosis and effective treatment. NF with RA can be treated effectively with repeat debridement and NPWT.

Tramadol hydrochloride/acetaminophen combination versus non-steroidal anti-inflammatory drug for the treatment of perioperative pain after total knee arthroplasty: A prospective, randomized, open-label clinical trial.

BACKGROUND: While many of the commonly used treatments for perioperative pain after total knee arthroplasty (TKA) have been recognized as effective, there is still insufficient evidence for oral medication. In orthopedics, non-steroidal anti-inflammatory drugs (NSAIDs) have been commonly used for perioperative pain; however, serious adverse events have been reported. Conversely, tramadol hydrochloride/acetaminophen combination (TRAM/APAP) therapy has been shown to reduce pain, particularly for chronic pain in Japan. This study aimed to determine TRAM/APAP efficacy in comparison with NSAIDs for perioperative pain after TKA. METHODS: Two hundred eighty patients were enrolled in this study; 137 patients were treated with TRAM/APAP, and 143 patients were treated with NSAID from postoperative (PO) day 2. The primary endpoint was a comparison between the pain visual analog scale (VAS) change from baseline (PO day 2) and PO day 4, day 7, day 10, and day 14. The second endpoint was the number of days until the patient achieved independence from cane walking. RESULTS: Analysis of endpoints included 130 and 139 patients in the TRAM/APAP and NSAID groups, respectively. The pain VAS change in the TRAM/APAP group on any of the measurement days was significantly improved compared with the NSAID group (P < 0.01). Similarly, the TRAM/APAP group achieved cane-walking independence significantly faster than the NSAID group (P < 0.01). CONCLUSION: Efficacy for perioperative pain management after TKA of TRAM/APAP was shown to be superior to that of NSAID; TRAM/APAP was also effective in improving the progress of rehabilitation.

The efficacy of abatacept in Japanese patients with rheumatoid arthritis: 104 weeks radiographic and clinical results in clinical practice.

OBJECTIVE: We aimed to assess the efficacy of abatacept in Japanese patients with rheumatoid arthritis (RA) in clinical practice. METHODS: We examined 92 patients who received abatacept for 104 weeks. Analysis of radiographic efficacy was conducted using van der Heijde-modified total Sharp score (mTSS). Disease activity score was assessed using disease activity score in 28 joints (DAS28) and simplified disease activity index (SDAI) by last observation carried forward. RESULTS: The change in mTSS was 0.61 at 52 weeks and 0.27 at 52-104 weeks. Structural remission occurred in 64.9% at 52 weeks and 76.6% at 104 weeks. The significant risk factors for joint damage progression at 52 weeks were prednisolone use, baseline C-reactive protein level (CRP), and erythrocyte sedimentation rate (ESR), as well as average DAS28-CRP and DAS28-ESR scores, SDAI, CRP, ESR, and matrix metalloproteinase-3 (MMP-3) levels. The clinical remission rates were 47.8% by DAS28-CRP, 39.1% by DAS28-ESR, and 30.4% by SDAI at 52 weeks, were 59.8% by DAS28-CRP, 48.9% by DAS28-ESR, and 43.5% by SDAI at 104 weeks. CONCLUSION: This study suggested efficacy of abatacept treatment in Japanese patient with RA for 104 weeks in daily clinical practice. Abatacept lead to suppress joint destruction for 104 weeks.

Scoliosis-related factors in patients with rheumatoid arthritis: A cross-sectional study.

OBJECTIVES: This study aimed to identify the prevalence of scoliosis and scoliosis-related factors of rheumatoid arthritis (RA). METHODS: In this study, 411 patients who underwent coronal total spine and lower limb radiography were enrolled. Patients with a Cobb angle ≥10° were diagnosed with scoliosis. Statistical analysis was performed to compare between patients with and those without scoliosis, and between patients without scoliosis and those with a Cobb angle >20°. RESULTS: The prevalence of scoliosis in patients with RA was 30.7%. The mean Cobb angles were 8.5° ± 7.2° in all the patients, 16.1° ± 8.6° in patients with scoliosis, and 5.1° ± 2.3° in patients without scoliosis. According to a multivariate analysis, the scoliosis-related factors of RA were age and vertebral fracture. Significant differences in age, corticosteroid use, and malalignment of lower limbs were observed between patients with a Cobb angle >20° and those without scoliosis. CONCLUSIONS: With RA treatment, the need for corticosteroid use is reduced and vertebral fracture is prevented. Moreover, the joints and spinal and lower limb alignments should be examined.

Comparison of Muscle Mass Between Healthy Subjects and Patients With Malignant Tumors Undergoing Outpatient Treatment.

Background In recent years, advances in the treatment of malignant tumors have improved life expectancy and diversified treatment options. However, maintaining high activities of daily living in patients is essential for appropriately treating the primary disease, and interventions for patients with impaired motor function will lead to improved quality of life. Here, we compared the muscle mass of malignant tumor patients who are visiting bone metastasis outpatient clinics with that of healthy subjects. Methods We compared the muscle mass of 61 malignant tumor patients with an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (mean 66.3 ± 12.0 years; 30 males and 31 females) attending our bone metastasis outpatient clinic since 2018 with that of 315 healthy subjects (mean 65.0 ± 17.7 years; 110 males and 205 females). Body mass index, skeletal muscle mass, and body fat percentage were assessed by bioimpedance analysis, and the skeletal muscle mass index (SMI) was calculated. Results To eliminate age bias in the malignant tumor patients and healthy subjects, 1:1 propensity score matching was performed separately for males and females. There was no significant difference in right upper limb, left upper limb, right lower limb, or left lower limb mass or SMI between the two groups, whereas trunk muscle mass and muscle mass were significantly higher in the healthy females compared with malignant tumor females. Conclusion There was no significant difference in the SMI measured by bioimpedance analysis between the two groups in either males or females, while muscle mass and trunk muscle mass were significantly lower in female malignant tumor patients than in healthy subjects. These results suggest that even malignant tumor patients whose performance status was maintained enough to allow outpatient visits still had impaired motor function.

Prevention of Severe Post-operative Urinary Retention after Spinal Surgery for Lumbar Spinal Stenosis: A Technical Review and Five-patient Case Series.

Introduction: Post-operative urinary retention is a common complication of posterior spine surgery for lumbar spinal stenosis. However, it can result in considerable difficulty for the patient, especially when it is severe, as in cases of complete retention. Therefore, it is crucial to consider its risk factors. This report provides a retrospective review of cases with severe post-operative urinary retention with the aim of elucidating its possible risk factors. Case Presentation: Data of five patients with post-operative urinary retention after posterior spine surgery for lumbar spinal stenosis, operated in our facility from 2013 to 2020, were analyzed. Their age, preoperative Japanese Orthopaedic Association (JOA) score, presence of pre-operative bladder and bowel disorders (BBD), presence of pre-operative muscle weakness, the mean number of vertebral levels operated on, complications such as intraoperative dural tear and hematoma, operative time, estimated blood loss, JOA score in the early post-operative period, and the recovery period for the urinary retention symptoms were examined. The mean pre-operative JOA score was 8.4, and the mean number of operated levels was 2.8. The incidence of pre-operative BBD, pre-operative muscle weakness, intraoperative dural tears, and post-operative hematoma was two each. The mean operative time was 242 min, mean estimated blood loss was 352 g, and the mean JOA score in the early post-operative period was 5.8. The recovery period for urinary retention ranged from 4 days to 9 months postoperatively; one patient also had cervical and thoracic spinal stenosis and underwent decompression of all stenotic levels for relief from complete urinary retention. Conclusion: In our retrospective review of cases with severe post-operative urinary retention after lumbar spinal stenosis surgery, all patients had severe pre-operative symptoms and spinal stenosis at multiple levels. An awareness of potential risk factors and carefully and gently performing the intraoperative procedures can facilitate lesser damage to the spinal nerve.

Automated Differentiation Between Osteoporotic Vertebral Fracture and Malignant Vertebral Fracture on MRI Using a Deep Convolutional Neural Network.

STUDY DESIGN: Retrospective study of magnetic resonance imaging (MRI). OBJECTIVES: To assess the ability of a convolutional neural network (CNN) model to differentiate osteoporotic vertebral fractures (OVFs) and malignant vertebral compression fractures (MVFs) using short-TI inversion recovery (STIR) and T1-weighted images (T1WI) and to compare it to the performance of three spine surgeons. SUMMARY OF BACKGROUND DATA: Differentiating between OVFs and MVFs is crucial for appropriate clinical staging and treatment planning. However, an accurate diagnosis is sometimes difficult. Recently, CNN modeling-an artificial intelligence technique-has gained popularity in the radiology field. METHODS: We enrolled 50 patients with OVFs and 47 patients with MVFs who underwent thoracolumbar MRI. Sagittal STIR images and sagittal T1WI were used to train and validate the CNN models. To assess the performance of the CNN, the receiver operating characteristic curve was plotted and the area under the curve was calculated. We also compared the accuracy, sensitivity, and specificity of the diagnosis made by the CNN and three spine surgeons. RESULTS: The area under the curve of receiver operating characteristic curves of the CNN based on STIR images and T1WI were 0.967 and 0.984, respectively. The CNN model based on STIR images showed a performance of 93.8% accuracy, 92.5% sensitivity, and 94.9% specificity. On the other hand, the CNN model based on T1WI showed a performance of 96.4% accuracy, 98.1% sensitivity, and 94.9% specificity. The accuracy and specificity of the CNN using both STIR and T1WI were statistically equal to or better than that of three spine surgeons. There were no significant differences in sensitivity based on both STIR images and T1WI between the CNN and spine surgeons. CONCLUSION: We successfully differentiated OVFs and MVFs based on MRI with high accuracy using the CNN model, which was statistically equal or superior to that of the spine surgeons.Level of Evidence: 4.

Usefulness of Simultaneous Magnetic Resonance Neurography and Apparent T2 Mapping for the Diagnosis of Cervical Radiculopathy.

STUDY DESIGN: Retrospective observational study. PURPOSE: We investigated the correlation between T2 relaxation times and clinical symptoms in patients with cervical radiculopathy caused by cervical disk herniation. OVERVIEW OF LITERATURE: There are currently no imaging modalities that can assess the affected cervical nerve roots quantitatively. METHODS: A total of 14 patients with unilateral radicular symptoms and five healthy subjects were subjected to simultaneous apparent T2 mapping and neurography with nerve-sheath signal increased with inked rest-tissue rapid acquisition of relaxation enhancement signaling (SHINKEI-Quant) using a 3-Tesla magnetic resonance imaging. The Visual Analog Scale (VAS) score for neck pain and upper arm pain was used to evaluate clinical symptoms. T2 relaxation times of the cervical dorsal root ganglia of the brachial plexus were measured bilaterally from C4 to C8 in patients with radicular symptoms and from C5 to C8 in healthy controls. The T2 ratio was calculated as the affected side to unaffected side. RESULTS: When comparing nerve roots bilaterally at each spinal level, no significant differences in T2 relaxation times were found between patients and healthy subjects. However, T2 relaxation times of nerve roots in the patients with unilateral radicular symptoms were significantly prolonged on the involved side compared with the uninvolved side (p<0.05). The VAS score for upper arm pain was not significantly correlated with the T2 relaxation times, but was positively correlated with the T2 ratio. CONCLUSIONS: In patients with cervical radiculopathy, the SHINKEI-Quant technique can be used to quantitatively evaluate the compressed cervical nerve roots. The VAS score for upper arm pain was positively correlated with the T2 ratio. This suggests that the SHINKEI-Quant is a potential tool for the diagnosis of cervical nerve entrapment.

Bone union-promoting effect of romosozumab in a rat posterolateral lumbar fusion model.

This study investigated the effect of romosozumab on bone union in a rat posterolateral lumbar fixation model. Posterolateral lumbar fixation was performed on 8-week-old male Sprague Dawley rats (n = 20). For bone grafting, autogenous bone (40 mg) was harvested from the spinous processes of the 10th thoracic vertebra until the 2nd lumbar vertebra and implanted between the intervertebral joints and transverse processes of the 4th and 5th lumbar vertebrae on both sides. Rats were matched by body weight and equally divided into two groups: R group (Evenity®, 25 mg/kg) and control (C) group (saline). Subcutaneous injections were administered twice a week until 8 weeks after surgery. Computed tomography was performed at surgery and week 8 after surgery. The area and percentage of bone trabeculae in the total area of bone fusion were calculated. Statistical analysis was performed using an unpaired t test (p < 0.05). We found that the R group rats had significantly higher mean bone union rate and volume than did the C group rats at all time courses starting week 4 after surgery. The R group had significantly higher increase rates than did the C group at weeks 4 and 6 after surgery. The percentage of bone trabeculae area in the R group was approximately 1.7 times larger than that in the C group. Thus, we demonstrated that romosozumab administration has stimulatory effects on bony outgrowth at bone graft sites. We attribute this to the modeling effect of romosozumab.

Improvements in Intractable Lumbar and LowerExtremity Symptoms after Systemic Administration of Tocilizumab, an Anti-interleukin-6 Receptor Antibody.

STUDY DESIGN: Prospective cohort study (open-label, single-arm, and non-blinded). PURPOSE: This study aims to determine the effects of systemic administration of tocilizumab, an anti-interleukin-6 (IL-6) receptor antibody on refractory low back pain and leg symptoms. OVERVIEW OF LITERATURE: IL-6 overexpression is associated with neuropathic pain pathogenesis, which is potentially followed by chronic low back pain, including leg pain and numbness. This finding suggest that inhibition of IL-6 at the site of pain or in the transmission pathway could provide novel therapeutic targets for chronic low back pain. METHODS: This prospective, single-arm study included 11 patients (eight men; mean age, 62.7 years) with ≥3-months' chronic pain history due to lumbar disease. Subcutaneous TCZ injections were administered twice, at a 2-week interval. We evaluated low back pain, leg pain, and leg numbness using numeric rating scales and the Oswestry Disability Index (ODI; baseline and 6 months postinjection); serum IL-6 and tumor necrosis factor-α levels (baseline and 1 month postinjection); and clinical adverse events. RESULTS: Intractable symptoms reduced after TCZ administration. Low back pain improved for 6 months. Improvements in leg pain and numbness peaked at 4 and 1 month, respectively. Improvements in ODI were significant at 1 month and peaked at 4 months. Serum IL-6 was increased at 1 month. IL-6 responders (i.e., patients with IL-6 increases >10 pg/mL) showed particularly significant improvements in leg pain at 2 weeks, 1 month, and 2 months compared with nonresponders. We observed no apparent adverse events. CONCLUSIONS: Systemic TCZ administration improved symptoms effectively for 6 months, with peak improvements at 1-4 months and no adverse events. Changing serum IL-6 levels correlated with leg pain improvements; further studies are warranted to elucidate the mechanistic connections between lumbar disorders and inflammatory cytokines.

Early mobilization reduces the medical care cost and the risk of disuse syndrome in patients with acute osteoporotic vertebral fractures.

STUDY DESIGN: A retrospective observational study. PURPOSE: To compare two conservative treatments for acute osteoporotic vertebral fractures (OVFs). OVERVIEW OF LITERATURE: Several studies have reported conservative treatments for OVFs in terms of using a brace, rehabilitation, and bed rest. However, there is no consensus about the conservative treatment for OVFs. METHODS: We evaluated 68 patients with acute OVF treated in our hospital from 2007 to 2011. Thirty-four patients treated in prolonged bed rest (PBR) regimen underwent rehabilitation wearing a Jewett's brace after three weeks of bed rest. In contrast, the other 34 patients underwent rehabilitation wearing a Jewett's brace as soon as possible, which we called a stir-up (SU) regimen. We compared two treatment groups for medical costs, hospital length of stay (LOS), pain according to the numeric rating scale (NRS), the activities of daily living (ADL), and imaging studies. RESULTS: The average hospital LOS was significantly shorter in patients treated by the SU regimen, which resulted in the medical costs reduction. There was no significant difference in the NRS through 6 months between the two groups. Although many patients in both groups experienced at least one level reduction in ADL at 6 months after the injury, patients in the SU group tended to maintain their pre-injury ADL, which almost agrees with past reports. In terms of imaging studies, patients in the PBR group showed milder vertebral compression rate over time. Pseudoarthrosis occurred in 2 patients in the SU group, who presented with mild pain, which had little influence on their daily lives. CONCLUSION: We compared two conservative treatments for OVFs. Early rehabilitation was useful treatment for OVFs to minimize the risk for disuse syndrome, maintain pre-injury ADL status, and reduce the medical costs.

Percutaneously-quantified advanced glycation end-products (AGEs) accumulation associates with low back pain and lower extremity symptoms in middle-aged low back pain patients.

Advanced glycation end-products (AGEs) have been reported as a possible biomarker of ageing and metabolic diseases; however, its role in the clinical progression of these diseases remains unclear. We aimed to evaluate how AGEs are associated with clinical symptoms and comorbidities in lower back pain (LBP) patients. This prospective cohort study enrolled 636 LBP patients. They were subjected to quantified AGE (qAGE) analysis using skin autofluorescence, and their clinical symptoms and comorbidities, such as diabetes, renal failure with haemodialysis treatment, and osteoporosis, were measured. LBP, lower extremity pain, and numbness were evaluated using a visual analogue scale (VAS). The measured qAGE was significantly higher in subjects with any comorbidity. Age also showed a strong positive correlation with qAGE. qAGE and VAS for leg numbness were positively correlated. Furthermore, in LBP patients under 50-years-old, qAGE was positively correlated with VAS for LBP, lower extremity pain, and numbness. In conclusion, qAGE, as measured by skin autofluorescence measurement, was significantly higher in LBP patients with diabetes and dialysis, as well as in osteoporosis patients. Furthermore, qAGE showed potential as a biomarker for LBP, lower extremity pain, and numbness in patients under 50-years-old. If accumulated AGEs are identified at a young age, researchers should be vigilant for the development of osteoporosis and LBP-related clinical symptoms later in life.

Time-Course Changes in Bone Metabolism Markers and Density in Patients with Osteoporosis Treated with Romosozumab: A Multicenter Retrospective Study.

PURPOSE: In this multicenter retrospective observational study, we examined the early effects of romosozumab in patients with severe osteoporosis in terms of time-course changes in bone metabolism marker, improvement in bone density, and adverse effects. MATERIALS AND METHODS: Patients with severe osteoporosis were included. We investigated the progress of TRACP 5b and P1NP before and 1-2 months after the administration of romosozumab. We also investigated the bone density of lumbar spine, femoral neck, and the entire femur, measured by the DXA method, before and 5-7 months after the administration of romosozumab. RESULTS: A total of 70 patients (7 males and 63 females, age 75.0±3.6 years) participated in this study. Significant improvements in TRACP 5b and P1NP levels were observed before and 1-2 months after romosozumab administration. The average bone density of lumbar spine, femoral neck, and the entire femur were measured before and 5-7 months after romosozumab administration; and a significant increase only observed in the lumbar spine. CONCLUSION: Consistent with the findings of previous clinical studies, romosozumab has both bone formation-enhancing and bone resorption effects (dual effect). In addition, romosozumab also demonstrated improvement in bone density from the early phase after the administration, though the result was only seen in the lumbar spine.