Introduction
Although lumbar lesions such as spondylolisthesis, scoliosis, and vertebral fracture are not specific to rheumatoid arthritis (RA), the prevalence is high in RA patients. However, no ...longitudinal study has evaluated lumbar lesions in RA. This study aimed to investigate the incidence of and risk factors for lumbar lesions in RA by a prospective longitudinal cohort study.
Materials and methods
The study cohort comprised 110 patients with RA from the ‘analysis of factors for RA spinal disorders (AFFORD)’ study who completed the secondary survey at a single orthopaedic outpatient RA clinic. Radiological examination included standing radiographs and magnetic resonance imaging (MRI) of the lumbar spine. New development of spondylolisthesis, scoliosis, and vertebral fracture were assessed between baseline and secondary survey.
Results
The incidences of spondylolisthesis, scoliosis, and vertebral fracture were 42%, 16%, and 12%, respectively, during a mean follow-up of 7 years. The independent risk factor for de novo scoliosis was poor control of RA (adjusted odds ratio aOR 4.81,
p
= 0.011), while the independent risk factors for new vertebral fracture was use of glucocorticoid at secondary survey (aOR 14.87,
p
= 0.012). Patients with de novo scoliosis exhibited more severe low back pain and lower quality of life than those without.
Conclusion
The incidence of scoliosis was related in patients with poor control of RA, while new vertebral fracture was more common in patients with use of glucocorticoid. Control of disease activity might be important in preventing radiological lumbar disorders in RA.
Compensatory mechanisms, such as a decrease in thoracic spine kyphosis and posterior tilting or rotation of the pelvis, aim to achieve optimal alignment of the spine. However, the effect of muscle ...strength on these compensatory mechanisms has not been elucidated. This study aimed to investigate the impact of back muscle and lower extremity strength on compensatory mechanisms in elderly people. Overall, 409 community-dwelling elderly participants (164 men, 245 women) were included. Age, disc degeneration, and 2 or more vertebral fractures showed a significant increase of risk for sagittal vertical axis (SVA) deterioration. Conversely, stronger back, hip flexor, and knee extensor muscles reduced the risk for SVA deterioration. To investigate the association of each muscle's strength with compensatory mechanisms, 162 subjects with pelvic incidence-lumbar lordosis > 10° were selected. The linear regression model for thoracic kyphosis demonstrated a negative correlation with back muscle strength and positive correlation with vertebral fracture. The regression analysis for pelvic tilt demonstrated a positive correlation with knee extensor strength. Back, hip flexor, and knee extensor muscle strength were associated with sagittal spinal alignment. Back muscle strength was important for the decrease in thoracic kyphosis, and knee extensor strength was associated with pelvic tilt.
Hypertrophy of the ligamentum flavum (LF) is a major cause of lumbar spinal stenosis (LSS), and the pathology involves disruption of elastic fibers, fibrosis with increased cellularity and collagens, ...and/or calcification. Previous studies have implicated the increased expression of the proteoglycan family in hypertrophied LF. Furthermore, the gene expression profile in a rabbit experimental model of LF hypertrophy revealed that biglycan (BGN) is upregulated in hypertrophied LF by mechanical stress. However, the expression and function of BGN in human LF has not been well elucidated. To investigate the involvement of BGN in the pathomechanism of human ligamentum hypertrophy, first we confirmed increased expression of BGN by immunohistochemistry in the extracellular matrix of hypertrophied LF of LSS patients compared to LF without hypertrophy. Experiments using primary cell cultures revealed that BGN promoted cell proliferation. Furthermore, BGN induces changes in cell morphology and promotes myofibroblastic differentiation and cell migration. These effects are observed for both cells from hypertrophied and non-hypertrophied LF. The present study revealed hyper-expression of BGN in hypertrophied LF and function of increased proteoglycan in LF cells. BGN may play a crucial role in the pathophysiology of LF hypertrophy through cell proliferation, myofibroblastic differentiation, and cell migration.
Purpose
An osteoporotic vertebral fracture (OVF) is a common disease that causes disabilities in elderly patients. In particular, patients with nonunion following an OVF often experience severe back ...pain and require surgical intervention. However, nonunion diagnosis generally takes more than six months. Although several studies have advocated the use of magnetic resonance imaging (MRI) observations as predictive factors, they exhibit insufficient accuracy. The purpose of this study was to create a predictive model for OVF nonunion using machine learning (ML).
Methods
We used datasets from two prospective cohort studies for OVF nonunion prediction based on conservative treatment. Among 573 patients with acute OVFs exceeding 65 years in age enrolled in this study, 505 were analyzed. The demographic data, fracture type, and MRI observations of both studies were analyzed using ML. The ML architecture utilized in this study included a logistic regression model, decision tree, extreme gradient boosting (XGBoost), and random forest (RF). The datasets were processed using Python.
Results
The two ML algorithms, XGBoost and RF, exhibited higher area under the receiver operating characteristic curves (AUCs) than the logistic regression and decision tree models (AUC = 0.860 and 0.845 for RF and XGBoost, respectively). The present study found that MRI findings, anterior height ratio, kyphotic angle, BMI, VAS, age, posterior wall injury, fracture level, and smoking habit ranked as important features in the ML algorithms.
Conclusion
ML-based algorithms might be more effective than conventional methods for nonunion prediction following OVFs.
Fibrosis is one of the main pathologies caused by hypertrophy of the ligamentum flavum (LF), which leads to lumbar spinal stenosis (LSS). The fibroblast growth factor (FGF) family is a key mediator ...of fibrosis. However, acidic fibroblast growth factor (FGF-1) expression and function are not well understood in LF. This study sought to evaluate FGF-1 expression in the hypertrophied and non-hypertrophied human LF, and to investigate its function using primary human LF cell cultures.
We obtained hypertrophied lumbar LF from LSS patients and non-hypertrophied lumbar LF from control patients during surgery. Immunohistochemistry and qPCR were performed to evaluate FGF-1 expression in LF tissue. The function of FGF-1 and transforming growth factor beta 1 (TGF-β1) was also investigated using primary LF cell culture. The effects on cell morphology and cell proliferation were examined using a crystal violet staining assay and MTT assay, respectively. Immunocytochemistry, western blotting, and qPCR were performed to evaluate the effect of FGF-1 on TGF-β1-induced myofibroblast differentiation and fibrosis.
Immunohistochemistry and qPCR showed higher FGF-1 expression in hypertrophied LF compared to control LF. Crystal violet staining and MTT assay revealed that FGF-1 decreases LF cell size and inhibits their proliferation in a dose-dependent manner, whereas TGF-β1 increases cell size and promotes proliferation. Immunocytochemistry and western blotting further demonstrated that TGF-β1 increases, while FGF-1 decreases, α-SMA expression in LF cells. Moreover, FGF-1 also caused downregulation of collagen type 1 and type 3 expression in LF cells.
FGF-1 is highly upregulated in the LF of LSS patients. Meanwhile, in vitro, FGF-1 exhibits antagonistic effects to TGF-β1 by inhibiting cell proliferation and decreasing LF cell size as well as the expression of fibrosis markers. These results suggest that FGF-1 has an anti-fibrotic role in the pathophysiology of LF hypertrophy.
STUDY DESIGN.Retrospective cohort study.
OBJECTIVE.To elucidate the postoperative time-course of improvements in physical and mental well-being in patients with cervical spondylotic myelopathy (CSM).
...SUMMARY OF BACKGROUND DATA.Spinal surgeons should understand the postoperative course in detail. However, data are still needed regarding the time-course of improvements in well-being, a fundamental aspect of human life, after cervical surgery for CSM.
METHODS.One hundred consecutive patients who underwent laminoplasty for CSM, with complete clinical data preoperatively and 3 months and 2 years postoperatively, were enrolled. The Short Form-36 physical component summary (PCS) and mental component summary (MCS) scores were used as parameters of physical and mental well-being, respectively, and 4.0 was defined as the minimal clinically important difference (MCID) for both parameters.
RESULTS.On average, PCS and MCS scores were significantly improved after surgery (p < 0.001, p=0.004, respectively). Moreover, 64 and 48 patients achieved meaningful improvement (>MCID) in PCS and MCS scores at 3 months postoperatively, with maintained improvement (to 2 years) in 46/64 (71.9%) and 34/48 patients (70.8%), respectively (PCS vs. MCSp = 0.912). Additionally, 15/36 patients (41.7%) and 8/52 patients (15.4%) achieved late improvement (meaningful improvement at 2 years but not at 3 months) in PCS and MCS scores, respectively (PCS vs. MCSp = 0.007). In multivariate regression analysis, improvement in cJOA score was significantly associated with PCS improvement, but not MCS improvement, at both 3 months and 2 years (p = 0.001, p > 0.001, respectively).
CONCLUSION.The overall outcome of physical well-being improvement is decided within 3 months postoperatively, in proportion to the recovery in myelopathy, with a relatively high chance of meaningful improvement over the next 21 months. The outcome of improvement in mental well-being is decided within 3 months postoperatively, independently from the recovery in myelopathy, with a low chance of meaningful improvement over the next 21 months.Level of Evidence3
STUDY DESIGN.Retrospective cohort study.
OBJECTIVE.The aim of this study was to investigate changes in mental well-being after surgery for cervical spondylotic myelopathy (CSM) and identify factors ...associated with improvement.
SUMMARY OF BACKGROUND DATA.Posterior cervical surgery with laminoplasty significantly improves myelopathy and physical function in patients with CSM. However, its impact on mental well-being is unclear.
METHODS.Patients who underwent laminoplasty for CSM and had >2 years of follow-up were reviewed (n = 111). The mental component summary (MCS) score was used as a measure of mental well-being. The trend in MCS score change was evaluated using the Jonckheere-Terpstra trend test. Preoperative clinical scores were compared between patients with improvements greater and less than the minimal clinically important difference (MCID). Significant variables were included in a multinomial logistic regression analysis and further validated in a receiver-operating characteristic (ROC) curve analysis. Additionally, the results were confirmed in a long-term observation cohort of patients followed up for >5 years (n = 46).
RESULTS.The improvement in the average MCS score (5.6) was greater than the MCID (4.0). The trend of improvement was sustained for 2 years (P = 0.002), but not for 5 years (P = 0.130). In terms of individual cases, 56 patients (50.5%) achieved MCS score improvement greater than the MCID. These patients showed significantly lower preoperative MCS scores than those without meaningful improvement (P < 0.001). The preoperative “social functioning (SF)” score was independently associated with MCS score improvement (P = 0.001). ROC curve analysis validated the ability of preoperative SF to predict MCS score improvement at 2 and 5 years postoperatively (area under the curve0.744, 0.893, respectively).
CONCLUSION.Half of the patients achieved meaningful improvement in mental well-being. A lower preoperative SF score was independently associated with improvement. These results may help identify patients who could experience an improvement in mental well-being after surgery and develop novel approaches to achieve further improvement.Level of Evidence3
Ligamentum flavum (LF) hypertrophy is a major cause of lumbar spinal canal stenosis. Although mechanical stress is thought to be a major factor involved in LF hypertrophy, the exact mechanism by ...which it causes hypertrophy has not yet been fully elucidated. Here, changes in gene expression due to long‐term mechanical stress were analyzed using RNA‐seq in a rabbit LF hypertrophy model. In combination with previously reported analysis results, periostin was identified as a molecule whose expression fluctuates due to mechanical stress. The expression and function of periostin were further investigated using human LF tissues and primary LF cell cultures. Periostin was abundantly expressed in human hypertrophied LF tissues, and periostin gene expression was significantly correlated with LF thickness. In vitro, mechanical stress increased gene expressions of periostin, transforming growth factor‐β1, α‐smooth muscle actin, collagen type 1 alpha 1, and interleukin‐6 (IL‐6) in LF cells. Periostin blockade suppressed the mechanical stress‐induced gene expression of IL‐6 while periostin treatment increased IL‐6 gene expression. Our results suggest that periostin is upregulated by mechanical stress and promotes inflammation by upregulating IL‐6 expression, which leads to LF degeneration and hypertrophy. Periostin may be a pivotal molecule for LF hypertrophy and a promising therapeutic target for lumbar spinal stenosis.
Level 3 retrospective cohort case-control study.
This study aimed to investigate the risk factors for distal junctional kyphosis (DJK) caused by osteoporotic vertebral fractures following spinal ...reconstruction surgery, with a focus on the sagittal stable vertebra.
Despite the rarity of reports on DJK in this setting, DJK was reported to reduce when the lower instrumented vertebra (LIV) was extended to the sagittal stable vertebra in the posterior corrective fixation for Scheuermann's disease.
This study included 46 patients who underwent spinal reconstruction surgery for thoracolumbar osteoporotic vertebral fractures and kyphosis and were followed up for 1 year postoperatively. DJK was defined as an advanced kyphosis angle >10° between the LIV and one lower vertebra. The patients were divided into groups with and without DJK. The risk factors of the two groups, such as patient background, surgery-related factors, radiographic parameters, and clinical outcomes, were analyzed.
The DJK and non-DJK groups included 14 and 32 patients, respectively, without significant differences in patient background. Those with instability in the distal adjacent LIV disc had a significantly higher risk of DJK occurrence (28.6% vs. 3.2%, p=0.027). DJK occurrence significantly increased in those with the sagittal stable vertebra not included in the fixation range (57.1% vs. 18.8%, p=0.020). Other preoperative radiographic parameters were not significantly different. Instability in the distal adjacent LIV disc (adjusted odds ratio, 14.50; p=0.029) and the exclusion of the sagittal stable vertebra from the fixation range (adjusted odds ratio, 5.29; p=0.020) were significant risk factors for DJK occurrence.
Regarding spinal reconstruction surgery in patients with osteoporotic vertebral fractures, instability in the distal adjacent LIV disc and the exclusion of the sagittal stable vertebra from the fixation range were risk factors for DJK occurrence in the short term.
Purpose
Residual symptoms indicating incomplete remission of lower leg numbness or low back pain may occur after spine surgery. The purpose was to elucidate the pattern of residual symptoms 5 years ...after minimally invasive lumbar decompression surgery using a cluster analysis.
Methods
The study comprised 193 patients with lumbar spinal stenosis (LSS) (108 men, 85 women) ranging in age from 40 to 86 years (mean, 67.9 years). Each patient underwent 5-year follow-up. The Japanese Orthopedic Association score and visual analog scale scores for low back pain, leg pain, and leg numbness at 5 years were entered into the cluster analysis to characterize postoperative residual symptoms. Other clinical data were analyzed to detect the factors significantly related to each cluster.
Results
The analysis yielded four clusters representing different patterns of residual symptoms. Patients in cluster 1 (57.0%) were substantially improved and had few residual symptoms of LSS. Patients in cluster 2 (11.4%) were poorly improved and had major residual symptoms. Patients in cluster 3 (17.6%) were greatly improved but had mild residual low back pain. Patients in cluster 4 (14.0%) were improved but had severe residual leg numbness. Prognostic factors of cluster 2 were a short maximum walking distance, motor weakness, resting lower leg numbness, cofounding scoliosis, and high sagittal vertical axis.
Conclusions
This is the first study to identify specific patterns of residual symptoms of LSS after decompression surgery. Our results will contribute to acquisition of preoperative informed consent and identification of patients with the best chance of postoperative improvement.