Association between preoperative neutrophil-lymphocyte ratio, uric acid, and postoperative delirium in elderly patients undergoing degenerative spine surgery.

PURPOSE: There are few reports regarding the association between the neutrophil-lymphocyte ratio (NLR), uric acid, and the development of postoperative delirium (POD) in patients who are undergoing spine surgeries. We investigated the associations between the NLR, uric acid as a natural antioxidant, and POD in elderly patients undergoing degenerative spine surgery. PATIENTS AND METHODS: This was a single-center, observational, and retrospective study conducted in Japan. We enrolled 410 patients who underwent degenerative spine surgery. POD was diagnosed after the surgeries by psychiatrists, based on the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V). We performed a multivariable logistic regression analysis to clarify whether the NLR and uric acid values were associated with the development of POD in the patients. RESULTS: 129 of the 410 patients were excluded from the analysis. Of the 281 patients (137 females, 144 males), 32 patients (11.4%) were diagnosed with POD. The multivariable logistic regression analysis revealed that the preoperative uric acid level (adjusted odds ratio [aOR]: 0.67, 95% confidence interval [CI]: 0.49-0.90, p = 0.008) and age (aOR: 1.09, 95% CI: 1.02-1.16, p = 0.008) were significantly associated with POD. The preoperative NLR (aOR: 0.82, 95% CI: 0.60-1.13, p = 0.227) and antihyperuricemic medication (aOR: 0.97, 95% CI: 0.24-3.82, p = 0.959) were not significantly associated with POD. CONCLUSION: Our results demonstrated that in elderly patients undergoing degenerative spine surgery, the preoperative NLR was not significantly associated with POD, but a lower preoperative uric acid value was an independent risk factor for developing POD. Uric acid could have a neuroprotective impact on POD in patients with degenerative spine diseases.

Association of cervical atherosclerosis on Doppler ultrasonography and postoperative delirium in patients undergoing spinal surgery: a single-center, retrospective, observational study.

PURPOSE: This study aimed to evaluate the association between cervical atherosclerosis on Doppler ultrasonography and postoperative delirium (POD) in patients undergoing spinal surgery. METHODS: In this retrospective observational study using prospectively collected data, 295 consecutive patients aged > 50 years underwent spine surgery at a single institution between March 2015 and February 2021. Cervical atherosclerosis was defined as the intima-media thickness (IMT) of the common carotid artery (CCA) being ≥ 1.1 mm on pulsed-wave Doppler ultrasonography. Univariate and multivariate logistic regression analyses were performed with the prevalence of postoperative delirium as a dependent variable. Age, sex, body mass index, medical history, American Society of Anesthesiologists Physical Status (ASA-PS), CHADS2 score (an assessment score for stroke), instrumentation, duration of surgery, blood loss, and cervical arteriosclerosis were the independent variables. RESULTS: Twenty-seven patients of 295 (9.2%) developed delirium postoperatively. Forty-one (13.9%) of the 295 patients had cervical atherosclerosis. Their univariate analyses showed that age (P = 0.001), hypertension (P = 0.016), cancer (P = 0.046), antiplatelet agent use (P < 0.001), ASA-PS ≥ 3 (P < 0.001), CHADS2 score (P < 0.001), cervical atherosclerosis (P = 0.008), and right CCA-IMT (P = 0.007) were significantly associated with POD. However, multivariate logistic regression analyses showed older age (odds ratio [OR], 1.109; 95% confidence interval [CI] 1.035-1.188; P = 0.03) and antiplatelet agent use (OR, 3.472; 95% CI 1.221-9.870; P = 0.020) to be significantly associated with POD. CONCLUSIONS: There was a significant association between POD and the prevalence of cervical atherosclerosis using the univariate logistic regression analysis. Furthermore, multivariate logistic regression analyses showed that older age and antiplatelet agent use were independently associated with POD.

A delayed diagnostic case with complaints of severe lower back pain and sciatic nerve symptoms caused by osteoid osteoma of the sacrum: A case report.

BACKGROUND: Osteoid sacral osteomas are rare. Patients present with severe lower back pain and, rarely, sciatic nerve symptoms. CASE PRESENTATION: Herein, we report a patient with delayed diagnosis with complaints of severe lower back pain and sciatic nerve symptoms compressed by a sacral osteoid osteoma. En bloc tumor resection was performed using computed tomography (CT)-based navigation. Complete resolution of symptoms was achieved immediately after surgery. CONCLUSION: Even if a patient with an osteoid osteoma has sciatic symptoms, spinal surgeons should recognize a subgroup of patients with unexpected spinal or pelvic tumors compressing the nerve root.

Greater medial proximal tibial slope is associated with bone marrow lesions in middle-aged women with early knee osteoarthritis.

BACKGROUND: Bone marrow lesion (BML) is an important magnetic resonance finding (MRI) finding that predicts knee osteoarthritis. The purpose of this study was to investigate the influence of proximal tibial morphology on BML, including the spreading root sign (SRS), in women without radiographic knee osteoarthritis (OA). It was hypothesized that varus alignment and a greater posterior tibial slopes (PTS) are associated with BML. MATERIALS AND METHODS: A total of 359 female volunteers without knee OA who were participants in the Iwaki Health Promotion Project in 2017 or 2019 were enrolled. Participants were divided into the non-OA and early knee OA (EKOA) groups based on the Luyten's classification criteria. The presence of pathological cartilage lesions, BMLs, attritions, meniscal lesions and effusions was scored on T2-weighted fat-suppressed magnetic resonance imaging (MRI) according to the Whole-Organ MRI Scoring system. The medial proximal tibial angle (MPTA) and medial and lateral PTS (MPTS and LPTS, respectively) were measured. Regression and receiver operating characteristic (ROC) analyses were performed to reveal the relationship between BMLs and proximal tibial morphological parameters. RESULTS: Of the 359 participants, 54 (15%) were classified as having EKOA. The prevalence of cartilage lesions, BMLs, attritions, meniscal lesions and effusions was higher in the EKOA group than in the non-OA group. The two groups had no significant difference in the proximal tibial parameters. Regression analysis revealed that age and a smaller MPTA were associated with BML in both groups. Attrition (p = 0.029) and the MPTS (p = 0.025) were positively associated with BML in the EKOA group. CONCLUSION: The prevalence of BMLs was higher in women with EKOA and correlated with the varus and greater posterior slopes in those without radiographic knee OA. LEVEL OF EVIDENCE: Level III, retrospective case-control study.

Usefulness of digital tomosynthesis in diagnosing cervical ossification of the posterior longitudinal ligament: a comparative study with other imaging modalities.

PURPOSE: The diagnosis and classification of ossification of the posterior longitudinal ligament (OPLL) can be difficult with radiography alone; therefore, computed tomography (CT) is also usually performed. There are many reports on the usefulness of digital tomosynthesis (DTS) for image analysis in orthopedics. This study aimed to compare the accuracy of DTS with radiography and CT for the diagnosis and classification of cervical OPLL (C-OPLL). MATERIALS AND METHODS: We included 31 patients with OPLL and 30 with cervical spondylotic myelopathy. The patients' cervical spine radiography, DTS, and CT images were each evaluated twice by three specialists and three residents. RESULTS: In the intra-observer reliability study, there was one observer with a fair level of kappa values for radiography and DTS among three residents. The kappa values for CT were the best for all observers. In the inter-observer reliability study, the interclass correlation coefficient (ICC) values were high for both diagnosis and classification by specialists at the almost perfect level for all three imaging modalities. On the other hand, the ICC values for both diagnosis and classification for radiography by the residents were lower than those for DTS and CT. CONCLUSIONS: This study revealed that DTS may be an alternative to CT for the diagnosis and classification of C-OPLL by specialists. Caution should be exercised in diagnosing and classifying C-OPLL using radiography and DTS by residents, and the use of CT is recommended.

Prevalence of whiplash injury and its association with quality of life in local residents in Japan: A cross sectional study.

BACKGROUND: Associations between whiplash injuries and quality of life (QOL) have been previously published by conducting surveys among patients. This study aimed to investigate the prevalence of whiplash injuries in a Japanese community, and the association between whiplash injuries and QOL was also determined. METHODS: In all, 1140 volunteers participated in this study, filled out a questionnaire about whether they had experienced a whiplash injury, or had any neck pain or neck-shoulder stiffness in the previous 3 months, and completed the Medical Outcomes Study 36-Item Short-Form Health Survey. QOL was evaluated from the eight domain scores, and the Physical Component Summary (PCS) and Mental Component Summary (MCS) scores. We compared the characteristics, habits, history, medication, body mass index, and health-related QOL (eight domains, PCS and MCS scores) between the groups with whiplash injuries and no whiplash injuries for each sex. Multiple linear regressions with the forced-entry procedure were performed to evaluate the effects of a whiplash injury on the PCS and MCS. A p-value of <0.05 was considered statistically significant. RESULTS: The prevalence of whiplash injuries was 7.7% and 9.6% in men and women, respectively. The percentage of those who experienced whiplash injuries with symptoms persisting for more than 3 months was 34.3% and 24.2% in men and women, respectively. The prevalence of neck symptoms was significantly higher in the whiplash injury group than in the non-whiplash injury group. Multiple linear regression analysis showed that, although whiplash injuries were associated with poor health-related QOL in men, age was more associated with health-related QOL than whiplash injuries in both sexes. CONCLUSION: The prevalence of whiplash injuries was 7.7% and 9.6% in men and women in local residents in Japan, respectively. Whiplash injuries were poorly associated with a poor health-related QOL in men (P = 0.015).

Occupational ionizing radiation-induced skin injury among orthopedic surgeons: A clinical survey.

BACKGROUND: This study aimed to assess orthopedic surgeons' attitudes and behaviors toward occupational radiation exposure and investigate the prevalence of occupational radiation-induced skin injury among orthopedic surgeons. Similarly, risk factors for the presence of radiation-induced skin injury were investigated. METHODS: Overall, 108 orthopedic surgeons were administered self-reported questionnaires about occupational radiation exposure, and their hands were then photographed. Their fields of expertise were classified into spine, arthroplasty, sports medicine, hand, oncology, rheumatoid arthritis, pediatric orthopedic, and resident. Dermatologists evaluated the surgeons' skin conditions and classified into 3 grades of injury: grade 0, no clinical symptoms; grade 1, careful observation required; and grade 2, detailed examination required. Logistic regression analysis was performed to investigate the factors related to the presence of radiation-induced skin injury. Crude and adjusted logistic regression analysis using the backward stepwise selection method was similarly conducted. Receiver operating characteristic curve (ROC) analysis was performed to estimate the predictive power of exposure time, occupational period, and accumulated annual exposure time for radiation-induced skin injury. RESULTS: In total, 93.5% of the surgeons were careful about occupational radiation exposure, of which 76.8% used a dosimeter. Skin changes in the hands were self-reported by 42.5% of the surgeons, and radiation-induced skin injury was diagnosed in 31.4%. The accuracy of the self-reported skin changes was 100% for grade 2 and 61.5% for grade 1. Adjusted regression analysis showed that dermatologists' diagnosis-related factors were self-reported skin changes (odds ratio [OR] 3.1) and spine surgeons (OR 3.2). ROC analysis demonstrated that an occupational period >21 years and an accumulated exposure time >6696 min were considered risk factors, with ORs of 4.07 and 5.99, respectively. CONCLUSIONS: Orthopedic surgeons, particularly spine surgeons, should be regularly examined by dermatologists early in their careers for early detection of radiation-induced skin injury on the hands.

Effect of teriparatide on ligamentum flavum mesenchymal stem cells isolated from patients with ossification of the posterior longitudinal ligament.

Ossification of the posterior longitudinal ligament (OPLL) within the spinal canal sometimes leads to severe myelopathy. Teriparatide (TPD) is a recombinant human parathyroid hormone (PTH) (1-34), which promotes osteogenesis of mesenchymal stem cells (MSCs) via PTH 1 receptor (PTH1R). Although ligamentum flavum (LF)-MSCs from patients with OPLL have a high osteogenic potency, the effect of TPD on them remains unknown. In this study, we determined PTH1R expression in LF-MSCs from patients with OPLL and investigated whether TPD promotes osteogenic differentiation in them. First, LF-MSCs were isolated from patients with OPLL and cervical spondylotic myelopathy (CSM) (controls). Cultured LF-MSCs were treated with different concentrations of TPD on days 0, 7, and 14. On day 21, osteogenic gene expression was quantified. Mineralization was measured based on optical density after Alizarin Red S staining. LF-MSCs from both groups expressed PTH1R at the same level. TPD did not enhance osteogenic gene expression and mineralization in LF-MSCs from both groups. TPD did not promote the osteogenic differentiation of LF-MSCs from patients with OPLL. Thus, it may be safe for patients with OPLL. However, further confirmation of our results with in vivo studies is necessary.

Cervical arteriosclerosis is associated with preoperative clinical symptoms in patients with cervical spondylotic myelopathy.

PURPOSE: This study aims to clarify the association between cervical spondylotic myelopathy (CSM) and cervical arteriosclerosis using ultrasonography that comprehensively includes spinal cord stenosis. METHODS: Eighty-two consecutive patients aged over 60 years who underwent spine surgery were divided into those with CSM (n = 31; CSM group) and those with lumbar spinal stenosis without cervical myelopathy (n = 51; LSS group). Maximum spinal cord compression (MSCC) was evaluated for cervical stenosis severity using magnetic resonance (MR) images. The intima-media thickness (IMT) of the common carotid artery (CCA) and pulsatility index (PI) of the bilateral internal carotid artery (ICA) and vertebral artery (VA) were evaluated for cervical arteriosclerosis using pulsed-wave Doppler ultrasonography. Symptom severity was evaluated using the Japanese Orthopaedic Association (JOA) score. Spearman's correlation coefficient was used to determine the relationship between the JOA score and MSCC or IMT and PI in each group. Stepwise multiple linear regression analyses were conducted with the JOA score as a dependent variable and age, sex, body mass index, cervical arteriosclerosis assessment, and MSCC as independent variables. RESULTS: Bilateral IMT and left-side ICA-PI were significantly negatively correlated with JOA scores in the CSM group (Right-CCA-IMT: R = - 0.412, Left-IMT: R = - 0.549, Left-ICA -PI: R = - 0.205, P < 0.05), but not in the LSS group. Multiple linear regression analyses showed that CCA-IMT was the strongest independent factor associated with the preoperative JOA score. CONCLUSIONS: Cervical arteriosclerosis was associated with preoperative clinical symptoms in CSM patients.

The effect of low back pain and neck-shoulder stiffness on health-related quality of life: a cross-sectional population-based study.

BACKGROUND: This cross-sectional study sought to determine the neck-shoulder stiffness/low back pain (NSS/LBP) comorbidity rate in a Japanese community population and to compare the quality of life (QOL) in individuals with comorbid NSS/LBP, asymptomatic individuals, and those with symptoms of NSS or LBP alone. METHODS: The sample included 1122 subjects (426 men; 696 women) with NSS and LBP symptoms in the previous 3 months, and were grouped according to NSS, LBP, comorbid NSS and LBP symptoms (Comorbid), or no symptoms (NP). They completed the MOS 36-Item Short-Form Health Survey (SF-36). Health QOL was evaluated by the eight domain scores and the Physical Component Summary (PCS) and Mental Component Summary (MCS) scores after adjusting for age. The primary outcome was to examine the association between NSS/LBP, NSS, or LBP and bodily pain of the eight domains of SF-36. Secondary outcome was to compare health-related QOL among the four groups. RESULTS: Morbidity was 45.6% for NSS and 51.9% for LBP. Comorbidity affected 23% of men and 33% of women. Comorbid NSS/LBP, NSS, and LBP alone were independently associated with bodily pain after adjusting for potential confounders. Men who exhibited comorbidity had significantly lower MCS scores than asymptomatic men. Women who exhibited comorbidity and LBP had significantly lower MCS scores than those with no symptoms or NSS alone. Women who exhibited comorbidity had significantly lower MCS scores than those with no symptoms or LBP alone. CONCLUSIONS: Comorbidity of the two diseases is prevalent in 23% of the men and 33% of women in the Japanese sample. Although NSS, LBP, and comorbidity were independently associated with QOL in terms of pain, QOL was worse in individuals who exhibited comorbidity than in those without symptoms or with NSS alone.

Prevalence and associated factors of radiographic vertebral fractures in men: Rural population cross-sectional observation study in Japan.

BACKGROUND: Osteoporotic fractures constitute a major health concern in both women and men, particularly with the aging population. Many potential risk factors of vertebral fractures (VFx) have been identified in women, but not in men. Several reports have focused on the quality of life (QOL) of clinically diagnosed VFx, but not much has been reported on quantified QOL scores of incidental radiographic VFx in men. This cross-sectional study aimed to investigate the associated factors and the influence of incident radiographic VFx on QOL of men. METHODS: A total of 401 volunteer men aged 40 years or older (40-92 years) participated in this study. The mean age was 60.5 ± 11.8 years. Prevalent VFx were identified on the lateral lumbar spinal radiographs using the semiquantitative method. Bone mineral density, body composition, smoking, alcohol intake, past medical history, Mini-Mental State Examination, grip strength, gait speed, and biochemical markers were examined. QOL was evaluated using the 36-Item Short-Form Health Survey and the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire. RESULTS: Of the 401 subjects, 35 men (8.7%) had the prevalence of VFx. After adjustment for age, the presence of VFx was significantly associated with IGF-1 (odds ratio 0.985; p = 0.02). QOL scores were not significantly associated with VFx after adjustment for age. CONCLUSIONS: IGF-1 is the mediator of growth hormone, and IGF-1 stimulates the proliferation, differentiation, and mineralization of osteoblastic cells. The prevalence of VFx in men was 8.7%, and IGF-1 was significantly lower in the VFx group than in the non-VFx group.

Accuracy of pedicle screw placement by fluoroscopy, a three-dimensional printed model, local electrical conductivity measurement device, and intraoperative computed tomography navigation in scoliosis patients.

INTRODUCTION: There are several assisted methods for the accurate placement of pedicle screw (PS), including fluoroscopy, a three-dimensional (3D) printed model, a local electrical conductivity measurement device (LECMD), and intraoperative computed tomography (CT) navigation. OBJECTIVES: This study aimed to investigate the accuracy of PS placement and clinical results using different assisted methods. METHODS: This study included 553 pedicle screws in 31 patients. We divided patients into the fluoroscopy (F) group (n = 79), 3D printed model and fluoroscopy (3D + F) group (n = 150), LECMD, 3D printed model, and fluoroscopy (LECMD + 3D + F) group (n = 171), and the intraoperative CT navigation (N) group (n = 153). We evaluated the operative time, intraoperative bleeding, number of fusion vertebrae, correction rate of the main curve, apical vertebral translation, grade of PS perforation (Grade 0: no perforation; Grade 1: < 2 mm; Grade 2: 2‒4 mm; Grade 3: > 4 mm), and accuracy of PS placement. RESULTS: The N group had a significantly longer operative time. There were no significant differences in the clinical results excluding the operative time. The accuracy of PS placement was 93.7%, 91.3%, 93.6%, and 93.5% in the F, 3D + F, LECMD + 3D + F, and N groups, respectively. The Grade 2 perforation rate was 2.5%, 0%, 0.6%, and 0.7% in the F, 3D + F, LECMD + 3D + F, and N groups, respectively. CONCLUSIONS: There were no significant differences in the accuracy of PS placement and clinical results excluding the operative time. The 3D printed model, LECMD, or intraoperative CT navigation would be useful to prevent Grade 2 perforation.

Can prophylactic C4/5 foraminotomy prevent C5 palsy after cervical laminoplasty with and without posterior instrumented fusion with maximal expansion?

OBJECTIVE: To prospectively examine whether laminoplasty with maximal expansion induces C5 palsy, even with prophylactic bilateral C4/5 foraminotomy. METHODS: Thirty-five consecutive patients with cervical myelopathy underwent laminoplasty (n = 19: LP group) or posterior decompression and fusion (n = 16: PDF group) with maximal expansion. Prophylactic bilateral C4/5 foraminotomy was performed alternately in consecutive five patients undergoing each type of surgery. In each type of surgery, the first and third consecutive five patients did not undergo foraminotomy (NF subgroup: 20 patients), while the second and fourth consecutive five patients underwent foraminotomy (F subgroup: 15 patients). The widths between the gutters was equivalent to the diameter of the spinal canal, and an inclination angle of the lamina of approximately 90° was created during laminoplasty. The incidence and severity of postoperative C5 palsy were investigated. Patients with a manual muscle testing score for the deltoid muscle and/or biceps brachii muscle of ≤ 2 were diagnosed with severe palsy. RESULTS: The respective incidences of C5 palsy in the F and NF subgroups were 33% and 20% in the LP group and 50% and 20% in the PDF group. Severe palsy occurred in 67% and 0% of patients who had developed palsy in F and NF subgroups, respectively, in the LP group, and in 100% of patients in the PDF group. Furthermore, 40% of the patients with severe palsy took more than 6 months to recover. CONCLUSIONS: Laminoplasty with maximal expansion induced C5 palsy in both the LP and PDF groups, even with the addition of prophylactic bilateral C4/5 foraminotomy.

Prevalence of cervical canal stenosis in farmers: Epidemiological study based on radiographic parameter of spinal cord injury patients.

BACKGROUND: Farming is one of the effective community activities for preventing the need for new long-term care insurance services. This study was conducted to compare spinal canal diameters between patients injured during orchard work (i.e., cultivating apples) and other situations that lead to cervical spinal cord injury without major fracture or dislocation and to investigate the frequency of cervical spinal canal stenosis among farmers in a Japanese community. METHODS: Subjects were 23 patients with cervical spinal cord injury without major fracture and dislocation. Charts and radiographs of these patients were retrospectively reviewed to evaluate the characteristics of the spinal cord injury. The spinal canal diameter at the injury level in the mid-sagittal plane of magnetic resonance imaging (MRI) and mechanism of injury were compared between patients injured by orchard work and other situations. Moreover, 358 Japanese general residents were evaluated for the prevalence of cervical canal stenosis using MRI and comparisons were made between farmers group and non-farmers group. RESULTS: Spinal canal diameters at the injury level were 5.8 ± 1.4 mm in patients injured during orchard work and 5.6 ± 1.0 mm in those injured in other situations; there were no differences between the two groups. Head contusion as mechanism of injury was more frequent in the orchard work group than in other situations group. Among farmers, the rate of spinal canal stenosis increased with age, and it was 62.3% in men and 66.2% in women. CONCLUSIONS: The frequency of cervical spinal canal stenosis was high with age regardless of farming work. In addition, head contusion might be a characteristic mechanism that causes spinal cord injury during orchard work. Therefore, screening of cervical degenerative conditions among farmers and education for prevention of cervical spinal cord injury during farming work are necessary.

Improvement in the results of the simple-foot-tapping test and cross-sectional area of the dural sac in patients with C5 palsy after posterior cervical spine surgery.

INTRODUCTION: The smaller cross-sectional areas of the dural sacs in patients without C5 palsy after posterior cervical spine surgery may lead to less neurological improvement. OBJECTIVES: The aim of this retrospective study was to clarify the differences in the cross-sectional area of the dural sac in the cervical spine and neurological improvement in patients with and without C5 palsy after posterior cervical spinal surgery. METHODS: We retrospectively evaluated the postoperative cross-sectional areas of the dural sacs and neurological outcomes in patients with and without C5 palsy after posterior cervical spine surgery. We compared the postoperative cross-sectional areas of the dural sac at C4/5 and C5/6 on magnetic resonance images between the C5 palsy group (n = 19) and the no-C5 palsy group (n = 84) after posterior cervical spinal surgery 1 year postoperatively. Performance tests, namely, the 10-s grip-and-release test and the 10-s single-foot-tapping (FT) test, were compared between the two groups. RESULTS: Postoperative cross-sectional areas of the dural sac at C4/5 and C5/6 (233.3 mm2 and 226.6 mm2, respectively) in the C5 palsy group were significantly larger (P = 0.0036 and P = 0.0039, respectively) than those (195.0 mm2 and 193.8 mm2, respectively) in the no-C5 palsy group. Postoperative gain in the grip-and-release test was similar between the two groups. Postoperative gain in the FT test (4.9 times) in the C5 palsy group was significantly larger (P = 0.0060) than that (1.8 times) in the no-C5 palsy group. CONCLUSIONS: In the C5 palsy group 1 year after posterior cervical spine surgery, the cross-sectional areas of the dural sac were larger, and the 10-s single FT test improved noticeably.

Facilitation of Chemotaxis Activity of Mesenchymal Stem Cells via Stromal Cell-Derived Factor-1 and Its Receptor May Promote Ectopic Ossification of Human Spinal Ligaments.

Mesenchymal stem cells (MSCs) have been used to elucidate the pathogenesis of numerous diseases. Our recent study showed that MSCs may conduce to the ossification of spinal ligaments. Stromal cell-derived factor-1 (SDF-1) and CXC chemokine receptor 4 (CXCR4) regulate MSC migration. Moreover, their expression is elevated in sites of damage and remodeling in pathologic states. We explored the possible role of the SDF-1/CXCR4 axis in the chemotactic behavior of MSCs in the ossification of spinal ligaments. Specimens of thoracic vertebra ossified ligamentum flavum (OLF) and non-OLF plaques were received from patients in whom we had performed spine surgery. Paraffin-embedded tissue sections were prepared for immunohistochemical staining. Cultured MSCs from the ligamentum flavum were prepared for in vitro analyses. We observed SDF-1 and CXCR4 localization immunohistochemically in the perivascular area and collagenous matrix of ligaments and in chondrocytes near the ossification front of OLF. And then, immunohistochemical staining showed a close relationship between MSCs and the SDF-1/CXCR4 axis. In the in vitro analyses, expression of the SDF-1/CXCR4 and the migratory capacity of MSCs in OLF were remarkably higher compared with non-OLF MSCs. Furthermore, the migration of MSCs was upregulated by SDF-1 and downregulated by treatment with AMD3100 (C28H54N88HCl), a specific antagonist for CXCR4. All in vitro test data showed a significant difference in MSCs from OLF compared with non-OLF MSCs. Our results reveal that the SDF-1/CXCR4 axis may contribute to an MSC-mediated increase in the ossification process, indicating that the SDF-1/CXCR4 axis may become a potential target for a novel therapeutic strategy for ossification of spinal ligaments.

Predicting radiological vertebral fractures with a combined physical function and body composition scoring system.

The objective of this study was to investigate the incidence of vertebral fractures (VFx) and the value of physical function (PF) and body composition (BC) for predicting VFx in a Japanese population. This study included 307 subjects (113 men, 194 women) at least 40 years of age who were assessed at community health check-ups in 2008 and 2016. PF was assessed by grip strength and by single-leg stance, timed up-and-go, and 30-s chair stand tests, each scored from 0 to 3 for a possible total of 12 points (higher scores reflect lower function). BC was scored on bioelectrical impedance measurements of trunk and appendage muscle volume, with 6 possible points. We diagnosed radiological VFx semiquantitatively on lateral views of the lumbar spine, and measured bone mineral status by quantitative ultrasound (QUS) of the calcaneus. We conducted logistic regression analysis with VFx as the dependent variable and age, sex, BMI, QUS, PF score, and BC score as independent variables. In 8 years, 36 participants (12%) sustained new VFx. After correcting for age, sex, BMI, and QUS, the odds of VFx increased with a PF score ≥ 8 (OR 5.6; 95% CI 1.21-25.90; P = 0.028) and increased further with a PF + BC score ≥ 9 (OR 8.1; 95% CI 1.80-36.00; P < 0.01). Both PF and BC are important for predicting fragility fractures. The scoring system used here may reflect small differences better than categorical (single cutoff) definitions of poor function.

A study of the factors associated with cervical spinal disc degeneration, with a focus on bone metabolism and amino acids, in the Japanese population: a cross sectional study.

BACKGROUND: The physical and biochemical factors responsible for cervical disc degeneration, and resulting in various spinal disorders, remain unclear. This study aimed to evaluate the correlation between cervical spinal canal stenosis and degeneration of intervertebral discs, and to analyze the factors related to disc degeneration in the Japanese population. METHODS: Three hundred and forty-four Japanese general residents underwent investigations, including magnetic resonance imaging of the cervical spine, in our health check project. We measured anteroposterior diameters at the levels of the cervical spinal disc in mid sagittal plane magnetic resonance imaging and evaluated disc degeneration. Spearman correlation coefficient was used to evaluate whether the diameters were correlated with disc degenerative scores. Stepwise multiple linear regression analysis was conducted with the score of disc degeneration as the dependent variable; and age, physical measurement values, bone mineral density of the forearm, and the value of serum bone metabolic markers and amino acids as the independent variables for each sex. RESULTS: As the age increased, the anteroposterior diameters decreased in both sexes. The minimum anteroposterior diameters were correlated with the disc degenerative scores (Spearman r = - 0.59, p < 0.001 in men, Spearman r = - 0.53, p < 0.001 in women). In multiple linear regression analysis, age, cross-linked N-telopeptide of type 1 collagen and isoleucine were significantly correlated with the cervical disc degenerative score in men (R2 = 0.47), and age and lysine were significantly correlated with the degenerative score in women (R2 = 0.50). CONCLUSION: The factors responsible for cervical disc degeneration differed between men and women. Whether modifying these significant factors is possible, or whether this intervention would contribute to prevention of disc degeneration requires future studies.

Associations between neck symptoms and LDL cholesterol in a cross-sectional population-based study.

BACKGROUND: Studies have reported associations between neck pain and degenerative changes in the cervical spine in women, and between neck pain and obesity or metabolic syndrome. The present study investigated associations between neck pain or stiffness and lipid profiles in subjects recruited from the general population of a Japanese community. METHODS: The 1122 volunteers who participated in this study included 426 men (age 52.6 ± 15.5 years; body mass index 23.6 ± 3.2) and 696 women (age 55.3 ± 15.3 years; body mass index 22.2 ± 3.4). Each subject filled out a questionnaire about any neck pain or neck-shoulder stiffness experienced in the previous 3 months. We recorded the following laboratory results related to metabolic factors, including lipid profiles: total cholesterol, LDL and HDL cholesterol, triglycerides, free fatty acids, glucose, and hemoglobin A1c. We conducted logistic and linear regression analyses using the prevalence of neck pain or neck-shoulder stiffness as the dependent variable and age, sex, body mass index, and laboratory data as independent variables. RESULTS: There was no significant difference in the prevalence of neck pain between men (20.5%) and women (21.5%). However, the prevalence of neck and shoulder stiffness was significantly higher in women (60.3%) than in men (38.0%; P < 0.05). Logistic and linear regression analyses showed a significant negative correlation between the prevalence of neck pain and LDL cholesterol (odds ratio [OR], 0.958; 95% CI, 0.921-0.997), and between the prevalence of neck-shoulder stiffness and age (OR, 1.025; 95% CI, 1.013-1.038) and gender (OR, 0.362; 95% CI, 0.25-0.494). CONCLUSION: LDL cholesterol was correlated with neck pain in this cross-sectional population-based study.

Serum pentosidine concentration is associated with radiographic severity of lumbar spondylosis in a general Japanese population.

The aim of this study was to investigate the relationship between the radiographic severity of lumbar spondylosis (LS) and serum bone metabolic markers. A total of 681 individuals volunteered for this study (269 men, 412 women; age: 54.9 ± 14.3; body mass index [BMI]: 23.1 ± 3.3 kg/m2). Lateral lumbar radiographs were evaluated in each intervertebral section (L1/2 to L5/S1) using the Kellgren-Lawrence grade (KL). If at least one intervertebral section was graded as KL 2 or greater, the participants were considered to have LS. The summation of each section of intervertebral section was used as the radiographic severity value of LS. In addition, bone status was evaluated with an osteo-sono assessment index (OSI) at the calcaneus. Serum bone alkaline phosphatase (µg/mL), N-telopeptide of type I collagen (nMBCE/L), and pentosidine (pmol/mL) concentrations were examined and used as the bone metabolism index. Stepwise multiple linear regression analysis was conducted with the radiographic severity value of LS as the dependent variable and age, sex, BMI, OSI, and the value of serum bone metabolic markers as the independent variables. The total number of LS participants was 470 (69.0 %); the frequency of LS was higher in men (n = 198) than in women (n = 272; P = 0.036, χ 2 test). The mean severity value of LS was 7.1 ± 4.4, and the mean value of pentosidine was 120.7 ± 54.8 pmol/mL. On multiple regression analysis, age (B = 0.190, ß = 0.611), sex (men = 1, women = 2; B = -0.900, ß = -0.099), BMI (B = 0.185, ß = 0.136), and pentosidine (B = 0.009, ß = 0.115) were significantly correlated with the severity of LS. Serum pentosidine concentration was positively correlated with the radiographic severity of LS in this cross-sectional study.