The predictive value of a novel site-specific MRI-based bone quality assessment,endplate bone quality (EBQ), for severe cage subsidence among patients undergoing standalone lateral lumbar interbody fusion

BACKGROUND CONTEXTStudies have shown that site-specific bone density measurements had more predictive value for complications than standard whole-region measurements. Recently, MRI-based assessments of vertebral bone quality (VBQ) were introduced. However, there have been few studies that investigate the association between site-specific MRI bone assessment and osteoporosis-related complications in patients undergoing lumbar interbody fusion. In this work, we created a novel site-specific MRI-based assessment of the endplate bone quality (EBQ) and assessed its predictive value for severe cage subsidence following standalone lateral lumbar interbody fusion (SA-LLIF).PURPOSETo investigate the predictive value of a novel MRI-based bone assessment for severe cage subsidence after SA-LLIF.STUDY DESIGN/SETTINGRetrospective cohort study.PATIENT SAMPLEPatients who underwent SA-LLIF from 2008 to 2019 at a single, academic institution with available preoperative lumbar CT and T1-weighted MRIs.OUTCOME MEASURESAssociation between EBQ and severe subsidence after SA-LLIF.METHODSWe retrospectively reviewed the records of SA-LLIF patients treated between 2008 and 2019. EBQ was measured using preoperative non-contrast T1-weighted MRIs of the lumbar spine. EBQ was defined as the average value of signal intensity of both endplates divided by that of the cerebrospinal fluid space at the level of L3. Bivariate and multivariable analyses with generalized linear mixed models were performed and set binary severe subsidence as the outcome.RESULTSTwo hundred five levels in 89 patients were included. Fifty levels (24.4%) demonstrated severe subsidence. Bone mineral density measured by quantitative computed tomography was significantly lower in the subsidence group. Both VBQ and EBQ were significantly higher in the subsidence group. The EBQ plus Modic change (MC) model demonstrated that the effect of EBQ was independent of MC. In multivariate analyses adjusted with QCT-vBMD, EBQ showed a significant association with cage subsidence whereas VBQ only showed a marginal trend. The EBQ-based prediction model for severe subsidence showed better goodness of fit compared to the VBQ-based model.CONCLUSIONSHigh EBQ was an independent factor for severe cage subsidence after SA-LLIF and the EBQ-based model showed better goodness of fit compared to VBQ- or MC-based models. EBQ assessment before SA-LLIF may provide insight into a patient's risk for severe subsidence.     

Bone morphogenic protein-2 signaling in human disc degeneration and correlation to the Pfirrmann MRI grading system

BACKGROUND CONTEXTBack and neck pain secondary to disc degeneration is a major public health burden. There is a need for therapeutic treatments to restore intervertebral disc (IVD) composition and function.PURPOSETo quantify ALK3, BMP-2, pSMAD1/5/8 and MMP-13 expression in IVD specimens collected from patients undergoing surgery for disc degeneration, to correlate ALK3, BMP-2, pSMAD1/5/8 and MMP-13 expression in IVD specimens to the 5-level Pfirrmann MRI grading system, and to compare ALK3, BMP-2, pSMAD1/5/8 and MMP-13 expression between cervical and lumbar degenerative disc specimens.STUDY DESIGNAn immunohistochemical study assessing ALK3, BMP-2, pSMAD1/5/8, and MMP-13 expression levels in human control and degenerative IVD specimens.METHODSHuman IVD specimens were collected from surgical patients who underwent discectomy and interbody fusion at our institution between 1/2015 and 8/2017. Each patient underwent MRI prior to surgery. The degree of disc degeneration was measured according to the 5-level Pfirrmann MRI grading system. Patients were categorized into either the 1) control group (Pfirrmann grades I-II) or 2) degenerative group (Pfirrmann grades III-V). Histology slides of the collected IVD specimens were prepared and immunohistochemical staining was performed to assess ALK3, BMP-2, pSMAD1/5/8, and MMP-13 expression levels in the control and degenerative specimens. Expression levels were also correlated to the Pfirrmann criteria. Lastly, the degenerative specimens were stratified according to their vertebral level and expression levels between the degenerative lumbar and cervical discs were compared.RESULTSFifty-two patients were enrolled; however, 2 control and 2 degenerative patients were excluded due to incomplete data sets. Of the remaining 48 patients, there were 12 control and 36 degenerative specimens. Degenerative specimens had increased expression levels of BMP-2 (p=.0006) and pSMAD1/5/8 (p<.0001). Pfirrmann grade 3 (p=.0365) and grade 4 (p=.0008) discs had significantly higher BMP-2 expression as compared to grade 2 discs. Pfirrmann grade 4 discs had higher pSMAD1/5/8 expression as compared to grade 2 discs (p<.0001). There were no differences in ALK3 or MMP-13 expression between the control and degenerative discs (p>.05). Stratifying the degenerative specimens according to their vertebral level showed no significant differences in expression levels between the lumbar and cervical discs (p>.05).CONCLUSIONSBMP-2 and pSMAD1/5/8 signaling activity was significantly upregulated in the human degenerative specimens, while ALK3 and MMP-13 expression were not significantly changed. The expression levels of BMP-2 and pSMAD1/5/8 correlate positively with the degree of disc degeneration measured according to the Pfirrmann MRI grading system.CLINICAL SIGNIFICANCEBMP-SMAD signaling represents a promising therapeutic target to restore IVD composition and function in the setting of disc degeneration.     

腰椎椎间隙高度与上位椎体高度的比值与椎间盘退行性变Pfirrmann分级的相关性

目的 探讨腰椎椎间隙高度与上位椎体高度的比值与椎间盘退行性变程度之间的关系,为腰椎椎间盘退行性疾病的诊断和治疗提供客观准确的依据。方法 回顾性分析2019年1月—2019年6月来本院就诊的61例腰椎椎间盘退行性变患者临床资料。在腰椎侧位X线片上测量腰椎椎间隙及相应上位椎体的高度,并计算椎间隙高度与上位椎体高度的比值;在腰椎矢状位MRI上评估腰椎椎间盘退行性变Pfirrmann分级;比较不同Pfirrmann分级椎间盘的椎间隙高度与上位椎体高度比值的差异,并采用Spearman相关分析研究椎间隙高度与上位椎体高度比值与相应节段椎间盘Pfirrmann分级之间的相关性。结果 除L₁/L₂节段,其余各节段椎间隙高度与上位椎体高度比值均随着Pfirrmann分级增加而逐渐减小,差异均有统计学意义（P < 0.05）。相同Pfirrmann分级的不同节段椎间盘之间椎间隙高度与上位椎体高度比值差异无统计学意义（P > 0.05）。Spearman相关分析结果显示,L₂/L₃、L₃/L₄、L₄/L₅、L₅/S₁节段Pfirrmann分级与椎间隙高度与上位椎体高度比值呈负相关（r =-0.568,P < 0.05）。结论 临床上测量L₂/L₃、L₃/L₄、L₄/L₅、L₅/S₁节段椎间隙高度与上位椎体高度比值对腰椎椎间盘退行性疾病的诊断可能具有重要意义。     

Analysis of the influence of species,intervertebral disc height and Pfirrmann classification on failure load of an injured disc using a novel disc herniation model

Background ContextAnnular repair devices offer a solution to recurrent disc herniations by closing an annular defect and lowering the risk of reherniation. Given the significant risk of neurologic injury from device failure it is imperative that a reliable preclinical model exists to demonstrate a high load to failure for the disc repair devices.PurposeTo establish a preclinical model for disc herniation and demonstrate how changes in species, intervertebral disc height and Pfirrmann classification impacts failure load on an injured disc. We hypothesized that: (1) The force required for disc herniation would be variable across disc morphologies and species, and (2) for human discs the force to herniation would inversely correlate with the degree of disc degeneration.Study designAnimal and human cadaveric biomechanical model of disc herniation.MethodsWe tested calf lumbar spines, bovine tail segments and human lumbar spines. We first divided individual lumbar or tail segments to include the vertebral bodies and disc. We then hydrated the specimens by placing them in a saline bath overnight. A magnetic resonance images were acquired from human specimens and a Pfirrmann classification was made. A stab incision measuring 25% of the diameter of the disc was then done to each specimen along the posterior intervertebral disc space. Each specimen was placed in custom test fixtures on a servo-hydraulic test frame (MTS, Eden Prarie, MN) such that the superior body was attached to a 10,000 lb load cell and the inferior body was supported on the piston. A compressive ramping load was placed on the specimen in load control at 4 MPa/sec stopping at 75% of the disc height. Load was recorded throughout the test and failure load calculated. Once the test was completed each specimen was sliced through the center of the disc and photos were taken of the cut surface.ResultsFifteen each of calf, human, and bovine tail segments were tested. The failure load varied significantly between specimens (p<.001) with human specimens having the highest average failure load (8154±2049 N). Disc height was higher for lumbar/bovine tail segments as compared to calf specimens (p<.001) with bovine tails having the highest disc height (7.1±1.7 mm). Similarly, human lumbar discs had a cross sectional area that was greater than both bovine tail/calf lumbar spines (p<.001). There was no correlation between disc height and failure load within each individual species (p>.05). Cross sectional area and failure load did not correlate with failure load for human lumbar spine and bovine tails (p>.05) but did correlate with calf spine (r=0.53, p=.04). There was a statistically significant inverse correlation between disc height and Pfirrmann classification for human lumbar spines (r=?0.84, p<.001). There was also a statistically significant inverse relationship between Pfirrmann classification and failure load (r=?0.58, p=.02).ConclusionsWe have established a model for disc herniation and have shown how results of this model vary between species, disc morphology, and Pfirrmann classification. Both hypotheses were accepted: The force required for disc herniation was variable across species, and the force to herniation for human spines was inversely correlated with the degree of disc degeneration. We recommend that models using human intervertebral discs should include data on Pfirrmann classification, while biomechanical models using calf spines should report cross sectional area. Failure loads do not vary based on dimensions for bovine tails.Clinical SignificanceOur analysis of models for disc herniation will allow for quicker, reliable comparisons of failure forces required to induce a disc herniation. Future work with these models may facilitate rapid testing of devices to repair a torn/ruptured annulus.     

Bone quality in patients with osteoporosis undergoing lumbar fusion surgery: analysis of the MRI-based vertebral bone quality score and the bone microstructure derived from microcomputed tomography

BACKGROUND CONTEXTOsteoporosis is a risk factor for instrumentation failure in spine surgery. Bone strength is commonly assessed by bone mineral density (BMD) as a surrogate marker. However, BMD represents only a portion of bone strength and does not capture the qualitative dimensions of bone. Recently, the magnetic resonance imaging (MRI)-based vertebral bone quality (VBQ) score was introduced as a novel marker of bone quality. However, it is still unclear if the VBQ score correlates with in-vivo bone microstructure.PURPOSEThe aims of the study were (1) to demonstrate differences in MRI-based (VBQ) and in-vivo (microcomputed tomography; μCT) bone quality between osteopenic/osteoporotic and normal bone, (2) to show the correlation between VBQ, bone microstructure and volumetric BMD (vBMD), and (3) to determine the predictive value of the VBQ score for the prevalence of osteopenia/osteoporosis.STUDY DESIGN/SETTINGRetrospective cross-sectional study.PATIENT SAMPLE267 patients who underwent posterior lumbar fusion surgery from 2014 to 2021 at a single academic institution. Bone biopsies were harvested intraoperatively in 118 patients.OUTCOME MEASURESVBMD, VBQ score, and bone microstructure parameters derived from μCT.METHODSQuantitative computed tomography (QCT) measurements were performed at the lumbar spine and the L1/L2 average was used to categorize patients with a vBMD ≤120mg/cm³ as osteopenic/osteoporotic. The VBQ score was determined by dividing the median signal intensity of the L1–L4 vertebrae by the signal intensity of the cerebrospinal fluid using sagittal T1-weighted MRI scans. Intraoperative bone biopsies from the posterior superior iliac spine were obtained and evaluated with μCT. VBQ scores and μCT parameters were compared between the normal and the osteopenic/osteoporotic group. Correlations between VBQ score, μCT parameters and vBMD were assessed with Spearman's correlation (ρ). Receiver operating characteristic (ROC) analysis was performed to determine the VBQ score as a predictor for osteopenia/osteoporosis. Multiple linear regression analysis with vBMD L1/L2 as outcome was used to identify independent predictors from VBQ, μCT parameters and demographics.RESULTS267 patients (55.8% female, age 63.3 years, BMI 29.7 kg/m²; n=118 with bone biopsy) with a prevalence of osteopenia/osteoporosis of 65.2% were analyzed. In the osteopenic/osteoporotic group the VBQ score, structured model index (SMI), and trabecular separation (Tb.Sp) were significantly higher, whereas bone volume fraction (BV/TV), connectivity density (Conn.D) and trabecular number (Tb.N) were significantly lower. There were significant correlations between VBQ and μCT parameters ranging from ρ=-.387 to ρ=0.314 as well as between vBMD and μCT parameters ranging from ρ=-.425 to ρ=.421, and vBMD and VBQ (ρ=-.300, p<.001). ROC analysis discriminated osteopenia/osteoporosis with a sensitivity of 84.7% and a specificity of 40.6% at a VBQ score threshold value of 2.18. Age, BV/TV and trabecular thickness (Tb.Th), but not VBQ, were significant independent predictors for vBMD (corrected R²=0.434).CONCLUSIONSThis study demonstrated for the first time that the VBQ score is associated with trabecular microstructure determined by μCT. The bone microstructure and VBQ score were significantly different in patients with impaired vBMD. However, the ability to predict osteopenia/osteoporosis with the VBQ score was moderate. The VBQ score appears to reflect additional bone quality characteristics and might have a complementary role to vBMD. This enhances our understanding of the biological background of the radiographic VBQ score and might be a take-off point to evaluate the clinical utility of it as non-invasive screening tool for bone quality.     

Asymmetry between the superior and inferior endplates is a risk factor for lumbar disc degeneration

Endplate pathology plays an important role in the development of lumbar disc degeneration. Previous research paid little attention to differences between the superior and inferior endplates as a possible risk factor for disc degeneration. The purpose of this study was to test the hypothesis that asymmetry between the superior and inferior endplates is a risk factor for the development of lumbar disc degeneration. A total of 134 patients with lumbar disc herniation (LDH) and 100 healthy adults (“Controls”) underwent magnetic resonance imaging scans. Each disc was categorized as non‐degenerated (Pfirrmann grades I–II) or degenerated (Pfirrmann grades III–V) and get the following three groups: “Degenerated LDH” discs (n = 145), “Non‐degenerated LDH” discs (n = 525) and “Non‐degenerated Control” discs (n = 500). On mid‐sagittal image, the lumbar endplate morphology could be categorized into three types: Flat, concave, and irregular. Superior and inferior endplates of a given disc were “symmetric” if both were of the same type, and “asymmetric” if they were of different types. The proportion of asymmetric endplates at L4–5 was higher in the “Degenerated LDH” discs group (47%) than in the “Non‐degenerated LDH” discs group (21%) or “Non‐degenerated Control” discs group (7%) (p < 0.05). At L5‐S1 the proportions were 73%, 55%, and 38% (p < 0.05). Asymmetry of superior and inferior endplates in the mid‐sagittal plane is a risk factor for lumbar disc degeneration. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2469–2475, 2018.

     

Influences of disc degeneration and bone mineral density on the structural properties of lumbar end plates

Background contextImplants subsidence is a frequent complication of interbody fusion, which can result in pain, deformity, nerve damage, and even failure of surgery. The end plates as the interface between implants and the vertebral bodies play a very important role in sharing the compression on the vertebral bodies. The information on the structural property distribution of the end plate and its relationship with bone mineral density (BMD) and disc degeneration will be of great significance for the reduction in implants subsidence and improvement in related operative procedures to increase the success rate of interbody fusion.PurposeTo investigate the structural property distribution of the lumbar end plate; the effects of disc degeneration on the biomechanical properties of the lumbar end plate; and the relationship between the biomechanical properties of the lumbar end plate and BMD.Study designA biomechanical study was conducted in human cadaveric lumbar spine models.MethodsIndentation tests were performed at 24 standardized test sites in 120 bony end plates of intact human vertebrae (L1–L5) using a 1.5-mm–diameter, hemispherical indenter at a speed of 0.2 mm/s. The failure load at each test site was determined using the load-displacement curve. Disc condition was evaluated using a four-point grading scale and bone density was measured using the lateral dual-energy radiograph absorptiometry scans. All end plates were divided into different disc degeneration groups based on the states of the adjacent degenerative discs and BMD groups according to BMD values of the corresponding vertebral bodies. The experimental results were statistically analyzed using the SPSS 15.0 with the disc degeneration and BMD being considered as independent factor, and the failure loads of the superior and inferior end plates were also compared.ResultsThe peripheral regions of lumbar end plates were stronger than the central regions (p<.05), with the posterolateral sites in front of vertebral pedicles being the strongest regions. The inferior lumbar end plates were found to be stronger than the superior lumbar end plates (p<.05). The disc degeneration was negatively correlated with the failure loads of the lumbar end plates (r_s=?0.563; p<.01). With increasing disc degeneration, the decreases of failure loads were nonuniform across the lumbar end plate, and the central region became weak with little strength change on the end plate periphery. The BMD was positively correlated with the failure loads of the lumbar end plates (r_s=0.812; p<.01). The failure loads decreased uniformly across the end plate surfaces as the BMD dropped, and the BMD decrease did not change the structural property distributions of lumbar end plates.ConclusionsPreoperative evaluation of the states of intervertebral discs and BMD of patients is necessary for predicting risks of implants subsidence after interbody fusion. For patients with or without disc degeneration or osteoporosis, the implants should be placed at the peripheral regions, especially the posterolateral sites, to acquire higher mechanical strength to reduce subsidence as much as possible.     

Vertebral bone quality score predicts fragility fractures independently of bone mineral density

BackgroundCurrent evidence suggests that dual-energy x-ray absorptiometry (DXA) scans, the conventional method defining osteoporosis, is underutilized and, when used, may underestimate patient risk for skeletal fragility. It has recently been suggested that other imaging modalities may better estimate bone quality, such as the magnetic resonance imaging (MRI)-based vertebral bone quality (VBQ) score which also may assess vertebral compression fracture risk in patients with spine metastases.PurposeTo evaluate whether VBQ score is predictive of fragility fractures in a population with pre-existing low bone density and at high-risk for fracture.Study Design/SettingRetrospective single-center cohort.Patient SamplePatients followed at a metabolic bone clinic for osteopenia and/or osteoporosis.Outcome MeasuresRadiographically-documented new-onset fragility fracture.MethodsPatients with a DXA and MRI scans at the time of consultation and ≥2-year follow-up were included. Details were gathered about patient demographics, health history, current medication use, and serological studies of kidney function and bone turnover. For each patient, VBQ score was calculated using T1-weighted lumbar MRI images. Univariable and multivariable analyses were used to identify the independent predictors of a new fragility fracture. To support the construct validity of VBQ, patient VBQ scores were compared to those in a cohort of 45 healthy adults.ResultsSeventy-two (39.1%) study participants suffered fragility fractures, the occurrence of which was associated with higher VBQ score (3.50 vs. 3.01; p<.001), chronic glucocorticoid use (30.6% vs. 15.2%; p=.014), and a history of prior fragility fracture (36.1% vs. 21.4%; p=.030). Mean VBQ score across all patients in the study cohort was significantly higher than the mean VBQ score in the healthy controls (p<.001). In multivariable analysis, new-onset fracture was independently associated with history of prior fracture (OR=6.94; 95% confidence interval [2.48–19.40]; p<.001), higher VBQ score (OR=2.40 per point; [1.30–4.44]; p=.003), higher body mass index (OR=1.09 per kg/m²; [1.01–1.17]; p=.03), and chronic glucocorticoid use (OR=2.89; [1.03–8.17]; p=0.043). Notably, DXA bone mineral density (BMD) was not found to be significantly predictive of new-onset fractures in the multivariable analysis (p=.081).ConclusionsHere we demonstrate the novel, MRI-derived VBQ score is both an independent predictor of fragility fracture in at-risk patients and a superior predictor of fracture risk than DXA-measured BMD. Given the frequency with which MRIs are obtained by patients undergoing spine surgery consultation, we believe the VBQ score could be a valuable tool for estimating bone quality in order to optimize the management of these patients.     

ISSLS prize in clinical science 2022: accelerated disc degeneration after pubertal growth spurt differentiates adults with low back pain from their asymptomatic peers

Purpose

In this prospective observational cohort study, the development of lumbar intervertebral discs (LIVD) on magnetic resonance imaging (MRI) was investigated from childhood to adulthood with emphasis on the possible association of disc degeneration (DD) to low back pain (LBP).

Methods

In 2021, 89 subjects who were enrolled in 1994 in a longitudinal study with lumbar spine MRI at ages 8, 11 and 18 were invited to participate in a long-term follow-up comprising a clinical examination, selected patient-reported outcome measures and a lumbar spine MRI. We assessed all MRIs (three lowest LIVDs) with the Pfirrmann summary score, and the ratio of signal intensity of nucleus pulposus to signal intensity of cerebrospinal fluid (SINDL). We further analyzed whether disc changes at any age were associated with self-reported LBP at age 34.

Results

Of the 48 subjects in the follow-up, 35 reported LBP at age 34. The Pfirrmann summary score significantly increased with age (p < 0.001). Subjects reporting LBP at age 34 demonstrated statistically significantly higher summary scores at age 18 and 34 compared to asymptomatic subjects (p = 0.004 at age 18, and p = 0.039 at age 34). SINDL significantly decreased with age (p < 0.001 for all levels separately), but no significant differences between subjects with or without LBP at age 34 were noticed.

Conclusion

Subjects with LBP at age 34 had more widespread or severe DD already at age 18 compared to those without LBP.

     

Patient physiology influences the MRI-based vertebral bone quality score

BACKGROUND CONTEXTOsteoporosis is a critical issue affecting postmenopausal women and the aging population. A novel magnetic resonance imaging (MRI)-based vertebral bone quality (VBQ) score has been proposed as a method to identify poor bone quality and predict fragility fractures. The diagnostic accuracy of this tool is not well understood.PURPOSETo examine the ability of VBQ to predict osteoporosis and osteopenia, its correlation with dual-energy x-ray absorptiometry (DEXA), and the influence of patient-specific factors upon the score.STUDY DESIGNRetrospective cohort study.PATIENT SAMPLEPatients over the age of 18 with a DEXA scan and noncontrast, T1-weighted MRI of the lumbar spine completed within a 2-year period.OUTCOME MEASURESArea-under-curve (AUC) values of the VBQ score predicting osteopenia and osteoporosis when controlling for patient characteristics.METHODSPatients with noncontrast, T1-weighted MRIs of the lumbar spine and DEXA scans completed within a 2-year time frame were retrospectively reviewed. Patient demographics and medical risk factors for osteoporosis were identified and compared. VBQ scores were measured by two trained researchers and interrater reliability was calculated. Patients were separated into three groups defined by lowest DEXA T-score: Healthy Bone, Osteopenia, and Osteoporosis. analysis of variance, Kruskal-Wallis test, chi-square, t tests, Mann-Whitney U tests, and multivariate linear regression were performed to examine the relationship between patient characteristics, DEXA t-scores, and VBQ scores. Receiver operating characteristic analysis and AUC values were generated for the prediction of osteopenia and osteoporosis.RESULTSA total of 156 patients were included for analysis. Sufficient inter-rater reliability was determined for VBQ measures (intraclass correlation coefficient: 0.81). Most patients were female (83%), postmenopausal (81%), and had hyperlipidemia (64%). Patients with hyperlipidemia and healthy bone density by DEXA had elevated baseline VBQ scores (p<.001) reflective of values seen in osteopenia and osteoporosis. The AUC of the VBQ score predicting osteopenia and osteoporosis changed to be more concordant with DEXA results after controlling for hyperlipidemia (AUC=0.72, 0.70 vs. AUC=0.88, 0.89; p<.001). Sub-analysis of hyperlipidemia subtypes revealed that elevated high-density lipoprotein is associated with elevated VBQ scores.CONCLUSIONSHyperlipidemia increased the MRI-based VBQ score in our healthy bone population. The high signal intensities resembled values seen in osteopenia and osteoporosis, suggesting that physiologic variables which impact bone composition may influence the VBQ score. Specifically, elevated high-density lipoprotein may contribute to this. The microarchitectural changes and the clinical implications of these factors need further exploration.     

Novel MRI-based score for assessment of bone density in operative spine patients

BackgroundGood bone quality is key in avoiding a multitude of afflictions, including osteoporotic fragility fractures and poor outcomes after spine surgery. In patients undergoing instrumented spine fusion, bone quality often dictates screw pullout strength, insertional torque, and vertebral body loading properties. While dual-energy X-ray absorptiometry (DEXA) screening is the current method of assessing bone mineral density, the majority of patients do not have DEXA measurements available before undergoing surgical instrumentation.PurposeTo create a simple magnetic resonance imaging (MRI)-based score to evaluate bone quality and evaluate the degree to which it correlates with conventional DEXA scores.Study Design/SettingRetrospective cohort.Patient SamplePatients ≥18 years of age undergoing spine surgery for degenerative conditions between 2013 and 2018.Outcome MeasuresCorrelation of the vertebral bone quality (VBQ) score with DEXA T-scores, and association between VBQ score and presence of osteopenia/osteoporosis.MethodsUsing noncontrast T1-weighted MRIs of the lumbar spine, the novel VBQ score was calculated for each patient. DEXA T-scores of the femoral neck and total hip were obtained and were compared with patient VBQ scores using linear regression and Pearson's correlation.ResultsAmong 68 patients included in this study, 37 were found to have osteopenia/osteoporosis (T-score < −1.0) based on DEXA. A greater VBQ score was significantly associated with the presence of osteopenia/osteoporosis with a predictive accuracy of 81%. VBQ scores correlated moderately with femoral neck T-scores, the lowest overall T-scores of each patient, and correlated fairly with total hip T-scores.ConclusionsThis is the first study to correlate the novel VBQ score obtained from MRIs with DEXA T-score. We found this score to be a significant predictor of healthy versus osteopenic/osteoporotic bone with an accuracy of 81%, and found that VBQ score was moderately correlated with femoral neck and overall lowest T-score.     

The impact of degenerative disc disease on regional volumetric bone mineral density (vBMD) measured by quantitative computed tomography

BACKGROUND CONTEXTIt has been reported that degenerative disc disease (DDD) is associated with higher spinal bone mineral density (BMD) based on previous studies that used dual X-ray absorptiometry (DXA). However, DDD is often associated with proliferative bone changes and can lead to an overestimation of BMD measured with DXA. Trabecular volumetric BMD (vBMD) in the vertebral body measured with quantitative computed tomography (QCT) is less affected by those changes and can be a favorable alternative to DXA for patients with degenerative spinal changes.PURPOSEThe purpose of this study is to investigate the effect of DDD on regional trabecular vBMDs in the vertebral body measured by QCT.STUDY DESIGN/SETTINGCross-sectional observational study at a single academic institution.PATIENTS SAMPLEConsecutive patients undergoing posterior lumbar spinal fusion between 2014 and 2017 who had a routine preoperative CT scan and magnetic resonance imaging (MRI) within a 90-day interval.OUTCOME MEASURESRegional trabecular vBMDs in the vertebral body by QCT.METHODSQCT measurements were conducted in L1–S1 vertebral trabecular bone. Any apparent sclerotic lesions that might affect vBMD values were excluded from the region of interest. The vBMDs of each level were defined as the average vBMD of the upper and lower vertebrae. To evaluate DDD, Pfirrmann grade, Modic grade, total end plate score, and vacuum phenomenon were documented. Univariate regression analysis and multivariate analyses with a linear mixed model adjusted with individual variability of segmental vBMDs were conducted with vBMD as the response variable.RESULTSOf 143 patients and 715 disc levels, 125 patients and 596 discs met our inclusion criteria. Mean vBMD (±standard deviation [SD]) of all levels was 119.0±39.6 mg/cm³. After adjusting for all covariates, Pfirrmann grade was not an independent contributor to vBMD, but the presence of any Modic change (type 1, β=6.8, p≤.001; type 2, β=6.7, p<.001; type 3, β=43.6, p<.001), high TEPS (score 10–12, β=14.2, p<.001), or vacuum phenomenon (β=9.0, p<.001) was shown to be independent contributors to vBMD.CONCLUSIONSOur results showed that the presence of certain end plate lesions (Modic changes and high TEPS) on MRI was significantly associated with increased regional QCT-vBMDs in the vertebral body, but no significant association was observed with disc nucleus pathology, unless it was associated with a vacuum phenomenon. When end plate lesions with Modic changes and high TEPS are present at the measuring level, care must be taken to interpret vBMD values, which might be overestimations even if the trabecular area appears normal.     

Preoperative MRI-based vertebral bone quality (VBQ) score assessment in patients undergoing lumbar spinal fusion

BACKGROUND CONTEXTThe importance of bone status assessment in spine surgery is well recognized. The current gold standard for assessing bone mineral density is dual-energy X-ray absorptiometry (DEXA). However, DEXA has been shown to overestimate BMD in patients with spinal degenerative disease and obesity. Consequently, alternative radiographic measurements using data routinely gathered during preoperative evaluation have been explored for the evaluation of bone quality and fracture risk. Opportunistic quantitative computed tomography (QCT) and more recently, the MRI-based vertebral bone quality (VBQ) score, have both been shown to correlate with DEXA T-scores and predict osteoporotic fractures. However, to date the direct association between VBQ and QCT has not been studied.PURPOSEThe objective of this study was to evaluate the correlation between VBQ and spine QCT BMD measurements and assess whether the recently described novel VBQ score can predict the presence of osteopenia/osteoporosis diagnosed with QCT.STUDY DESIGN/SETTINGCross-sectional study using retrospectively collected data.PATIENT SAMPLEPatients undergoing lumbar fusion from 2014-2019 at a single, academic institution with available preoperative lumbar CT and T1-weighted MRIs were included.OUTCOME MEASURESCorrelation of the VBQ score with BMD measured by QCT, and association between VBQ score and presence of osteopenia/osteoporosis.METHODSAsynchronous QCT measurements were performed. The average L1-L2 BMD was calculated and patients were categorized as either normal BMD (>120 mg/cm³) or osteopenic/osteoporotic (≤120 mg/cm³). The VBQ score was calculated by dividing the median signal intensity of the L1-L4 vertebral bodies by the signal intensity of the cerebrospinal fluid on midsagittal T1-weighted MRI images. Inter-observer reliability testing of the VBQ measurements was performed. Demographic data and the VBQ score were compared between the normal and osteopenic/osteoporotic group. To determine the area-under-curve (AUC) of the VBQ score as a predictor of osteopenia/osteoporosis receiver operating characteristic (ROC) analysis was performed. VBQ scores were compared with QCT BMD using the Pearson's correlation.RESULTSA total of 198 patients (53% female) were included. The mean age was 62 years and the mean BMI was 28.2 kg/m². The inter-observer reliability of the VBQ measurements was excellent (ICC of 0.90). When comparing the patients with normal QCT BMD to those with osteopenia/osteoporosis, the patients with osteopenia/osteoporosis were significantly older (64.9 vs. 56.7 years, p<.0001). The osteopenic/osteoporotic group had significantly higher VBQ scores (2.6 vs. 2.2, p<.0001). The VBQ score showed a statistically significant negative correlation with QCT BMD (correlation coefficient = -0.358, 95% CI -0.473 - -0.23, p<.001). Using a VBQ score cutoff value of 2.388, the categorical VBQ score yielded a sensitivity of 74.3% and a specificity of 57.0% with an AUC of 0.7079 to differentiate patients with osteopenia/osteoporosis and with normal BMD.CONCLUSIONSWe found that the VBQ score showed moderate diagnostic ability to differentiate patients with normal BMD versus osteopenic/osteoporotic BMD based on QCT. VBQ may be an interesting adjunct to clinically performed bone density measurements in the future.     

Biomechanical changes in the lumbar spine following spaceflight and factors associated with postspaceflight disc herniation

Background ContextFor chronic low back pain, the causal mechanisms between pathological features from imaging and patient symptoms are unclear. For instance, disc herniations can often be present without symptoms. There remains a need for improved knowledge of the pathophysiological mechanisms that explore spinal tissue damage and clinical manifestations of pain and disability. Spaceflight and astronaut health provides a rare opportunity to study potential low back pain mechanisms longitudinally. Spaceflight disrupts diurnal loading on the spine and several lines of evidence indicate that astronauts are at a heightened risk for low back pain and disc herniation following spaceflight.PurposeTo examine the relationship between prolonged exposure to microgravity and the elevated incidence of postflight disc herniation, we conducted a longitudinal study to track the spinal health of twelve NASA astronauts before and after approximately 6 months in space. We hypothesize that the incidence of postflight disc herniation and low back complaints associates with spaceflight-included muscle atrophy and pre-existing spinal pathology.Study DesignThis is a prospective longitudinal study.Patient SampleOur sample included a cohort of twelve astronaut crewmembers.Outcome MeasuresFrom 3T MRI, we quantified disc water content (ms), disc degeneration (Pfirrmann grade), vertebral endplate irregularities, facet arthropathy and/ fluid, high intensity zones, disc herniation, multifidus total cross-sectional area (cm²), multifidus lean muscle cross-sectional area (cm²), and muscle quality/composition (%). From quantitative fluoroscopy we quantified, maximum flexion-extension ROM (°), maximum lateral bending ROM (°), and maximum translation (%). Lastly, patient outcomes and clinical notes were used for identifying postflight symptoms associated with disc herniations from 3T MRI.MethodsAdvanced imaging data from 3T MRI were collected at three separate time points in relation to spending six months in space: (1) within a year before launch (“pre-flight”), (2) within a week after return to Earth (“post-flight”), and (3) between 1 and 2 months after return to Earth (“recovery”). Fluoroscopy of segmental kinematics was collected at preflight and postflight timepoints. We assessed the effect of spaceflight and postflight recovery on longitudinal changes in spinal structure and function, as well as differences between crew members who did and did not present a symptomatic disc herniation following spaceflight.ResultsHalf of our astronauts (n=6) experienced new symptoms associated with a new or previously asymptomatic lumbar disc protrusion or extrusion following spaceflight. We observed decreased multifidus muscle quality following spaceflight in the lower lumbar spine, with a reduced percentage of lean muscle at L4L5 (-6.2%, p=.009) and L5S1 (-7.0%, p=.006) associated with the incidence of new disc herniation. Additionally, we observed reduced lumbar segment flexion-extension ROM for L2L3 (-17.2%, p=.006) and L3L4 (-20.5%, p=.02) following spaceflight, and furthermore that reduced ROM among the upper three lumbar segments (-24.1%, p=.01) associated with the incidence of disc herniation. Existing endplate pathology was most prevalent in the upper lumbar spine and associated with reduced segmental ROM (-20.5%, p=.02).ConclusionsIn conclusion from a 10-year study investigating the effects of spaceflight on the lumbar spine and risk for disc herniation, we found the incidence of lumbar disc herniation following spaceflight associates with compromised multifidus muscle quality and spinal segment kinematics, as well as pre-existing spinal endplate irregularities. These findings suggest differential effects of spinal stiffness and muscle loss in the upper versus lower lumbar spine regions that may specifically provoke risk for symptomatic disc herniation in the lower lumbar spine following spaceflight. Results from this study provide a unique longitudinal assessment of mechanisms and possible risk factors for developing disc herniations and related low back pain. Furthermore, these findings will help inform physiologic countermeasures to maintain spinal health in astronauts during long-duration missions in space.     

BNIP3与LC3B在椎间盘退行性变过程中的作用

目的研究BCL2/腺病毒E1B19k Da相互作用蛋白3(BNIP3)基因及微管相关蛋白轻链3B(LC3B)基因在退变椎间盘中的表达情况,探讨其与椎间盘退行性变分级之间的相关性。方法收集2016年4月—2016年7月因腰椎椎间盘突出症于本院接受手术治疗的21例患者的退变腰椎椎间盘标本25个,依据Pfirrmann分级分成5组,分别采用实时荧光定量PCR技术和蛋白质印迹法检测BNIP3、LC3B的m RNA和蛋白表达量,用实时荧光定量PCR技术检测Bcl-2、Bax、Caspase-3的mRNA表达量,并分析BNIP3表达量、LC3B表达量、细胞自噬、细胞凋亡与Pfirrmann分级之间的关系。结果退变椎间盘组织中BNIP3、LC3B在mRNA和蛋白水平的表达均随椎间盘退行性变程度加重而减少。Bcl-2 m RNA的表达随椎间盘退行性变程度加重而减少,Bax与Casepase-3 mRNA的表达随椎间盘退行性变程度加重而增多。结论随着椎间盘退行性变程度的加重,BNIP3与LC3B的表达减少,组织内细胞凋亡水平升高,细胞自噬对组织的保护作用逐渐下降。提示BNIP3与LC3B在腰椎椎间盘退行性变过程中具有重要的调节作用,可能是细胞自噬和凋亡之间的桥梁蛋白。     

Rat disc torsional mechanics: effect of lumbar and caudal levels and axial compression load

Background contextRat models with altered loading are used to study disc degeneration and mechano-transduction. Given the prominent role of mechanics in disc function and degeneration, it is critical to measure mechanical behavior to evaluate changes after model interventions. Axial compression mechanics of the rat disc are representative of the human disc when normalized by geometry, and differences between the lumbar and caudal disc have been quantified in axial compression. No study has quantified rat disc torsional mechanics.PurposeCompare the torsional mechanical behavior of rat lumbar and caudal discs, determine the contribution of combined axial load on torsional mechanics, and compare the torsional properties of rat discs to human lumbar discs.Study designCadaveric biomechanical study.MethodsCyclic torsion without compressive load followed by cyclic torsion with a fixed compressive load was applied to rat lumbar and caudal disc levels.ResultsThe apparent torsional modulus was higher in the lumbar region than in the caudal region: 0.081±0.026 (MPa/°, mean±SD) for lumbar axially loaded; 0.066±0.028 for caudal axially loaded; 0.091±0.033 for lumbar in pure torsion; and 0.056±0.035 for caudal in pure torsion. These values were similar to human disc properties reported in the literature ranging from 0.024 to 0.21 MPa/°.ConclusionsUse of the caudal disc as a model may be appropriate if the mechanical focus is within the linear region of the loading regime. These results provide support for use of this animal model in basic science studies with respect to torsional mechanics.     

Disc degeneration of cervical spine on MRI in patients with lumbar disc herniation: comparison study with asymptomatic volunteers

An association between progression of cervical disc degeneration and that of lumbar disc degeneration has been considered to exist. To date, however, this association has not yet been adequately studied. Age-related changes in the cervical intervertebral discs were evaluated by magnetic resonance imaging (MRI) in patients with lumbar disc herniation, and compared with the MRI findings of healthy volunteers without lower back pain. The purpose of this study was to clarify whether the prevalence of asymptomatic cervical disc degeneration is higher in patients with lumbar disc herniation than in healthy volunteers. The study was conducted on 51 patients who were diagnosed as having lumbar disc herniation and underwent cervical spine MRI. The patients consisted of 34 males and 17 females ranging in age from 21–83 years (mean 46.9 ± 14.5 years) at the time of the study. The control group was composed of 113 healthy volunteers (70 males and 43 females) aged 24–77 years (mean 48.9 ± 14.7 years), without neck pain or low back pain. The percentage of subjects with degenerative changes in the cervical discs was 98.0% in the lumbar disc herniation group and 88.5% in the control group (p = 0.034). The presence of lumbar disc herniation was associated significantly with decrease in signal intensity of intervertebral disc and posterior disc protrusion in the cervical spine. None of the MRI findings was significantly associated with the gender, smoking, sports activities, or BMI. As compared to healthy volunteers, patients with lumbar disc herniation showed a higher prevalence of decrease in signal intensity of intervertebral disc and posterior disc protrusion on MRI of the cervical spine. The result of this study suggests that disc degeneration appears to be a systemic phenomenon.     

Vertebral bone quality score independently predicts cage subsidence following transforaminal lumbar interbody fusion

BACKGROUND CONTEXTCage subsidence following transforaminal lumbar interbody fusion (TLIF) has been associated with poor bone quality. Current evidence suggests that the magnetic resonance imaging (MRI)-based vertebral bone quality (VBQ) score correlates with poor bone quality.PURPOSETo our knowledge, this is the first study to assess whether the VBQ score can predict the occurrence of postoperative cage subsidence after TLIF surgery.DESIGN/SETTINGRetrospective single-center cohort.PATIENT SAMPLEPatients undergoing single-level TLIF for degenerative spine disease between February 2014 and October 2021.OUTCOME MEASURESExtent of subsidence.METHODSDemographic, procedure-related, and radiographic data were collected for study patients. VBQ scores were determined from preoperative T1-weighted MRI. Subsidence was defined as ≥2 mm of migration of the cage into the superior or inferior end plate or both. Univariate and multivariate logistic regression were used to determine the correlation between potential risk factors for subsidence and actual subsidence rates.RESULTSSubsidence was observed among 42 of the 74 study patients. The mean VBQ scores were 2.9±0.5 for patients with subsidence and 2.5±0.5 for patients without subsidence. The difference among groups was significant (p=.003). On multivariate logistic regression, a higher VBQ score was significantly associated with an increased risk of subsidence (OR=1.5, 95% CI=1.160–1.973, p=.004) and was the only significant independent predictor of subsidence after TLIF.CONCLUSIONWe found that a higher VBQ score was significantly associated with cage subsidence following TLIF. The MRI-VBQ score may be a valuable tool for assisting in identifying patients at risk of cage subsidence following TLIF.     

Spine Explorer: a deep learning based fully automated program for efficient and reliable quantifications of the vertebrae and discs on sagittal lumbar spine MR images

BACKGROUND CONTEXTAlthough quantitative measurements improve the assessment of disc degeneration, acquirement of quantitative measurements relies on manual segmentation on lumbar magnetic resonance images (MRIs), which may introduce subjective bias. To date, only a few semiautomatic systems have been developed to quantify important components on MRIs.PURPOSETo develop a deep learning based program (Spine Explorer) for automated segmentation and quantification of the vertebrae and intervertebral discs on lumbar spine MRIs.STUDY DESIGNCross-sectional study.PATIENT SAMPLEThe study was extended on the Hangzhou Lumbar Spine Study, a population-based study of mainland Chinese with focuses on lumbar degenerative changes. From this population-based database, 50 sets lumbar MRIs were randomly selected as training dataset, and another 50 as test dataset.OUTCOME MEASURESRegions of vertebrae and discs were manually segmented on T2W sagittal MRIs to train a convolutional neural network for automated segmentation. Intersection-over-union was calculated to evaluate segmentation performance. Computational definitions were proposed to acquire quantitative morphometric and signal measurements for lumbar vertebrae and discs. MRIs in the test dataset were automatically measured with Spine Explorer and manually with ImageJ.METHODSIntraclass correlation coefficient (ICC) were calculated to examine inter-software agreements. Correlations between disc measurements and Pfirrmann score as well as age were examined to assess measurement validity.RESULTSThe trained Spine Explorer automatically segments and measures a lumbar MRI in half a second, with mean Intersection-over-union of 94.7% and 92.6% for the vertebra and disc, respectively. For both vertebra and disc measurements acquired with Spine Explorer and ImageJ, the agreements were excellent (ICC=0.81~1.00). Disc measurements significantly correlated to Pfirrmann score, and greater age was associated with greater anterior disc bulging area (r=0.35~0.44) and fewer signal measurements (r=−0.62~−0.77) as automatically acquired with Spine Explorer.CONCLUSIONSSpine Explorer is an efficient, accurate, and reliable tool to acquire comprehensive quantitative measurements for lumbar vertebra and disc. Implication of such deep learning based program can facilitate clinical studies of the lumbar spine.     

Cytokine evaluation in individuals with low back pain using discographic lavage

Background contextThe pathophysiology underlying degenerative disc disease and its implication in painful syndromes remain unclear. However, spine magnetic resonance imaging (MRI) can demonstrate changes in disc water content and the annulus; provocative discography purportedly identifies degenerate discs causing serious low back pain; and biochemical assays have identified local inflammatory markers. No study to date has correlated pain on disc injection during discography evaluation with relevant MRI findings and biochemical markers.PurposeThe purpose of this study was to correlate concordant pain on during discography to biochemical markers obtained by disc lavage and MRI findings.Study designThis is a Phase 1 Diagnostic Test Assessment Cohort Study (Sackett and Haynes).Patient sampleThe patient sample included 21 symptomatic patients with suspected discogenic pain and three Phase 1 control subjects.Outcome measuresThe outcome measures included discography pain scores, MRI degenerative grades, and immunoreactivity to various inflammatory cytokine concentrations present in disc lavage samples.MethodsTwenty-one symptomatic patients with lumbar degenerative disc disease and three control subjects underwent discography, MRI, and biochemical analysis of disc lavage fluid. Lumbar MRI was scored for Pfirrmann grading of the lumbar discs, and annular disruption was identified by nuclear disc lavage. Disc lavage samples were analyzed for biochemical markers by high-sensitivity immunoassay.ResultsEighty-three discs from 24 patients were studied: 67 discs from 21 patients with axial back pain (suspected discogenic pain group) and 16 discs from 3 scoliosis patients without back pain (Phase 1 control subjects). Among the biochemical markers surveyed, interferon gamma (IFN-γ) immunoreactivity was most consistently identified in patients with axial back pain. Discs with annular disruption and concordant pain reproduction at a visual analog scale of 7 to 10/10 had greater IFN-γ immunoreactivity than those without this finding (p=.003); however, at least some IFN-γ immunoreactivity was found in all but one disc in the symptomatic group.ConclusionsAmong the potential inflammatory markers tested in this Phase 1 study, IFN-γ immunoreactivity was most commonly elevated in discogram “positive” discs but absent in asymptomatic controls. However, this marker was also frequently elevated in degenerative but “negative” discography discs. From these findings, Phase 2 and Phase 3 validity studies are reasonable to pursue. Phase 4 utility studies may be performed concurrently to assess this method's predictive value in outcome studies.