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Purpose: The purpose of this study is to describe and assess the impact of multi-domain biopsychosocial (BPS) recovery on outcomes following lumbar spine fusion. We hypothesized that discrete patterns of BPS recovery (e.g., clusters) would be identified, and then associated with postoperative outcomes and preoperative patient data., Methods: Patient-reported outcomes for pain, disability, depression, anxiety, fatigue, and social roles were collected at multiple timepoints for patients undergoing lumbar fusion between baseline and one year. Multivariable latent class mixed models assessed composite recovery as a function of (1) pain, (2) pain and disability, and (3) pain, disability, and additional BPS factors. Patients were assigned to clusters based on their composite recovery trajectories over time., Results: Using all BPS outcomes from 510 patients undergoing lumbar fusion, three multi-domain postoperative recovery clusters were identified: Gradual BPS Responders (11%), Rapid BPS Responders (36%), and Rebound Responders (53%). Modeling recovery from pain alone or pain and disability alone failed to generate meaningful or distinct recovery clusters. BPS recovery clusters were associated with number of levels fused and preoperative opioid use. Postoperative opioid use (p < 0.01) and hospital length of stay (p < 0.01) were associated with BPS recovery clusters even after adjusting for confounding factors., Conclusion: This study describes distinct clusters of recovery following lumbar spine fusion derived from multiple BPS factors, which are related to patient-specific preoperative factors and postoperative outcomes. Understanding postoperative recovery trajectories across multiple health domains will advance our understanding of how BPS factors interact with surgical outcomes and could inform personalized care plans., (© 2023. The Author(s).)

Vertebral endplate bone marrow lesions, visualized on magnetic resonance imaging (MRI) as Modic changes (MC), are associated with chronic low back pain (cLBP). Since guidelines recommend against routine spinal MRI for cLBP in primary care, MC may be underdiagnosed. Serum biomarkers for MC would allow early diagnosis, inform clinical care decisions, and supplement treatment monitoring. We aimed to discover biomarkers in the blood serum that correlate with MC pathophysiological processes. For this single-site cross-sectional study, we recruited 54 subjects with 38 cLBP patients and 16 volunteers without a history of LBP. All subjects completed an Oswestry Disability Index (ODI) questionnaire and 10-cm Visual Analog Score (VAS) for LBP (VASback) and leg pain. Lumbar T1-weighted and fat-saturated T2-weighted MRI were acquired at 3T and used for MC classification in each endplate. Blood serum was collected on the day of MRI. Biomarkers related to disc resorption and bone marrow fibrosis were analyzed with enzyme-linked immune-absorbent assays. The concentration of biomarkers between no MC and any type of MC (AnyMC), MC1, and MC2 were compared. The Area Under the Curve (AUC) of the Receiver Operating Characteristics were calculated for each biomarker and for bivariable biomarker models. We found that biomarkers related to type III and type IV collagen degradation and formation tended to correlate with the presence of MC ( p = 0.060-0.088). The bivariable model with the highest AUC was PRO-C3 + C4M and had a moderate diagnostic value for AnyMC in cLBP patients (AUC = 0.73, specificity = 78.9%, sensitivity = 73.7%). In conclusion, serum biomarkers related to the formation and degradation of type III and type IV collagen, which are key molecules in bone marrow fibrosis, correlated with MC presence. Bone marrow fibrosis may be an important pathophysiological process in MC that should be targeted in larger biomarker and treatment studies., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Purpose: The positive association between low back pain and MRI evidence of vertebral endplate bone marrow lesions, often called Modic changes (MC), offers the exciting prospect of diagnosing a specific phenotype of chronic low back pain (LBP). However, imprecision in the reporting of MC has introduced substantial challenges, as variations in both imaging equipment and scanning parameters can impact conspicuity of MC. This review discusses key methodological factors that impact MC classification and recommends guidelines for more consistent MC reporting that will allow for better integration of research into this LBP phenotype., Methods: Non-systematic literature review., Results: The high diagnostic specificity of MC classification for a painful level contributes to the significant association observed between MC and LBP, whereas low and variable sensitivity underlies the between- and within-study variability in observed associations. Poor sensitivity may be owing to the presence of other pain generators, to the limited MRI resolution, and to the imperfect reliability of MC classification, which lowers diagnostic sensitivity and thus influences the association between MC and LBP. Importantly, magnetic field strength and pulse sequence parameters also impact detection of MC. Advances in pulse sequences may improve reliability and prove valuable for quantifying lesion severity., Conclusions: Comparison of MC data between studies can be problematic. Various methodological factors impact detection and classification of MC, and the lack of reporting guidelines hinders interpretation and comparison of findings. Thus, it is critical to adopt imaging and reporting standards that codify acceptable methodological criteria. These slides can be retrieved under Electronic Supplementary Material.

Study Design: Descriptive histologic and magnetic resonance imaging study of human cadaveric spines., Objective: To identify and characterize common endplate pathologies to form a histologic foundation for an etiology-based classification system., Summary of Background Data: Irregularities at the spinal disc-vertebra interface are associated with back pain and intervertebral disc herniation injuries. However, there is currently a lack of consensus regarding terminology for classification. This limits the potential for advancing understanding of back pain mechanisms, and prohibits meaningful comparisons for identifying priorities for prevention and treatment. Prior classification systems largely rely on observations from clinical imaging, which may miss subtle pathologic features., Methods: Fifteen cadaveric spines with moderate to severe disc degeneration were obtained and scanned with MRI in the sagittal plane using two-dimensional T1-weighted and T2-weighted fast spin-echo sequences. Eighty-nine lumbar and lower thoracic bone-disc-bone motion segments were extracted, fixed, sectioned, and stained for histologic evaluation. Focal endplate irregularities were identified and categorized based on features that inferred causation. The presence, type, and anatomic location were recorded. A classification system with three major categories of focal endplate irregularities was created., Results: Disc-vertebra avulsion and vertebral rim degeneration were more common than subchondral nodes: 50% of irregularities were classified as rim degeneration (75/150), 35% were classified as avulsions (52/150), and 15% were classified as nodes (23/150). Ninety percent of avulsions were subclassified as "tidemark avulsions," a highly prevalent form of endplate irregularity in which the outer annulus separates from the vertebra at the tidemark. These tidemark avulsions have not been previously described, yet are visible on T2-weighted MRI as high-intensity regions., Conclusion: This study provides histologic basis for a system to classify focal endplate irregularities. Included is a previously unidentified but prevalent finding of tidemark avulsions, which are visible with both histology and magnetic resonance imaging. These observations will help clinicians better organize patients into meaningful groups to facilitate diagnosis, treatment, and clinical research., Level of Evidence: 3.

Background Context: The objective of the North American Spine Society (NASS) evidence-based clinical guideline on the diagnosis and treatment of degenerative lumbar spondylolisthesis is to provide evidence-based recommendations on key clinical questions concerning the diagnosis and treatment of degenerative lumbar spondylolisthesis. The guideline is intended to address these questions based on the highest quality clinical literature available on this subject as of January 2007. The goal of the guideline recommendations is to assist the practitioner in delivering optimum, efficacious treatment of and functional recovery from this common disorder., Purpose: To provide an evidence-based, educational tool to assist spine care providers in improving the quality and efficiency of care delivered to patients with degenerative lumbar spondylolisthesis., Study Design: Systematic review and evidence-based clinical guideline., Methods: This report is from the Degenerative Lumbar Spondylolisthesis Work Group of the NASS Evidence-Based Clinical Guideline Development Committee. The work group was comprised of multidisciplinary spine care specialists, all of whom were trained in the principles of evidence-based analysis. Each member participated in the development of a series of clinical questions to be addressed by the group. The final questions agreed on by the group are the subject of this report. A literature search addressing each question and using a specific search protocol was performed on English language references found in MEDLINE, EMBASE (Drugs and Pharmacology) and four additional, evidence-based, databases. The relevant literature was then independently rated by at least three reviewers using the NASS-adopted standardized levels of evidence. An evidentiary table was created for each of the questions. Final grades of recommendation for the answer to each clinical question were arrived at via face-to-face meetings among members of the work group using standardized grades of recommendation. When Level I-IV evidence was insufficient to support a recommendation to answer a specific clinical question, expert consensus was arrived at by the work group through the modified nominal group technique and is clearly identified as such in the guideline., Results: Nineteen clinical questions were formulated, addressing issues of prognosis, diagnosis, and treatment of degenerative lumbar spondylolisthesis. The answers to these 19 clinical questions are summarized in this document. The respective recommendations were graded by the strength of the supporting literature that was stratified by levels of evidence., Conclusions: A clinical guideline for degenerative lumbar spondylolisthesis has been created using the techniques of evidence-based medicine and using the best available evidence as a tool to aid practitioners involved with the care of this condition. The entire guideline document, including the evidentiary tables, suggestions for future research, and all references, is available electronically at the NASS Web site (www.spine.org) and will remain updated on a timely schedule.

This paper presents the first reported measurements of lumbar intervertebral disc pressure in vivo during spinal manipulation. A pressure transducer was inserted into the nucleus pulposus of one normal-appearing lumbar disc in an asymptomatic adult volunteer. Pressures were recorded during several body positions and maneuvers, then during spinal manipulation, and lastly during a repetition of the preintervention body positions. Baseline pressures in the prone and side-lying positions measured 110 kPa and 150 kPa, respectively. During the manipulation, pressure rose to a peak of 890 kPa over 250 ms. Immediately following, pressures in the prone and side-lying positions measured 150 kPa and 165 kPa, respectively. These data do not support the hypotheses that manipulation can reduce a herniation by decreasing intradiscal pressure, or cause a herniation by raising pressure to failure levels. Further work may lead to a better understanding of this treatment method.

Background Context: Discectomy is a surgical technique commonly used to treat bulging or herniated discs causing nerve root compression. Clinical data suggest discectomy may also help patients with contained discs and no clear neural compromise. However, the mechanisms of clinical efficacy are uncertain, and consequently bases for treatment optimization are limited., Purpose: To determine the effect of percutaneous plasma decompression on the histologic, morphologic, biochemical and biomechanical features of degenerating intervertebral discs., Study Design: An adult porcine model of disc degeneration was used to establish a degenerative baseline against which to evaluate discectomy efficacy., Outcome Measures: Cytokines interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor (TNF)-alpha were measured from tissue samples using enzyme-linked immunosorbent assay. Histology and morphology images were rated for degenerative findings (of cells and matrix) in both the nucleus and annulus. Proteoglycan content was determined, and intact specimen stiffness and flexibility were measured biomechanically. Magnetic resonance images were collected for biomechanical specimens., Methods: Using a retroperitoneal surgical approach, stab incisions were made in four or five lumbar discs per spine in 12 minipigs. Animals were allocated into one of three groups: 6-week recovery, 12-week recovery and percutaneous plasma decompression using an electrosurgical device at 6 weeks with recovery for 6 additional weeks. Four additional animals served as controls., Results: Discs treated with discectomy had a significant increase in IL-8 and a decrease in IL-1 as compared with the 12-week, nontreated discs. There were no significant differences in morphologic and biomechanical parameters or proteoglycan content between treated discs and time-matched, nontreated discs., Conclusions: Our results demonstrate that percutaneous plasma discectomy alters the expression of inflammatory cytokines in degenerated discs, leading to a decrease in IL-1 and an increase in IL-8. Whereas both IL-1 and IL-8 have hyperalgesic properties, IL-1 is likely to be a more important pathophysiologic factor in painful disc disorders than IL-8. Therefore, the alteration in cytokine expression that we observed is consistent with this effect as a mechanism of pain relief after discectomy. In addition, given that IL-1 is catabolic in injured tissue and IL-8 is anabolic, our results suggest that a percutaneous plasma discectomy may be capable of initiating a repair response in the disc.

PurposeClinical management of disc degeneration in patients with chronic low back pain (cLBP) is hampered by the challenge of distinguishing pathologic changes relating to pain from physiologic changes related to aging. The goal of this study was to use imaging biomarkers of disc biochemical composition to distinguish degenerative changes associated with cLBP from normal aging.MethodsT1ρ MRI data were acquired from 133 prospectively enrolled subjects for this observational study (80 cLBP, 53 controls; mean ± SD age = 43.9 ± 13.4 years; 61 females, 72 males). The mean T1ρ relaxation time in the nucleus pulposus (NP-T1ρ; n = 650 discs) was used as a quantitative biomarker of disc biochemical composition. Linear regression was used to assess associations between NP-T1ρ and age, sex, spinal level, and study group, and their interactions.ResultsNP-T1ρ values were lower in cLBP patients than controls (70.8 ± 22.8 vs. 76.4 ± 22.2 ms, p = 0.009). Group differences were largest at L5-S1 (ΔT1ρcLBP-control = -11.3 ms, p

PurposeFat infiltration (FI) of the paraspinal muscles (PSMs) measured using MRI is an aspect of muscle quality and is considered to be worse in chronic low back pain (cLBP) patients. However, there is not a clear association between paraspinal muscle FI and cLBP, leaving the clinical importance of paraspinal muscle composition unestablished. The spatial distribution of FI in the PSMs may inform mechanistic understanding of non-specific cLBP as it relates to degenerative intervertebral disc (IVD) pathology. We hypothesized that paraspinal muscle fat-mapping would reveal distinct FI distribution patterns in relation to cLBP symptoms and proximity to symptomatic IVD degeneration.MethodsFrom advanced-sequence water-fat MRI of 40 axial cLBP patients and 21 controls, we examined the spatial distribution of paraspinal muscle FI in relation to the center of rotation at the L4L5 disc. Using statistical parametric mapping, we compared FI patterns for multifidus (MF), erector spinae (ES), and psoas between patients and controls, and to the presence and severity of adjacent degenerative IVD pathology.ResultsThe spatial distribution of PSMs FI differs between PSMs and according to symptoms and the adjacent degenerative IVD pathology. Furthermore, the region of MF closest to the disc center of rotation appears most susceptible to FI in the presence of symptomatic IVD degeneration.ConclusionOur study identified spatial distribution patterns of FI in the PSMs as a potential diagnostic biomarker that may also provide granular mechanistic insights into spine biomechanics related to cLBP, as well as advancing the use of prior summary measures limited to overall muscle FI.

PurposeThe composition of the subchondral bone marrow and cartilage endplate (CEP) could affect intervertebral disc health by influencing vertebral perfusion and nutrient diffusion. However, the relative contributions of these factors to disc degeneration in patients with chronic low back pain (cLBP) have not been quantified. The goal of this study was to use compositional biomarkers derived from quantitative MRI to establish how CEP composition (surrogate for permeability) and vertebral bone marrow fat fraction (BMFF, surrogate for perfusion) relate to disc degeneration.MethodsMRI data from 60 patients with cLBP were included in this prospective observational study (28 female, 32 male; age = 40.0 ± 11.9 years, 19-65 [mean ± SD, min-max]). Ultra-short echo-time MRI was used to calculate CEP T2* relaxation times (reflecting biochemical composition), water-fat MRI was used to calculate vertebral BMFF, and T1ρ MRI was used to calculate T1ρ relaxation times in the nucleus pulposus (NP T1ρ, reflecting proteoglycan content and degenerative grade). Univariate linear regression was used to assess the independent effects of CEP T2* and vertebral BMFF on NP T1ρ. Mixed effects multivariable linear regression accounting for age, sex, and BMI was used to assess the combined relationship between variables.ResultsCEP T2* and vertebral BMFF were independently associated with NP T1ρ (p = 0.003 and 0.0001, respectively). After adjusting for age, sex, and BMI, NP T1ρ remained significantly associated with CEP T2* (p = 0.0001) but not vertebral BMFF (p = 0.43).ConclusionPoor CEP composition plays a significant role in disc degeneration severity and can affect disc health both with and without deficits in vertebral perfusion.

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.

PurposeVertebral endplate bone marrow lesions ("Modic changes", MC) are associated with chronic low back pain (CLBP). Bone marrow composition in MC is poorly understood. The goals of this study were to: (1) measure bone marrow fat fraction (BMF) in CLBP patients with MC using water-fat MRI and (2) assess the relationship between BMF measurements and patient-reported clinical characteristics.MethodsIn this cross-sectional study, 42 CLBP patients (men, n = 21; age, 48 ± 12.4 years) and 18 asymptomatic controls (men, n = 10; 42.7 ± 12.8 years) underwent 3 T MRI between January 2016 and July 2018. Imaging consisted of T1- and T2-weighted sequences to evaluate MC and spoiled gradient-recalled echo sequence with asymmetric echoes and least-squares fitting to measure BMF. BMF was compared between vertebrae with and without MC using mixed effects models. The relationship between the BMF measurements and patient-reported disability scores was examined using regression.ResultsTwenty-seven subjects (26 CLBP, 1 control) had MC, and MC presence coincided with significantly altered BMF. In MC 1, BMF was lower than endplates without MC (absolute difference -22.3%; p

BackgroundThere is an interplay between the intervertebral disc (IVD) and the adjacent bone marrow that may play a role in the development of IVD degeneration and might influence chronic lower back pain (CLBP).PurposeTo apply novel quantitative MRI techniques to assess the relationship between vertebral bone marrow fat (BMF) and biochemical changes in the adjacent IVD.Study typeProspective.SubjectsForty-six subjects (26 female and 20 male) with a mean age of 47.3 ± 12.0 years.Field strength/sequence3 T MRI; a combined T1ρ and T2 mapping pulse sequence and a 3D spoiled gradient recalled sequence with six echoes and iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) reconstruction algorithm.AssessmentUsing quantitative MRI, the vertebral BMF fraction was measured as well as the biochemical composition (proteoglycan and collagen content) of the IVD. Furthermore, clinical Pfirrmann grading, Oswestry disability index (ODI), and visual analog scale (VAS) was assessed.Statistical testsMixed random effects models accounting for multiple measurements per subject were used to assess the relationships between disc measurements and BMF.ResultsThe relationships between BMF (mean) and T1ρ /T2 (mean and SD) were significant, with P

Study designCross-sectional cohort study of chronic low back pain (CLBP) patients and matched controls.ObjectiveTo explore the interplay between vertebral endplate damage and adjacent paraspinal muscle (PSM) quality, and to test their association in a cohort of patients with CLBP and matched controls.Summary of background dataNonspecific CLBP is challenging to diagnose, in part, due to uncertainty regarding the source of pain. Delineating interactions among potential CLBP mechanisms may enhance diagnosis and treatment customization.MethodsWe collected advanced MRI imaging on 52 adult subjects, including 38 CLBP patients and 14 age- and sex-matched asymptomatic control subjects. Mean multifidus and erector spinae fat fraction (FF) was measured throughout the spine using an IDEAL MRI sequence. Presence of cartilage endplate (CEP) defects was determined at each disc level using UTE MRI. Logistic regression was used to test association of PSM FF, CEP defects, modic changes (MC), disc degeneration, and their interplay.ResultsWe observed that CEP defects were the strongest predictor of nonspecific CLBP (OR: 14.1, P

Management of patients suffering from low back pain (LBP) is challenging and requires development of diagnostic techniques to identify specific patient subgroups and phenotypes in order to customize treatment and predict clinical outcome. The Back Pain Consortium (BACPAC) Research Program Spine Imaging Working Group has developed standard operating procedures (SOPs) for spinal imaging protocols to be used in all BACPAC studies. These SOPs include procedures to conduct spinal imaging assessments with guidelines for standardizing the collection, reading/grading (using structured reporting with semi-quantitative evaluation using ordinal rating scales), and storage of images. This article presents the approach to image acquisition and evaluation recommended by the BACPAC Spine Imaging Working Group. While the approach is specific to BACPAC studies, it is general enough to be applied at other centers performing magnetic resonance imaging (MRI) acquisitions in patients with LBP. The herein presented SOPs are meant to improve understanding of pain mechanisms and facilitate patient phenotyping by codifying MRI-based methods that provide standardized, non-invasive assessments of spinal pathologies. Finally, these recommended procedures may facilitate the integration of better harmonized MRI data of the lumbar spine across studies and sites within and outside of BACPAC studies. [ABSTRACT FROM AUTHOR]

Background Context: Prolonged microgravity exposure is associated with localized low back pain and an elevated risk of post-flight disc herniation. Although the mechanisms by which microgravity impairs the spine are unclear, they should be foundational for developing in-flight countermeasures for maintaining astronaut spine health. Because human spine anatomy has adapted to upright posture on Earth, observations of how spaceflight affects the spine should also provide new and potentially important information on spine biomechanics that benefit the general population.Purpose: This study compares quantitative measures of lumbar spine anatomy, health, and biomechanics in astronauts before and after 6 months of microgravity exposure on board the International Space Station (ISS).Study Design: This is a prospective longitudinal study.Sample: Six astronaut crewmember volunteers from the National Aeronautics and Space Administration (NASA) with 6-month missions aboard the ISS comprised our study sample.Outcome Measures: For multifidus and erector spinae at L3-L4, measures include cross-sectional area (CSA), functional cross-sectional area (FCSA), and FCSA/CSA. Other measures include supine lumbar lordosis (L1-S1), active (standing) and passive (lying) flexion-extension range of motion (FE ROM) for each lumbar disc segment, disc water content from T2-weighted intensity, Pfirrmann grade, vertebral end plate pathology, and subject-reported incidence of chronic low back pain or disc injuries at 1-year follow-up.Methods: 3T magnetic resonance imaging and dynamic fluoroscopy of the lumbar spine were collected for each subject at two time points: approximately 30 days before launch (pre-flight) and 1 day following 6 months spaceflight on the ISS (post-flight). Outcome measures were compared between time points using paired t tests and regression analyses.Results: Supine lumbar lordosis decreased (flattened) by an average of 11% (p=.019). Active FE ROM decreased for the middle three lumbar discs (L2-L3: -22.1%, p=.049; L3-L4: -17.3%, p=.016; L4-L5: -30.3%, p=.004). By contrast, no significant passive FE ROM changes in these discs were observed (p>.05). Disc water content did not differ systematically from pre- to post-flight. Multifidus and erector spinae changed variably between subjects, with five of six subjects experiencing an average decrease 20% for FCSA and 8%-9% for CSA in both muscles. For all subjects, changes in multifidus FCSA strongly correlated with changes in lordosis (r2=0.86, p=.008) and active FE ROM at L4-L5 (r2=0.94, p=.007). Additionally, changes in multifidus FCSA/CSA correlated with changes in lordosis (r2=0.69, p=.03). Although multifidus-associated changes in lordosis and ROM were present among all subjects, only those with severe, pre-flight end plate irregularities (two of six subjects) had post-flight lumbar symptoms (including chronic low back pain or disc herniation).Conclusions: We observed that multifidus atrophy, rather than intervertebral disc swelling, associated strongly with lumbar flattening and increased stiffness. Because these changes have been previously linked with detrimental spine biomechanics and pain in terrestrial populations, when combined with evidence of pre-flight vertebral end plate insufficiency, they may elevate injury risk for astronauts upon return to gravity loading. Our results also have implications for deconditioned spines on Earth. We anticipate that our results will inform new astronaut countermeasures that target the multifidus muscles, and research on the role of muscular stability in relation to chronic low back pain and disc injury. [ABSTRACT FROM AUTHOR]