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BACKGROUND: Endoscopic spine surgery has recently grown in popularity due to the potential benefits of reduced pain and faster recovery time as compared to open surgery. Biportal spinal endoscopy has been successfully applied to lumbar disc herniations and lumbar spinal stenosis. Obesity is associated with increased risk of complications in spine surgery. Few prior studies have investigated the impact of obesity and associated medical comorbidities with biportal spinal endoscopy. METHODS: This study was a prospectively collected, retrospectively analyzed comparative cohort design. Patients were divided into cohorts of normal body weight (Bone Mass Index (BMI)18.0-24.9), overweight (BMI 25.0-29.9) and obese (BMI > 30.0) as defined by the World Health Organization (WHO). Patients underwent biportal spinal endoscopy by a single surgeon at a single institution for treatment of lumbar disc herniations and lumbar spinal stenosis. Demographic data, surgical complications, and patient-reported outcomes were analyzed. Statistics were calculated amongst treatment groups using analysis of variance and chi square where appropriate. Statistical significance was determined as p

PURPOSE: The purpose of this study was to understand potential baseline transcriptional expression differences in paraspinal skeletal muscle from patients with different underlying lumbar pathologies by comparing multifidus gene expression profiles across individuals with either disc herniation, facet arthropathy, or degenerative spondylolisthesis. METHODS: Multifidus biopsies were obtained from patients (n = 44) undergoing lumbar surgery for either disc herniation, facet arthropathy, or degenerative spondylolisthesis. Diagnostic categories were based on magnetic resonance images, radiology reports, and intraoperative reports. Gene expression for 42 genes was analysed using qPCR. A one-way analysis of variance was performed for each gene to determine differences in expression across diagnostic groups. Corrections for multiple comparisons across genes (Benjamini-Hochberg) and for between-group post hoc comparisons (Sidak) were applied. RESULTS: Adipogenic gene (ADIPOQ) expression was higher in the disc herniation group when compared to the facet arthropathy group (p = 0.032). Adipogenic gene (PPARD) expression was higher in the degenerative spondylolisthesis group when compared to the disc herniation group (p = 0.013), although absolute gene expression levels for all groups was low. Fibrogenic gene (COL3A1) had significantly higher expression in the disc herniation group and facet arthropathy group when compared to the degenerative spondylolisthesis group (p

BackgroundHorner syndrome often occurs with cervical myelopathies and might provide insight into the underlying disease and prognosis.ObjectivesTo describe the clinical and imaging features of dogs with cervical myelopathy and concurrent Horner syndrome and to determine association of Horner syndrome with diseases or magnetic resonance images (MRI).AnimalsNinety-three client-owned dogs with cervical myelopathy and concurrent Horner syndrome and 99 randomly selected client-owned dogs with cervical myelopathy without Horner syndrome (control cases).MethodsRetrospective study. Medical records were reviewed to identify Horner and control cases and clinical findings recorded. MRI were reviewed, and lesions characterized and recorded. Descriptive and comparative statistics were performed.ResultsNon-compressive disease occurred more frequently in the Horner group compared with controls (58%; 95% CI: 48-68 vs 9%; 95% CI: 5-16; P

OBJECTIVES: Chiropractic spinal manipulative therapy (CSMT) and lumbar discectomy are both used for lumbar disc herniation (LDH) and lumbosacral radiculopathy (LSR); however, limited research has examined the relationship between these therapies. We hypothesised that adults receiving CSMT for newly diagnosed LDH or LSR would have reduced odds of lumbar discectomy over 1-year and 2-year follow-up compared with those receiving other care. DESIGN: Retrospective cohort study. SETTING: 101 million patient US health records network (TriNetX), queried on 24 October 2022, yielding data from 2012 query. PARTICIPANTS: Adults age 18-49 with newly diagnosed LDH/LSR (first date of diagnosis) were included. Exclusions were prior lumbar surgery, absolute indications for surgery, trauma, spondylolisthesis and scoliosis. Propensity score matching controlled for variables associated with the likelihood of discectomy (eg, demographics, medications). INTERVENTIONS: Patients were divided into cohorts according to receipt of CSMT. PRIMARY AND SECONDARY OUTCOME MEASURES: ORs for lumbar discectomy; calculated by dividing odds in the CSMT cohort by odds in the cohort receiving other care. RESULTS: After matching, there were 5785 patients per cohort (mean age 36.9±8.2). The ORs (95% CI) for discectomy were significantly reduced in the CSMT cohort compared with the cohort receiving other care over 1-year (0.69 (0.52 to 0.90), p=0.006) and 2-year follow-up (0.77 (0.60 to 0.99), p=0.040). E-value sensitivity analysis estimated the strength in terms of risk ratio an unmeasured confounding variable would need to account for study results, yielding point estimates for each follow-up (1 year: 2.26; 2 years: 1.92), which no variables in the literature reached. CONCLUSIONS: Our findings suggest receiving CSMT compared with other care for newly diagnosed LDH/LSR is associated with significantly reduced odds of discectomy over 2-year follow-up. Given socioeconomic variables were unavailable and an observational design precludes inferring causality, the efficacy of CSMT for LDH/LSR should be examined via randomised controlled trial to eliminate residual confounding.

The intervertebral disc is a complex structure that experiences multiaxial stresses regularly. Disc failure through herniation is a common cause of lower back pain, which causes reduced mobility and debilitating pain, resulting in heavy socioeconomic burdens. Unfortunately, herniation etiology is not well understood, partially due to challenges in replicating herniation in vitro. Previous studies suggest that flexion elevated risks of herniation. Thus, the objective of this study was to use a multiscale and multiphasic finite element model to evaluate the risk of failure under torque- or muscle-driven flexion. Models were developed to represent torque-driven flexion with the instantaneous center of rotation (ICR) located on the disc, and the more physiologically representative muscle-driven flexion with the ICR located anterior of the disc. Model predictions highlighted disparate disc mechanics regarding bulk deformation, stress-bearing mechanisms, and intradiscal stress-strain distributions. Specifically, failure was predicted to initiate at the bone-disc boundary under torque-driven flexion, which may explain why endplate junction failure, instead of herniation, has been the more common failure mode observed in vitro. By contrast, failure was predicted to initiate in the posterolateral annulus fibrosus under muscle-driven flexion, resulting in consistent herniation. Our findings also suggested that muscle-driven flexion combined with axial compression could be sufficient for provoking herniation in vitro and in silico. In conclusion, this study provided a computational framework for designing in vitro testing protocols that can advance the assessment of disc failure behavior and the performance of engineered disc implants.

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.

Two FGF4 retrogenes (FGF4L1 on chromosome 18 and FGF4L2 on chromosome 12) have been identified to cause dwarfism across many dog breeds. Some breeds are nearly homozygous for both retrogenes (e.g., Dachshunds) and others are homozygous for just one (e.g., Beagles and Scottish Terriers). Since most breeds do not segregate both of these retrogenes, it is challenging to evaluate their individual effects on long bone length and body size. We identified two dog breeds selected for hunting ability, the Alpine Dachsbracke and the Schweizer Niederlaufhund, that segregate both of these retrogenes. Using individual measurements of height at the shoulder, back length, head width, thorax depth and width, and thoracic limb measurements, we evaluated the combined effects of FGF4 retrogenes within these breeds. We applied multivariable linear regression analysis to determine the effects of retrogene copy numbers on the measurements. Copy numbers of both retrogenes had significant effects reducing height at the shoulders and antebrachial length, with FGF4L1 having a much greater effect than FGF4L2. FGF4L1 alone influenced the degree of carpal valgus and FGF4L2 alone increased head width. Neither retrogene had an effect on thorax width or depth. Selectively breeding dogs with FGF4L1 and without FGF4L2 would likely lead to a reduction in the FGF4L2-related risk of intervertebral disc herniation while maintaining the reduction in leg length resulting from FGF4L1.

BackgroundSerum phosphorylated neurofilament-heavy chain (pNF-H) has not been longitudinally evaluated in dogs that develop progressive myelomalacia (PMM) after Type I intervertebral disc herniation (IVDH).ObjectivesTo determine if serum pNF-H concentrations would predict outcome of neuroligical disease in dogs with acute, severe thoracolumbar myelopathy secondary to Type I IVDH.AnimalsThirty-nine client-owned dogs with thoracolumbar myelopathy secondary to IVDH.MethodsProspective controlled cohort study. Serum was collected from dogs undergoing hemilaminectomy at multiple timepoints. Final neurological status was established at 12 months and groups were stratified accordingly. Comparisons between outcome and pNF-H concentration at each timepoint was examined using Kruskal-Wallis analysis of variance on ranks and receiver operator characteristics curve analysis.ResultsMedian serum pNF-H concentrations were not significantly different between deep pain negative dogs that did or did not recover at any timepoint (baseline: 0.37 ng/mL [0-0.9 ng/mL] vs 0 ng/mL [0-0.9 ng/mL], P > 1; 24 hours: 1.25 ng/mL [0.35-7.23 ng/mL] vs 1.53 ng/mL [0-11.94 ng/mL], P > 1; 48 hours: 1.22 ng/mL [0.63-6.62 ng/mL] vs 2.12 ng/mL [0-20.72 ng/mL], P >  1; 72 hours: 2.77 ng/mL [1.33-6.62 ng/mL] vs 16.69 ng/mL [4.02-40.12 ng/mL], P >  1). Dogs that developed PMM had significantly higher serum pNF-H concentrations after surgery compared to all other cohorts at 24 hours: 39.88 ng/mL (25.74-50.68 ng/mL); P

BackgroundSerum phosphorylated neurofilament-heavy chain (pNF-H) has not been longitudinally evaluated in dogs that develop progressive myelomalacia (PMM) after Type I intervertebral disc herniation (IVDH).ObjectivesTo determine if serum pNF-H concentrations would predict outcome of neuroligical disease in dogs with acute, severe thoracolumbar myelopathy secondary to Type I IVDH.AnimalsThirty-nine client-owned dogs with thoracolumbar myelopathy secondary to IVDH.MethodsProspective controlled cohort study. Serum was collected from dogs undergoing hemilaminectomy at multiple timepoints. Final neurological status was established at 12 months and groups were stratified accordingly. Comparisons between outcome and pNF-H concentration at each timepoint was examined using Kruskal-Wallis analysis of variance on ranks and receiver operator characteristics curve analysis.ResultsMedian serum pNF-H concentrations were not significantly different between deep pain negative dogs that did or did not recover at any timepoint (baseline: 0.37 ng/mL [0-0.9 ng/mL] vs 0 ng/mL [0-0.9 ng/mL], P > 1; 24 hours: 1.25 ng/mL [0.35-7.23 ng/mL] vs 1.53 ng/mL [0-11.94 ng/mL], P > 1; 48 hours: 1.22 ng/mL [0.63-6.62 ng/mL] vs 2.12 ng/mL [0-20.72 ng/mL], P >  1; 72 hours: 2.77 ng/mL [1.33-6.62 ng/mL] vs 16.69 ng/mL [4.02-40.12 ng/mL], P >  1). Dogs that developed PMM had significantly higher serum pNF-H concentrations after surgery compared to all other cohorts at 24 hours: 39.88 ng/mL (25.74-50.68 ng/mL); P

Two transcribed retrocopies of the fibroblast growth factor 4 (FGF4) gene have previously been described in the domestic dog. An FGF4 retrocopy on chr18 is associated with disproportionate dwarfism, while an FGF4 retrocopy on chr12 is associated with both disproportionate dwarfism and intervertebral disc disease (IVDD). In this study, whole-genome sequencing data were queried to identify other FGF4 retrocopies that could be contributing to phenotypic diversity in canids. Additionally, dogs with surgically confirmed IVDD were assayed for novel FGF4 retrocopies. Five additional and distinct FGF4 retrocopies were identified in canids including a copy unique to red wolves (Canis rufus). The FGF4 retrocopies identified in domestic dogs were identical to domestic dog FGF4 haplotypes, which are distinct from modern wolf FGF4 haplotypes, indicating that these retrotransposition events likely occurred after domestication. The identification of multiple, full length FGF4 retrocopies with open reading frames in canids indicates that gene retrotransposition events occur much more frequently than previously thought and provide a mechanism for continued genetic and phenotypic diversity in canids.

Degenerative changes of the intervertebral disc (IVD) are a leading cause of disability affecting humans worldwide and has been attributed primarily to trauma and the accumulation of pathology during aging. While genetic defects have also been associated with disc degeneration, the precise mechanisms driving the initiation and progression of disease have remained elusive due to a paucity of genetic animal models. Here, we discuss a novel conditional mouse genetic model of endplate-oriented disc herniations in adult mice. Using conditional mouse genetics, we show increased mechanical stiffness and reveal dysregulation of typical gene expression profiles of the IVD in adhesion G-protein coupled receptor G6 (Adgrg6) mutant mice prior to the onset of endplate-oriented disc herniations in adult mice. We observed increased STAT3 activation prior to IVD defects and go on to demonstrate that treatment of Adgrg6 conditional mutant mice with a small molecule inhibitor of STAT3 activation ameliorates endplate-oriented herniations. These findings establish ADGRG6 and STAT3 as novel regulators of IVD endplate and growth plate integrity in the mouse, and implicate ADGRG6/STAT3 signaling as promising therapeutic targets for endplate-oriented disc degeneration.

Two FGF4 retrogenes on chromosomes 12 (12-FGF4RG) and 18 (18-FGF4RG) contribute to short-limbed phenotypes in dogs. 12-FGF4RG has also been associated with intervertebral disc disease (IVDD). Both of these retrogenes were found to be widespread among dog breeds with allele frequencies ranging from 0.02 to 1; however, their additive contribution to disease is unknown. Surgical cases of IVDD (n = 569) were evaluated for age of onset, disc calcification, and genotypes for the FGF4 retrogenes. Multivariable linear regression analysis identified the presence of one or two copies of 12-FGF4RG associated with significantly younger age at first surgery in a dominant manner. 18-FGF4RG had only a minor effect in dogs with one copy. Multivariable logistic regression showed that 12-FGF4RG had an additive effect on radiographic disc calcification, while 18-FGF4RG had no effect. Multivariable logistic regression using mixed breed cases and controls identified only 12-FGF4RG as highly associated with disc herniation in a dominant manner (Odds Ratio, OR, 18.42, 95% Confidence Interval (CI) 7.44 to 50.26; P < 0.001). The relative risk for disc surgery associated with 12-FGF4RG varied from 5.5 to 15.1 within segregating breeds and mixed breeds. The FGF4 retrogene on CFA12 acts in a dominant manner to decrease the age of onset and increase the overall risk of disc disease in dogs. Other modifiers of risk may be present within certain breeds, including the FGF4 retrogene on CFA18.

Degenerative changes of the intervertebral disc (IVD) are a leading cause of disability affecting humans worldwide and has been attributed primarily to trauma and the accumulation of pathology during aging. While genetic defects have also been associated with disc degeneration, the precise mechanisms driving the initiation and progression of disease have remained elusive due to a paucity of genetic animal models. Here, we discuss a novel conditional mouse genetic model of endplate-oriented disc herniations in adult mice. Using conditional mouse genetics, we show increased mechanical stiffness and reveal dysregulation of typical gene expression profiles of the IVD in adhesion G-protein coupled receptor G6 (Adgrg6) mutant mice prior to the onset of endplate-oriented disc herniations in adult mice. We observed increased STAT3 activation prior to IVD defects and go on to demonstrate that treatment of Adgrg6 conditional mutant mice with a small molecule inhibitor of STAT3 activation ameliorates endplate-oriented herniations. These findings establish ADGRG6 and STAT3 as novel regulators of IVD endplate and growth plate integrity in the mouse, and implicate ADGRG6/STAT3 signaling as promising therapeutic targets for endplate-oriented disc degeneration.

Study designDescriptive histologic and magnetic resonance imaging study of human cadaveric spines.ObjectiveTo identify and characterize common endplate pathologies to form a histologic foundation for an etiology-based classification system.Summary of background dataIrregularities 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.MethodsFifteen 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.ResultsDisc-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.ConclusionThis 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 evidence3.

Study designSystematic review and meta-analysis of comparative studies.ObjectiveTo characterize the association of annular defect width after lumbar discectomy with the risk of symptom recurrence and reoperation.Summary of background dataLarge annular defect width after lumbar discectomy has been reported to increase risk of symptom recurrence. However, this association has not been evaluated in a systematic manner.MethodsA systematic literature search of MEDLINE and EMBASE was performed to identify comparative studies of large versus small annular defects following lumbar discectomy that reported symptom recurrence or reoperation rates. Main outcomes were reported with pooled odds ratios (OR) and 95% confidence intervals (CIs). Sensitivity analyses were performed to assess the robustness of the meta-analysis findings.ResultsAfter screening 696 records, we included data from 7 comparative studies involving 1653 lumbar discectomy patients, of whom 499 (30%) had large annular defects and 1154 (70%) had small annular defects. Methodological quality of studies was good overall. The median follow-up period was 2.9 years. The risk of symptom recurrence (OR = 2.5, 95% CI = 1.3-4.5, P = 0.004) and reoperation (OR = 2.3, 95% CI = 1.5-3.7, P

Study designSystematic review and meta-analysis of comparative studies.ObjectiveTo characterize the association of annular defect width after lumbar discectomy with the risk of symptom recurrence and reoperation.Summary of background dataLarge annular defect width after lumbar discectomy has been reported to increase risk of symptom recurrence. However, this association has not been evaluated in a systematic manner.MethodsA systematic literature search of MEDLINE and EMBASE was performed to identify comparative studies of large versus small annular defects following lumbar discectomy that reported symptom recurrence or reoperation rates. Main outcomes were reported with pooled odds ratios (OR) and 95% confidence intervals (CIs). Sensitivity analyses were performed to assess the robustness of the meta-analysis findings.ResultsAfter screening 696 records, we included data from 7 comparative studies involving 1653 lumbar discectomy patients, of whom 499 (30%) had large annular defects and 1154 (70%) had small annular defects. Methodological quality of studies was good overall. The median follow-up period was 2.9 years. The risk of symptom recurrence (OR = 2.5, 95% CI = 1.3-4.5, P = 0.004) and reoperation (OR = 2.3, 95% CI = 1.5-3.7, P

Background contextProlonged 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.PurposeThis 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 designThis is a prospective longitudinal study.SampleSix astronaut crewmember volunteers from the National Aeronautics and Space Administration (NASA) with 6-month missions aboard the ISS comprised our study sample.Outcome measuresFor 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.Methods3T 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.ResultsSupine 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).ConclusionsWe 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.

Damage at the intervertebral disc-vertebra interface associates with back pain and disc herniation. However, the structural and biomechanical properties of the disc-vertebra interface remain underexplored. We sought to measure mechanical properties and failure mechanisms, quantify architectural features, and assess structure-function relationships at this vulnerable location. Vertebra-disc-vertebra specimens from human cadaver thoracic spines were scanned with micro-computed tomography (μCT), surface speckle-coated, and loaded to failure in uniaxial tension. Digital image correlation (DIC) was used to calculate local surface strains. Failure surfaces were scanned using scanning electron microscopy (SEM), and adjacent sagittal slices were analyzed with histology and SEM. Seventy-one percent of specimens failed initially at the cartilage endplate-bone interface of the inner annulus region. Histology and SEM both indicated a lack of structural integration between the cartilage endplate (CEP) and bone. The interface failure strength was increased in samples with higher trabecular bone volume fraction in the vertebral endplates. Furthermore, failure strength decreased with degeneration, and in discs with thicker CEPs. Our findings indicate that poor structural connectivity between the CEP and vertebra may explain the structural weakness at this region, and provide insight into structural features that may contribute to risk for disc-vertebra interface injury. The disc-vertebra interface is the site of failure in the majority of herniation injuries. Here we show new structure-function relationships at this interface that may motivate the development of diagnostics, prevention strategies, and treatments to improve the prognosis for many low back pain patients with disc-vertebra interface injuries. © 2017 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 36:192-201, 2018.

Damage at the intervertebral disc-vertebra interface associates with back pain and disc herniation. However, the structural and biomechanical properties of the disc-vertebra interface remain underexplored. We sought to measure mechanical properties and failure mechanisms, quantify architectural features, and assess structure-function relationships at this vulnerable location. Vertebra-disc-vertebra specimens from human cadaver thoracic spines were scanned with micro-computed tomography (μCT), surface speckle-coated, and loaded to failure in uniaxial tension. Digital image correlation (DIC) was used to calculate local surface strains. Failure surfaces were scanned using scanning electron microscopy (SEM), and adjacent sagittal slices were analyzed with histology and SEM. Seventy-one percent of specimens failed initially at the cartilage endplate-bone interface of the inner annulus region. Histology and SEM both indicated a lack of structural integration between the cartilage endplate (CEP) and bone. The interface failure strength was increased in samples with higher trabecular bone volume fraction in the vertebral endplates. Furthermore, failure strength decreased with degeneration, and in discs with thicker CEPs. Our findings indicate that poor structural connectivity between the CEP and vertebra may explain the structural weakness at this region, and provide insight into structural features that may contribute to risk for disc-vertebra interface injury. The disc-vertebra interface is the site of failure in the majority of herniation injuries. Here we show new structure-function relationships at this interface that may motivate the development of diagnostics, prevention strategies, and treatments to improve the prognosis for many low back pain patients with disc-vertebra interface injuries. © 2017 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 36:192-201, 2018.

Chondrodystrophy in dogs is defined by dysplastic, shortened long bones and premature degeneration and calcification of intervertebral discs. Independent genome-wide association analyses for skeletal dysplasia (short limbs) within a single breed (PBonferroni = 0.01) and intervertebral disc disease (IVDD) across breeds (PBonferroni = 4.0 × 10-10) both identified a significant association to the same region on CFA12. Whole genome sequencing identified a highly expressed FGF4 retrogene within this shared region. The FGF4 retrogene segregated with limb length and had an odds ratio of 51.23 (95% CI = 46.69, 56.20) for IVDD. Long bone length in dogs is a unique example of multiple disease-causing retrocopies of the same parental gene in a mammalian species. FGF signaling abnormalities have been associated with skeletal dysplasia in humans, and our findings present opportunities for both selective elimination of a medically and financially devastating disease in dogs and further understanding of the ever-growing complexity of retrogene biology.

Chondrodystrophy in dogs is defined by dysplastic, shortened long bones and premature degeneration and calcification of intervertebral discs. Independent genome-wide association analyses for skeletal dysplasia (short limbs) within a single breed (PBonferroni = 0.01) and intervertebral disc disease (IVDD) across breeds (PBonferroni = 4.0 × 10-10) both identified a significant association to the same region on CFA12. Whole genome sequencing identified a highly expressed FGF4 retrogene within this shared region. The FGF4 retrogene segregated with limb length and had an odds ratio of 51.23 (95% CI = 46.69, 56.20) for IVDD. Long bone length in dogs is a unique example of multiple disease-causing retrocopies of the same parental gene in a mammalian species. FGF signaling abnormalities have been associated with skeletal dysplasia in humans, and our findings present opportunities for both selective elimination of a medically and financially devastating disease in dogs and further understanding of the ever-growing complexity of retrogene biology.

PurposeDisc herniation risk is quadrupled following spaceflight. This study tested the hypothesis that swelling-induced disc height increases (comparable to those reported in spaceflight) stiffen the spine and elevate annular strain and nuclear pressure during forward bending.MethodsEight human lumbar motion segments were secured to custom-designed testing jigs and subjected to baseline flexion and compression and pure moment flexibility tests. Discs were then free-swelled in saline to varying supraphysiologic heights consistent with prolonged weightlessness and re-tested to assess biomechanical changes.ResultsSwelling-induced disc height changes correlated positively with intradiscal pressure (p

Study designSecondary analysis of randomized and nonrandomized prospective cohorts.ObjectiveTo examine the effect of patient treatment expectations on treatment outcomes for patients with intervertebral disc herniation.Summary of background dataPatient expectations about treatment effectiveness may have important relationships with clinical outcomes.MethodsSubgroup and reanalysis of the Spine Patient Outcomes Research Trial, a randomized trial and comprehensive cohort study enrolling patients between March 2000 and November 2004 from 13 multidisciplinary spine clinics in 11 US states. Overall, 501 randomized and 744 observational patients (1244 total) who were surgical candidates with radiculopathy and imaging confirmed lumbar intervertebral disc herniation were enrolled. The primary study compared surgical discectomy to usual nonoperative care; this subgroup analysis reassessed outcomes on the basis of treatment expectations at baseline. Expectations about symptomatic and functional improvement for both surgery and nonoperative care were assessed on 5-point scales (1="No Chance (0%)" to 5="Certain (100%)"). Outcomes were assessed using longitudinal regression models analyzed by treatment received.ResultsAmong 1244 IDH SPORT participants, 1168 provided data on both outcomes and baseline expectations and were included in the current analysis: 467 from the randomized and 701 from the observational cohort. Low expectations of outcomes with surgery predicted poorer outcome regardless of treatment. High expectations of outcomes with nonoperative care predicted better nonoperative outcomes but did not affect surgical results. These differences were of similar magnitude to the difference in outcomes between surgery and nonoperative care.ConclusionHigh expectations of treatment benefit had clinically significant positive associations with outcomes.Level of evidence2.

The purpose of this study was to determine the clinical validity of functional flexion-extension roentgenograms of the lumbar spine in a defined patient population. One hundred and one adults with low-back pain or functional disorders underwent passive functional flexion-extension examinations. Their roentgenograms were analyzed using a computer-assisted method to determine segmental motion parameters such as rotation and translation of the lumbar vertebrae. The patient population was broken down into five groups with similar pathologies or physical conditions, and their motion parameters compared to a normal population and to each other. It was found that all of the patient groups exhibited significantly hypomobile motion, spread equally among all levels, in comparison to the normal population, except for the group of high-performance athletes, who had significant hypermobility. The uniform spread of hypomobility limits the ability to distinguish with any confidence between the four pathologic groups by their motion. Thus, we believe that the analysis of the segmental motion of the lumbar spine using passive flexion-extension roentgenograms does not aid in differentiating the underlying pathologic condition of patients with low-back pain, and that no useful information can be derived form this procedure, especially in relation to the need for surgical intervention.