Paraspinal muscle gene expression across different aetiologies in individuals undergoing surgery for lumbar spine pathology.

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 < 0.001 and p = 0.038, respectively). When adjusted for multiple comparisons, only COL3A1 remained significant (p = 0.012). CONCLUSION: Individuals with disc herniation and facet arthropathy demonstrate higher COL3A1 gene expression compared to those with degenerative spondylolisthesis. Future research is required to further understand the biological relevance of these transcriptional differences.

Paraspinal Muscle Health is Related to Fibrogenic, Adipogenic, and Myogenic Gene Expression in Patients with Lumbar Spine Pathology.

BACKGROUND: Lumbar spine pathology is a common feature of lower back and/or lower extremity pain and is associated with observable degenerative changes in the lumbar paraspinal muscles that are associated with poor clinical prognosis. Despite the commonly observed phenotype of muscle degeneration in this patient population, its underlying molecular mechanisms are not well understood. The aim of this study was to investigate the relationships between groups of genes within the atrophic, myogenic, fibrogenic, adipogenic, and inflammatory pathways and multifidus muscle health in individuals undergoing surgery for lumbar spine pathology. METHODS: Multifidus muscle biopsies were obtained from patients (n = 59) undergoing surgery for lumbar spine pathology to analyze 42 genes from relevant adipogenic/metabolic, atrophic, fibrogenic, inflammatory, and myogenic gene pathways using quantitative polymerase chain reaction. Multifidus muscle morphology was examined preoperatively in these patients at the level and side of biopsy using T2-weighted magnetic resonance imaging to determine whole muscle compartment area, lean muscle area, fat cross-sectional areas, and proportion of fat within the muscle compartment. These measures were used to investigate the relationships between gene expression patterns and muscle size and quality. RESULTS: Relationships between gene expression and imaging revealed significant associations between decreased expression of adipogenic/metabolic gene (PPARD), increased expression of fibrogenic gene (COL3A1), and lower fat fraction on MRI (r = -0.346, p = 0.018, and r = 0.386, p = 0.047 respectively). Decreased expression of myogenic gene (mTOR) was related to greater lean muscle cross-sectional area (r = 0.388, p = 0.045). CONCLUSION: Fibrogenic and adipogenic/metabolic genes were related to pre-operative muscle quality, and myogenic genes were related to pre-operative muscle size. These findings provide insight into molecular pathways associated with muscle health in the presence of lumbar spine pathology, establishing a foundation for future research that addresses how these changes impact outcomes in this patient population.

Regional differences between superficial and deep lumbar multifidus in patients with chronic lumbar spine pathology.

BACKGROUND: Due to its unique arrangement, the deep and superficial fibers of the multifidus may have differential roles for maintaining spine stabilization and lumbar posture; the superficial multifidus is responsible for lumbar extension and the deep multifidus for intersegmental stability. In patients with chronic lumbar spine pathology, muscle activation patterns have been shown to be attenuated or delayed in the deep, but not superficial, multifidus. This has been interpreted as pain differentially influencing the deep region. However, it is unclear if degenerative changes affecting the composition and function of the multifidus differs between the superficial and deep regions, an alternative explanation for these electrophysiological changes. Therefore, the goal of this study was to investigate macrostructural and microstructural differences between the superficial and deep regions of the multifidus muscle in patients with lumbar spine pathology. METHODS: In 16 patients undergoing lumbar spinal surgery for degenerative conditions, multifidus biopsies were acquired at two distinct locations: 1) the most superficial portion of muscle adjacent to the spinous process and 2) approximately 1 cm lateral to the spinous process and deeper at the spinolaminar border of the affected vertebral level. Structural features related to muscle function were histologically compared between these superficial and deep regions, including tissue composition, fat fraction, fiber cross sectional area, fiber type, regeneration, degeneration, vascularity and inflammation. RESULTS: No significant differences in fat signal fraction, muscle area, fiber cross sectional area, muscle regeneration, muscle degeneration, or vascularization were found between the superficial and deep regions of the multifidus. Total collagen content between the two regions was the same. However, the superficial region of the multifidus was found to have less loose and more dense collagen than the deep region. CONCLUSIONS: The results of our study did not support that the deep region of the multifidus is more degenerated in patients with lumbar spine pathology, as gross degenerative changes in muscle microstructure and macrostructure were the same in the superficial and deep regions of the multifidus. In these patients, the multifidus is not protected in order to maintain mobility and structural stability of the spine.

Correction to: Intervertebral disc penetration by antibiotics used prophylactically in spinal surgery: implications for the current standards and treatment of disc infections.

Unfortunately, the complete conflict of interest statement was missed out in the original publication. The same is given below.

Intervertebral disc penetration by antibiotics used prophylactically in spinal surgery: implications for the current standards and treatment of disc infections.

PURPOSE: The presence of Propionibacterium acnes in a substantial component of resected disc specimens obtained from patients undergoing discectomy or microdiscectomy has led to the suggestion that this prominent human skin and oral commensal may exacerbate the pathology of degenerative disc disease. This hypothesis, therefore, raises the exciting possibility that antibiotics could play an important role in treating this debilitating condition. To date, however, little information about antibiotic penetration into the intervertebral disc is available. METHODS: Intervertebral disc tissue obtained from 54 microdiscectomy patients given prophylactic cefazolin (n = 25), clindamycin (n = 17) or vancomycin (n = 12) was assayed by high-performance liquid chromatography, with cefaclor as an internal standard, to determine the concentration of antibiotic penetrating into the disc tissue. RESULTS: Intervertebral disc tissues from patients receiving the positively charged antibiotic clindamycin contained a significantly greater percentage of the antibacterial dose than the tissue from patients receiving negatively charged cefazolin (P < 0.0001) and vancomycin, which has a slight positive charge (P < 0.0001). CONCLUSION: Positively charged antibiotics appear more appropriate for future studies investigating potential options for the treatment of low-virulence disc infections. These slides can be retrieved under Electronic Supplementary Material.

Utilization of CT scanning associated with complex spine surgery.

BACKGROUND: Due to the risk associated with exposure to ionizing radiation, there is an urgent need to identify areas of CT scanning overutilization. While increased use of diagnostic spinal imaging has been documented, no previous research has estimated the magnitude of follow-up imaging used to evaluate the postoperative spine. METHODS: This retrospective cohort study quantifies the association between spinal surgery and CT utilization. An insurance database (Humana, Inc.) with ≈ 19 million enrollees was employed, representing 8 consecutive years (2007-2014). Surgical and imaging procedures were captured by anatomic-specific CPT codes. Complex surgeries included all cervical, thoracic and lumbar instrumented spine fusions. Simple surgeries included discectomy and laminectomy. Imaging was restricted to CT and MRI. Postoperative imaging frequency extended to 5-years post-surgery. RESULTS: There were 140,660 complex spinal procedures and 39,943 discectomies and 49,889 laminectomies. MRI was the predominate preoperative imaging modality for all surgical procedures (median: 80%; range: 73-82%). Postoperatively, CT prevalence following complex procedures increased more than two-fold from 6 months (18%) to 5 years (≥40%), and patients having a postoperative CT averaged two scans. For simple procedures, the prevalence of postoperative CT scanning never exceeded 30%. CONCLUSIONS: CT scanning is used frequently for follow-up imaging evaluation following complex spine surgery. There is emerging evidence of an increased cancer risk due to ionizing radiation exposure with CT. In the setting of complex spine surgery, actions to mitigate this risk should be considered and include reducing nonessential scans, using the lowest possible radiation dose protocols, exerting greater selectivity in monitoring the developing fusion construct, and adopting non-ferromagnetic implant biomaterials that facilitate MRI postoperatively.

Paraspinal muscles in individuals undergoing surgery for lumbar spine pathology lack a myogenic response to an acute bout of resistance exercise.

Background: Lumbar spine pathology (LSP) is a common source of low back or leg pain, and paraspinal muscle in these patients demonstrates fatty and fibrotic infiltration, and cellular degeneration that do not reverse with exercise-based rehabilitation. However, it is unclear of this lack of response is due to insufficient exercise stimulus, or an inability to mount a growth response. The purpose of this study was to compare paraspinal muscle gene expression between individuals with LSP who do and do not undergo an acute bout of resistance exercise. Methods: Paraspinal muscle biopsies were obtained from 64 individuals with LSP undergoing spinal surgery. Eight participants performed an acute bout of machine-based lumbar extension resistance exercise preoperatively. Gene expression for 42 genes associated with adipogenic/metabolic, atrophic, fibrogenic, inflammatory, and myogenic pathways was measured, and differential expression between exercised and non-exercised groups was evaluated for (a) the full cohort, and (b) an age, gender, acuity, and etiology matched sub-cohort. Principal components analyses were used to identify gene expression clustering across clinical phenotypes. Results: The exercised cohort demonstrated upregulation of inflammatory gene IL1B, inhibition of extracellular matrix components (increased MMP3&9, decreased TIMP1&3, COL1A1) and metabolic/adipogenic genes (FABP4, PPARD, WNT10B), and downregulation of myogenic (MYOD, ANKRD2B) and atrophic (FOXO3) genes compared to the non-exercised cohort, with similar patterns in the matched sub-analysis. There were no clinical phenotypes significantly associated with gene expression profiles. Conclusion: An acute bout of moderate-high intensity resistance exercise did not result in upregulation of myogenic genes in individuals with LSP. The response was characterized by mixed metabolic and fibrotic gene expression, upregulation of inflammation, and downregulation of myogenesis.

The effect of fatty infiltration, revision surgery, and sex on lumbar multifidus passive mechanical properties.

Purpose: Previous research has demonstrated increased stiffness in the multifidus muscle compared to other paraspinal muscles at the fiber bundle level. We aimed to compare single fiber and fiber bundle passive mechanical properties of multifidus muscle: (1) in 40 patients undergoing primary versus revision surgery and (2) in muscle with mild versus severe fatty infiltration. Methods: The degree of muscle fatty infiltration was graded using the patients' spine magnetic resonance images. Average single fiber and fiber bundle passive mechanical properties across three tests were compared between primary (N = 30) and revision (N = 10) surgery status, between mild and severe fatty infiltration levels, between sexes, and with age from passive stress-strain tests of excised multifidus muscle intraoperative biopsies. Results: At the single fiber level, elastic modulus was unaffected by degree of fatty infiltration or surgery status. Female sex (p = 0.001) and younger age (p = 0.04) were associated with lower multifidus fiber elastic modulus. At the fiber bundle level, which includes connective tissue around fibers, severe fatty infiltration (p = 0.01) and younger age (p = 0.06) were associated with lower elastic modulus. Primary surgery also demonstrated a moderate, but non-significant effect for lower elastic modulus (p = 0.10). Conclusions: Our results demonstrate that female sex is the primary driver for reduced single fiber elastic modulus of the multifidus, while severity of fatty infiltration is the primary driver for reduced elastic modulus at the level of the fiber bundle in individuals with lumbar spine pathology.

Do design variations in the artificial disc influence cervical spine biomechanics? A finite element investigation.

Various ball and socket-type designs of cervical artificial discs are in use or under investigation. Many artificial disc designs claim to restore the normal kinematics of the cervical spine. What differentiates one type of design from another design is currently not well understood. In this study, authors examined various clinically relevant parameters using a finite element model of C3-C7 cervical spine to study the effects of variations of ball and socket disc designs. Four variations of ball and socket-type artificial disc were placed at the C5-C6 level in an experimentally validated finite element model. Biomechanical effects of the shape (oval vs. spherical ball) and location (inferior vs. superior ball) were studied in detail. Range of motion, facet loading, implant stresses and capsule ligament strains were computed to investigate the influence of disc designs on resulting biomechanics. Motions at the implant level tended to increase following disc replacement. No major kinematic differences were observed among the disc designs tested. However, implant stresses were substantially higher in the spherical designs when compared to the oval designs. For both spherical and oval designs, the facet loads were lower for the designs with an inferior ball component. The capsule ligament strains were lower for the oval design with an inferior ball component. Overall, the oval design with an inferior ball component, produced motion, facet loads, implant stresses and capsule ligament strains closest to the intact spine, which may be key to long-term implant survival.

Biomechanical evaluation of transfacet screw fixation for stabilization of multilevel cervical corpectomies.

STUDY DESIGN: Cadaveric biomechanical investigation. OBJECTIVES: To test the feasibility of transfacet screws as a minimally invasive posterior fixation device for the cervical spine by comparing the biomechanical stability of transfacet screws to lateral mass screws and rods in a multilevel cervical corpectomy model. SUMMARY OF BACKGROUND DATA: Minimally invasive surgery (MIS) of the spine has gained increasing acceptance and popularity. However, a minimally invasive means of instrumenting the posterior cervical spine has yet to be discovered. Posterior transfacet screws have been described as a means of posterior fixation. In addition, they have the potential of being placed percutaneously through stab incisions. However, validation of transfacet screws in an unstable cervical model in which posterior instrumentation may be necessary has not been carried out till date. METHODS: Sixteen cadaveric cervical spines were randomized to transfacet or lateral mass instrumentation groups. The spines were tested in the following conditions: (a) intact, (b) after multilevel corpectomies with strut graft placement with stand-alone posterior fixation, and (c) with an additional anterior plate over the strut graft. Corpectomy site loading was measured with a custom-designed strut graft. Data were collected for spinal stiffness, range of motion, and strut graft loading, and was analyzed using 2-way analysis of variance (P<0.05). RESULTS: Stand-alone transfacet screw fixation was found to provide inferior spinal stability and resulted in increased spinal motion and graft loading compared with the other constructs (P<0.05 for all). CONCLUSIONS: It is unclear what kind of mechanical stiffness is necessary to stabilize the cervical spine and obtain solid fusion. However, decreased stability and increased graft loading suggest that transfacet screws may not be the ideal method of posterior fixation to supplement multilevel anterior cervical corpectomies and fusions despite their potential as a minimally invasive method for posterior cervical instrumentation.

Psychiatric disorders and risk of transition to chronicity in men with first onset low back pain.

OBJECTIVE: To assess whether pre-existing psychiatric diagnoses increase the likelihood of transitioning from sub-acute to chronic back pain. DESIGN: Prospective cohort study. METHODS: Men (N = 140) experiencing a first onset of low back pain (LBP) were examined for lifetime psychiatric disorders approximately 8 weeks post pain-onset using the Diagnostic Interview Schedule (DIS-III-R), then re-evaluated at 6 months after pain onset to determine who did or did not progress to pain chronicity. OUTCOME MEASURE: Transition to chronic pain and disability was based on 6-month self-report measures of pain intensity and perceived disability. RESULTS: Men with a pre-pain lifetime diagnosis of major depressive disorder had 5 times greater risk of transitioning to chronic LBP (odds ratio [OR] = 4.99; 95% confidence interval [CI] 1.49-16.76). Increased risk was also associated with a pre-pain lifetime diagnosis of generalized anxiety (OR = 2.45; 95% CI 1.06-5.68), post-traumatic stress (OR = 3.23; 95% CI 1.11-9.44), and with current nicotine dependence (OR = 2.49; 95% CI 1.15-5.40). There were no statistically significant effects for abuse or dependence of alcohol or other psychoactive substances. DISCUSSION: Lifetime history of major depression or a major anxiety disorder may represent potential psychosocial "yellow flags" for the transition to chronicity in men with first-onset LBP. Screening for lifetime depressive or anxiety disorders may identify individuals at higher risk, who may benefit from referral for more intensive rehabilitation.

Cell populations and muscle fiber morphology associated with acute and chronic muscle degeneration in lumbar spine pathology.

Many chronic musculoskeletal conditions are associated with loss of muscle volume and quality, resulting in functional decline. While atrophy has long been implicated as the mechanism of muscle loss in these conditions, recent evidence has emerged demonstrating a degenerative phenotype of muscle loss consisting of disrupted muscle fiber membranes, infiltration of cells into muscle fibers, and as previously describer, possible replacement of muscle fibers by adipose tissue. Here, we use human lumbar spine pathology as a model system to provide a more comprehensive analysis of the morphological features of this mode of muscle loss between early and late stages of disease, including an analysis of the cell populations found in paraspinal muscle biopsies from humans with acute vs chronic lumbar spine pathology. Using longitudinal sections, we show that degeneration of muscle fibers is localized within a fiber (ie, focal), and is characterized by discontinuous or ragged membrane disruption, cellular infiltration, and apparently vacant space containing limited numbers of nuclei and hyper-contractile cell debris. Samples from patients with acute and chronic pathology demonstrate similar magnitudes of muscle degeneration, however, larger proportions of PDGFRß-positive progenitor cells and leukocytes were observed in the acute group, with no differences in myogenic cells, macrophages, or T-cells. By better understanding the cell population behaviors over the course of disease, therapies can be optimized to address the appropriate targets and timing of administration to minimize the functional consequences of muscle degeneration in lumbar spine pathology.

Preventing progression to chronicity in first onset, subacute low back pain: an exploratory study.

OBJECTIVES: To evaluate the effects of a behavioral medicine intervention, relative to an attention control, in preventing chronic pain and disability in patients with first-onset, subacute low back pain (LBP) with limitations in work-role function. DESIGN: A 2-group, experimental design with randomization to behavioral medicine or attention control groups. SETTING: Orthopedic clinic at a Naval Medical Center. PARTICIPANTS: Sixty-seven participants with first-onset LBP of 6 to 10 weeks of duration and impairment in work function, of whom 50 completed all 4 therapy sessions and follow-up 6 months after pain onset. INTERVENTION: Four 1-hour individual treatment sessions of either behavioral medicine, focused on back function and pain education, self-management training, graded activity increases, fear reduction, and pain belief change; or attention control condition, focused on empathy, support, and reassurance. MAIN OUTCOME MEASURES: The primary outcome was proportion of participants classified as recovered, according to pre-established clinical cutoffs on standardized measures, signifying absence of chronic pain and disability at 6 months after pain onset. Secondary analyses were conducted on pain, disability, health status, and functional work category. Intervention credibility and pain belief manipulation checks were also evaluated. RESULTS: Chi square analyses comparing proportions recovered at 6 months after pain onset for behavioral medicine and attention control participants found relative rates of 52% versus 31% in the modified intent-to-treat sample (P=.09) and 54% versus 23% for those completing all 4 sessions and 6-month follow-up (P=.02). At 12 months, 79% of recovered and 68% of chronic pain participants still met criteria for their respective groups (P<.0001). Recovered participants also had higher rates of functional work status recovery at 12 months (recovered: 96% full duty and 4% light duty; chronic pain: 61% full duty, 18% light duty, and 21% medical discharge, respectively; P=.03). CONCLUSIONS: Early intervention using a behavioral medicine rehabilitation approach may enhance recovery and reduce chronic pain and disability in patients with first-onset, subacute LBP. Effects are stronger for participants attending all 4 sessions and the follow-up assessment.

Association of Annular Defect Width After Lumbar Discectomy With Risk of Symptom Recurrence and Reoperation: Systematic Review and Meta-analysis of Comparative Studies.

STUDY DESIGN: Systematic review and meta-analysis of comparative studies. OBJECTIVE: To characterize the association of annular defect width after lumbar discectomy with the risk of symptom recurrence and reoperation. SUMMARY OF BACKGROUND DATA: Large 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. METHODS: A 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. RESULTS: After 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 < 0.001) was higher in patients with large versus small annular defects. Publication bias was not evident. The associations between annular defect width and risk of symptom recurrence and reoperation remained statistically significant in all sensitivity analyses. CONCLUSION: Annular defect width after lumbar discectomy is an under-reported modifier of patient outcome. Risk for symptom recurrence and reoperation is higher in patients with large versus small annular defects following lumbar discectomy. LEVEL OF EVIDENCE: 2.

Randomized Controlled Trial of Nurse-Delivered Cognitive-Behavioral Therapy Versus Supportive Psychotherapy Telehealth Interventions for Chronic Back Pain.

This study evaluated a nurse-delivered, telehealth intervention of cognitive-behavioral therapy (CBT) versus supportive psychotherapy for chronic back pain. Participants (N = 61) had chronic back pain (pain "daily" ≥6 months at an intensity of ≥4 of 10 scale) and were randomized to an 8-week, 12-session, CBT or to supportive care (SC) matched for frequency, format, and time, with each treatment delivered by a primary care nurse. The primary outcome was the Roland Morris Disability Questionnaire (RMDQ). Secondary outcomes included the numeric rating scale (NRS) and the Patient Global Impressions Scale (CGI). CBT participants (n = 30) showed significant improvements on the RMDQ (mean = 11.4 [SD = 5.9] vs 9.4 [SD = 6.1] at baseline and post-treatment, respectively, P < .05; d = .33), NRS (mean = 4.9 [SD = 2.1] vs 4.0 [SD = 1.9], respectively, P < .05; d = .45), and on the CGI (39.1% reporting "much improved" or "very much improved"). SC participants (n = 31) also showed significant improvements on the RMDQ (mean = 11.1 [SD = 5.4] vs 9.1 [SD = 5.2], respectively, P < .05; d = .38), the NRS, (mean = 5.0 [SD = 1.9] vs 3.8 [SD = 2.1], respectively, P < .05; d = .60), and 26.7% reporting "much improved" or "very much improved" on the CGI. Between groups comparisons of CBT and SC showed no differences on the study outcomes (Ps > .10). The results suggest that telehealth, nurse-delivered CBT, and SC treatments for chronic back pain can offer significant and relatively comparable benefits. PERSPECTIVE: This article describes the benefits of training primary care nurses to deliver evidence-based behavioral therapies for low back pain. Because of the high prevalence of chronic pain and the growing emphasis on nonopioid therapies, training nurses to provide behavior therapies could be a cost-effective way to improve pain management.

A rat osteoporotic spine model for the evaluation of bioresorbable bone cements.

BACKGROUND CONTEXT: As the aging population increases, the rising prevalence of osteoporosis-related spine fractures will have a dramatic impact on health care. At present, mainstay treatment relies on systemic medications intended to prevent diminishing bone mineral density (BMD) and bone mass. However, an adjunctive treatment strategy is to target specific areas of the skeletal system that are prone to clinically significant osteoporotic fractures. We term this strategy the "local treatment of osteoporosis" or osteoplasty. Potential use of osteoplasty involves the percutaneous injection of bioresorbable and bioactive bone cements into bones at risk of sustaining osteoporotic fractures. Calcium sulfate (CaSO(4)) is among the candidate bioresorbable bone cements with the material attributes desirable for potential application with osteoplasty, yet previous studies on the osteoconductive properties of CaSO(4) have been limited to animal models exhibiting normal bone biology and architecture. However, osteoporotic bone physiology may potentially interfere with the material properties of common osteoconductive biomaterials, such as that of CaSO(4). To further test this hypothesis, a suitable animal model is needed to evaluate the in vivo behavior of potential biomaterials in osteoporotic bone. PURPOSE: The purpose of this study is to evaluate the caudal (proximal tail) rat vertebral body as an appropriate system for the in vivo evaluation of bone cement performance in the osteoporotic spine. STUDY DESIGN: (1) Micro-computed tomography radiomorphometry study and (2) biomechanical vertebral compression analysis. METHODS: Female Sprague Dawley rats were ovarectomized (OVX) at age 8 weeks and subsequently maintained on a low-calcium diet for 3 months. Normal nonovarectomized female rats (NL) of similar age and size were maintained on regular rodent feed. Micro-CT analysis was performed on both the lumbar and caudal vertebrae (levels 5-7) of both groups. The following bone radiomorphometric parameters were determined: bone mineral density (BMD), average cortical thickness (ACT), average trabecular thickness (TbTh), and average trabecular spacing (TbSp). Strength and stiffness of both NL and OVX vertebral bodies were assessed under axial compression at 0.1 mm/s, whereas displacement (mm) and force (N) were measured at 10 Hz until completion to failure. After the implantation of an injectable form of CaSO(4) bone cement into caudal vertebrae, radiomorphometric analysis of cement volume, based on its unique CT absorption profile, was performed over the 8-week time period, as well as the subsequent bone response of both NL and OVX caudal vertebrae to CaSO4. RESULTS: OVX caudal vertebrae showed an 18% decrease in BMD, a 28% decrease in diaphyseal ACT, a 55% decrease in TbTh, and a 2.4-fold increase in TbSp compared with NL (p<.05). Additionally, lumbar vertebrae exhibited a 21% decrease in BMD, a 24% decrease in anterior body ACT, a 48% decrease in TbTh, and a 4.7-fold increase in TbSp (p<.05). Failure testing of OVX caudal vertebral bodies revealed a 29% decrease in strength and a 60% decrease in stiffness compared with NL (p<.01). After implantation into OVX caudal vertebrae, CaSO(4) cement exhibited a 50% decrease in initial cement volume at 2 weeks and complete resorption by 4 weeks, whereas CaSO(4) injected into NL vertebrae exhibited a 79% decrease in initial cement volume at 4 weeks, trace amounts at 6 weeks, and complete resorption by 8 weeks. At 8 weeks, NL vertebrae implanted with CaSO(4) cement exhibited increased cortical bone thickness compared with NL sham vertebrae. This CaSO(4) cement-mediated bone augmentation was altered in osteoporotic vertebrae that exhibited porous irregular cortical bone not noted in cement-treated NL vertebrae or OVX sham vertebrae. CONCLUSIONS: Future investigation of potential biomaterials intended for the local treatment of osteoporosis will require their study within an appropriate osteoporosis animal model. The OVX rat caudal spine exhibits pathologic bone changes consistent with the osteoporosis phenotype, including decreased BMD, diminished trabecular network density, cortical thinning, and decreased mechanical strength. These derangements in bone microarchitecture and physiology may contribute toward the accelerated cement resorption and altered bone response to CaSO4 observed in this study. Important advantages of the OVX rat caudal spine are the rapid and minimally invasive surgical exposure of the vertebral body and the ease of cement injection. We propose that the OVX rat caudal spine represents a valuable and cost-effective tool in the armamentarium of investigators evaluating biomaterials designed for implantation into the osteoporotic spine.

Lumbar multifidus muscle degenerates in individuals with chronic degenerative lumbar spine pathology.

Histological and cell-level changes in the lumbar musculature in individuals with chronic lumbar spine degenerative conditions are not well characterized. Although prior literature supports evidence of changes in fiber type and size, little information exists describing the tissue quality and biology of pathological features of muscle in this population. The purpose of this study was to quantify multifidus tissue composition and structure, inflammation, vascularity, and degeneration in individuals with chronic degenerative lumbar spine pathology. Human multifidus biopsies were acquired from 22 consecutive patients undergoing surgery for chronic degenerative lumbar spine pathology. Relative fractions of muscle, adipose, and extracellular matrix were quantified along with muscle fiber type and cross-sectional area (CSA) and markers of inflammation, vascularity, satellite cell density, and muscle degeneration. On average, multifidus biopsies contained 48.5% muscle, 11.7% adipose tissue, and 26.1% collagen tissue. Elevated inflammatory cell counts (48.5 ± 30.0 macrophages/mm2 ) and decreased vascularity (275.6 ± 69.4 vessels/mm2 ) were also observed compared to normative values. Satellite cell densities were on average 13 ± 9 cells per every 100 muscle fibers. Large fiber CSA (3,996.0 ± 1,909.2 µm2 ) and a predominance of type I fibers (61.8 ± 18.0%) were observed in addition to evidence of pathological degeneration-regeneration cycling (18.8 ± 9.4% centrally nucleated fibers, and 55.2 ± 24.2% of muscle regions containing degeneration). High levels of muscle degeneration, inflammation, and decreased vascularity were commonly seen in human multifidus biopsies of individuals with lumbar spine pathology in comparison to normative data. Evidence of active muscle degeneration suggests that changes in muscle tissue are more complex than simple atrophy. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2700-2706, 2017.

Propionibacterium acnes biofilm is present in intervertebral discs of patients undergoing microdiscectomy.

BACKGROUND: In previous studies, Propionibacterium acnes was cultured from intervertebral disc tissue of ~25% of patients undergoing microdiscectomy, suggesting a possible link between chronic bacterial infection and disc degeneration. However, given the prominence of P. acnes as a skin commensal, such analyses often struggled to exclude the alternate possibility that these organisms represent perioperative microbiologic contamination. This investigation seeks to validate P. acnes prevalence in resected disc cultures, while providing microscopic evidence of P. acnes biofilm in the intervertebral discs. METHODS: Specimens from 368 patients undergoing microdiscectomy for disc herniation were divided into several fragments, one being homogenized, subjected to quantitative anaerobic culture, and assessed for bacterial growth, and a second fragment frozen for additional analyses. Colonies were identified by MALDI-TOF mass spectrometry and P. acnes phylotyping was conducted by multiplex PCR. For a sub-set of specimens, bacteria localization within the disc was assessed by microscopy using confocal laser scanning and FISH. RESULTS: Bacteria were cultured from 162 discs (44%), including 119 cases (32.3%) with P. acnes. In 89 cases, P. acnes was cultured exclusively; in 30 cases, it was isolated in combination with other bacteria (primarily coagulase-negative Staphylococcus spp.) Among positive specimens, the median P. acnes bacterial burden was 350 CFU/g (12 - ~20,000 CFU/g). Thirty-eight P. acnes isolates were subjected to molecular sub-typing, identifying 4 of 6 defined phylogroups: IA1, IB, IC, and II. Eight culture-positive specimens were evaluated by fluorescence microscopy and revealed P. acnes in situ. Notably, these bacteria demonstrated a biofilm distribution within the disc matrix. P. acnes bacteria were more prevalent in males than females (39% vs. 23%, p = 0.0013). CONCLUSIONS: This study confirms that P. acnes is prevalent in herniated disc tissue. Moreover, it provides the first visual evidence of P. acnes biofilms within such specimens, consistent with infection rather than microbiologic contamination.

High-molecular-weight hyaluronan inhibits macrophage proliferation and cytokine release in the early wound of a preclinical postlaminectomy rat model.

BACKGROUND CONTEXT: Failed back syndrome, a condition that affects 3-14% of postoperative spine patients, is characterized by the recurrence of radicular pain after spinal decompression. The source of this pain in some patients is thought by many investigators to be the result of epidural scarring and nerve root tethering, but this is controversial. We have previously demonstrated that in a disc-injury model the untreated postlaminectomy rats develop a significant proliferative fibrous response at 8 weeks with spinal nerve scarring to the disc and adjacent pedicle, and increased sensitivity to tactile allodynia testing in the related sensory dermatome. Topical high-molecular-weight hyaluronan (HMW HA) moderates both the proliferative fibrosis and the behavioral pain response. PURPOSE: Our purpose is to study the time-related changes in the proinflammatory cytokine and monocyte/macrophage profiles in the epidural space in the early postlaminectomy untreated and HMW HA gel treated groups. STUDY DESIGN/SETTING: A modified rat laminectomy with disc injury model was employed to assess epidural fibrosis between and around the spinal nerves using a quantitative immunohistochemistry assessment approach along with correlative enzyme-linked immunosorbent assay analysis. METHODS: Lumbar laminectomies at L5 and L6 with a L5-L6 disc injury were performed on 120 adult male Sprague-Dawley rats. The rats were then randomized into one of two groups: untreated and treated. The treatment group received a one-time topical application of 0.1 cc of HMW HA gel directly to the laminectomy site just before wound closure. The rats were then randomly subdivided into survival periods of 24 hours, 72 hours, and 7 days. Immunohistochemistry was performed on fresh frozen sections and stained for interleukin-1 beta (IL-1beta) and monocytes/macrophages (ED-1) using monoclonal antibodies and 3, 3' diaminobenzidine (DAB) chromogen. The amount of stain in each specimen was then quantified using the National Institutes of Health computer imaging analysis system. RESULTS: The semiquantified data from the histological specimens demonstrated significant decreases in the IL-1beta and IL-6 infiltration observed at 24 hours in the epidural space and around the right nerve root (p=.0296 and 0.0195, respectively) in the HA gel treated group. Additionally, significant decreases in the monocyte/macrophage infiltration were observed at 72 hours in the epidural space around the left nerve root (p=.0039) and right nerve root (p=.0072) in the HA gel treated group. At 7 days, IL-1beta, IL-6, and macrophage infiltration of the wound had declined in both the HA gel and the untreated groups. The enzyme-linked immunosorbent assay data support the same pattern as seen in the histological results. CONCLUSION: These results demonstrate that treatment of postlaminectomy wounds with HMW HA gel decreases the number of monocytes and macrophages and the concentration of certain cytokines in the early inflammatory phase of healing. There are several plausible explanations for this effect. First, the HMW HA may block the interaction of short-chain low-molecular-weight HA with proinflammatory cell surface receptors. The interaction of these short-chain oligo-HA fragments, upon cell-surface receptor binding, induces changes in inflammatory cells that lead to increased cell motility and migration into the wound area. Second, the addition of exogenous HMW HA may cause a dilution effect in the wound, thereby decreasing the concentration of inflammatory cells in the extracellular matrix of the region of injury. Finally, the migration of inflammatory cells may be decreased in the viscous environment of the HMW HA. The first explanation is believed by the authors of this paper to be the more likely mechanism. HMW HA probably mutes the proinflammatory effects of the low-molecular weight fragments, leading to decreased inflammation, and thus decreased fibrosis and scar formation noted in the chronic model.