Explore the vast range of titles available.

Purpose Low back pain (LBP) is the most disabling condition worldwide. Although LBP relates to different spinal pathologies, vertebral bone marrow lesions visualized as Modic changes on MRI have a high specificity for discogenic LBP. This review summarizes the pathobiology of Modic changes and suggests a disease model. Methods Non-systematic literature review. Results Chemical and mechanical stimulation of nociceptors adjacent to damaged endplates are likely a source of pain. Modic changes are adjacent to a degenerated intervertebral disc and have three generally interconvertible types suggesting that the different Modic change types represent different stages of the same pathological process, which is characterized by inflammation, high bone turnover, and fibrosis. A disease model is suggested where disc/endplate damage and the persistence of an inflammatory stimulus (i.e., occult discitis or autoimmune response against disc material) create predisposing conditions. The risk to develop Modic changes likely depends on the inflammatory potential of the disc and the capacity of the bone marrow to respond to it. Bone marrow lesions in osteoarthritic knee joints share many characteristics with Modic changes adjacent to degenerated discs and suggest that damage-associated molecular patterns and marrow fat metabolism are important pathogenetic factors. There is no consensus on the ideal therapy. Non-surgical treatment approaches including intradiscal steroid injections, anti-TNF-α antibody, antibiotics, and bisphosphonates have some demonstrated efficacy in mostly non-replicated clinical studies in reducing Modic changes in the short term, but with unknown long-term benefits. New diagnostic tools and animal models are required to improve painful Modic change identification and classification, and to clarify the pathogenesis. Conclusion Modic changes are likely to be more than just a coincidental imaging finding in LBP patients and rather represent an underlying pathology that should be a target for therapy.

Poor solute transport through the cartilage endplate (CEP) impairs disc nutrition and could be a key factor that limits the success of intradiscal biologic therapies. Here we demonstrate that treating the CEP with matrix metalloproteinase-8 (MMP-8) reduces the matrix constituents that impede solute uptake and thereby improves nutrient diffusion. Human CEP tissues harvested from four fresh cadaveric lumbar spines (age range: 38-66 years old) were treated with MMP-8. Treatment caused a dose-dependent reduction in sGAG, localized reductions to the amount of collagen, and alterations to collagen structure. These matrix modifications corresponded with 16-24% increases in the uptake of a small solute (376 Da). Interestingly, the effects of MMP-8 treatment depended on the extent of non-enzymatic glycation: treated CEPs with high concentrations of advanced glycation end products (AGEs) exhibited the lowest uptake compared to treated CEPs with low concentrations of AGEs. Moreover, AGE concentrations were donor-specific, and the donor tissues with the highest AGE concentrations appeared to have lower uptake than would be expected based on the initial amounts of collagen and sGAG. Finally, increasing solute uptake in the CEP improved cell viability inside diffusion chambers, which supports the nutritional relevance of enhancing the transport properties of the CEP. Taken together, our results provide new insights and in vitro proof-of-concept for a treatment approach that could improve disc nutrition for biologic therapy: specifically, matrix reduction by MMP-8 can enhance solute uptake and nutrient diffusion through the CEP, and AGE concentration appears to be an important, patient-specific factor that influences the efficacy of this approach.

Extracellular matrix (ECM) remodeling is important during bone development and repair. Because matrix metalloproteinase 13 (MMP13, collagenase-3) plays a role in long bone development, we have examined its role during adult skeletal repair. In this study we find that MMP13 is expressed by hypertrophic chondrocytes and osteoblasts in the fracture callus. We demonstrate that MMP13 is required for proper resorption of hypertrophic cartilage and for normal bone remodeling during non-stabilized fracture healing, which occurs via endochondral ossification. However, no difference in callus strength was detected in the absence of MMP13. Transplant of wild-type bone marrow, which reconstitutes cells only of the hematopoietic lineage, did not rescue the endochondral repair defect, indicating that impaired healing in Mmp13-/- mice is intrinsic to cartilage and bone. Mmp13-/- mice also exhibited altered bone remodeling during healing of stabilized fractures and cortical defects via intramembranous ossification. This indicates that the bone phenotype occurs independently from the cartilage phenotype. Taken together, our findings demonstrate that MMP13 is involved in normal remodeling of bone and cartilage during adult skeletal repair, and that MMP13 may act directly in the initial stages of ECM degradation in these tissues prior to invasion of blood vessels and osteoclasts.

PurposeThe 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.MethodsPatient-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.ResultsUsing 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.ConclusionThis 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.

A new musculoskeletal model for the lumbar spine is described in this paper. This model features a rigid pelvis and sacrum, the five lumbar vertebrae, and a rigid torso consisting of a lumped thoracic spine and ribcage. The motion of the individual lumbar vertebrae was defined as a fraction of the net lumbar movement about the three rotational degrees of freedom: flexion–extension lateral bending, and axial rotation. Additionally, the eight main muscle groups of the lumbar spine were incorporated using 238 muscle fascicles with prescriptions for the parameters in the Hill-type muscle models obtained with the help of an extensive literature survey. The features of the model include the abilities to predict joint reactions, muscle forces, and muscle activation patterns. To illustrate the capabilities of the model and validate its physiological similarity, the model’s predictions for the moment arms of the muscles are shown for a range of flexion–extension motions of the lower back. The model uses the OpenSim platform and is freely available on https://www.simtk.org/home/lumbarspine to other spinal researchers interested in analyzing the kinematics of the spine. The model can also be integrated with existing OpenSim models to build more comprehensive models of the human body.

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.

PurposeMRS was shown to reliably quantify relative levels of degenerative pain biomarkers, differentiating painful versus non-painful discs in patients with chronic discogenic low back pain (DLBP), and this correlates with surgical success rates. We now report results based on more patients and longer follow-up.MethodsDisc MRS was performed in DLBP patients who subsequently received lumbar surgery. Custom post-processing (NOCISCAN-LS®; Aclarion Inc.) calculated disc-specific NOCISCORES® that reflect relative differences in degenerative pain biomarkers for diagnosing chemically painful discs. Outcomes in 78 patients were evaluated using Oswestry Disability Index (ODI) scores. Surgical success (≥ 15-point ODI improvement) was compared between surgeries that were “Concordant” (Group C) versus “Discordant” (Group D) with NOCISCORE-based diagnosis for painful discs.ResultsSuccess rates were higher for Group C versus Group D: 6 months (88% vs. 62%; p = 0.01), 12 months (91% vs. 56%; p < 0.001), and 24 months (85% vs. 63%; p = 0.07). Success rates for Group C surgeries were also higher than Group D surgeries in a variety of sub-group comparisons. Group C had a greater reduction in ODI from pre-operative to follow-up than Group D [absolute change (% change), (p)]: 6 months: − 35 (− 61%) versus − 23 (− 39%), (p < 0.05); 12 months: − 39 (− 69%) versus − 22 (− 39%), (p < 0.01); and 24 months:  − 38 (− 66%) versus − 26 (− 48%), (p < 0.05).ConclusionMore successful, sustained outcomes were obtained when surgically treating chemically painful discs identified by NOCISCAN-LS post-processed disc MRS exams. Results suggest that NOCISCAN-LS provides a valuable new diagnostic tool to help clinicians better select treatment levels.

Study design Cross-sectional cohort analysis of patients with Modic Changes (MC). Objective Our goal was to characterize the molecular and cellular features of MC bone marrow and adjacent discs. We hypothesized that MC associate with biologic cross-talk between discs and bone marrow, the presence of which may have both diagnostic and therapeutic implications. Background data MC are vertebral bone marrow lesions that can be a diagnostic indicator for discogenic low back pain. Yet, the pathobiology of MC is largely unknown. Methods Patients with Modic type 1 or 2 changes (MC1, MC2) undergoing at least 2-level lumbar interbody fusion with one surgical level having MC and one without MC (control level). Two discs (MC, control) and two bone marrow aspirates (MC, control) were collected per patient. Marrow cellularity was analyzed using flow cytometry. Myelopoietic differentiation potential of bone marrow cells was quantified to gauge marrow function, as was the relative gene expression profiles of the marrow and disc cells. Disc/bone marrow cross-talk was assessed by comparing MC disc/bone marrow features relative to unaffected levels. Results Thirteen MC1 and eleven MC2 patients were included. We observed pro-osteoclastic changes in MC2 discs, an inflammatory dysmyelopoiesis with fibrogenic changes in MC1 and MC2 marrow, and up-regulation of neurotrophic receptors in MC1 and MC2 bone marrow and discs. Conclusion Our data reveal a fibrogenic and pro-inflammatory cross-talk between MC bone marrow and adjacent discs. This provides insight into the pain generator at MC levels and informs novel therapeutic targets for treatment of MC-associated LBP.

Chronic low back pain (CLBP) is a significant US healthcare burden with millions of lumbar spine procedures annually. Diagnostic tests are essential to guide treatment but provocative discography (PD), the most common diagnostic procedure, is without robust evidence of its value. A non-invasive alternative using Magnetic Resonance Spectroscopy (MRS) offers a potential solution. We assess cost-effectiveness of MRS with NOCISCAN diagnostic algorithm compared to PD for identifying lumbar discs requiring surgical intervention. We conducted cost-effectiveness analysis using modelling. We used data from a clinical study of 139 CLBP patients who met criteria for and received PD of lumbar spine and presented with an ODI score ≥40; comparing PD and MRS-based diagnostics. We considered diagnostic costs, adverse events, surgical costs and outcomes based on a 15-point improvement on the Oswestry Disability Index. Incremental cost-effectiveness ratios (ICERS) and probabilistic sensitivity analyses were determined. Some authors have consulted for Aclarion. Mean total cost per PD patient was $59,711, and $57,998 for MRS, demonstrating $1712 cost savings per MRS diagnosed patient. Diagnostic costs ($1950 for PD; $1450 for MRS), saved $500 per MRS patient. PD incurred adverse event costs ($57,323) for 1% of patients, which MRS eliminated. MRS-based diagnosis showed 78% surgical success, whereas PD achieved 68%. MRS was the dominant diagnostic strategy, with better clinical outcomes and cost savings. Probabilistic sensitivity analysis confirmed MRS dominance and was cost-effective across a wide range of willingness-to-pay thresholds and across 2 different scenarios which vary base-case outcomes and surgical rates. This study demonstrates cost-effectiveness dominance of MRS with the Nociscan diagnostic algorithm over PD for identifying CLBP surgical candidates. MRS provides significant cost savings and leads to better surgical outcomes, making it a preferred choice for insurers and health systems.