Proteomic analysis of serum in a population-based cohort did not reveal a biomarker for Modic changes.

Introduction: Modic changes (MC) are bone marrow lesions of vertebral bones, which can be detected with magnetic resonance imaging (MRI) adjacent to degenerated intervertebral discs. Defined by their appearance on T1 and T2 weighted images, there are three interconvertible types: MC1, MC2, and MC3. The inter-observer variability of the MRI diagnosis is high, therefore a diagnostic serum biomarker complementing the MRI to facilitate diagnosis and follow-up would be of great value. Methods: We used a highly sensitive and reproducible proteomics approach: DIA/SWATH-MS to find serum biomarkers in a subset of the Northern Finland Birth Cohort 1966. Separately, we measured a panel of factors involved in inflammation and angiogenesis to confirm some potential biomarkers published before with an ELISA-based method called V-Plex. Results: We found neither an association between the serum concentrations of the proteins detected with DIA/SWATH-MS with the presence of MC, nor a correlation with the size of the MC lesions. We did not find any association between the factors measured with the V-Plex and the presence of MC or their size. Conclusion: Altogether, our study suggests that a robust and generally usable biomarker to facilitate the diagnosis of MC cannot readily be found in serum.

Effects of Bariatric Surgery on Knee Articular Cartilage and Osteoarthritis Symptoms-A 12-Month Follow-Up Using T2 Relaxation Time and WOMAC Osteoarthritis Index.

BACKGROUND: Obesity is a significant risk factor for osteoarthritis (OA). The most effective treatment for morbid obesity is bariatric surgery. PURPOSE: To study the effects of potential surgically induced weight loss on knee articular cartilage and OA symptoms of obese patients over a 12-month follow-up. STUDY TYPE: Prospective longitudinal cohort study. SUBJECTS: 45 obese patients (38 female, BMI = 42.3 ± 6.5 kg/m2) who underwent gastric bypass (intervention group), and 46 age-matched conservative-care controls (37 female, BMI = 39.8 ± 4.6 kg/m2). FIELD STRENGTH/SEQUENCE: Multiecho spin echo sequence at 3 T. ASSESSMENT: Knee cartilage T2 measurements and WOMAC Indices were measured presurgery and after 12 months. The intervention group was split into successful (≥20% total weight loss (TWL)) and unsuccessful (<20% TWL) weight loss groups. T2 and WOMAC indices were also measured in controls at baseline and after 12 months. Changes among the three groups were analyzed. STATISTICAL TESTS: Analysis of variance (significance level 0.05). RESULTS: Twenty-six (58%) intervention patients achieved ≥20% TWL. The <20% TWL group demonstrated significantly more T2 reduction in the deep lateral femur over 12 months compared with the ≥20% TWL group (-3.83 ± 8.18 msec vs. 2.47 ± 6.54 msec, respectively), whereas no significant differences were observed on the medial femoral compartment (P = 0.385, P = 0.551, and P = 0.511 for bulk, superficial and deep regions, respectively). Changes in WOMAC indices over 12 months were significantly greater in the ≥20% TWL group compared with controls. In the <20% TWL group, pain significantly improved over 12 months compared with controls, while stiffness and function changes were not statistically significant (P = 0.063 and P = 0.051, respectively). DATA CONCLUSION: Cartilage matrix, measured by T2, showed improvement on lateral femoral cartilage with <20% TWL compared with ≥20% TWL. Bariatric surgery provided significant improvements in knee symptoms with ≥20% TWL compared with conservative WL. This effect is also seen to some extent with <20% TWL compared with conservative WL. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 4.

Effectiveness of a classification-based approach to low back pain in primary care - a benchmarking controlled trial.

OBJECTIVE: The aim of this study was to assess the effectiveness of classification-based approach for low back pain care in Finnish primary care. DESIGN: A benchmarking controlled trial design was used. SUBJECTS/PATIENTS: Three primary healthcare areas and 654 low back pain patients with or without sciatica. METHODS: Classification-based care (using the STarT Back Tool) was implemented using organizational-, healthcare professional-, and patient-level interventions. The primary outcome was change in Patient-Reported Outcomes Measurement Information System, Physical Function (PROMIS PF-20) from baseline to 12 months. RESULTS: No difference was found between the intervention and control in change in PROMIS PF-20 over the 12-month follow-up (mean difference 0.33 confidence interval -2.27 to 2.9, p = 0.473). Low back pain-related healthcare use, imaging, and sick leave days were significantly lower in the intervention group. Reduction in intensity of low back pain appeared to be already achieved at the 3-month follow-up (mean difference -1.3, confidence interval -2.1 to -0.5) in the intervention group, while in the control group the same level of reduction was observed at 12 months (mean difference 0.7, confidence interval -0.2 to 1.5, treatment*time p = 0.003).  Conclusion: Although classification-based care did not appear to influence physical functioning, more rapid reductions in pain intensity and reductions in healthcare use and sick leave days were observed in the intervention group.

Discovery of circulating blood biomarkers in patients with and without Modic changes of the lumbar spine: a preliminary analysis.

PURPOSE: The following study aimed to determine the existence of blood biomarkers in symptomatic patients with or without lumbar Modic changes (MC). METHODS: A cross-sectional sub-analyses of a prospective cohort was performed. Fasting blood samples were collected from patients with and without lumbar MC who had undergone spinal fusion or microdiscectomy. An 80-plex panel and CCL5/RANTES were used to assess preoperative plasma cytokine concentrations. Patient demographics and imaging phenotypes were also assessed. RESULTS: Thirty-one subjects were analysed (n = 18 no MC; n = 13 MC). No significant differences were found in age, sex, body mass index, smoking and alcohol history, and surgical procedure (i.e. fusion, decompression) between the two groups (p > 0.05). Several statistically significant blood biomarkers in MC patients were identified, including elevated levels of C-C Motif Chemokine Ligand 5 (CCL5, p = 0.0006), while Macrophage Migration Inhibitory Factor (MIF) was significantly lower (p = 0.009). Additionally, C-X-C Motif Chemokine Ligand 5 (CXCL5, p = 0.052), Pentraxin 3 (PTX3, p = 0.06) and Galectin-3 (Gal-3, p = 0.07) showed potential relevance. Moreover, MC patients exhibited significantly higher levels of disc degeneration (p = 0.0001) and displacement severity (p = 0.020). Based on multivariate analyses and controlling for disc degeneration/displacement, CCL5 (OR 1.02; 95% CI 1.002-1.033; p = 0.028) and MIF (OR 0.60; 95% CI 0.382-0.951; p = 0.030) were independently associated with MC patients. CONCLUSION: This "proof-of-concept" study is the first to identify specific and significantly circulating blood biomarkers associated with symptomatic patients with lumbar MC, independent of disc alterations of degeneration and/or bulges/herniations. Specifically, differences in CCL5 and MIF protein levels were significantly noted in MC patients compared to those without MC.

Associations of socioeconomic and lifestyle characteristics, psychological symptoms, multimorbidity, and multisite pain with sciatica - a 15-year longitudinal study.

BACKGROUND CONTEXT: Sciatica is defined as pain radiating from the low back to the leg, usually below the knee. It is a disabling condition that causes a major burden to health care and society. Previous evidence of the multifactorial etiology of sciatica comes mostly from cross-sectional studies. Larger, longitudinal studies with a multidimensional set of variables are needed. PURPOSE: To examine how socioeconomic and lifestyle characteristics, psychological symptoms, multimorbidity, and multisite pain are associated with sciatica. STUDY DESIGN: A longitudinal study of the Northern Finland Birth Cohort 1966. PATIENT SAMPLE: In total 6,683 working-aged members of the Northern Finland Birth Cohort 1966. OUTCOME MEASURES: Self-reported sciatic pain status over a 15-year study period. METHODS: We conducted a 15-year longitudinal study from the age of 31 to 46. We used multivariable generalized estimation equations analysis to examine how socioeconomic characteristics (low education, unemployment, and living alone), lifestyle characteristics (overweight, obesity, current smoking, and physical inactivity), psychological symptoms (depression, anxiety), multimorbidity, and multisite pain were associated with sciatica. RESULTS: At the age of 31, 21.1% of the study population reported sciatic pain and at the age of 46, 36.7%. Multisite pain was clearly the strongest factor associated with sciatica (odds ratio [OR] 2.61, 95% confidence interval [CI] 2.34‒2.92). In descending order of effect size, older age, low education, psychological symptoms, multimorbidity, overweight, obesity, physical inactivity and current smoking were positively associated with sciatica. Their ORs varied between 1.17 and 2.18. Living alone was negatively associated with sciatica (OR 0.81, 95% CI 0.72‒0.90). CONCLUSIONS: Multisite pain had the strongest association with sciatica. The effect sizes of the other factors were clearly smaller. To our knowledge this is the first study to evaluate the association of multisite pain with sciatica. This finding may have considerable implications for clinical work treating patients with sciatica.

Pressure Pain Sensitivity and Chronotype: A Population-based Study of Middle-aged Finns.

Evening chronotype individuals experience pain more often than morning chronotypes, but relationships with pain sensitivity have rarely been studied. We examined whether chronotype is associated with pressure pain sensitivity, with special reference to mental health disorders, insomnia, and chronic musculoskeletal (MSK) pain as potential moderating factors. The study sample consisted of members of the Northern Finland Birth Cohort 1966 aged 46. Pressure pain threshold and tolerance were measured via the standardized protocol, categorized as lowest quartile versus others. Chronotype (morning [M; the reference], intermediate [I], and evening [E]) was defined using the Short Morningness-Eveningness questionnaire. Sex-stratified binary logistic regression models were separately adjusted for education, body mass index, long-term diseases (fully adjusted model), and for mental health disorders, insomnia, and chronic MSK pain (a residual confounding analysis). Interaction terms (Chronotype × Mental health/insomnia/chronic MSK pain) were tested. The study had 2,132 males and 2,830 females. The E-type males had 1.5-fold odds of having a low pain threshold (fully adjusted odds ratio [OR] 1.45, 95% confidence interval 1.05-2.00) and pressure pain tolerance (fully adjusted OR 1.47, 1.07-2.02), in comparison to M-types. Having a mental health disorder intensified the association with low pain threshold fourfold (4.06, 1.56-10.6). Being an E-type female was also associated with a low pain threshold, but the association was statistically nonsignificant (fully adjusted OR 1.18, .90-1.53). No statistically significant interactions were found among females. These results emphasize the role of chronotype in pain sensitivity and add an understanding of pain experience in light of innate circadian types. PERSPECTIVE: Male evening chronotypes are more sensitive to pain than morning chronotypes. Diagnosed mental health disorders in particular indicate a low pain threshold for evening chronotype males.

Semiautomatic Assessment of Facet Tropism From Lumbar Spine MRI Using Deep Learning: A Northern Finland Birth Cohort Study.

STUDY DESIGN: This is a retrospective, cross-sectional, population-based study that automatically measured the facet joint (FJ) angles from T2-weighted axial magnetic resonance imagings (MRIs) of the lumbar spine using deep learning (DL). OBJECTIVE: This work aimed to introduce a semiautomatic framework that measures the FJ angles using DL and study facet tropism (FT) in a large Finnish population-based cohort. SUMMARY OF DATA: T2-weighted axial MRIs of the lumbar spine (L3/4 through L5/S1) for (n=1288) in the NFBC1966 Finnish population-based cohort were used for this study. MATERIALS AND METHODS: A DL model was developed and trained on 430 participants' MRI images. The authors computed FJ angles from the model's prediction for each level, that is, L3/4 through L5/S1, for the male and female subgroups. Inter-rater and intrarater reliability was analyzed for 60 participants using annotations made by two radiologists and a musculoskeletal researcher. With the developed method, we examined FT in the entire NFBC1966 cohort, adopting the literature definitions of FT thresholds at 7° and 10°. The rater agreement was evaluated both for the annotations and the FJ angles computed based on the annotations. FJ asymmetry ( - was used to evaluate the agreement and correlation between the raters. Bland-Altman analysis was used to assess the agreement and systemic bias in the FJ asymmetry. The authors used the Dice score as the metric to compare the annotations between the raters. The authors evaluated the model predictions on the independent test set and compared them against the ground truth annotations. RESULTS: This model scored Dice (92.7±0.1) and intersection over union (87.1±0.2) aggregated across all the regions of interest, that is, vertebral body (VB), FJs, and posterior arch (PA). The mean FJ angles measured for the male and female subgroups were in agreement with the literature findings. Intrarater reliability was high, with a Dice score of VB (97.3), FJ (82.5), and PA (90.3). The inter-rater reliability was better between the radiologists with a Dice score of VB (96.4), FJ (75.5), and PA (85.8) than between the radiologists and the musculoskeletal researcher. The prevalence of FT was higher in the male subgroup, with L4/5 found to be the most affected region. CONCLUSION: The authors developed a DL-based framework that enabled us to study FT in a large cohort. Using the proposed method, the authors present the prevalence of FT in a Finnish population-based cohort.

Cartilaginous endplates: A comprehensive review on a neglected structure in intervertebral disc research.

The cartilaginous endplates (CEP) are key components of the intervertebral disc (IVD) necessary for sustaining the nutrition of the disc while distributing mechanical loads and preventing the disc from bulging into the adjacent vertebral body. The size, shape, and composition of the CEP are essential in maintaining its function, and degeneration of the CEP is considered a contributor to early IVD degeneration. In addition, the CEP is implicated in Modic changes, which are often associated with low back pain. This review aims to tackle the current knowledge of the CEP regarding its structure, composition, permeability, and mechanical role in a healthy disc, how they change with degeneration, and how they connect to IVD degeneration and low back pain. Additionally, the authors suggest a standardized naming convention regarding the CEP and bony endplate and suggest avoiding the term vertebral endplate. Currently, there is limited data on the CEP itself as reported data is often a combination of CEP and bony endplate, or the CEP is considered as articular cartilage. However, it is clear the CEP is a unique tissue type that differs from articular cartilage, bony endplate, and other IVD tissues. Thus, future research should investigate the CEP separately to fully understand its role in healthy and degenerated IVDs. Further, most IVD regeneration therapies in development failed to address, or even considered the CEP, despite its key role in nutrition and mechanical stability within the IVD. Thus, the CEP should be considered and potentially targeted for future sustainable treatments.