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.

Association between vertebral cross-sectional area and lumbar disc displacement - a population-based study.

PURPOSE: Vertebral dimensions may constitute a potential risk factor for degenerative changes in the spine. Previous studies have found a positive association between vertebral height and both type 2 Modic changes and intervertebral disc height loss. Also, vertebral endplate size has been associated with disc degeneration. However, only a few studies have investigated the association between vertebral dimensions and lumbar disc displacement (LDD). This study aimed to investigate the association between vertebral cross-sectional area (CSA) and LDD among the general middle-aged Finnish population. We hypothesized that larger vertebral CSA is associated with LDD. MATERIALS AND METHODS: The study was conducted by using data from the Northern Finland Birth Cohort 1966 (NFBC1966). At the age of 46, a subpopulation of NFBC1966 underwent clinical examinations including magnetic resonance imaging (MRI) (n = 1249). MRI scans were used to measure L4 CSA and evaluate the presence of LDD (bulge, protrusion, and extrusion/sequestration) in the adjacent discs. The association between L4 CSA and LDD was analysed using logistic regression, with adjustment for sex, education, body mass index, leisure-time physical activity, smoking, diet, and L4 height. RESULTS: Larger L4 CSA was associated with LDD; an increase of 1 cm2 in vertebral CSA elevated the odds of LDD relative to no LDD by 10% (adjusted odds ratio 1.10, 95% CI 1.01-1.19). The association was similar among either sex. CONCLUSIONS: Larger L4 vertebral CSA was associated with LDD in our study sample. Even though smaller vertebral size exposes our vertebrae to osteoporotic fractures, it simultaneously seems to protect us from LDD.

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.

The Örebro Musculoskeletal Pain Screening Questionnaire-Short Form and 2-year follow-up of registered work disability.

BACKGROUND: The Örebro Musculoskeletal Pain Screening Questionnaire (ÖMPSQ) was developed to identify psychological and functioning-related risk factors among individuals with musculoskeletal pain at risk of work disability. This study aimed to examine whether the short version of the ÖMPSQ (ÖMPSQ-SF) can be used for this purpose, using registry-based outcomes. METHODS: The ÖMPSQ-SF was completed by the members of the Northern Finland Birth Cohort 1966 at the age of 46 years (baseline). These data were enriched with national registers, including information on sick leaves and disability pensions (indicators of work disability). The associations between the ÖMPSQ-SF categories (low-, medium- and high risk) and work disability over a 2-year follow-up were analysed using negative binomial regression and binary logistic regression models. We made adjustments for sex, baseline education level, weight status and smoking. RESULTS: Overall, 4063 participants provided full data. Of these, 90% belonged to the low-risk, 7% to the medium-risk and 3% to the high-risk group. Compared to the low-risk group, the high-risk group had a 7.5 [Wald 95% confidence interval (CI) 6.2-9.0] times higher number of sick leave days and 16.1 (95% CI 7.1-36.8) times higher odds of disability pension after adjustments in the 2-year follow-up. CONCLUSIONS: : Our study suggests that the ÖMPSQ-SF could be used for predicting registry-based work disability at midlife. Those allocated to the high-risk group seemed to have a particularly great need of early interventions to support their work ability.

Family structure and multisite musculoskeletal pain in adolescence: a Northern Finland Birth Cohort 1986 study.

BACKGROUND: Family structure is suggested to be associated with adolescent pain, but evidence on its association with multisite MS pain is sparse. The purpose of this cross-sectional study was to investigate the potential associations between family structure ('single-parent family', 'reconstructed family', and 'two-parent family') and multisite musculoskeletal (MS) pain in adolescence. METHODS: The dataset was based on the 16-year-old Northern Finland Birth Cohort 1986 adolescents with available data on family structure, multisite MS pain, and a potential confounder (n = 5,878). The associations between family structure and multisite MS pain were analyzed with binomial logistic regression and modelled as unadjusted, as the evaluated potential confounder, mother's educational level, did not meet the criteria for a confounder. RESULTS: Overall, 13% of the adolescents had a 'single-parent family' and 8% a 'reconstructed family'. Adolescents living in a single-parent family had 36% higher odds of multisite MS pain compared to adolescents from two-parent families (the reference) (Odds Ratio [OR]: 1.36, 95% Confidence Interval [CI]: 1.17 to 1.59). Belonging to a 'reconstructed family' was associated with 39% higher odds of multisite MS pain (OR 1.39, 1.14 to 1.69). CONCLUSION: Family structure may have a role in adolescent multisite MS pain. Future research is needed on causality between family structure and multisite MS pain, to establish if there is a need for targeted support.

The role of co-occurring insomnia and mental distress in the association between lumbar disc degeneration and low back pain related disability.

BACKGROUND: Lumbar disc degeneration (LDD) is associated with low back pain (LBP). Although both insomnia and mental distress appear to influence the pain experience, their role in the association between LDD and LBP is uncertain. Our objective was to investigate the role of co-occurring insomnia and mental distress in the association between LDD and LBP-related disability. METHODS: A total of 1080 individuals who had experienced LBP during the previous year underwent 1.5-T lumbar magnetic resonance imaging, responded to questionnaires, and participated in a clinical examination at the age of 47. Full data was available for 843 individuals. The presence of LBP and LBP-related disability (numerical rating scale, range 0-10) were assessed using a questionnaire. LDD was assessed by a Pfirrmann-based sum score (range 0-15, higher values indicating higher LDD). The role of insomnia (according to the five-item Athens Insomnia Scale) and mental distress (according to the Hopkins Symptom Check List-25) in the association between the LDD sum score and LBP-related disability was analyzed using linear regression with adjustments for sex, smoking, body mass index, education, leisure-time physical activity, occupational physical exposure, Modic changes, and disc herniations. RESULTS: A positive association between LDD and LBP-related disability was observed among those with absence of both mental distress and insomnia (adjusted B = 0.132, 95% CI = 0.028-0.236, p = 0.013), and among those with either isolated mental distress (B = 0.345 CI = 0.039-0.650, p = 0.028) or isolated insomnia (B = 0.207, CI = 0.040-0.373, p = 0.015). However, among individuals with co-occurring insomnia and mental distress, the association was not significant (B = -0.093, CI = -0.346-0.161, p = 0.470). CONCLUSIONS: LDD does not associate with LBP-related disability when insomnia and mental distress co-occur. This finding may be useful when planning treatment and rehabilitation that aim to reduce disability among individuals with LDD and LBP. Future prospective research is warranted.

Early disc degeneration in radiotherapy-treated childhood brain tumor survivors.

BACKGROUND: Childhood brain tumor (BT) survivors have an increased risk of treatment-related late effects, which can reduce health-related quality of life and increase morbidity. This study aimed to investigate lumbar disc degeneration in magnetic resonance imaging (MRI) in adult survivors of radiotherapy-treated childhood BT compared to age and sex-matched population controls. METHODS: In this cross-sectional comparative study, 127 survivors were identified from hospital registries. After a mean follow-up of 20.7 years (range 5-33.1), 67 survivors (mean age 28.4, range 16.2-43.5) were investigated with MRI and compared to 75 sex-matched population-based controls. Evaluated MRI phenotypes included Pfirrmann grading, , intervertebral disc protrusions, extrusions, and high-intensity-zone-lesions (HIZ). Groups were also compared for known risk factors of lumbar intervertebral disc (IVD) degeneration. RESULTS: Childhood BT survivors had higher Pfirrmann grades than controls at all lumbar levels (all p < 0.001). Lumbar disc protrusions at L4-5 (p = 0.02) and extrusions at L3-4 (p = 0.04), L4-5 (p = 0.004), and L5-S1 (p = 0.01) were significantly more common in the BT group compared to the control. The survivor cohort also had significantly more HIZ-lesons than the controls (n=13 and n=1, p=0.003). Age at diagnosis was associated with lower degree of IVD degeneration (p < 0.01). Blood pressure correlated with IVD degeneration (P < 0.05). CONCLUSIONS: Signs of early disc degeneration related to tumor treatment can be seen in the IVDs of survivors. Disc degeneration was more severe in children treated in adolescence.

Integrative analysis of metabolomic, genomic, and imaging-based phenotypes identify very-low-density lipoprotein as a potential risk factor for lumbar Modic changes.

PURPOSE: Modic changes (MC) on magnetic resonance imaging (MRI) have been associated with the development and severity of low back pain (LBP). The etiology of MC remains elusive, but it has been suggested that altered metabolism may be a risk factor. As such, this study aimed to identify metabolomic biomarkers for MC phenotypes of the lumbar spine via a combined metabolomic-genomic approach. METHODS: A population cohort of 3,584 southern Chinese underwent lumbar spine MRI. Blood samples were genotyped with single-nucleotide polymorphisms (SNP) arrays (n = 2,482) and serum metabolomics profiling using magnetic resonance spectroscopy (n = 757), covering 130 metabolites representing three molecular windows, were assessed. Genome-wide association studies (GWAS) were performed on each metabolite, to construct polygenic scores for predicting metabolite levels in subjects who had GWAS but not metabolomic data. Associations between predicted metabolite levels and MC phenotypes were assessed using linear/logistic regression and least absolute shrinkage and selection operator (LASSO). Two-sample Mendelian randomization analysis tested for causal relationships between metabolic biomarkers and MC. RESULTS: 20.4% had MC (10.6% type 1, 67.2% type 2, 22.2% mixed types). Significant MC metabolomic biomarkers were mean diameter of very-low-density lipoprotein (VLDL)/low-density lipoprotein (LDL) particles and cholesterol esters/phospholipids in large LDL. Mendelian randomization indicated that decreased VLDL mean diameter may lead to MC. CONCLUSIONS: This large-scale study is the first to address metabolomics in subject with/without lumbar MC. Causality studies implicate VLDL related to MC, noting a metabolic etiology. Our study substantiates the field of "spino-metabolomics" and illustrates the power of integrating metabolomics-genomics-imaging phenotypes to discover biomarkers for spinal disorders, paving the way for more personalized spine care for patients.

Learning-based fully automated prediction of lumbar disc degeneration progression with specified clinical parameters and preliminary validation.

BACKGROUND: Lumbar disc degeneration (LDD) may be related to aging, biomechanical and genetic factors. Despite the extensive work on understanding its etiology, there is currently no automated tool for accurate prediction of its progression. PURPOSE: We aim to establish a novel deep learning-based pipeline to predict the progression of LDD-related findings using lumbar MRIs. MATERIALS AND METHODS: We utilized our dataset with MRIs acquired from 1,343 individual participants (taken at the baseline and the 5-year follow-up timepoint), and progression assessments (the Schneiderman score, disc bulging, and Pfirrmann grading) that were labelled by spine specialists with over ten years clinical experience. Our new pipeline was realized by integrating the MRI-SegFlow and the Visual Geometry Group-Medium (VGG-M) for automated disc region detection and LDD progression prediction correspondingly. The LDD progression was quantified by comparing the Schneiderman score, disc bulging and Pfirrmann grading at the baseline and at follow-up. A fivefold cross-validation was conducted to assess the predictive performance of the new pipeline. RESULTS: Our pipeline achieved very good performances on the LDD progression prediction, with high progression prediction accuracy of the Schneiderman score (Accuracy: 90.2 ± 0.9%), disc bulging (Accuracy: 90.4% ± 1.1%), and Pfirrmann grading (Accuracy: 89.9% ± 2.1%). CONCLUSION: This is the first attempt of using deep learning to predict LDD progression on a large dataset with 5-year follow-up. Requiring no human interference, our pipeline can potentially achieve similar predictive performances in new settings with minimal efforts.

Association of lumbar disc degeneration with low back pain in middle age in the Northern Finland Birth Cohort 1966.

BACKGROUND: Although it has been suggested that lumbar disc degeneration (LDD) is a significant risk factor for low back pain (LBP), its role remains uncertain. Our objective was to clarify the association between LDD and LBP and whether mental distress modifies the association. METHODS: Participants of a birth cohort underwent 1.5-T lumbar magnetic resonance imaging at the age of 47. The association between the sum score of LDD (Pfirrmann classification, range 0-15) and LBP (categorized into "no pain", "mild-to-moderate pain", "bothersome-and-frequent pain") was assessed using logistic regression analysis, with sex, smoking, body mass index, physical activity, occupational exposure, education, and presence of Modic changes and disc herniations as confounders. The modifying role of mental distress (according to the Hopkins Symptom Check List-25 [HSCL-25], the Beck Depression Inventory and the Generalized Anxiety Disorder Scale) in the association was analyzed using linear regression. RESULTS: Of the study population (n = 1505), 15.2% had bothersome and frequent LBP, and 29.0% had no LBP. A higher LDD sum score increased the odds of belonging to the "mild-to-moderate pain" category (adjusted OR corresponding to an increase of one point in the LDD sum score 1.11, 95% CI 1.04-1.18, P = 0.003) and the "bothersome-and-frequent pain" category (adjusted OR 1.20, 95% CI 1.10-1.31, P < 0.001), relative to the "no pain" category. Mental distress significantly modified the association between LDD and LBP, as a linear positive association was consistently observed among individuals without mental distress according to HSCL-25 (adjusted B 0.16, 95% CI 0.07-0.26, P < 0.001), but not among individuals with higher mental distress. CONCLUSIONS: LDD was significantly associated with both mild-to-moderate and bothersome-and-frequent LBP. However, the co-occurrence of mental distress diminished the association between LDD and LBP bothersomeness. Our results strongly suggest that mental symptoms affect the pain experience.

Participatory Ergonomics Intervention to Prevent Work Disability Among Workers with Low Back Pain: A Randomized Clinical Trial in Workplace Setting.

Purpose In order to support people with low back pain (LBP) to stay at work, work arrangements are regarded important. This study aimed to evaluate the effectiveness of a workplace intervention using a participatory approach on work disability of workers with ongoing or recurrent LBP. Methods A total of 107 workers with LBP, with duration of pain for at least two consecutive weeks or recurrent pain of any duration during the last year, were randomized either to the intervention (n = 51) or control group (n = 56). The intervention included arrangements at the workplace, along with individual guidance provided by an occupational physiotherapist (OPT). The randomized intervention study used standard counselling and guidance by an OPT without workplace intervention as a comparison. Surveys were completed at baseline, and 6 and 12 months after baseline. Results There were no statistically significant differences between the intervention and control groups on the primary outcome measure, i.e. self-assessed work ability. We found no between-group differences in perceived health, self-assessed work productivity, number of sickness absence days and severity of back pain. However, there were significant positive within-group changes in the intervention group in the intensity of LBP, perceived health and the number of sickness absence days due to LBP. Conclusion Workplace arrangements are feasible using participatory ergonomics, but more quantitative and qualitative research is needed on its utilization and effectiveness among workers with LBP.

Genetic Risk Score for Serum 25-Hydroxyvitamin D Concentration Helps to Guide Personalized Vitamin D Supplementation in Healthy Finnish Adults.

BACKGROUND: Genetic factors modify serum 25-hydroxyvitamin D [25(OH)D] concentration and can affect the optimal intake of vitamin D. OBJECTIVES: We aimed to personalize vitamin D supplementation by applying knowledge of genetic factors affecting serum 25(OH)D concentration. METHODS: We performed a genome-wide association study of serum 25(OH)D concentration in the Finnish Health 2011 cohort (n = 3339) using linear regression and applied the results to develop a population-matched genetic risk score (GRS) for serum 25(OH)D. This GRS was used to tailor vitamin D supplementation for 96 participants of a longitudinal Digital Health Revolution (DHR) Study. The GRS, serum 25(OH)D concentrations, and personalized supplementation and dietary advice were electronically returned to participants. Serum 25(OH)D concentrations were assessed using immunoassays and vitamin D intake using FFQs. In data analyses, cross-sectional and repeated-measures statistical tests and models were applied as described in detail elsewhere. RESULTS: GC vitamin D-binding protein and cytochrome P450 family 2 subfamily R polypeptide 1 genes showed genome-wide significant associations with serum 25(OH)D concentration. One single nucleotide polymorphism from each locus (rs4588 and rs10741657) was used to develop the GRS. After returning data to the DHR Study participants, daily vitamin D supplement users increased from 32.6% to 60.2% (P = 6.5 × 10-6) and serum 25(OH)D concentration from 64.4 ± 20.9 nmol/L to 68.5 ± 19.2 nmol/L (P = 0.006) between August and November. Notably, the difference in serum 25(OH)D concentrations between participants with no risk alleles and those with 3 or 4 risk alleles decreased from 20.7 nmol/L to 8.0 nmol/L (P = 0.0063). CONCLUSIONS: We developed and applied a population-matched GRS to identify individuals genetically predisposed to low serum 25(OH)D concentration. We show how the electronic return of individual genetic risk, serum 25(OH)D concentrations, and factors affecting vitamin D status can be used to tailor vitamin D supplementation. This model could be applied to other populations and countries.

Serum biomarkers for Modic changes in patients with chronic low back pain.

PURPOSE: Lumbar Modic change (MC) can serve as a diagnostic marker as well as an independent source of chronic low back pain (CLBP). This study aimed to test for the existence of serum biomarkers in CLBP patients with MC. METHODS: Age- and sex-matched CLBP patients with confirmed MC on lumbar MRI (n = 40) and pain-free controls (n = 40) were assessed. MC was classified into M1, predominating M1, predominating M2 and M2. MC volumes were calculated. Fasting blood samples were assessed for inflammatory mediators, signalling molecules, growth factors and bone turnover markers. Serum concentrations of 46 biomarkers were measured. RESULTS: Median concentrations of interleukin (IL)-15 (p < 0.001), IL-8 (p < 0.001), tumour necrosis factor (TNF)-alpha (p < 0.001), Eotaxin-1 (p < 0.05), Eotaxin-3 (p < 0.001), monocyte chemotactic protein (MCP)-1 (p < 0.05), macrophage inflammatory protein (MIP)-1alpha (p < 0.01), TEK receptor tyrosine kinase (Tie)-2 (p < 0.001), vascular cell adhesion molecule (VCAM)-1 (p < 0.001), RANTES (p < 0.001), C telopeptide of type I collagen (CTX)-1 (p < 0.001), vascular endothelial growth factor (VEGF)-C (p < 0.001), VEGF-D (p < 0.05), fms-related tyrosine kinase (Flt)-1 (p < 0.01) and intercellular adhesion molecule (ICAM)-1 (p < 0.01) were significantly higher among controls. IL-1sRII (23.2 vs. 15.5 ng/ml, p < 0.001) and hepatocyte growth factor (HGF)-1 (169 vs. 105 pg/ml, p < 0.01) concentrations were significantly higher among patients. Type or volume of MC was not associated with biomarker concentrations. CONCLUSIONS: This is the first study to assess the blood serum biomarker profile in individuals with CLBP with MC. Several biomarkers were suppressed, while two markers (IL-1sRII and HGF) were elevated among MC patients, irrespective of MC type or size, with CLBP compared with asymptomatic controls.

Patient education booklet to support evidence-based low back pain care in primary care - a cluster randomized controlled trial.

BACKGROUND: Inappropriate imaging and low-value care for low back pain (LBP) are common. A new patient-education booklet was created to overcome identified barriers to the delivery of recommended care, including the use of inappropriate imaging. Our aim was to assess the effectiveness of this booklet as part of primary care for LBP patients in comparison to usual care. METHODS: A cluster-randomized trial was performed. The intervention involved providing practitioners with the new patient-education booklet and a 30-min training session on its use. The booklet was provided during the clinical consult to all consenting LBP patients in the intervention group. Primary outcomes were the proportion of patients presenting with LBP who underwent imaging examinations during the first three months of follow-up and PROMIS PF-20 (Patient-Reported Outcomes Measurement Information System, 20-item physical functioning short form) change between baseline and three-month follow-up. Secondary outcomes, including sick leave and imaging examinations at 12 months, were investigated. Logistic regression using GEE-estimation was used for dichotomous outcomes, Poisson regression using GEE-estimation for count outcomes, and linear mixed models for continuous outcomes. RESULTS: Using the patient education booklet appeared to substantially reduce the proportion of LBP patients who underwent an imaging examination at three months, but the result was not statistically significant (OR 0.57, 95% confidence interval (Cl) 0.27 to 1.22). At 12 months, the effect was slightly larger and statistically significant (OR 0.50, 95%Cl 0.30 to 0.83, p = 0.008). No difference was observed in the PROMIS PF-20 T-score change between baseline and 3 months or 12 months (p = 0.365 and p = 0.923, respectively). The number of sick leave days in the intervention group was less than that in the control group at 3 months (RR 0.47, 95%Cl 0.26 to 0.83, p = 0.010) and at 12 months (RR 0.36, 95%Cl 0.18 to 0.72, p = 0.004). CONCLUSIONS: The booklet appeared to be effective in reducing the proportion of LBP patients who underwent imaging examinations over 12 months. The intervention had no discernible effect on the PROMIS PF20 T-score change. The number of sick leave days was substantially lower in the intervention group. TRIAL REGISTRATION: ISRCTN, ISRCTN14389368 , Registered 4 April 2019-Retrospectively registered.

Genome-wide meta-analysis identifies genetic locus on chromosome 9 associated with Modic changes.

BACKGROUND: Low back pain (LBP) is a common disabling condition. Lumbar disc degeneration (LDD) may be a contributing factor for LBP. Modic change (MC), a distinct phenotype of LDD, is presented as a pathological bone marrow signal change adjacent to vertebral endplate on MRI. It is strongly associated with LBP and has heritability around 30%. Our objective was to identify genetic loci associated with MC using a genome-wide meta-analysis. METHODS: Presence of MC was evaluated in lumbar MRI in the Northern Finland Birth Cohort 1966 (n=1182) and TwinsUK (n=647). Genome-wide association analyses were carried out using linear regression model. Inverse-variance weighting approach was used in the meta-analysis. RESULTS: A locus associated with MC (p<5e-8) was found on chromosome 9 with the lead SNP rs1934268 in an intron of the PTPRD gene. It is located in the binding region of BCL11A, SPI1 and PBX3 transcription factors. The SNP was nominally associated with LBP in TwinsUK (p=0.001) but not associated in the UK Biobank (p=0.914). Suggestive signals (p<1e-5) were identified near XKR4, SCIN, MGMT, DLG2, ZNF184 and OPRK1. CONCLUSION: PTPRD is a novel candidate gene for MC that may act via the development of cartilage or nervous system; further work is needed to define the mechanisms underlying the pathways leading to development of MC. This is the first genome-wide meta-analysis of MC, and the results pave the way for further studies on the genetic factors underlying the various features of spine degeneration and LBP.

Accumulated unhealthy behaviors and psychosocial problems in adolescence are associated with labor market exclusion in early adulthood - a northern Finland birth cohort 1986 study.

BACKGROUND: The relevance of health-related behaviors to exclusion from the labor market in early adulthood remains poorly studied in relation to the magnitude of the problem. We explored whether adolescents' accumulated unhealthy behaviors and psychosocial problems are associated with later labor market exclusion, and whether multisite musculoskeletal pain (MMSP) impacts these relations. METHODS: We gathered questionnaire data on unhealthy behaviors and psychosocial problems and MMSP among adolescents aged 15 to 16 belonging to the Northern Finland Birth Cohort 1986. The findings were combined with registry data on unemployment, employment and permanent work disability during a five-year follow-up between the ages of 25 and 29 (n = 6692). In the statistical modeling we used education, family leave and socioeconomic status of childhood family as potential confounders, as well as latent class and logistic regression analyses. RESULTS: The Externalizing behavior cluster associated with over one year of unemployment (RR 1.64, CI 1.25-2.14) and permanent work disability (OR 2.49, CI 1.07-5.78) in the follow-up among the men. The Sedentary cluster also associated with over one year (RR 1.41, CI 1.13-1.75) and under one year of unemployment (RR 1.25, CI 1.02-1.52) and no employment days (RR 1.93, CI 1.26-2.95) among the men. Obese male participants were at risk of over one year of unemployment (RR 1.50, CI 1.08-2.09) and no employment days (RR 1.93, CI 1.07-3.50). Among the women, the Multiple risk behavior cluster related significantly to over one year of unemployment (RR 1.77, CI 1.37-2.28). MMSP had no influence on the associations. CONCLUSIONS: Unhealthy behavior patterns and psychosocial problems in adolescence have long-term consequences for exclusion from the labor market in early adulthood, especially among men. Simultaneously supporting psychological well-being and healthy behaviors in adolescence may reduce labor market inclusion difficulties in the early phase of working life.

Association between device-measured physical activity and lumbar Modic changes.

BACKGROUND: Modic changes (MC) in the lumbar spine are considered one potential etiological factor behind low back pain (LBP). Multiple risk factors for MC have been suggested, including male gender, smoking and factors affecting hyperloading and mechanical stress such as high body mass index (BMI), strenuous physical work and high occupational and leisure-time physical activity (PA). So far, the effect of PA on the occurrence of MC has remained under debate due to contradictory findings. The purpose of this study was to investigate the possible association between device-measured moderate-to-vigorous PA (MVPA) (≥ 3.5 METs) and lumbar MC. METHODS: The study had 1374 participants from the Northern Finland Birth Cohort 1966. At the age of 46-48, PA was measured by a wrist-worn accelerometer, and lumbar magnetic resonance imaging (MRI) was carried out to determine MC. We analyzed the association between Type 1 (MC1) and Type 2 (MC2) MC and daily amount of MVPA (min/day) using sex-stratified logistic regression models before and after adjustment for BMI, socioeconomic status, smoking, and accelerometer wear time. RESULTS: Among men, increased amount of MVPA was positively associated with any MC (adjusted OR corresponding to every 60 min/day of MVPA 1.41; 95% confidence interval (CI) 1.01 to 1.95) and MC2 (OR 1.54; 95% CI 1.14 to 2.08), but not with MC1 (OR 1.06; 95% CI 0.80 to 1.39). Among women, we only found a positive association between MVPA and MC1 before adjustments (unadjusted OR 1.42; 95% CI 1.06 to 1.92). CONCLUSION: Among men, increased amount of MVPA was associated with increased odds of any MC and particularly MC2. Among women, MVPA was not independently associated with MC.

Serum Biomarkers for Connective Tissue and Basement Membrane Remodeling are Associated with Vertebral Endplate Bone Marrow Lesions as Seen on MRI (Modic Changes).

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

Assessment of construct validity of the Finnish versions of the Disabilities of Arm, Shoulder and Hand Instrument and the Michigan Hand Outcomes Questionnaire.

STUDY DESIGN: Cross-sectional study. INTRODUCTION: There is a lack of information on the measurement properties of patient-reported upper extremity instruments and their association to health-related quality of life (HRQoL). PURPOSE OF THE STUDY: This study aimed to examine and compare the measurement properties and construct validity of the Disabilities of Arm, Shoulder, and Hand (DASH) Instrument and the Michigan Hand Questionnaire (MHQ) using a heterogeneous sample of patients with hand and wrist problems. METHODS: Two hundred fifty consecutive patients visiting a general orthopedic outpatient clinic due to various hand/wrist problems were invited to participate in the study. A total of 193 (77%) participants provided sufficient patient-reported outcome data and were included in the analysis. Participants completed the DASH, the MHQ, the EQ-5D-3L, and pain on a visual analog scale instruments. Grip and key pinch forces were measured. Scale targeting, relatedness of demographics, and construct validity of the DASH and the MHQ were assessed. RESULTS: Both the DASH and the MHQ had good targeting, but the DASH had wider coverage. The convergence between the DASH and the MHQ was high. The DASH was more closely related to HRQoL than the MHQ in terms of EQ-5D scores. DISCUSSION: The DASH instrument appeared to measure hand function and disability from a perspective of HRQoL superior to the MHQ among patients with heterogeneous hand and wrist complaints. CONCLUSION: The DASH performs well in measuring the HRQoL-related hand outcomes while the MHQ might be more specific for the affected hand.

What low back pain is and why we need to pay attention.

Low back pain is a very common symptom. It occurs in high-income, middle-income, and low-income countries and all age groups from children to the elderly population. Globally, years lived with disability caused by low back pain increased by 54% between 1990 and 2015, mainly because of population increase and ageing, with the biggest increase seen in low-income and middle-income countries. Low back pain is now the leading cause of disability worldwide. For nearly all people with low back pain, it is not possible to identify a specific nociceptive cause. Only a small proportion of people have a well understood pathological cause-eg, a vertebral fracture, malignancy, or infection. People with physically demanding jobs, physical and mental comorbidities, smokers, and obese individuals are at greatest risk of reporting low back pain. Disabling low back pain is over-represented among people with low socioeconomic status. Most people with new episodes of low back pain recover quickly; however, recurrence is common and in a small proportion of people, low back pain becomes persistent and disabling. Initial high pain intensity, psychological distress, and accompanying pain at multiple body sites increases the risk of persistent disabling low back pain. Increasing evidence shows that central pain-modulating mechanisms and pain cognitions have important roles in the development of persistent disabling low back pain. Cost, health-care use, and disability from low back pain vary substantially between countries and are influenced by local culture and social systems, as well as by beliefs about cause and effect. Disability and costs attributed to low back pain are projected to increase in coming decades, in particular in low-income and middle-income countries, where health and other systems are often fragile and not equipped to cope with this growing burden. Intensified research efforts and global initiatives are clearly needed to address the burden of low back pain as a public health problem.