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.

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.

Diagnostic Performance, Triage Safety, and Usability of a Clinical Decision Support System Within a University Hospital Emergency Department: Algorithm Performance and Usability Study.

Background: Computerized clinical decision support systems (CDSSs) are increasingly adopted in health care to optimize resources and streamline patient flow. However, they often lack scientific validation against standard medical care. Objective: The purpose of this study was to assess the performance, safety, and usability of a CDSS in a university hospital emergency department setting in Kuopio, Finland. Methods: Patients entering the emergency department were asked to voluntarily participate in this study. Patients aged 17 years or younger, patients with cognitive impairments, and patients who entered the unit in an ambulance or with the need for immediate care were excluded. Patients completed the CDSS web-based form and usability questionnaire when waiting for the triage nurse's evaluation. The CDSS data were anonymized and did not affect the patients' usual evaluation or treatment. Retrospectively, 2 medical doctors evaluated the urgency of each patient's condition by using the triage nurse's information, and urgent and nonurgent groups were created. The International Statistical Classification of Diseases, Tenth Revision diagnoses were collected from the electronic health records. Usability was assessed by using a positive version of the System Usability Scale questionnaire. Results: In total, our analyses included 248 patients. Regarding urgency, the mean sensitivities were 85% and 19%, respectively, for urgent and nonurgent cases when assessing the performance of CDSS evaluations in comparison to that of physicians. The mean sensitivities were 85% and 35%, respectively, when comparing the evaluations between the two physicians. Our CDSS did not miss any cases that were evaluated to be emergencies by physicians; thus, all emergency cases evaluated by physicians were evaluated as either urgent cases or emergency cases by the CDSS. In differential diagnosis, the CDSS had an exact match accuracy of 45.5% (97/213). The usability was good, with a mean System Usability Scale score of 78.2 (SD 16.8). Conclusions: In a university hospital emergency department setting with a large real-world population, our CDSS was found to be equally as sensitive in urgent patient cases as physicians and was found to have an acceptable differential diagnosis accuracy, with good usability. These results suggest that this CDSS can be safely assessed further in a real-world setting. A CDSS could accelerate triage by providing patient-provided data in advance of patients' initial consultations and categorize patient cases as urgent and nonurgent cases upon patients' arrival to the emergency department.

Association of accelerometer-measured physical activity, back static muscular endurance and abdominal obesity with radicular pain and non-specific low back pain.

Low back pain (LBP) is the leading cause of disability worldwide and often associated with lifestyle factors. However, studies further examining the role of these lifestyle factors in non-specific low back pain in comparison with radicular pain are sparse. The aim of this cross sectional study was to investigate how diverse lifestyle factors are associated with LBP. The study population of 3385 middle aged adults with and without low back pain was drawn from a large Birth 1966 Cohort. Outcome measures were steps per day, abdominal obesity, physical activity and endurance of the back muscles. Back static muscular endurance, abdominal obesity and physical activity were measured by means of the Biering-Sørensen test, waist circumference and a wrist worn accelerometer, respectively. Logistic regression analysis was applied to estimate associations of back static muscular endurance, abdominal obesity and accelerometer-measured physical activity with non-specific low back pain and radicular pain. An additional 1000 steps per day were associated with 4% lower odds of having non-specific low back pain. Participants with abdominal obesity had 46% higher odds of having radicular pain, whereas increases of 10 s in back static muscular endurance and 10 min in daily vigorous physical activity were associated with 5% and 7% lower odds of having radicular pain, respectively. In this population-based study, non-specific low back pain and radicular pain were associated with different lifestyle and physical factors at midlife. Non-specific low back pain was associated only with the average daily number of steps, whereas abdominal obesity was the strongest determinant of radicular pain, followed by vigorous physical activity and back static muscular endurance. The findings of this study contribute to better understand the role of lifestyle factors in both non-specific low back pain and radicular pain. Future longitudinal studies are required to explore causality.

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.

External Validation of SpineNet, an Open-Source Deep Learning Model for Grading Lumbar Disk Degeneration MRI Features, Using the Northern Finland Birth Cohort 1966.

STUDY DESIGN: This is a retrospective observational study to externally validate a deep learning image classification model. OBJECTIVE: Deep learning models such as SpineNet offer the possibility of automating the process of disk degeneration (DD) classification from magnetic resonance imaging (MRI). External validation is an essential step to their development. The aim of this study was to externally validate SpineNet predictions for DD using Pfirrmann classification and Modic changes (MCs) on data from the Northern Finland Birth Cohort 1966 (NFBC1966). SUMMARY OF DATA: We validated SpineNet using data from 1331 NFBC1966 participants for whom both lumbar spine MRI data and consensus DD gradings were available. MATERIALS AND METHODS: SpineNet returned Pfirrmann grade and MC presence from T2-weighted sagittal lumbar MRI sequences from NFBC1966, a data set geographically and temporally separated from its training data set. A range of agreement and reliability metrics were used to compare predictions with expert radiologists. Subsets of data that match SpineNet training data more closely were also tested. RESULTS: Balanced accuracy for DD was 78% (77%-79%) and for MC 86% (85%-86%). Interrater reliability for Pfirrmann grading was Lin concordance correlation coefficient=0.86 (0.85-0.87) and Cohen κ=0.68 (0.67-0.69). In a low back pain subset, these reliability metrics remained largely unchanged. In total, 20.83% of disks were rated differently by SpineNet compared with the human raters, but only 0.85% of disks had a grade difference >1. Interrater reliability for MC detection was κ=0.74 (0.72-0.75). In the low back pain subset, this metric was almost unchanged at κ=0.76 (0.73-0.79). CONCLUSIONS: In this study, SpineNet has been benchmarked against expert human raters in the research setting. It has matched human reliability and demonstrates robust performance despite the multiple challenges facing model generalizability.

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.

Lower thoracic spine extension mobility is associated with higher intensity of thoracic spine pain.

OBJECTIVES: To evaluate the association of thoracic spine (TS) posture and mobility with TS pain. METHODS: Participants with TS pain reported maximum, average, and night pain in TS area, and pain summary score was calculated. Upright and sitting TS postures were evaluated by inspection. TS posture and mobility (flexion and extension) were recorded using an inclinometer and a tape measure, respectively. Correlations between posture and mobility assessments were calculated using Spearman rank correlation, the association of TS posture and mobility with TS pain by logistic regression analysis. RESULTS: The participants' (n = 73, 52 females, age range 22-56) TS pain duration was 12 weeks on average. The correlations for measurements of TS posture and flexion mobility were higher than correlations of other TS measurements being between 0.53 and 0.82. Decreased extension mobility of the upper (from 1st to 6th TS segments; Th1-Th6) TS was associated with higher worst pain (OR 1.04, 95% CI 1.00-1.07) and whole TS with pain sum score (OR 1.05, 95% CI 1.01-1.08). Less kyphotic whole TS was associated with lower pain sum score (OR 0.96, 95% CI 0.92-1.00). Greater flexion mobility of upper and lower (Th6-Th12) TS were associated with lower pain sum score (OR 0.96, 95% CI 0.91-1.00, and OR 0.96, 95% CI 0.91-1.00, respectively). CONCLUSIONS: Reduced thoracic extension mobility was associated with higher pain scores and the greater flexion mobility with lower pain scores. Future research is warranted to evaluate if treatments geared toward TS extension mobility improvements would result in lower TS pain.

Oral Zoledronic acid bisphosphonate for the treatment of chronic low back pain with associated Modic changes: A pilot randomized controlled trial.

To assess the safety and efficacy of oral 50 mg Zoledronic acid (ZA) bisphosphate once-a-week for 6-weeks to placebo among patients with chronic low back pain (cLBP) and Modic changes (MC) on MRI. A parallel, double-blinded randomized controlled study was performed at a single center, consisted of 25 subjects with cLBP and MC that received ZA (n = 13) or placebo (n = 12). Evaluation was at baseline, 2-weeks, 4-weeks, 3-months and 6-months for assessment of LBP/leg pain intensity, disability (Oswestry-Disability-Index: ODI), health-related quality-of-life (RAND-36), and mental component summary scores (MCS). Type 2 MC at baseline (56%) were prevalent. In the ZA group, LBP intensity was lower at 4-weeks in comparison to placebo (5.1 ± 1.9 vs. 6.9 ± 1.8, p = 0.038) (minimal clinically important difference [MCID] = 1.5). LBP intensity reduced at 4-weeks and 3-months in the ZA-treated group in comparison to baseline. Although there was no difference in ODI, subscale RAND-36 metrics for physical function (p = 0.038), energy/fatigue (p = 0.040) and pain (p = 0.003) were improved at 3-months compared to placebo, with moderate significant difference for pain at 6-months (p = 0.051). Correlated MCS scores to baseline also improved at 3-months (p = 0.035) and 6-months (p = 0.028) by 6.9 and 6.8, respectively, (MCID = 3.8). A reduction in MC endplate affected area at 6-month follow-up was noted in the ZA group (-0.67 ± 0.69 cm2 ), while in the placebo group no change in size was observed (0.0 ± 0.15; p = 0.041). Three subjects withdrew from the study and no long-lasting adverse events. Oral ZA was a safe and effective treatment that reduced MC volume, improved LBP symptoms and quality-of-life measures in cLBP subjects with MCs.

The Association of Lumbosacral Transitional Vertebrae with Low Back Pain and Lumbar Degenerative Findings in MRI: A Large Cohort Study.

STUDY DESIGN: A cross-sectional study of the Northern Finland Birth Cohort 1966 (NFBC1966). OBJECTIVE: To evaluate the association of lumbosacral transitional vertebrae (LSTV) with low back pain (LBP) and associated degenerative findings using magnetic resonance (MR) imaging. SUMMARY OF BACKGROUND DATA: LSTV is a common finding with a prevalence of 10% to 29%. LSTV causes biomechanical alterations leading to accelerated lumbar degeneration. However, its association with degenerative findings on MRI and LBP is unclear. METHODS: One thousand four hundred sixty eight lumbar spine MRI scans from the NFBC1966 acquired at a mean age of 47 years were assessed for the presence of LSTV and degenerative changes. Castellvi classification was utilized to identify LSTV anatomy. Additionally, 100 controls without LSTV were collected. Self-reported LBP with a duration of more than 30 days in the past year was deemed clinically relevant. For the statistical analyses, chi square test, independent samples t test and multinomial logistic regression analyses were used. RESULTS: LSTV was found in 310 (21.1%) subjects. After adjusting for age, sex, and disc degeneration (DD) sum, subjects with Castellvi type III reported prolonged LBP significantly more frequently than the controls (odds ratio [OR] = 8.9, P = 0.001). We observed a higher prevalence of facet degeneration (FD) at all levels from L3/L4 to L5/S1 in type I, and L3/L4 to L4/L5 in types II-IV. DD was more prevalent at L4/L5 in types II-IV. Disc protrusion/extrusion occurred more frequently at L3/L4 and L4/L5 in type II, and at L3/L4 in type III. Castellvi type II had a higher prevalence of type 1 Modic changes at levels from L3/L4 to L4/L5. CONCLUSION: LSTVs were a common finding within this study, and Castellvi type III LSTVs were associated with LBP. Degenerative findings were associated with LSTV anatomy and occurred more commonly above the transitional level.Level of Evidence: 3.

Association Between Vertebral Dimensions and Lumbar Modic Changes.

STUDY DESIGN: Population-based birth cohort study. OBJECTIVE: The aim of this study was to evaluate the relationship between vertebral dimensions and lumbar MC. SUMMARY OF BACKGROUND DATA: Low back pain (LBP) has become the leading cause of disability worldwide. Modic changes (MC) of the lumbar spine are one potential LBP-associated etiological factor. Mechanical stress is considered to play a key role in the development of MC through damage to endplates. There is speculation that vertebral dimensions play a role in some degenerative changes in the spine. Previous studies have also shown a positive association between moderate-to-vigorous physical activity (MVPA) and both vertebral dimensions and MC. In this study, we aimed to evaluate the relationship between vertebral dimensions and MC. METHODS: The study population consisted of 1221 participants from the Northern Finland Birth Cohort 1966 who underwent lumbar magnetic resonance imaging (MRI) and physical activity measurements at the age of 46-48. The presence of Type 1 (MC1) and Type 2 (MC2) MC and the height, axial cross-sectional area (CSA), and volume of the L4 vertebra were determined from MRI scans. MVPA (≥3.5 metabolic equivalents) was measured by a wrist-worn accelerometer. We analyzed the association between lumbar MC and vertebral height, CSA, and volume using logistic regression models before and after adjustment for sex, height, weight, smoking, education level, and MVPA. RESULTS: Vertebral height was positively associated with the presence of MC2 (odds ratio [OR] 3.51; 95% confidence interval [CI] 1.43-8.65), whereas vertebral CSA was not associated with the presence of lumbar MC. Vertebral volume was positively associated with the presence of any MC (OR 1.04; 95% CI 1.00-1.07), but the association did not persist when analyzing MC1 and MC2 separately. CONCLUSION: Vertebral height was associated with the presence of MC2. Further studies are needed to clarify the role of vertebral dimensions as independent risk factors for MC.Level of Evidence: 3.

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.

Association Between Modic Changes and Low Back Pain in Middle Age: A Northern Finland Birth Cohort Study.

STUDY DESIGN: A cross-sectional study of the Northern Finland Birth Cohort 1966 (NFBC1966). OBJECTIVE: The aim of this study was to evaluate the association between the type, size, and location of lumbar Modic changes (MC), and prolonged disabling low back pain (LBP). SUMMARY OF BACKGROUND DATA: LBP is the leading cause of disability worldwide and it affects all age- and socioeconomical groups. Only a small proportion of LBP patients are diagnosed with a specific cause: In most cases no single nociceptive cause for the pain can be identified. MC are visualized in magnetic resonance imaging (MRI) as a signal intensity change in vertebral bone marrow and have been proposed to represent a specific degenerative imaging phenotype associated with LBP. MC can be classified into several subtypes, of which inflammatory Type 1 (MC1) is suggested as being more likely to be associated with LBP. METHODS: We assessed lumbar MRI (n = 1512) for the presence, type, and size of MC. The associations of MC characteristics with prolonged (≥30 days during the past year) and disabling (bothersomeness of LBP at least 6 on a 0-10 Numeric Rating Scale) LBP, evaluated at the time of imaging at 47 years, were analyzed using binary logistic regression, adjusted for sex, BMI, smoking, educational status, lumbar disc degeneration, and disc herniations. RESULTS: Any MC and MC1 were associated with prolonged disabling LBP (odds ratio [OR] after full adjustments 1.50 [95% confidence interval, CI 1.05-2.15] and 1.50 [95% CI 1.10-2.05], respectively). Furthermore, MC covering the whole anterior-posterior direction or the whole endplate, as well as the height of MC, were significantly associated with prolonged disabling LBP (OR after full adjustments 1.59 [95% CI 1.14-2.20], 1.67 [95% CI 1.13-2.46] and 1.26 [95% CI 1.13-1.42], respectively). CONCLUSION: Our study showed a significant and independent association between MC and clinically relevant LBP. LEVEL OF EVIDENCE: 3.

Lumbosacral transitional vertebrae are associated with lumbar degeneration: retrospective evaluation of 3855 consecutive abdominal CT scans.

OBJECTIVES: To assess the prevalence of lumbosacral transitional vertebra (LSTV) and associated spinal degenerative changes on abdominal CT scans in Caucasian population. MATERIAL AND METHODS: A total of 3855 abdominal CT scans of the year 2017 from a single hospital were retrospectively assessed for LSTV, disc degeneration (DD), and facet joint degeneration (FD). An age- and sex-matched 150-subject control group without LSTV was picked at random. Multivariable logistic regression was used for the analysis. RESULTS: LSTV was found in 1101 (29%) scans: Castellvi type I in 68%, type II in 16%, type III in 13%, and type IV in 3% of scans. Age- and sex-adjusted prevalence of DD was significantly higher in Castellvi type II and III groups at multiple lumbar levels, and in IV group at L4/5 than in control group (p < 0.001-0.034). At L5/S1, the prevalence of DD was significantly higher in the control group than in type II, III, or IV groups (p < 0.001-0.017). After combining Castellvi types II, III, and IV into one group, significant differences were found at all lumbar levels except L2/3 (p < 0.001-0.016). Prevalence of FD was significantly higher at L4/5 in Castellvi groups I, II, and III than in the control group (p < 0.001-0.002). When Castellvi types II, III, and IV were combined into one group, significant differences were found at lumbar levels L2/3, L3/4, and L4/5 (p < 0.001-0.021). CONCLUSION: Lumbosacral vertebrae of Castellvi types II, III, and IV are associated with greater lumbar degeneration, warranting meticulous evaluation of spinal anatomy, even on CT. KEY POINTS: • Lumbosacral transitional vertebra is a common incidental finding on abdominal CT scans with a high prevalence of 29%. • When assessing whole lumbar spine, lumbosacral vertebrae of Castellvi types II, III, and IV were associated with greater lumbar degeneration, warranting careful evaluation of the lumbar spine on abdominal CT scans.

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.

Intervertebral Disc Biology: Genetic Basis of Disc Degeneration.

PURPOSE OF REVIEW: This review aims to highlight recent advances in understanding the genetic basis of intervertebral disc degeneration (IDD). RECENT FINDINGS: It has been known for some time that IDD is highly heritable. Recent studies, and in particular the availability of agnostic techniques such as genome-wide association studies, have identified new variants in a variety of genes which contribute to the risk of IDD and to back pain. SUMMARY: A variety of genetic variants are involved in IDD. Some are shared with variants predisposing to back pain, but few have been identified reliably in either phenotype. Further research is required to explain fully the high heritability and how the genetic variants influence cell biology to lead to IDD.

Strong association between vertebral endplate defect and Modic change in the general population.

Modic change (MC) is considered an independent risk factor for low back pain (LBP) but its aetiology remains unclear. In this cross-sectional, large-scale population-based study we sought to characterise associations between endplate defect (ED) and MC in a population sample of broad age range. The study population consisted of 831 twin volunteers (including 4155 discs and 8310 endplates) from TwinsUK. Lumbar T2-weighted MR images were coded for ED and MC. Total endplate (TEP) score was calculated at each intervertebral disc while receiver operating curves (ROC) were calculated to define critical endplate values predictive of MC. MC was detected in 32.1% of the subjects, with a significantly higher prevalence at lower lumbar levels (3.5% at L1/2-L3/4 vs. 15.9% at L4/5-L5/S1, p < 0.001). TEP score was strongly and independently associated with MC at each lumbar level (risk estimates from 1.49 to 2.44; all p ≤ 0.001) after adjustment for age, sex, BMI and twin pairing. ROC analysis showed a TEP score cut-off of 6 above which there was a significantly higher prevalence of MC. In conclusion, ED were strongly associated with MC at every lumbar level. These findings support the hypothesis that endplate defect is a major initiating factor for the cascade of events that may include disc degeneration (DD) and MC.

Endplate Defect Is Heritable, Associated With Low Back Pain and Triggers Intervertebral Disc Degeneration: A Longitudinal Study From TwinsUK.

STUDY DESIGN: Longitudinal study of spine magnetic resonance imaging (MRI) in a large-scale population-based study. OBJECTIVE: To determine the order of appearance of degenerative change in vertebral bodies and intervertebral discs. We also sought to define the influence of endplate defect on low back pain (LBP) and to determine whether there is a genetic influence on endplate defect. SUMMARY OF BACKGROUND DATA: Endplate defect is a magnetic resonance imaging trait, found to be associated with intervertebral disc degeneration. There is a lack of understanding regarding the mechanism underlying lumbar disc degeneration (LDD). Recent attention has shifted to vertebral endplate defects and their role in spine degeneration pathology. METHODS: Individuals from the TwinsUK spine study having longitudinal T2-weighted lumbar MR scans at baseline (n = 996) and a decade later (n = 438) were included. LDD, vertebral endplate defect by calculating a total endplate score, and Modic change (MC) were assessed using standard techniques. Mixed-effects models were used to determine the association between the features of spine pathology, adjusted for covariates. Endplate defect heritability was estimated using variance component analysis. RESULTS: Significant association was found between endplate defect, LDD, MRI features of LDD and MC was observed. Endplate defect was associated with severe disabling LBP (P ≤ 0.013) in multivariate analysis. An association between disc degeneration (DD) at baseline and MC at follow-up was shown at upper lumbar levels. Total endplate score was heritable with estimated additive genetic component A = 55.3% (95% CI 43.0-65.4). CONCLUSION: Endplate defect, LDD, and MC are all independent risk factors for episodes of severe and disabling LBP. Longitudinal analysis showed DD is followed by MC. Endplate defect has significant heritability of 55%. However, whether endplate defect triggers DD or these pathological changes occur concurrently could not be conclusively determined. LEVEL OF EVIDENCE: 2.

Vertebral Endplate Defect as Initiating Factor in Intervertebral Disc Degeneration: Strong Association Between Endplate Defect and Disc Degeneration in the General Population.

STUDY DESIGN: Cross-sectional study of spine magnetic resonance in a population, predominantly female, sample. OBJECTIVE: To determine the relationship between vertebral endplate defect and intervertebral disc degeneration (DD) in general population. SUMMARY OF BACKGROUND DATA: Precise understanding of the mechanisms leading to DD development is lacking. In a degenerating disc, mechanical and structural changes lead to further worsening of disc integrity. Increasing attention has been paid to vertebral endplate defects as having a possible role in the etiopathogenesis of DD. METHODS: The study population comprised 831 twin volunteers from TwinsUK (mean age 54 ±â€Š8 yr, 95.8% female). Lumbar T2-weighted magnetic resonance images were coded for endplate defects from 8310 endplates into six grades. Total endplate score (TEP score) was achieved by summing both endplate defect grades from the same disc level. DD was evaluated using two different classifications; Pfirrmann grading, and a quantitative trait for DD based on a 4-point grading system. Multivariable regression analysis was used to determine relationships between the traits of interest and the known risk factors for DD, age, and body mass index (BMI). A receiver operator curve for TEP score predicting DD was generated, and survival analysis paired with Cox proportional hazards models analysis performed. RESULTS: There was statistically significant association between DD and age and BMI. These associations lost significance when TEP score was included as predictor in multivariable model. TEP score was strongly and independently associated at every lumbar disc level with DD (Pfirmann P≤0.001; 4-point grading systems P < 1e-16). A cut-off point score of 5 for TEP score was found above which there was a higher DD prevalence. Across all age subgroups, probabilities of having DD were significantly increased in those considered TEP score positive (≥5). CONCLUSION: Our large, population-based study has shown that endplate defect was strongly and independently associated with DD at every lumbar disc level. These results provide a mechanism by which increasing age and BMI predispose to DD. LEVEL OF EVIDENCE: 2.

The relationship between Modic changes and intervertebral disc degeneration.

BACKGROUND: Recent reported results have added to the weight of evidence supporting association between disc degeneration and Modic changes. Endplate or Modic changes are also associated with increased body mass index. The most recent study from Teichtahl et al. titled 'Modic changes in the lumbar spine and their association with body composition, fat distribution and intervertebral disc height - a 3.0 T-MRI study' showed associations of Modic changes with quantitatively measured reduced disc height and fat mass index. However, there were some facts, which we would like to address in this Correspondence to their article. DISCUSSION: The different components of intervertebral disc degeneration such as loss of disc height and disc signal intensity have already been shown associated with endplate changes - but not disc height if it is assessed using newer more precise methods of quantitation of disc height. A possible protective effect of different adiposity distribution in the body to Modic change development would be of interest if observed in a longitudinal study in the future. Modic changes have been associated with different components of intervertebral disc degeneration such as loss of disc height and disc signal intensity previously. The influence of body fat distribution on endplate changes would be interesting to study longitudinally.