Reliability of T2-weighted signal intensity-based quantitative measurements and visual grading of lumbar disc degeneration on MRI.

BACKGROUND: Decrease in signal intensity (SI) of the nucleus pulposus (NP) on T2-weighted (T2W) images, a sign of disc degeneration (DD), is usually graded based on an observer's image interpretation. No gold standard for quantitative assessment of NP SI exists to date. PURPOSE: To compare different quantitative methods and visual gradings of lumbar DD and to evaluate the ability of the quantitative methods to differentiate DD grades. MATERIAL AND METHODS: The mean SI of 95 lumbar discs was measured from sagittal T2W images using three regions of interest (ROI): the whole disc, ellipsoid ROI on the NP, and targeted ROI on the most homogenous, brightest area of the NP. SI values were adjusted with cerebrospinal fluid (CSF) SI and compared with vertebral bone SI-adjusted values. DD was evaluated with Pfirrmann grading and visual grading of NP SI. Intra- and inter-observer agreements and relationships between measurements and visual gradings were assessed. RESULTS: Repeatability of all measurements was excellent. All measurements had a strong correlation with Pfirrmann grading and visual NP SI grading, and the CSF SI-adjusted values had a stronger correlation than the vertebral bone SI-adjusted values. The SI values obtained with the targeted ROI had the most significant differences between visual DD grades. CONCLUSION: Quantitative measurement of the NP SI provides a reliable method for evaluating lumbar DD. Targeted selection of the NP structures included in the measurement offers the best differentiation of DD grades. A reliable quantitative method for DD evaluation is needed for the development of machine-learning-based DD classification.

White Matter Hyperintensities after Five-Year Follow-Up and a Cross-Sectional FA Decrease in Bipolar I and Major Depressive Patients.

INTRODUCTION: An increase in brain white matter hyperintensities (WMHs) and a decrease in white matter fractional anisotrophy (FA) have been detected in bipolar I (BPI), II (BPII), and major depressive disorder (MDD) patients. Their relationship, and differences in diagnostic groups are obscure. Longitudinal studies are rare. OBJECTIVE: After 5-year follow-up, we evaluated WMHs in BPI, BPII, and MDD patients as compared with controls, and studied the effects of clinical variables. We also explored the associations of clinical variables with cross-sectional whole brain FA. METHODS: Eight BPI, 8 BPII, 6 MDD patients, and 19 controls participated in magnetic resonance imaging at baseline and follow-up. Diffusion weighted imaging was included at follow-up. WMHs were rated by the Coffey scale, and a tract-based spatial statistics method was used for diffusion data. The general linear model, ANOVA, Fisher's exact, Wilcoxon sign, and Kruskal-Wallis tests were used for statistical analyses. RESULTS: Periventricular WMHs were increased in BPI patients (p = 0.047) and associated with the duration of disorder and lifetime occurrence of substance use disorder (p = 0.018). FA decrease was found in the corpus callosum of BPI patients (p < 0.01). MDD patients showed FA decrease in the right cerebellar middle peduncle (RCMP) (p < 0.01). In BPI patients, the duration of disorder associated with FA increase in RCMP (p < 0.05). No FA decrease was detected in patients with WMHs as compared with those without. CONCLUSIONS: Preceding illness burden associated modestly with WMHs, and FA increase in RCMP in BPI patients. MDD patients had FA decrease in RCMP. No association with FA decrease and WMHs was found.

Disc Degeneration of Young Low Back Pain Patients: A Prospective 30-year Follow-up MRI Study.

STUDY DESIGN: A prospective follow-up study. OBJECTIVE: The aim of this study was to investigate whether early lumbar disc degeneration (DD) in young low back pain (LBP) patients predicts progression of degenerative changes, pain, or disability in a 30-year follow-up. SUMMARY OF BACKGROUND DATA: MRI is an accurate method for studying degenerative changes in intervertebral discs. Decreased signal intensity (SI) can be used as indication of decreased water content. Long-term prognosis of early DD remains unclear. METHODS: In an earlier study, 75 conscripts aged 20 years with LBP had their lumbar spine examined by MRI. At a follow-up of 30 years, the subjects were contacted; 35 of 69 filled a pain and disability questionnaire, and 26 of 35 were also reexamined clinically and by MRI. The images were evaluated for decreased SI and other degenerative changes. Association between decreased SI of a disc at baseline and the presence of more severe degenerative changes in the same disc space at follow-up was analyzed using Fisher exact test. Association between decreased baseline SI and pain/disability scores from the questionnaire was analyzed with Kruskal-Wallis H test. RESULTS: The total number of lumbar discs with decreased SI increased from 23 of 130 (18%) to 92 of 130 (71%)-from 0.9 to 3.5 per subject during the follow-up. Distribution of DD changed from being mostly in L4-L5 and L5-S1 discs to being almost even between the four lowermost discs. Discs that had even slightly decreased SI at baseline were more likely to have severely decreased SI at follow-up, compared to healthy discs (57% vs. 11%, P < 0.001). Other degenerative changes were also more common in these discs. Severity of DD at baseline did not have a significant association with current pain or disability. CONCLUSION: In young LBP patients, early degeneration in lumbar discs predicts progressive degenerative changes in the respective discs, but not pain, disability, or clinical symptoms. LEVEL OF EVIDENCE: 4.

Chronic low back pain in relation to Modic changes, bony endplate lesions, and disc degeneration in a prospective MRI study.

PURPOSE: To clarify the significance of Modic changes, bony endplate lesions, and disc degeneration as predictors of chronic low back pain (LBP) during 1-year follow-up. METHODS: 49 patients with severe, non-specific, chronic LBP, and Modic 1 lesion (M1) were prospectively studied with MRI and questionnaire. Changes in grade of disc degeneration, severity of Modic changes, Schmorl lesions, and bony endplate irregularities were evaluated and changes assessed in LBP intensity on numeric rating scale 0-10 and severity with Oswestry disability index 0-100 (ODI). Association between change in MRI findings and symptoms was computed using generalized estimating equations analysis. RESULTS: Although pain decreased in most patients during 1-year follow-up, it increased or persisted in 36 %. Change in M1, M2, bony endplate lesions, and signal intensity (SI) and height of the disc associated with change of pain intensity, while change in M1, bony endplate lesions, and disc height associated with change of ODI. Not only persistent M1s, increasing bony endplate lesions, decreasing disc height, and M2s, but also new M2s predicted persistence of pain, while decrease of M1s and SI of the disc and increase of size of M2s predicted decrease of pain. Changes in disc bulges did not associate with pain. CONCLUSIONS: In patients with chronic non-specific LBP, persisting M1, decreasing disc height, and increasing bony endplate lesions associated with persisting pain while decrease of SI of the disc with decrease of pain. Such changing MRI findings in the same disc space have earlier been shown to progress abnormally fast. They may be signs or biomarkers of a prolonged pain causing, deforming degenerative process, and should lead to considering early intervention or specific treatments to affect that process.

[Update on Current Care Guideline: Low back pain]. / Alaselkäkipu.

Classification to severe diseases, sciatic symptoms or non-specific back pain is recommended. Radiography in acute or subacute non-specific back pain is not recommended in the primary health care. In specialized care magnetic resonance imaging is the main imaging modality. Importance of patient information is emphasized. In acute non-specific pain avoidance of bed rest, advice and paracetamol are recommended. Indications for an emergency referral should be considered. In disabling pain for 6 weeks, multidisciplinary measures are needed. Pain over 3 months indicates intensive multidisciplinary rehabilitation, and also surgery may be considered.

Association between changes in lumbar Modic changes and low back symptoms over a two-year period.

BACKGROUND: The association of Modic changes (MC) with low back pain (LBP) is unclear. The purpose of our study was to investigate the associations between the extent of Type 1 (M1) and Type 2 (M2) MC and low back symptoms over a two-year period. METHODS: The subjects (n = 64, mean age 43.8 y; 55 [86%] women) were consecutive chronic LBP patients who had M1 or mixed M1/M2 on lumbar spine magnetic resonance imaging (MRI). Size and type of MC on sagittal lumbar MRI and clinical data regarding low back symptoms were recorded at baseline and two-year follow-up. The size (%) of each MC in relation to vertebral size was estimated from sagittal slices (midsagittal and left and right quarter), while proportions of M1 and M2 within the MC were evaluated from three separate slices covering the MC. The extent (%) of M1 and M2 was calculated as a product of the size of MC and the proportions of M1 and M2 within the MC, respectively. Changes in the extent of M1 and M2 were analysed for associations with changes in LBP intensity and the Oswestry disability index (ODI), using linear regression analysis. RESULTS: At baseline, the mean LBP intensity was 6.5 and the mean ODI was 33%. During follow-up, LBP intensity increased in 15 patients and decreased in 41, while ODI increased in 19 patients and decreased in 44. In univariate analyses, change in the extent of M1 associated significantly positively with changes in LBP intensity and ODI (beta 0.26, p = 0.036 and beta 0.30, p = 0.017; respectively), whereas the change in the extent of M2 did not associate with changes in LBP intensity and ODI (beta -0.24, p = 0.054 and beta -0.13, p = 0.306; respectively). After adjustment for age, gender, and size of MC at baseline, change in the extent of M1 remained significantly positively associated with change in ODI (beta 0.53, p = 0.003). CONCLUSION: Change in the extent of M1 associated positively with changes in low back symptoms.

Genetic influences on hand osteoarthritis in Finnish women--a replication study of candidate genes.

OBJECTIVES: Our aims were to replicate some previously reported associations of single nucleotide polymorphisms (SNPs) in five genes (A2BP1, COG5, GDF5, HFE, ESR1) with hand osteoarthritis (OA), and to examine whether genes (BCAP29, DIO2, DUS4L, DVWA, HLA, PTGS2, PARD3B, TGFB1 and TRIB1) associated with OA at other joint sites were associated with hand OA among Finnish women. DESIGN: We examined the bilateral hand radiographs of 542 occupationally active Finnish female dentists and teachers aged 45 to 63 and classified them according to the presence of OA by using reference images. Data regarding finger joint pain and other risk factors were collected using a questionnaire. We defined two hand OA phenotypes: radiographic OA in at least three joints (ROA) and symptomatic DIP OA. The genotypes were determined by PCR-based methods. In statistical analysis, we used SNPStats software, the chi-square test and logistic regression. RESULTS: Of the SNPs, rs716508 in A2BP1 was associated with ROA (OR = 0.7, 95% CI 0.5-0.9) and rs1800470 in TGFB1 with symptomatic DIP OA (1.8, 1.2-2.9). We found an interaction between ESR1 (rs9340799) and occupation: teachers with the minor allele were at an increased risk of symptomatic DIP OA (2.8, 1.3-6.5). We saw no association among the dentists. We also found that the carriage of the COG5 rs3757713 C allele increased the risk of ROA only among women with the BCAP29 rs10953541 CC genotype (2.6; 1.1-6.1). There was also a suggestive interaction between the HFE rs179945 and the ESR1 rs9340799, and the carriage of the minor allele of either of these SNPs was associated with an increased risk of symptomatic DIP OA (2.1, 1.3-2.5). CONCLUSIONS: Our results support the earlier findings of A2BP1 and TBGF1 being OA susceptibility genes and provide evidence of a possible gene-gene interaction in the genetic influence on hand OA predisposition.

Quality of chest radiograph reports.

BACKGROUND: Examination requests and imaging reports are the most important communication instruments between clinicians and radiologists. An accurate and clear report helps referring physicians make care decisions for their patients. PURPOSE: To evaluate the contents of initial and re-reported chest reports, assess the inter-observer agreement, and evaluate the clarity of the report contents from the viewpoint of the referring physicians. MATERIAL AND METHODS: The content and agreement of the reports were analyzed by comparing the initial reports with re-reports prepared by a chest radiologist. The referring physicians evaluated the contents of 50 reports regarding their medical facts, clarity, and intelligibility. The results were analyzed using cross-over tables, the Pearson Chi-Square, and kappa statistics. RESULTS: Radiologists mostly addressed the questions posed by the referring physicians. General radiologists included separate conclusions in their reports more frequently (22%) than the chest radiologist in her re-reports. Reports prepared by the chest radiologist contained nearly 50% more findings than the general radiologists' reports. Inter-observer agreement between the initial and specialist re-reported reports was 66%, but the kappa value was 0.31. The reports were considered clear/intelligible by the referring physicians in 68% of the initial reports by the general radiologists and in 94% of the re-reported studies by the chest radiologist. CONCLUSION: Radiology report quality was rather high despite their contents varying depending on the radiologist. Inter-observer agreement of the chest radiographs was low due to the non-structured reports containing different quantities of information, thus complicating the comparison. Referring physicians considered both short and long radiology reports to be clear.

The relations of obesity indicators and early metabolic disturbance with upper extremity pain.

OBJECTIVES: To determine whether signs of metabolic disturbance and especially visceral obesity are associated with upper extremity pain. DESIGN: Cohort study. SUBJECTS: One hundred and seventy-seven workers (154 women, 23 men; age 20-64 years, mean 45) seeking medical advice in the occupational health service for incipient upper extremity disorders were included. MEASURES: Weight, height, waist circumference, and hip circumference were measured. Visceral and liver fat content and carotid artery intima-media thickness were estimated with ultrasound. Pain intensity and pain interference with sleep were assessed with visual analog scales at baseline and after 2, 8, 12, 52, and 104 weeks follow-up. Generalized estimating equation approach was used to analyze the repeated measures data. RESULTS: All obesity indicators were associated with both pain intensity and pain interference with sleep. Visceral fat thickness was the strongest predictor of pain intensity and pain interference with sleep. Carotid intima-media thickness was neither associated with pain intensity nor with pain interference with sleep. CONCLUSIONS: Visceral obesity seems to be a risk factor for upper extremity pain. Further studies are needed to elucidate the underlying mechanisms and to clarify whether weight loss can be helpful in pain management.

Modic type I change may predict rapid progressive, deforming disc degeneration: a prospective 1-year follow-up study.

INTRODUCTION: This prospective magnetic resonance imaging (MRI) study in chronic low-back pain (CLBP) patients evaluated the natural course of degenerative lumbar spine changes in relation to Modic 1 type changes (M1) within 1 year. MATERIALS AND METHODS: From 3,811 consecutive CLBP patients referred to lumbar spine MRI 54 patients with a large M1 were selected using strict exclusion criteria to exclude specific back disorders. Follow-up MRI was obtained within 11-18 months. RESULTS: At baseline M1 was associated with an adjacent endplate lesion in 96% of the cases. In follow-up, an unstable M1 was associated both with an increase of endplate lesions, decrease of disc height and change in disc signal intensity, most found at L4/5 or L5/S1. In disc spaces without M1, progression of degenerative changes was rare. CONCLUSION: Endplate deformation, decreasing disc height and change of disc signal intensity appear essential features of accelerated degenerative process associated with M1.

Correlation of size and type of modic types 1 and 2 lesions with clinical symptoms: a descriptive study in a subgroup of patients with chronic low back pain on the basis of a university hospital patient sample.

STUDY DESIGN: Intensity of pain and level of disability (Oswestry Disability Index [ODI]) were compared with the relative size of Modic type 1 (M1) and Modic type 2 (M2) lesions. Clinical symptoms of patients having mixed M1-M2 lesion (n = 49) were compared with patients having a "pure" M1 lesion (n = 13). OBJECTIVE: To determine the relation of the sizes of M1 and M2 lesions and the type of Modic lesion (mixed M1-M2 or pure M1 lesion) with intensity of low back pain and level of perceived disability. SUMMARY OF BACKGROUND DATA: Endplate signal abnormalities, particularly M1 changes indicating edema and inflammation, have been suggested to play an important role in the etiopathogenesis of a subgroup of patients with nonspecific chronic low back pain (CLBP). However, their association with clinical symptoms has not been studied in detail previously. METHODS: Sixty-two CLBP patients with a large M1 lesion were selected from CLBP patients who were sent for the first time for standard lumbar spine magnetic resonance imaging at a university hospital. To exclude other causes of CLBP, as far as possible, strict exclusion criteria were used: any specific back disease, even a slight nerve root compression, a recent or major spine operation, or age older than 65 years. The relative sizes of M1 and M2 lesions were visually estimated from sagittal images for comparison with clinical symptoms. RESULTS: The majority of patients (91.9%; 57 of 62) had an M1 lesion at a single level, 92% of the lesions being at L4-L5 or L5-S1 level. Forty-nine patients (79.0%) had a mixed M1-M2 lesion, and 13 (21.0%) had a pure M1 lesion. The mean of the pain intensity score was 6.2, and, correspondingly, the Oswestry Disability Index was 30.4. The mean relative sagittal area of the largest M1 lesion was 24.6% (SD = 16.2), and that of the M2 lesion was 10.9% (SD = 11.6). Neither the pain intensity nor the ODI scores were found to correlate with the largest relative size of the M1 lesion. The patients with "pure" M1 lesion had statistically significantly more clinical symptoms than patients having a mixed M1-M2 lesion. CONCLUSION: We conclude that the size of M1 lesion does not directly correlate with the clinical symptoms but that the type of Modic lesion is more important. This study supports the previous observations that when the inflammatory process turns to the mixed M1-M2 lesions, clinical symptoms decrease.

Major depressive disorder and white matter abnormalities: a diffusion tensor imaging study with tract-based spatial statistics.

BACKGROUND: A few diffusion tensor imaging (DTI) studies have shown abnormalities in areas of white matter tracts involved in mood regulation in geriatric depressive patients, using a region-of-interest technique. A voxel-based morphometry DTI study of young depressive patients reported similar results. In this study, we explored the structure of the white matter of the whole brain with DTI in middle-aged major depressive disorder (MDD) patients, using novel tract-based spatial statistics. METHODS: Sixteen MDD patients and 20 controls underwent DTI. An automated tract-based spatial method (TBSS) was used to analyze the scans. RESULTS: Compared with controls, the MDD patients showed a trend for lower values of fractional anisotropy (FA) in the left sagittal stratum, and suggestive decreased FA in the right cingulate cortex and posterior body of corpus callosum. Regressing out the duration and severity of disorder in the model did not change the finding in the sagittal stratum, but dissipated the decrease of FA in latter regions. LIMITATIONS: Possibly by reason of a relatively small study sample for a TBSS, the results are suggestive, and should be replicated in further studies. CONCLUSIONS: A novel observer-independent DTI method showed decreased FA in the middle-aged MDD patients in white matter regions that have previously connected to the emotional regulation. Lower FA might imply underlying structural abnormalities that contribute to the dysfunction detected in the limbic-cortical network of depressive patients.

Association between interleukin 1 gene cluster polymorphisms and bilateral distal interphalangeal osteoarthritis.

OBJECTIVE: To examine the association of the interleukin 1 gene (IL1) cluster polymorphisms and their haplotypes with bilateral distal interphalangeal joint osteoarthritis (DIP OA). METHODS: Radiographs of both hands of 295 dentists and 248 teachers were examined and classified for the presence of OA using reference images. Bilateral DIP OA was defined by the presence of radiographic findings of grade 2 or more in at least 1 symmetrical pair of the DIP joints. We genotyped 10 single-nucleotide polymorphisms (SNP) in the IL1R1, IL1RL2, IL1A, IL1B, and IL1RN genes using polymerase chain reaction-based methods. Haplotypes were statistically reconstructed using the PHASE program. The association between the genotypes/diplotypes and bilateral DIP OA was examined with logistic regression analysis. RESULTS: Two IL1B SNP (rs1143634 and rs1143633) were associated with bilateral DIP OA. The carriers of the IL1B rs1143634 minor allele had an increased OA risk [odds ratio (OR) 1.6; 95% confidence interval (CI) 1.08-2.26] compared to the noncarriers. The association was stronger in the dentists. The distribution of the IL1B rs1143633 genotype fit a recessive mode of inheritance (OR 3.03, 95% CI 1.35-6.83, p = 0.006). Two IL1B-IL1RN extended haplotype alleles (211-1 and 121-1) were associated with bilateral DIP OA. An interaction between the IL1B rs1143634 and the IL1R1-IL1RL2 and IL1B-IL1RN extended haplotypes and occupation (increased risk of OA among dentists only) was observed. CONCLUSION: Our results provide further evidence for the role of IL1 gene cluster polymorphisms in the etiology of OA and suggest that some of these may predispose DIP joints to the effects of mechanical overload.

Modic changes and interleukin 1 gene locus polymorphisms in occupational cohort of middle-aged men.

According to recent systematic reviews, Modic changes are associated with low-back pain. However, their pathophysiology remains largely unknown. A previous study of Northern Finnish males implicated that IL1A and MMP3 polymorphisms play a role in type II Modic changes. The purpose of the current study was to examine the association of IL1 cluster polymorphisms with Modic changes amongst middle-aged men in Southern Finland. The final study sample consisted of 108 men from three different occupations, who underwent magnetic resonance imaging (MRI) with a 0.1 T-scanner. Six single nucleotide polymorphisms (SNP) in the IL1 gene cluster (IL1A c.1-889C>T; IL1B c.3954C>T; IL1RN c.1812G>A; IL1RN c.1887G>C; IL1RN c.11100T>C; IL1RN c.1506G>A) were genotyped with the SNP-TRAP method or by allele-specific primer extension on modified microarray. In all, 45 subjects had Modic changes at one or more disc levels. The presence of the minor allele of IL1A (c.1-889C>T) was associated with these changes (any Modic change p = 0.031, type II changes p = 0.036). The carriers of the T-allele had a 2.5-fold risk of Modic change and the association was independent of the other IL1 gene cluster loci studied. In addition, a minor haplotype, with a frequency of 7.5% in the study population, including the minor alleles of IL1A c.1-889C>T, IL1RN c.1812G>A, and IL1RN c.1506G>A, was significantly associated with Modic changes. This observation is in accordance with the previous finding from a different geographical area, and thus confirms the importance of the IL1A gene in the pathophysiology of Modic changes.

Relationship of Modic type 1 change with disc degeneration: a prospective MRI study.

OBJECTIVE: The objective was to study the natural course of Modic type 1 change (M1) in relation to lumbar disc degeneration. MATERIALS AND METHODS: Twenty-four chronic low back pain (LBP) patients with M1 on lumbar spine were selected from 1,015 patients with magnetic resonance imaging from a follow-up study lasting for 18-74 months. Exclusion criteria were any other specific back disorder, age >or=60 years, or a recent spine operation. The association between the development of M1 and degenerative disc changes was studied using multivariate modeling (complex samples logistic regression). RESULTS: At baseline, 20 of 28 (71%) disc spaces with M1 had a decreased disc height (DH) and 16 of 28 (57%) a dark nucleus pulposus, but ten of 28 (36%) a very dark annulus fibrosus and a paradoxically bright nucleus pulposus albeit decreased DH. During follow-up, DH decreased in 13 of 28 (46%) and signal intensity of nucleus pulposus (DSI) in eight of 28 (29%) disc spaces with M1, but it increased in four (14%) discs. In those without M1, only few changes occurred. The larger the M1, the more likely was the DH low or decreased further. Both the presence and changes in M1 were associated with a decrease in DH and changes in DSI and bulges. CONCLUSION: The degenerative process in discs with adjacent M1 seems to be accelerated and leads to advanced and deforming changes with special morphologic features. M1 may be a sign of a pathologic degenerative process in the discovertebral unit.

MRI follow-up of subchondral signal abnormalities in a selected group of chronic low back pain patients.

Subchondral signal abnormalities have been suggested to play an important role in chronic low back pain (LBP) syndromes. Their natural course is not well known. In this study the morphology and natural course of isolated subchondral signal abnormalities in the lumbosacral spine were analyzed with MRI. Twenty-four chronic LBP patients with a subchondral hypointensity on T1-weighted image (hyperintense on T2), indicating edema, were selected from a base population of 1,015 consecutive LBP patients to a follow-up MRI study within 18-72 months. Exclusion criteria were age >60 years, nerve root compression, a more specific back disease or a recent or major spine operation. The size and location of each subchondral signal abnormality and endplate lesion and the degree of degenerative disc changes were evaluated and compared between the baseline and follow-up studies. Most subchondral hypointensities were found at the L4/L5 or L5/S1 disc space, anteriorly and in both adjacent endplates. Almost all (53/54) hypointensities were associated with an endplate lesion. Twelve of the 54 subchondral hypointensities enlarged, six remained constant and 36 decreased or disappeared while five new ones appeared. Twenty-two (41%) hypointensities changed totally to hyperintensities or to mixed lesions. If the hypointensity increased, decreased or changed into hyperintensity, a change tended to develop in the adjacent endplate. If the hypointensity was absent or unchanged, endplate lesions did not tend to progress. In the absence of disc herniation or other specific spinal disease, subchondral hypointensities indicating edema are uncommon. They seem to have a highly variable course. There appears to be a link between endplate lesions and subchondral signal abnormalities. Further study is needed to explain the contribution of these findings to low back symptoms.

Common interleukin-6 promoter variants associate with the more severe forms of distal interphalangeal osteoarthritis.

INTRODUCTION: The objective of this study was to investigate the relationship of the IL-6 promoter variants G-597A, G-572C and G-174C (rs1800797, rs1800796 and rs1800795, respectively), which have been shown to affect both the transcription and secretion of IL-6, to symptomatic distal interphalangeal (DIP) osteoarthritis (OA). METHODS: A total of 535 women aged 45 to 63 years were included. Radiographs of both hands were taken and each DIP joint was evaluated (grade 0 to 4) for the presence of OA. Information on symptoms (pain, tenderness) in each joint was collected by using a self-administered questionnaire. Symptomatic DIP OA was defined by the presence of both radiographic findings of grade 2 or more and symptoms in at least two DIP joints, and symmetrical DIP OA by the presence of radiographic findings of grade 2 or more in at least one symmetrical pair of DIP joints. Common polymorphic loci in the IL-6 gene were amplified and the promoter haplotypes were reconstructed from genotype data with the PHASE program. Logistic regression analysis was used to examine the association between the IL-6 genotypes/diplotypes and the DIP OA outcome. RESULTS: The G alleles of two promoter single nucleotide polymorphisms (SNPs) G-597A and G-174C were more common among the subjects with symptomatic DIP OA than among those with no disease (P = 0.020 and 0.024, corrected for multiple testing). In addition, the carriage of at least one G allele in these positions increased the risk of disease (P = 0.006 and P = 0.008, respectively). Carrying a haplotype with the G allele in all three promoter SNPs increased the risk of symptomatic DIP OA more than fourfold (odds ratio (OR) 4.45, P = 0.001). Carriage of the G-G diplotype indicated an increased risk of both symmetrical DIP OA (OR 1.52, 95% confidence interval 1.01 to 2.28) and symptomatic DIP OA (OR 3.67, 95% confidence interval 1.50 to 9.00). CONCLUSION: The present study showed that the presence of G alleles at common IL-6 polymorphic promoter loci was associated with the more severe DIP OA outcomes, symmetrical and symptomatic.

Association between the aggrecan gene variable number of tandem repeats polymorphism and intervertebral disc degeneration.

STUDY DESIGN: Cross-sectional study. OBJECTIVE: To examine the association between an aggrecan variable number of tandem repeats (VNTR) polymorphism and intervertebral disc degeneration in middle-aged Finnish men. SUMMARY OF BACKGROUND DATA: An association between the aggrecan VNTR polymorphism and multilevel disc degeneration has been previously reported in young Japanese women. METHODS: Lumbar discs of 132 men representing 3 occupations (carpenters, machine drivers, and office workers) were evaluated on magnetic resonance imaging, using decreased signal intensity of the nucleus pulposus, disc bulges, and decreased disc height as signs of degeneration. The aggrecan gene VNTR region was analyzed by Southern hybridization. RESULTS: The allele A26 with 26 repeats was statistically significantly overrepresented among the persons with dark nucleus pulposus. Carrying 2 copies of the A26 allele increased the risk of dark nucleus pulposus (odds ratio = 2.77; 95% confidence interval, 1.24-6.16). Carrying the alleles with either less or more than 26 repeats decreased the risk of dark nucleus pulposus. The carpenters and machine drivers with the A26 allele had a statistically significantly higher risk of disc bulge and decreased disc height than the office workers without the allele. CONCLUSION: The findings provide additional support for the role of the aggrecan gene VNTR polymorphism in intervertebral disc degeneration.

Vitamin D receptor gene polymorphisms and susceptibility of hand osteoarthritis in Finnish women.

We examined whether polymorphisms of the vitamin D receptor (VDR) gene was associated with individual risk of hand osteoarthritis (OA). Radiographs of both hands of 295 dentists and of 248 teachers were examined and classified for the presence of OA using reference images. The VDR ApaI and TaqI genotypes were determined by PCR-based methods. No association was observed between the VDR polymorphisms and the odds of overall hand OA. However, the carriers of the VDR t allele or At haplotype were at almost half the odds of symmetrical hand OA (odds ratio [OR] = 0.60, 95% confidence interval [CI] = 0.38-0.94 and OR = 0.59, 95% CI = 0.38-0.93, respectively) compared with the carriers of the T allele and of the non-At haplotype, respectively. Increased odds of this disease, on the contrary, was observed for women with two copies of the VDR a allele (OR = 1.93, 95% CI = 1.99-3.70) compared with women with the AA genotype. Conversely, the VDR a allele carriage was associated with a tendency of lowered odds of osteophyte (OR = 0.51, 95% CI = 0.25-1.03). When the genotype data were used to construct haplotypes, the VDR AaTt joint genotype appeared to pose a remarkably lower odds (OR = 0.26, 95% CI = 0.08-0.91) of osteophyte compared with the AAtt joint genotype. As a novel finding we observed a joint effect of a low calcium intake and VDR polymorphisms on symmetrical OA; the OR was 2.64 (95% CI = 1.29-5.40) for carriers of the aT haplotype with low daily calcium intake compared with non-carriers of the haplotype with high daily calcium intake. Our results suggest that VDR gene polymorphisms play a role in the etiology of symmetrical hand OA. Moreover, the association between the VDR gene and OA may be modified by calcium intake.

Intervertebral disc degeneration in relation to the COL9A3 and the IL-1ss gene polymorphisms.

Disc degeneration is a complex condition in which environmental factors and multiple genes are expected to act together to determine the degenerative phenotype. Recently associations of COL9A2 (Trp2 allele) and COL9A3 (Trp3 allele) polymorphisms with lumbar disc disease characterized by sciatica have been reported. However, it is not known whether the Trp2 or Trp3 alleles contribute to disc degeneration (DD). In this study, the association between the collagen genes polymorphisms and lumbar DD was investigated. Furthermore, the influence of the IL-1beta(C(3954)-T) polymorphism on the association of collagen genes polymorphisms with DD was examined. Lumbar intervertebral discs of 135 middle-aged occupationally active men were evaluated with magnetic resonance imaging, using decreased signal intensity of the nucleus pulposus, disc bulges, and decreased disc height as signs of degeneration. Blood samples were analysed for the presence of COL9A3 and COL9A2 tryptophan alleles (Trp3 and Trp2 alleles). The COL11A2, COL2A1 and IL-1beta(C(3954)-T) polymorphisms were also analysed. Multivariate logistic regression analysis allowing for occupation and body mass index showed that the carriage of the Trp3 allele in the absence of the IL-1betaT(3954) allele increased the risk of dark nucleus pulposus (OR 7.0, 95% CI 1.3-38.8) and joint occurrence of degenerative changes (OR 8.0, 95% CI 1.4-44.7). There was no effect of the Trp3 allele on DD in the presence of the IL-1betaT(3954) allele. The carriers of the COL11A2 minor allele had an increased risk of disc bulges (OR 2.1, 95% CI 1.0-4.2) as compared with non-carriers. The results suggest that the effect of the COL9A3 gene polymorphism on DD might be modified by the IL-1beta gene polymorphism.