Katariina Luoma

Low back pain in relation to lumbar disc degeneration

STUDY DESIGN Cross-sectional magnetic resonance imaging (MRI) study. OBJECTIVES To study the relation of low back pain (LBP) to disc degeneration in the lumbar spine. BACKGROUND DATA Controversy still prevails about the relationship between disc degeneration and LBP. Classification of disc degeneration and symptoms varies, hampering comparison of study results. METHODS Subjects comprised 164 men aged 40-45 years-53 machine drivers, 51 construction carpenters, and 60 office workers. The data of different types of LBP, individual characteristics, and lifestyle factors were obtained from a questionnaire and a structured interview. Degeneration of discs L2/L3-L5/S1 (dark nucleus pulposus and posterior and anterior bulge) was assessed with MRI. RESULTS An increased risk of LBP (including all types) was found in relation to all signs of disc degeneration. An increased risk of sciatic pain was found in relation to posterior bulges, but local LBP was not related to disc degeneration. The risks of LBP and sciatic pain were strongly affected by occupation. CONCLUSIONS Low back pain is associated with signs of disc degeneration and sciatic pain with posterior disc bulges. Low back pain is strongly associated with occupation.

Possible association of interleukin 1 gene locus polymorphisms with low back pain

&NA; Based on a hypothesis that interleukin 1 (IL‐1) activity is associated with low back pain (LBP), we investigated relationships between previously described functional IL‐1 gene polymorphisms and LBP. The subjects were a subgroup of a Finnish study cohort. The IL‐1&agr;(C889–T), IL‐1&bgr;(C3954–T) and IL‐1 receptor antagonist (IL‐1RN)(G1812–A, G1887–C and T11100–C) polymorphisms were genotyped in 131 middle‐aged men from three occupational groups (machine drivers, carpenters and office workers). A questionnaire inquired about individual and lifestyle characteristics and the occurrence of LBP, the number of days with pain and days with limitation of daily activities because of pain, and pain intensity, during the past 12 months. Lumbar disc degeneration was determined with magnetic resonance imaging. Carriers of the IL‐1RNA1812 allele had an increased risk of LBP (OR 2.5, 95% CI 1.0–6.0) and carriers of this allele in combination with the IL‐1&agr;T889 or IL‐1&bgr;T3954 allele had a higher risk of and more days with LBP than non‐carriers. Pain intensity was associated with the simultaneous carriage of the IL‐1&agr;T889 and IL‐1RNA1812 alleles (OR 3.7, 95% CI 1.2–11.9). Multiple regression analyses allowing for occupation and disc degeneration showed that carriage of the IL‐1RNA1812 allele was associated with the occurrence of pain, the number of days with pain and days with limitations of daily activities. Carriage of the IL‐1&bgr;T3954 allele was associated with the number of days with pain. The results suggest a possible contribution of the IL‐1 gene locus polymorphisms to the pathogenesis of LBP. The possibility of chance findings cannot be excluded due to the small sample size.

Interleukin 1 polymorphisms and intervertebral disc degeneration.

Background: Enzymatic breakdown of the extracellular matrix, and possibly local inflammation, contributes to intervertebral disc degeneration. We investigated whether polymorphisms within the IL-1 gene locus are associated with lumbar disc degeneration and whether the effect of occupational physical load on disc degeneration is modified by the polymorphisms. Methods: Genotypes were determined from 133 middle-aged men who underwent magnetic resonance imaging of the lumbar spine. The participants represented 3 occupations: 40 were machine drivers, 42 carpenters, and 51 office workers. We evaluated decreased signal intensity of the nucleus pulposus, disc bulges, and decreased disc height as signs of degeneration in the L2/L3–L5/S1 discs. Results: The odds ratio for disc bulges was 2.4 (95% confidence interval = 1.2– 4.8) and 1.9 (1.0–3.7), in carriers of the IL-1αT889 or IL-1βT3954 alleles, respectively. The TT genotype of the IL-1α gene carried more than 3-fold risk of disc bulges as compared with the CC genotype. Conclusions: IL-1 gene cluster polymorphisms could affect the risk of disc degeneration. The effect of physical workload seems to be modified by the IL-1 gene polymorphisms.

Disc height and signal intensity of the nucleus pulposus on magnetic resonance imaging as indicators of lumbar disc degeneration.

Study Design. A cross-sectional magnetic resonance imaging (MRI) study of degeneration of the lumbar spine. Objectives. To compare the usefulness of disc height and that of T2-weighted signal intensity as indicators of disc degeneration. Summary of Background Data. Disc height and signal intensity have been used as indicators for disc degeneration. Their relation to each other and to early degeneration has not been well documented. There is evidence that physical load can affect disc height. Methods. Forty-one machine operators, 41 construction carpenters, and 46 office workers, aged 40–45 years, and 22 students aged 18–20 years were examined with sagittal magnetic resonance imaging. All study participants were men. The mean value of the anterior and posterior disc height and the relative T2-weighted signal intensity of the nucleus pulposus of discs L2–L3 to L5–S1 were measured. Results. Young men showed the lowest disc height but the highest relative signal intensity. Disc height showed an increasing trend from the office workers (sedentary) to blue-collar workers (more physical work) at all disc levels but L5–S1. Relative signal intensity showed a decreasing trend for these same worker types at all levels. In generalized linear modeling, signal intensity and the occupations, in reference to the young students, showed a significant effect on disc height. Conclusions. Relative signal intensity was lower in the middle-aged men than in the young men, indicating age-related disc degeneration. Despite the general positive association between disc narrowing and decreased relative signal intensity, disc narrowing may behave unexpectedly in relation to signal intensity and age. Signal intensity may be a more sensitive measure of disc degeneration. The validity of disc height as an indicator of early degeneration seems questionable.

Lumbosacral transitional vertebra: relation to disc degeneration and low back pain.

Study Design. Cross-sectional magnetic-resonance imaging (MRI) study. Objective. To investigate the relation of the lumbosacral transitional vertebra to signs of disc degeneration in MRI and to low back pain (LBP). Summary of Background Data. An association between the transitional vertebra and herniation in the disc above has been found in patients with LBP, but knowledge of the relation to other degenerative disc changes detected in MRI and to LBP is lacking. Methods. MR images of the lumbar spine of 138 middle-aged working men and 25 healthy young men were evaluated. The presence and type of lumbosacral transitional vertebra and of degenerative changes in intervertebral discs were evaluated. The history of low back symptoms was obtained with a questionnaire from the middle-aged men. Results. The prevalence of transitional vertebra was 30%. Transitional vertebra was associated with an increased risk of degenerative changes in the disc above among the young men and with a decreased risk in the disc below among the middle-aged men. Transitional vertebra, symmetric or asymmetric, was not associated with any type of LBP in the middle-aged men. Conclusions. Lumbosacral transitional vertebra increases the risk of early degeneration in the upper disc. This effect seems to be obscured by age-related changes in the middle age. The degenerative process is slowed down in the lower disc. For these effects, the presence of a transitional vertebra should be noticed when morphologic methods are used in research on lumbosacral spine. Transitional vertebra is not associated with any type of LBP.

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-1β(C3954-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-1β(C3954-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-1βT3954 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-1βT3954 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-1β gene polymorphism.

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.

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

IntroductionThe 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).MethodsA 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.ResultsThe 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).ConclusionThe 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 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.

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.