Seminars in Arthritis and Rheumatism ] (2015) ]]]–]]]

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Seminars in Arthritis and Rheumatism journal homepage: www.elsevier.com/locate/semarthrit

The association between lumbar spine radiographic features and low back pain: A systematic review and meta-analysis Joachim Raastad, PT, MSca, Michael Reiman, PT, DPTb, Remy Coeytaux, MD, PhDc, Leila Ledbetter, MLISd, Adam P. Goode, PT, DPT, PhDb,n a

Bergen University College, Bergen, Norway Department of Orthopedic Surgery, Duke University, Durham, NC c Department of Community and Family Medicine, Duke University, Durham, NC d Medical Center Library, Duke University, Durham, NC b

a r t i c l e in fo

Keywords: Low back pain; Radiographic features; Plain film radiography; Systematic review; Meta-analysis

a b s t r a c t Background/purpose: Low back pain (LBP) is a prevalent musculoskeletal condition and represents a substantial socioeconomic burden. Plain film radiography is a commonly used imaging technique. Radiographic features (RFs) such as disc space narrowing, osteophytes, spondylosis, endplate sclerosis, spondylolisthesis, and facet joint osteoarthritis have all been debated as potential pain generators in the lumbar spine. The aim of this study is to (1) determine the association between LBP and lumbar spine RFs in both community- and occupation-based groups and (2) to determine if there are differences in these associations between these two groups. Methods: A systematic electronic search of PubMed, EMBASE, CINAHL, and Cochrane was conducted with keywords related to LBP and lumbar spine RFs. The search was restricted from inception of each respective database to April 2014. Inclusion criteria consisted of observational studies of adults ( Z18 years) with and without nonspecific LBP. Studies were excluded if they investigated LBP related to infection, malignancy, or rheumatologic nature or were conducted in cadavers. Quality assessment was conducted with the Item Bank for Assessment of Risk of Bias and Precision for Observational Studies of Interventions or Exposures. Random effect models were used for all pooled analyses with associations represented by odds ratios (OR) and 95% confidence intervals (95% CIs). Statistical heterogeneity was assessed with I2, with significant heterogeneity represented as 4 50%. Results: Overall, 28 (22 community-based and six occupation-based) studies met the eligibility criteria consisting of 26,107 subjects. A significant, positive association was found between disc space narrowing and LBP, which did not differ (p ¼ 0.22) in both community- and occupation-based studies [OR ¼ 1.47 (95% CI: 1.36–1.58)] and [OR ¼ 1.76 (95% CI: 1.34–2.33)], respectively. No significant statistical heterogeneity was present in either estimate (I2 ¼ 0.0%). A significant association was found between spondylolisthesis and LBP in occupation-based studies [OR ¼ 2.21 (95% CI: 1.44–3.39)] that differed significantly (p o 0.01) from community-based studies [OR ¼ 1.12 (95% CI: 1.03–1.23)]. These individual estimates were also homogeneous (I2 ¼ 0.0%). The association between other radiographic features was modest (i.e., spondylosis and osteophytes) or non-significant (i.e., endplate sclerosis and facet joint). Quality of included studies varied, with the majority demonstrating good quality. Conclusion: A significant association was found between disc space narrowing in both community- and occupational-based populations without significant differences between the associations. A significant strong association was found between spondylolisthesis and LBP among the occupational group but was weakly associated in the community-based group, which supports that spondylolisthesis may contribute a specific cause for LBP. & 2015 Elsevier Inc. All rights reserved.

Contributions: Joachim S. Raastad, Adam P. Goode, Michael P. Reiman, Leila Ledbetter, and Remy Coeytaux planned, conducted, and reported the work presented in this article. Joachim S. Raastad had access to all the data and conducted the statistical analysis with Adam P. Goode. n Correspondence to: 2200 W Main St, Durham, NC 27705. E-mail address: [email protected]. http://dx.doi.org/10.1016/j.semarthrit.2014.10.006 0049-0172/& 2015 Elsevier Inc. All rights reserved.

Introduction Low back pain (LBP) is one of the most common musculoskeletal problems worldwide, with lifetime prevalence estimates as high as 84% [1,2]. LBP presents a substantial burden on the total

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costs of LBP exceeding those of coronary artery disease, and the combined cost of diabetes, stroke, respiratory infection, and rheumatoid diseases [3,4]. Furthermore, it has been reported that approximately 80%, 30%, and 10% of outpatient visits for chiropractor, physical therapy, and general practitioner services, respectively, are for LBP [5]. The prevalence of LBP in community- and occupation-based populations varies across the literature [6–8]. Occupational or physical demands might influence different radiographic features differently. Twin studies have found that the physical demands of different occupations did not influence the degree of disc space narrowing, indicating that disc space narrowing is likely influenced by genetics [9]. The physical demands of different occupations or sports have a relatively minor role in disc space narrowing and that the degree of disc space narrowing is more influenced by genetics or the natural degeneration of the disc that occurs with aging [10]. The literature investigating spondylolisthesis is more ambiguous, but there are indications that spondylolisthesis is more influenced by occupational demands [11,12]. Despite this, LBP is thought to be associated with flexing, bending, and awkward positions of the lumbar spine, which are common occupational demands in many occupations [8]. The association between LBP and degenerative changes in the lumbar spine is complex and varies by plain film radiographic feature. Disc space narrowing has been consistently associated with LBP in population-based studies [13–15]. However, vertebral osteophytes [14], endplate sclerosis [14], spondylolisthesis [16], and facet joint osteoarthritis [13] have all been debated as a source of LBP. Challenges in case definitions of LBP and differences in populations studied (i.e., community-based or occupationalbased) further create challenges to understanding this complex relationship. One previous systematic review conducted in 1997 on plain film radiographic features by van Tulder et al. [17] found that there was no firm evidence for the presence or absence of a causal relationship between radiographic findings and nonspecific LBP. There are several reasons to better understand the relationship between LBP and radiographic findings of degeneration in the lumbar spine. First, the prevalence of chronic LBP is rising and is associated with decreased physical function [18]. Second, plain film radiographgy is commonly used in clinical practice because it is relatively inexpensive and easily administered [19,20]. For these and other reasons, there has been a steady rise in the usage of plain film radiography for patients seeking care for LBP [21]. Lastly, the utilization of surgical, pharmacological, and physical treatments associated with the management of some of these degenerative changes is rising [22]. The aims of this systematic review and meta-analysis are (1) to determine the association between radiographic features (e.g., disc space narrowing, osteophytes, spondylosis, spondylolisthesis, endplate sclerosis, and facet joint osteoarthritis) of the lumbar spine and LBP, as assessed with plain film radiography in both communityand occupation-based populations, and (2) to identify potential differences in the association between specific radiographic findings and LBP between community- and occupation-based populations.

Search strategy A systematic, computerized search of the literature in PubMed, Cumulative Index to Nursing and Allied Health [24], Excerpta Medica (EMBASE), and The Cochrane Library (Cochrane) was conducted by a research and medical librarian (L.L.), who did not participate in aspects of screening, full-text review, or data abstraction, with the primary author (J.R.). The search was conducted with controlled vocabulary and keywords related to LBP and spine radiographic features. Keywords from the search were logically combined using the Boolean operators “OR” and “AND.” Our search time-frame was restricted from inception of each respective database to April 2014. The PubMed search strategy can be found in Appendix A. Subject headings and filters were modified to accommodate the different controlled vocabularies and methods of each database. A standardized filter for systematic reviews was applied only to the PubMed search. The filter focused the search to study types of interest for this review and removed publication types that failed to meet our inclusion criteria, such as editorials or letters to the editors. Filters were not applied when searching EMBASE, CINAHL, and Cochrane. For EMBASE, a filter was not applied since this database encompasses the Medline records found in PubMed. For CINAHL and Cochrane, a filter was not added due to the limited number of results yielded in the non-filtered searches. No restrictions to sample size or country of origin were made during the search. We did not search for or included studies that were not published in the peer-reviewed literature. Selection criteria Studies were included if (1) they consisted of adult subjects ( Z18 years); (2) they assessed radiographic vertebral disc space narrowing, spondylosis, spondylolisthesis, endplate sclerosis, osteophytes, or facet joint osteoarthritis of the lumbar spine among subjects with and without LBP; and (3) the study design was that of a cohort, case–control, or cross-sectional study. Longitudinal studies were included if the study question determined if degenerative radiographic features detected by plain film radiography predicted LBP. Exclusion criteria were as follows: (1) non-human or cadaver studies; (2) case reports, case series, posters, abstracts, or editorial letters; or (3) the etiology of LBP being from secondary causes (e.g., infections, inflammations, osteoporosis, or fractures). Identification and selection of literature Two independent reviewers (J.R. and A.P.G.) performed the title, abstract, and full-text screening for potential eligible studies. Titles and abstracts were retained for full-text review if one or both of the authors identified the study as being potentially eligible. Studies were ultimately included in this systematic review if they were determined by both authors to meet all of the eligibility criteria. Disagreements during full-text inclusion were resolved by discussion between the two authors until consensus agreement. EndNote 7.0 [25] was used to conduct all aspects of the title, abstract, and full-text review. Quality assessment

Materials and methods This systematic review and meta-analysis follows the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. The PRISMA guidelines include a 27-item checklist to guide the process of conducting systematic reviews and metaanalyses [23].

The Item Bank for Assessment of Risk of Bias and Precision for Observational Studies of Interventions or Exposures (IBARBPOSIE) was used to assess the methodological quality of each included full-text article [26]. This assessment tool, which contains 29 items answered as “yes” or “no” and “partial” or “unclear,” has been validated to assess the risk of bias and precision in observational

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studies [26]. Of the original 29 questions, questions 1, 8–12, 26, and 27 were deemed not applicable, due to assessment of potential harms and interventions, to this review and research question by two authors (J.R. and A.P.G.), and were removed before the assessment. These questions represented selection, reporting, and other biases. Each of the remaining 21 questions was discussed for applicability to each study design (i.e., cross-sectional, case–control, or cohort) by two authors (J.R. and A.P.G.). Questions 4–6, 16–20, and 23 were deemed not relevant to nonintervention observational cross-sectional designs and were removed. All of the remaining 21 questions were used when assessing cohort studies. All questions except questions 18, 19, and 23 were applied to case– control studies. These questions were not applied to case–control studies because of low applicability to the studies’ design. The questions and applicability of questions to different study designs in the IBARBPOSIE are presented in Appendix B. Questions that could not be answered with a “yes” or “no” were modified by changing the syntax or categorizing the answers “unclear,” “partially,” and “medium” as a “no,” as recommended by the authors. Results were categorized into five different groups according to what type of major bias they assessed [i.e., Selection, Information, Confounding, Reporting, and Other (precision bias, performance bias, study descriptors, and overall study quality)]. Scoring was conducted by assigning 1 point for each question that could be answered with a “yes.” The total possible score for crosssectional studies was 12 points, 18 points for case–control studies, and 21 for cohort studies. One reviewer (J.R.) assessed the study quality of all of the included full-text articles. A second reviewer (M.P.R.) then verified the results of the quality assessment. Disagreements or unclarities were resolved with discussions between the two reviewers until consensus was achieved. Data extraction Data were extracted individually for community- and occupation-based populations. The frequency, counts, 95% confidence intervals (95% CI), categorization grade of radiographic features, and odds ratios (OR) were extracted from the studies. If the studies reported the adjusted and unadjusted OR, it was extracted. If the adjusted or unadjusted OR was not reported, an unadjusted OR was calculated from the provided counts and proportions. If studies reported results for several categorization grades of radiographic features, the results for the most comparable categorization were chosen to make consistent comparisons between studies. If relevant data were not reported, the authors were contacted via e-mail and counts and proportions were requested so that an unadjusted OR could be calculated. Statistical analysis DerSimonian and Laird [27] random effects models were used for all pooled analyses, which incorporate both between- and within-study heterogeneity, to produce summary pooled odds ratios (ORs) and 95% confidence intervals (CI). Heterogeneity test statistics and their p values were used to assess consistency of reported ORs across studies. I-squared statistic (I2) was used to describe the percentage of total variation across studies due to heterogeneity rather than chance alone, with values of 450% defined as indicating substantial heterogeneity [28]. Significant heterogeneity was indicated with a p o 0.05. Differences in the pooled estimates for each radiographic feature were determined across community-based and occupation-based populations with tests for homogeneity of pooled ORs. Odds ratios with a difference in effects of p o 0.05 were considered to be independent of one another. We conducted sub-group analyses to determine if there

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were significant differences in associations between adjusted and unadjusted pooled estimates as well as by study design (i.e., crosssectional or case–control designs), each within specific radiographic feature. We initially planned to analyze pooled estimates by groups of participant age and gender in the presence of significant heterogeneity and 4 4 studies. However, due to low heterogeneity as well as limitations in the number of studies for some radiographic features, we were unable to stratify by these two factors. Precision of individual and overall pooled study estimates was determined with a confidence limit ratio (CLR). This ratio is the upper confidence limit divided by the lower confidence limit, with results closer to “1” indicating greater relative precision [29]. Publication bias was assessed with funnel plots and Eggers test statistics when 10 or more studies (i.e., disc space narrowing) were included in the meta-analysis. Due to low statistical power of publication bias testing, we did not formally test publication bias when less than 10 studies were included [30]. All analyses were conducted in Stata 12.0 (College Station, TX) [31].

Results Search and selection of studies Our search revealed 2508 unique titles that were identified through database, reference, and hand searches. Overall, 145 abstracts were screened and 66 full-texts were assessed for eligibility for inclusion. Moreover, 43 articles were excluded after full-text review (21 due to ineligible study design, three due to not relevant radiographic features, two due to being cadaver studies, four due to not using plain film radiography, and 13 for other reasons), resulting in 28 studies (N ¼ 26,107 subjects from 12 countries and four continents) included in the systematic review and meta-analysis (Fig. 1). Tables 1 and 2 describe the included patient populations, LBP definition, radiographic features, and outcomes for communitybased and occupational-based populations, respectively. Of the 28 studies, 22 were community-based, including 22,925 subjects; 56% were female, the mean age ranged from 38.7 years to 74.7 years, and the mean body mass index (BMI) ranged from 23.0 to 30.4 [14–16,32–50]. The most frequent study design was cross-sectional (N ¼ 18), followed by case–control (N ¼ 2) and cohort (N ¼ 1). The most frequently investigated radiographic finding was disc space narrowing (N ¼ 14), while facet joint osteoarthritis was the least studied (N ¼ 2). Six studies were occupation-based, including 3182 male subjects (no females were included in these studies) [51–56]. The mean weight ranged from 67.4 to 77.3 kg, and the mean age ranged from 18 to 42 years. Cross-sectional designs were also the most frequent among occupation-based studies (N ¼ 5) followed by cohort (N ¼ 1). Disc space narrowing was also the most frequently investigated radiographic feature (N ¼ 4), and osteophytes and endplate sclerosis were least frequently investigated (N ¼ 2). Table 3 describes the counts, proportions, adjusted odd ratios (aORs) and unadjusted odds ratios (uORs), 95% CI, and categorization grade of radiographic feature for each included communitybased study. A higher proportion of subjects with disc space narrowing, spondylosis, or osteophytes also reported LBP. However, for endplate sclerosis, the proportions were varying. Only one set of data was available for facet joint osteoarthritis, which showed that over half the proportion of subjects with facet joint osteoarthritis had LBP. The categorization for all the radiographic features varied greatly. The majority of studies categorized disc space narrowing as absent with a grade 0 and a grade 1–3 as disc space narrowing being present. For both osteophytes and spondylosis, the most commonly used grade for absent was 0–1 and grade

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Fig. 1. Flow diagram showing selection process of studies.

2–3 as present. The majority of studies investigating spondylolisthesis categorized o 3 mm of disc slippage as absent and 4 3 mm of disc slippage as being present. All three of the studies investigating endplate sclerosis utilized a different categorization grade. Similar findings can be found in studies investigating facet joint osteoarthritis. The aOR for the community-based populations for disc space narrowing ranged from 1.23 (95% CI: 1.02–1.50) to 1.71 (95% CI: 1.28–2.28) [34,45]. Osteophyte associations ranged from an aOR of 1.10 (95% CI: 0.80–1.60) to 1.53 (95% CI: 1.22–1.92) [14,34]. For spondylolisthesis, the aOR varied from 0.82 (95% CI: 0.49–1.37) to 1.12 (95% CI: 0.61–2.05) [16,37]. Spondylosis associations ranged from an aOR of 1.09 (95% CI: 0.74–1.61) to 1.80 (95% CI: 1.38–2.37) [34,42]. Endplate sclerosis associations varied from an aOR of 1.00 (95% CI: 0.70–1.40) to 1.03 (95% CI: 0.81–1.31) [14,34]. Facet joint osteoarthritis associations ranged between an aOR of 0.84 (95% CI: 0.61–1.15) and 1.44 (95% CI: 0.89–2.33) [36,47]. Table 4 describes the counts, proportions, aORs and uORs, 95% CI, and categorization grade of radiographic features for each included occupation-based study. Similar to community-based populations, a higher proportion of subjects with disc space narrowing, osteophytes, and spondylolisthesis reported the presence of LBP. A low proportion of the subjects with LBP had endplate sclerosis. Also, similar to community-based populations, the categorization grade of radiographic features in the occupation-based populations varied greatly. The majority of occupation-based populations categorized disc space narrowing as absent with grade 0 and being present with grade 1–3. There were two different studies that used two different categorization grades for osteophytes, one using grades and one using size to determine the radiographic presence or absence of osteophytes.

Of the three studies that investigated spondylolisthesis, only one reported the categorization grade, which was graded present according to the ratio of vertebral slip percentage. There were two different categorization grades for endplate sclerosis, one being absent with a grade 0 and present with a grade 1–3, and the other study defined a present with an irregular appearance of the endplate with thinning or focal loss of visualization of the subchondral cortical plate. None of the occupation-based populations reported an aOR. The occupation-based populations’ unadjusted association for disc space narrowing ranged from a uOR of 1.23 (95% CI: 0.48–3.15) to 2.47 (95% CI: 1.10–5.56) [52,55]. The uOR of osteophytes ranged from 1.38 (95% CI: 0.94–2.05) to 3.00 (95% CI: 1.23–7.33) [52,53]. Spondylolisthesis associations ranged from a uOR of 1.54 (95% CI: 0.60–3.95) to 2.43 (95% CI: 1.40–4.22) [51,56]. The results for endplate sclerosis showed a uOR of 1.11 (95% CI: 0.73–1.67) to 1.23 (95% CI: 0.50–3.03) [53,54]. No occupation-based populations were identified that investigated the association between LBP and spondylosis or facet joint osteoarthritis. Meta-analysis Figure 2 illustrates the pooled estimates, number of studies in each analysis, and heterogeneity statistics (I2 and Q p value) of each radiographic feature for both community-based and occupation-based populations. For community-based populations (Fig. 2, blue squares), the overall pooled estimate for disc space narrowing was 1.47 (95% CI: 1.36–1.58, CLR ¼ 1.16) without significant heterogeneity (I2 ¼ 0.0%, p ¼ 0.448). No evidence of publication bias was present with an Eggers Test (p ¼ 0.82). Similar associations were noted in overall pooled estimates and

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Table 1 Summary of community-based studies included in the review Study

Study population

RF LBP definition investigated

Cross-sectional studies BieringN ¼ 666, mean age ¼ 60 years; N men ¼ DNS Sørensen 360 (54%), N females ¼ 306 (46%); N LBP ¼ LIS LOS [32] 358(53.8%) from Denmark.

Chaiwanichsiri et al. [33]

N ¼ 792; N men ¼ 306 (38.6%), mean BMI ¼ LOS 23.63, mean age 61.39 years; N female ¼ LIS 486 (61.4%), mean BMI ¼ 26.03, mean age 60.88 years; N LBP ¼ 97 (12.2%) from Thailand.

Cho et al. [34]

N ¼ 4181; N men ¼ 1861 (44.5%), mean age ¼ 55.7 years, mean BMI ¼ 23.9; female ¼ 2320 (55.5%), mean age ¼ 57.2 years, mean BMI ¼ 24.6; N available radiograph ¼ 1772, N point prevalence LBP men ¼ 443 (23.8%) and female ¼ 955(41.2%), from Korea.

de Schepper et al. [15]

N ¼ 2819; N men ¼ 1204 (42.7%), mean age DSN ¼ 65.3 years, mean BMI ¼ 25.9, N LBP ¼ OST 173 (14.4%); N female ¼ 1615 (57.3%), mean age ¼ 65.9 years, mean BMI ¼ 26.6; N LBP ¼ 326 (20.2%) from the Netherlands.

Denard et al. [16]

N total ¼ 295 men, mean age ¼ 74 years, mean height ¼ 174 cm, mean BMI ¼ 28, 90% Caucasian, from USA.

LOS OST EPS DSN

LIS

Frymoyer et al. N total ¼ 292 men, age ¼ 18–55 years, N no DSN L3–S1 [35] LBP ¼ 96 (32.9%), N moderate LBP ¼ 134 OST (45.9%), N severe LBP ¼ 62(21.2%), N LBP both moderate and severe ¼ 196 (67.1%), from USA.

N ¼ 840; N men ¼ 317 (37.7%), mean age ¼ 60.1 years; N female ¼ 523 (62.3%), mean age ¼ 62.7 years; 37.6% African American, mean BMI men and women¼ 30.4, from USA. He et al. [48] N ¼ 4000, 2000 men (50%), mean age ¼ 72.4 years, N LBP ¼ 612 (30.6%) and 2000 women (50%), mean age ¼ 72.6 years, N LBP ¼ 1063(53%), from China. Horikawa et al. N ¼ 528; N men ¼ 205 (38.8%), mean age ¼ [37] 70.7 years; N female ¼ 323(61.2%), mean age ¼ 70.5 years, from Japan. Goode et al. [47]

DSN OST FOA

LIS

LOS LIS

Radiographic measurement

Questionnaire with LBP if yes to: “Have you had LBP during the last 10 years?”

DSN present if there was sclerosis or OST of the adjacent vertebrae; additionally, in L1–L4, DSN was present when a disc space was narrower than the one above it. LOS was present if there was marginal OST on the vertebral bodies. Interview by trained personnel with LBP if 4-Grade scale for lumbar LOS: grade 0 ¼ norlow back pain within 6 months. mal, grade 1 ¼ mild narrowing disc space with subchondral bone sclerosis, grade 2 ¼ moderate narrowing disc space with subchondral bone sclerosis and OST, and grade 3 ¼ marked DSN with OST or LIS. LIS—presence or absence of LIS was recorded. Questionnaire with three questions regarding LOS—5-grade Kellgren–Lawrence scale: grade 0 ¼ normal disc with no OST, grade LBP status “Do you have LBP at the present 1 ¼ slight anterior wear and OST time, that is, right now?” and “During the formation, grade 2 ¼ definite anterior last 6 months, have you had LBP lasting wear and mild DSN with OST formation, more than a day?” and “In your lifetime, grade 3 ¼ moderate DSN with OST and have you ever had LBP lasting more than a sclerosis, and grade 4 ¼ large OST marked day?” and a mannequin diagram. DSN and sclerosis of vertebral endplates. OST—4-grade scale: grade 0 ¼ none, grade 1 ¼ barely visible, grade 2 ¼ definite grade, and 3 ¼ large. EPS—2-grade scale: grade 0 ¼ none, grade 1 ¼ present. DSN—4-grade scale: grade 0 ¼ none, grade 1 ¼ probable, grade 2 ¼ definite, and grade 3 ¼ severe, bone to bone. Interview with LBP if yes to: “Did you have DNS and OST—3-grade Lane Atlas: grade 0 ¼ none, grade 1 ¼ mild, grade 2 ¼ complaints of the low back during the last moderate, and grade 3 ¼ severe. month?” CLBP if more than 1 year: “What is the duration of the present low back complaints?” Questionnaire with LBP if yes to: “In the past LIS—6-grade Meyerding Grading scale measured in slip %: grade 0 ¼ no slip, 12 months have you suffered lower back grade 1 ¼ 1–25%, grade 2 ¼ 26–50%, pain?” and a body drawing. grade 3 ¼ 51–75%, grade 4 ¼ 76–100%, and grade 5 ¼ complete slippage. Questionnaire derived from the McGill pain OST—presence or absence. DSN—two rules: first, an overall impression questionnaire divided subjects to three of the thickness of each disc space was groups: no pain, moderate pain, and severe defined as either narrow or normal, and pain. second, a relative narrowing of the height of the lumbosacral disc space; the disc space between L4 and L5 was defined as narrowed when its height was less than that of either the disc between L3 and L4 or the lumbosacral disc space. Interviewed with LBP if yes to: “On most OST and DSN—4- grade Burnett atlas: grade days, do you have pain, aching or stiffness 0 ¼ none, grade 1 ¼ mild, grade 2 ¼ in your low back?” moderate, and grade 3 ¼ severe. FOA was graded present or absent. LIS—6-grade Meyerding scale: grade 0 ¼ no slip, grade 1 ¼ Z5% and 25%, grade 2 ¼ 26–50%, grade 3 ¼ 51–75%, grade 4 ¼ 76– 100%, and grade 5 ¼ complete slippage. Questioned about the presence or absence of LOS—4-grade Weiner scale: grade 0 ¼ no lower back pain in the previous 6 months. disease, defined by normal disc height, no spur formation, no eburnation and no gas; grade 1 ¼ mild disease, defined by o25% DSN, small spur formation, minimal eburnation, and no gas; grade 2 ¼ moderate disease, defined by 25–75% DSN, moderate spur formation, moderate eburnation, and no gas; grade 3 ¼ advanced disease, defined by 4 75% DSN, large spur formation, marked eburnation, and presence of gas. Interviewed using a standardized questionnaire regarding LBP.

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Table 1 (continued ) Study

Study population

RF LBP definition investigated

Inaoka et al. [38]

N ¼ 838; N men ¼ 546 (65.9%); N female ¼ DSN 292 (34.1%), mean age ¼ 52 years, N LBP ¼ EPS OST 438 (52%) from Japan. LIS

Questionnaire including items such as LBP.

Lawrence [39]

N ¼ 1522; N male ¼ 713 (46.8%); N females DSN ¼ 809 (53.2%), over the age of 34 years, from Great Britain.

LBP: only one attack and it had lasted 3 months or less; CLBP if more than 3 months.

N ¼ 530; N male ¼ 241 (45.5%); N female ¼ 289 (54.5%), mean age ¼ 38.7 years, N LBP ¼ 386 (73%), from Australia. Muraki et al. N ¼ 2288; N men ¼ 818 (35.7%), mean age [42] ¼ 74.7 years, mean height ¼ 161.3 cm, mean weight ¼ 60.1 kg, mean BMI ¼ 23; N female ¼ 1470 (64.3%), mean age ¼ 74 years, mean height ¼ 148.6 cm, mean weight ¼ 50.9 kg, mean BMI ¼ 23, from Japan. Pye et al. [14] N ¼ 585; N men ¼ 286 (48.8%), mean age ¼ 65.3 years; N female ¼ 299 (51.2%), mean age ¼ 65.2 years; N LBP past year ¼ 115 (38.5%) females and 78 (27.3%) males; N LBP ever ¼ 183 (61.2%) female and 158 (55.2%) male, from United Kingdom. Symmons et al. N ¼ 477 women, N LBP ¼ 236 (49.5%), [50] part II baseline LBP group: mean age ¼ 53.8 years, mean height ¼ 161 cm, mean weight ¼ 67.3 kg, mean BMI ¼ 25.3, baseline no LBP group: mean age ¼ 54.2 years, mean height ¼ 162 cm, mean weight ¼ 67.2 Kg, mean BMI ¼ 25.2, follow-up LBP group: mean age ¼ 62.7 years, mean height ¼ 161 cm, mean weight ¼ 69.3 Kg, follow-up no LBP group: mean age ¼ 63.2 years, mean height ¼ 161 cm, mean weight ¼ 68.1 kg, from the Netherlands. Vogt et al. [43] N ¼ 788 Caucasian women, mean age ¼ 71.5 years, N LBP ¼ 256 (32.4%), No LBP ¼ 515 (67.6%), from USA. Leboeuf et al. [40]

Radiographic measurement

LIS—present if Z 3 mm anterior or posterior slippage in the vertebrae. DSN—slight when the space was less than three-fourth and more than half of the normal space at the adjacent level, and marked when the space was less than half. EPS: present when bony endplate thickness was 4 2 mm. OST: positive when their height was 4 2 mm. LIS: positive when 42 mm of vertebral sliding. DNS—5-grade scale: grade 0 ¼ no change, grade 1 ¼ slight anterior wear and OST formation, grade 2 ¼ definite anterior wear and OST formation, grade 3 ¼ OST formation and DSN, and grade 4 ¼ large OST, marked DSN, sclerosis of vertebral plates, and posterior subluxation. LIB—4-grade scale: each grade representing a 25% increase of forward slippage of the vertebra on the one below. LOS—5-grade Kellgren–Lawrence scale.

LIS

Present or pasts LBP sought from corresponding patient files.

LOS

Interview with LBP if yes to: “In the past month, have you had pain on most days lasting?”

DSN EPS OST

Questionnaire with LBP if yes to: “have you ever had back pain?” and “Have you ever had an episode of back pain in the past year?”

DSN OST

DSN—5-grade Kellgren scale: grade 0 ¼ Questionnaire with LBP if yes to all three no change, grade 1 ¼ slight anterior following questions: “Are you suffering wear and OST formation, grade 2 ¼ from back pain now?” “Have you suffered definite anterior wear and mild DSN from back pain in the past?” and “Have you with OST formation, grade 3 ¼ had back pan more than once in the past?” moderate DSN with OST formation and sclerosis, grade 4 ¼ large OST, marked DSN, and EPS. OST—3-grade scale: grade 0 ¼ same, grade 1 ¼ worse, and grade 2 ¼ much worse.

LIS

LBP if study participants reported back pain Present if Z3 mm slippage on one vertebra relative to the one below. in the lower lumbar region for at least some amount of time during the previous year. Questionnaire with LBP if participants had LIS—Present if Z3 mm slippage on one vertebra relative to the one below. experienced any lower back pain during the previous 4 weeks. The back pain symptoms (if any) were described as mild, moderate, or severe the past year Interviewed using a standardized DSN—4-grade scale: grade 0 ¼ normal, questionnaire regarding LBP. grade 1 ¼ mild narrowing (o30% reduction in disc height), grade 2 ¼ moderate narrowing(30–60% reduction in disc height), and grade 3 ¼ severe narrowing (460% reduction in disc height). Questionnaire regarding duration of LBP. LOS was graded as the total number of marginal proliferations, and the average size of marginal proliferations measured in mm beyond the normal contour.

Vogt et al. [44] N ¼ 470 African American women, mean age LIS ¼ 75.1 years, N LBP last year ¼ 309 (64.7%), N LBP last month ¼ 235 (50%), from USA.

Wang et al. [45]

N ¼ 4000; 2000 men (50%), mean age ¼ 72.4 years, N LBP ¼ 612 (30.6%); 2000 women (50%), mean age ¼ 72.6 years, N LBP ¼ 1063 (53%), from China.

Witt et al. [46]

N ¼ 304 outpatients over 20 years of age, N LOS LBP ¼ 238 (78.2%); N male ¼ 104(43.9%) OST and N female ¼ 134 (56.0%); N no LBP ¼ DSN

DSN

All RF—4-grade scale: grade 0 ¼ none, grade 1 ¼ mild, grade 2 ¼ moderate, and grade 3 ¼ severe.

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7

Table 1 (continued ) Study

Study population

RF LBP definition investigated

66 (21.8%), N male ¼ 43(65.8%) and N female ¼ 33 (34.1%), from Denmark. Case–control studies FOA Hicks et al. [36] N ¼ 320 older community-dwelling adults Z65 years; N men ¼ 177 (55%) and N DSN female ¼ 146 (45%); N CLBP ¼ 162 (50.5%), 141 White, 18 African American, and 3 Hispanic, mean age ¼ 73.6 years, mean BMI ¼ 29.0, N controls ¼ 158 (49.5%), 142 white, 15 African American, and 4 Hispanic, mean age ¼ 73.5 years, mean BMI ¼ 26.1, subjects from USA.

Horal [49]

Cohort studies Muraki et al. [41] (3.3year followup)

N ¼ 390; N males ¼ 238 (61%), mean age ¼ DSN 49.54 years; N females ¼ 152 (39%), mean LOS age ¼ 49.67 years, from Sweden.

N ¼ 2282; N men ¼ 758 (33.2%), mean age LOS ¼ 69.8 years, mean height ¼ 163 cm, mean BMI ¼ 23.3; N female ¼ 1524 (66.8%), mean age ¼ 68.3 years, mean height ¼ 150.4 cm, mean weight ¼ 52.1 kg, mean BMI ¼ 23.0, from the ROAD study, Japan.

Radiographic measurement

OST: N/A DSN: N/A CLBP if LBP of at least moderate intensity that FOA—4-grade scale: grade 0 ¼ normal, grade 1 ¼ narrowing of joint and/or mild occurred daily or almost every day for at eburnation, grade 2 ¼ moderate least the previous 3 months. narrowing þ moderate eburnation or hypertrophy, and grade 3 ¼ severe osteoarthritis with narrowing, eburnation, and OST DSN—4-grade scale: grade 1 ¼ no disease, defined by normal disc height, no spur formation, no eburnation, and no gas; grade 2 ¼ mild disease, defined by o25% DSN, small spur formation, minimal eburnation, and no gas; grade 2 ¼ moderate disease, defined by 25–75% DSN, moderate spur formation, moderate eburnation, and no gas; grade 3 ¼ advanced disease, defined by 4 75% DSN, large spur formation, marked eburnation, and gas present. LBP if sick-listed by physicians for lumbar DSN—6-grade scale which included each spine disorders during at least 1 week. reduction of the intervertebral distance as compared to the adjoining intervertebral space. Grade 1 ¼ no DSN, grade 2 ¼ moderate DSN on one level, grade 3 ¼ moderate DSN on many levels, grade 4 ¼ advanced DSN on one level, grade 5 ¼ advanced DSN on many levels, grade 6 ¼ moderate and advanced DSN on one or many levels. LOS—6-grade scale: grade 1 ¼ no LOS, grade 2 ¼ moderate LOS on one level, grade 3 ¼ moderate LOS on many levels, grade 4 ¼ advanced LOS on one level, grade 5 ¼ advanced LOS on many levels, and grade 6 ¼ moderate and advanced LOS on one or many levels. LBP if yes to: “Have you experienced lower back pain on most days during the past month in addition to now?”

LOS—5-grade Kellgren–Lawrence scale: grade 0 ¼ no radiographic features of OA, grade 1 ¼ minimal OST only, grade 2 ¼ definite OST with some sclerosis of the anterior part of the vertebral plate, grade 3 ¼ marked OST and sclerosis of the vertebral plates with slight DSN, and grade 4 ¼ large OST marked sclerosis of the vertebral plated and marked DSN.

DSN ¼ disc space narrowing; OST ¼ osteophytes; LIS ¼ spondylolisthesis; LOS ¼ spondylosis; EPS ¼ endplate sclerosis; FOA ¼ facet joint osteoarthritis; RF ¼ radiographic feature; LBP ¼ low back pain; BMI ¼ body mass index.

heterogeneity when stratified by adjusted and unadjusted estimates or by study design (i.e., cross-sectional and case–control) for community-based studies. The overall pooled estimate for osteophytes was 1.20 (95% CI: 1.06–1.37, CLR ¼ 1.29), without significant heterogeneity (I2 ¼ 18.0%, p ¼ 0.287). The overall pooled estimate for spondylolisthesis was 1.12 (95% CI: 1.03–1.23, CLR ¼ 1.19), without significant heterogeneity (I2 ¼ 1.0%, p ¼ 0.429). The overall pooled estimate for spondylosis was 1.32 (95% CI: 1.14–1.53, CLR ¼ 1.34), with significant heterogeneity (I2 ¼ 43.1%, p ¼ 0.071). The pooled estimate for endplate sclerosis was 1.24 (95% CI: 0.84–1.81, CLR ¼ 2.15), also with significant heterogeneity (I2 ¼ 77.1%, p ¼ 0.013). The overall pooled estimate for facet joint osteoarthritis was 1.07 (95% CI: 0.63–1.80, CLR ¼ 2.86), with significant heterogeneity (I2 ¼ 70.2%, p ¼ 0.067). For occupation-based populations (Fig. 2, red diamonds), the overall pooled estimate for disc space narrowing was 1.76 (95% CI: 1.34–2.33 CLR ¼ 1.74), without significant heterogeneity

(I2 ¼ 0.0%, p ¼ 0.625). The pooled estimate of osteophytes was 1.83 (95% CI: 0.88–3.79, CLR ¼ 4.31), with significant heterogeneity (I2 ¼ 59.1%, p ¼ 0.118). Results for spondylolisthesis showed an overall pooled estimate of 2.21 (95% CI: 1.44–3.39, CLR ¼ 2.35), without significant heterogeneity (I2 ¼ 0.0%, p ¼ 0.701). The overall pooled estimated for endplate sclerosis was 1.13 (95% CI: 0.78–1.65, CLR ¼ 2.11), without significant heterogeneity an I2 of 0.0% (p ¼ 0.839). A significant difference (p o 0.001) was found across ORs for spondylolisthesis for community- and occupation-based populations, indicating these effects are independent of one another. Most pooled associations did not differ across community- and occupation-based populations. No significant difference (p ¼ 0.22) was found between the pooled associations generated from community- and occupation-based populations investigating disc space narrowing; indicating homogeneity of odds ratios. The same was true for osteophytes (p ¼ 0.26) and endplate sclerosis (p ¼ 0.73).

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Table 2 Summary of occupation-based studies included in the review Study

Study population

Cross-sectional studies Libson et al. N ¼ 1598, with 936 asymptomatic, mean [51] age ¼ 30 years, and 662 symptomatic, mean age ¼ 22, Israeli military soldiers Riihimäki et al. N ¼ 216 concrete reinforcement workers, [53] mean age ¼ 37.7 years, mean height ¼ 174.9 cm, mean weight ¼ 79.3 kg, and N ¼ 201 house painters, mean age ¼ 38.6 years, mean height ¼ 174.1 cm, mean weight ¼ 77.3 kg, with at least 5 years of experience, from Finland Sairanen et al. N ¼ 226 lumberjacks, mean age ¼ 42 [56] years, average length of employment ¼ 20 years, N LBP ¼ 140 (62%), N no LBP ¼ 86 (38%), N ¼ 98 referents from an office and a cellulose and board mill, over half office workers and the rest repairmen or electricians, mean age ¼ 42 years, N LBP ¼ 57(58%), N no LBP ¼ 39(40%), from Finland Steinberg et al. N total ¼ 464 male, mean age ¼ 18 years, N [54] LBP ¼ 232 (50%), N no LBP ¼ 232, army recruits from Israel

Wiikeri et al. [55]

Cohort studies Nemoto et al. [52] (20-year follow-up)

RF investigated

LBP definition

Radiographic measurement

LIS

Screened prior to military placement or investigated for LBP.

N/R

DSN OST EPS

LBP if yes to: “During the past 12 months All RF—4-grade scale: grade 0 ¼ no have you had lumbago or other backache change, grade 1 ¼ slight change, grade or pain?” 2 ¼ moderate change, and grade 3 ¼ severe change.

DSN LIS

Interview with LBP if LBP lasting for at least DSN—4-grade scale, grade 1 ¼ slight 3 days. anterior wear and OST formation, grade 2 ¼ definite anterior wear and OST formation, grade 3 ¼ OST formation and DSN, and grade 4 ¼ large OST, marked DSN, sclerosis of vertebral plates, and posterior subluxation. LIS: N/R

EPS

Interview with LBP if they had experienced EPS—positive if irregular appearance of the endplate with thinning or focal loss periods of non-traumatic LBP (with or of visualization of the subchondral without leg radiation), which were cortical plate. severe enough to be treated by LIS—classified according to the ratio of medication and temporarily prevented vertebral slip percentage. them from strenuous physical activity. Interview by physical therapist, “Have you DSN—4-grade scale: none ¼ no signs of ever had back trouble?” Back trouble was disc degeneration, slight ¼ DSN defined as any back symptom the worker without other signs of disc was able to recall and considered degeneration, moderate ¼ DSN and negative for his health. OST, and severe ¼ DSN, OST, and EPS.

LIS L5–S1

N total ¼ 295 male concrete reinforcement DSN workers, mean age ¼ 39 years, median work experience ¼ 12 years, from Finland

N total ¼ 84 male military servicemen; baseline: N LBP ¼ 44, N no LBP ¼ 40, mean age LBP ¼ 18.3 years and no LBP ¼ 18.4 years, mean height LBP ¼ 172.8 cm and no LBP ¼ 171.1 cm, mean weight LBP ¼ 68.2 kg and no LBP ¼ 67.4 kg Follow-up: N LBP ¼ 44, N no LBP ¼ 40, mean age LBP ¼ 38.6 years and no LBP ¼ 38.4 years, mean height LBP ¼ 171.3 cm and no LBP ¼ 170.7 cm, mean weight LBP ¼ 74.5 kg and no LBP ¼ 73.3 kg, from Japan

OST DSN

Questionnaire with LBP if yes to: “current pain lasting Z7 consecutive days experienced during the prior year.”

OST—present if Z2 mm, Macnab classification. DSN—Z 1/3 decrease of the disc height, compared to that of at entry. Both RF—3-grade Lane atlas: grade 0 ¼ normal, grade 1 ¼ mild, and grade 2 ¼ moderate to severe.

DSN ¼ disc space narrowing; OST ¼ osteophytes; LIS ¼ spondylolisthesis; LOS ¼ spondylosis; EPS ¼ endplate sclerosis; FOA ¼ facet joint osteoarthritis; RF ¼ radiographic feature; LBP ¼ low back pain; BMI ¼ body mass index.

Quality assessment

Discussion

Figures 3 and 4 illustrate the summary of each included study’s quality score, and the percentage distribution of the major types of bias, that the insufficiently reported questions represented. The total score of the cross-sectional community-based populations ranged from 5/12 to 12/12 [16,34,39,47]. There was only one community-based cohort study [33]. This study was assigned a score of 15/21. The quality assessment results for communitybased case–control studies ranged from 8/18 to 13/18 [36,49]. The quality assessment scores for cross-sectional occupation-based studies ranged from 2/12 to 9/12 [51,53]. The score for the single occupation-based cohort study was 19/21 [52]. Questions relating to information bias were least reported (8–33%) for communitybased studies, and questions relating to “other” types bias were most reported (5–17%). Selection bias-related questions were most frequently reported (8%) in occupation-based studies, and information bias-related questions were least frequently reported (5–42%). Each study’s result for each of the criteria and their total quality score, for both community-based and occupation-based populations, are presented in Appendices C and D, respectively.

We set out to systematically review the published literature on the association between LBP and radiographic features in the lumbar spine and to determine if there were differences in these associations by community- versus occupational-based populations. The findings of this review indicate similar and significant associations between disc space narrowing and LBP in both community- and occupational-based populations. Spondylosis also had a significant association with LBP among community-based populations. We also found that associations between LBP and spondylolisthesis differed, with a significantly stronger association found in occupational-based populations compared to community-based. Osteophytes, endplate sclerosis, and facet joint osteoarthritis had a weak or non-significant association with LBP. The quality of included studies varied substantially; this did not appear to impact the pooling of study estimates as little to no heterogeneity was found in pooled estimates where quality may be an important factor for explaining heterogeneity. Our findings from this systematic review may aid in the development of specific guidelines for clinical care practice.

Table 3 The counts, proportions, unadjusted odds ratios and adjusted odds ratios, 95% confidence intervals, and categorization grade of radiographic features for each included community-based study Study

Disc space narrowing Cross-sectional studies Biering-Sørensen [32] Cho et al. [34] De Schepper et al. [15] Frymoyer et al. [35]

LBP

No LBP

Crude OR (95% CI)

Present (%)

Absent (%)

Present (%)

Absent (%)

115 (32) 124 (20) N/R

243 (68) 487 (80) N/R

71 (23) 126 (11) N/R

237 (77) 1035 (89) N/R

1.58 (1.12–2.23) 2.09 (1.60–2.74) N/R

45 (23)

151 (77)

19 (20)

77 (80)

260 118 462 N/R 130

Goode et al. [47] Inaoka et al. [38] Pye et al. [14] Symmonset al [50] part II Witt et al. [46] Spondylolisthesis Cross-sectional studies Biering-Sørensen (1984) [32] Chaiwanichsiri et al. [33] Denard et al. [16]

(61) (30) (59) (55)

163 269 320 N/R 106

(39) (70) (41) (45)

224 95 350 N/R 92

(54) (21) (47) (38)

193 356 390 N/R 149

(46) (79) (53) (62)

1315 (57)

Categorization grade of RF Absent

Present

N/R 1.71 (1.28–2.28) 1.40 (1.10–1.70)

0 0–1 0

1–3 2–3 1–3

1.21 (0.66–2.21)

N/R

1.44 (1.12–1.85) 1.64 (1.20—2.25) 1.61 (1.31–1.97) N/R 1.99 (1.38–2.86)

1.37 (1.04–1.81) N/R N/R 1.70 (1.10–2.40) N/R

DSN measured by an overall impression of the thickness of each disc space was defined as either narrow or normal. Additionally, a relative narrowing of that individual’s lumbar spine. Analyzed as an ordinal 0, 1, 2, and 3. Absent Slight-marked 0–1 2–4 0 1–3 0–1 2–4

1.50 (1.32–1.70) Both genders

1.31 (1.07–1.60)

Summary score r3

Summary score 4 3

894 (53)

781 (47)

1005 (43)

55 (23)

183 (77)

14 (21)

52 (79)

1.12 (0.58–2.17)

1.23 (1.02–1.50) N/R

N/R

N/R

N/R 90 (46)

N/R 105 (54)

N/R 61 (32)

N/R 127 (68)

N/R 1.87 (1.24–2.83)

1.35 (0.42–4.57) N/R

0 1

1–3 2–6

344 (56) N/R

267 (44) N/R

507 (44) N/R

654 (56) N/R

1.66 (1.36–2.02) N/R

1.53 (1.22–1.92) 1.20 (1.00–1.50)

0–1 0–1

2–3 2–3

31 (16)

165 (84)

11 (11)

85 (89)

1.45 (0.70–3.03)

N/R

379 (90)

44 (10)

361 (85)

66 (15)

1.28 (0.98 1.66)

1.11 (0.84–1.48)

Presence or absence of anterior, posterior, and lateral OST, when present, they were classified as traction or claw spurs. Analyzed as an ordinal 0, 1, 2, and 3.

52 (13) N/R 199 (84)

335 (87) N/R 37 (16)

50 (11) N/R 210 (87)

401 (89) N/R 31 (13)

1.24 (0.82–1.88) N/R 0.79 (0.47–1.33)

N/R 1.10 (0.80–1.60) N/R

r2 mm in size 0–1 Absent

4 2 mm is size 2–3 Present

125 (53)

113 (47)

36 (55)

30 (45)

0.92 (0.53–1.59)

N/R

0 mm in size

1–10 mm in size

10 (3)

348 (97)

9 (3)

299 (97)

0.95 (0.38–2.38)

N/R

N/R

N/R

372 (54)

323 (46)

62 (64)

35 (36)

1.15 (0.97–2.46)

N/R

Present

Absent

58 (30)

137 (70)

34 (34)

66 (66)

0.82 (0.49–1.37)

N/R

Magnitude of LIS was measured by dividing the slip distance by the caudal body width and expressed as a percentage. When there was a Z5% slip, LIS was considered present.

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Goode et al. [47] Inaoka et al. [38] Lawrence [39] Pye et al. [14] Symmons et al. [50] part II Wang et al. [45] A: Men B: Women Witt et al. [46] Case–control studies Hicks et al. [36] Horal [49] Osteophytes Cross-sectional studies Cho et al. [34] De Schepper et al. [15] Frymoyer et al. [35]

Adjusted OR (95% CI)

9

10

Table 3 (continued ) Study

LBP

No LBP

Crude OR (95% CI)

Adjusted OR (95% CI)

Absent (%)

Present (%)

Absent (%)

134 (35)

246 (65)

477 (30)

1136 (70)

1.30 (1.02–1.64)

261 (52)

238 (48)

801 (54)

694 (46)

0.95 (0.78–1.16)

Horikawa et al. [37]

25 (9)

242 (91)

22 (8)

239 (92)

1.12 (0.61–2.05)

N/R

Inaoka 2000 [38] Leboeuf et al. [40]

35 (9) 19 (5)

352 (91) 367 (95)

19 (4) 8 (6%)

432 (96) 136 (94)

2.26 (1.27–4.02) 0.88 (0.38–2.06)

1.16 (1.01–1.34) N/R

Vogt et al. [43] Vogt et al. [44] Spondylosis Cross-sectional studies Biering-Sørensen (1984) [32]

83 (32) N/R

179 (68) N/R

144 (27) N/R

381 (73) N/R

1.23 (0.89–1.70) N/R

1.30 (0.90–1.80) 1.00 (0.70–1.50)

210 (59)

148 (41)

177 (57)

131 (43)

1.05 (0.77–1.43)

N/R

Chaiwanichsiri et al. [33] Cho 2012 [34] Horikawa et al. [37] Muraki et al. [42] A: Men B: Women Witt et al. [46]

243 (56)

191 (44)

194 (54)

164 (46)

1.08 (0.81–1.42)

433 (71) 112 (42) N/R

178 (29) 155 (58) N/R

685 (61) 90 (34) N/R

437 (39) 171 (66) N/R

1.55 (1.26–1.92) 1.37 (0.97–1.95) N/R

121 (51)

117 (49)

35

31

0.92 (0.53–1.58)

164 (84)

31 (16)

141 (72)

54 (28)

47 (24)

151 (76)

219 (20)

859 (80)

He et al. [48] A: Men B: Women

Case–control studies Horal [49] Cohort studies Muraki et al. [41] A: Men B: Women Endplate sclerosis Cross-sectional studies Cho et al. [34] Inaoka et al. [38]

Absent N/R

Present

Absent if less than 5% forward or backward slip of one vertebra in relation to the inferior vertebra. o 3 mm anterior slippage Z3 mm anterior slippage r 2 mm of sliding 4 2 mm of sliding Slippage defined as forward slippage of a vertebra on the one below. Subluxation o3 mm Subluxation Z 3 mm Subluxation o3 mm Subluxation Z 3 mm

Present if a forward or backward slip of one vertebral body by 4 5% in relation to the inferior vertebra.

N/R

Absence of marginal OST on the on the vertebral bodies. 0–1

Presence of marginal OST on the on the vertebral bodies. 2–3

1.09 (0.74–1.61) N/R 1.44 (0.89–2.38)

0–1 0–1 0–2

2–4 2–3 Z3

1.80 (1.38–2.37) Was graduated as the total number of marginal proliferations, and the average size of marginal proliferations measured in mm beyond the normal contour.

2.03 (1.23–3.33)

N/R

1

2–6

1.22 (0.85–1.75) (both genders)

1.26 (0.88–1.81)

0–2

3–4

1.51 (1.16–1.95)

765 (66) 85 (22)

Pye et al. [14] N/R Facet joint osteoarthritis Cross-sectional studies Goode et al. [47] 247 (59) Case–control studies Hicks et al. [36] N/R

396 (34) 302 (78)

431 (71) 58 (13)

N/R

N/R

175 (41)

239 (57)

N/R

N/R

180 (29) 393 (87)

N/R

179 (43) N/R

0.81 (0.65–1.00) 1.91 (1.32–2.75)

1.03 (0.81–1.31) N/R

Absence Bony endplate thickness was r 2 mm.

N/R

1.00 (0.70–1.40)

0

Presence Bony endplate thickness was 4 2 mm. 1–3

1.05 (0.80–1.38)

0.84 (0.61–1.15)

Absent

Present

N/R

1.44 (0.89–2.33)

0

1–3

95% CI ¼ 95% confidence interval; LBP ¼ low back pain; N/R ¼ not reported; OR ¼ odds ratio; RF ¼ radiographic feature.

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Present (%)

Categorization grade of RF

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Table 4 The counts, proportions, unadjusted odds ratios and adjusted odds ratios, 95% confidence intervals, and categorization grade of radiographic features for each included occupation-based study Study

LBP

No LBP

Crude OR (95% CI) Adjusted OR (95% CI) Categorization grade of RF

RF present (%) RF absent (%) RF present (%) RF absent (%) Disc space narrowing Cross-sectional studies Riihimäki et al. [53] 122 Sairanen et al. [56] 190 Wiikeri et al. [55] 15 Cohort studies Nemoto et al. [52] 14

Absent

Present

1–3 2–4 Slight, moderate, or severe

(67) (71) (52)

60 (33) 76 (29) 14 (48)

132 (56) 51 (55) 43 (30)

103 (44) 41 (45) 99 (70)

1.59 (1.06–2.37) 2.01 (1.23–3.28) 2.47 (1.10–5.56)

N/R N/R N/R

0 1 None

(32)

30 (68)

11 (28)

29 (72)

1.23 (0.48–3.15)

N/R

Defined as Z1/3 decrease of the disc height, compared to that of at entry

(60)

73 (40)

122 (52)

112 (48)

1.38 (0.94–2.05)

N/R

0

1–3

(59)

18 (41)

13 (30)

27 (70)

3.00 (1.23–7.33)

N/R

o2 mm

Z2 mm

(5) (21) (6)

627 (95) 76 (79) 218 (94)

21 (2) 7 (15) 6 (3)

915 (98) 41 (85) 226 (97)

2.43 (1.40–4.22) 1.54 (0.60–3.95) 2.42 (0.90–6.41)

N/R N/R N/R

N/R N/R N/R N/R Presence classified according to the ratio of vertebral slip percentage.

Endplate sclerosis Cross-sectional studies Riihimäki et al. [53] 62 (34) Steinberg et al. [54] 11 (5)

121 (66) 221 (95)

74 (32) 9 (4)

160 (68) 223 (96)

1.11 (0.73–1.67) 1.23 (0.50–3.03)

N/R N/R

0 1–3 Present if there was an irregular appearance of the endplate with thinning or focal loss of visualization of the subchondral cortical plate.

Osteophytes Cross-sectional studies Riihimäki et al. [53] 110 Cohort studies Nemoto et al. [52] 26 Spondylolisthesis Cross-sectional studies Libson et al. [51] 35 Sairanen et al. [56] 20 Steinberg et al. [54] 14

95% CI ¼ 95% confidence interval; LBP ¼ low back pain; N/R ¼ not reported; OR ¼ odds ratio; RF ¼ radiographic feature.

Our results indicate that there is a significant association between disc space narrowing and LBP in both community- and occupation-based populations. The association was stronger among occupation-based populations but was not statistically different from community-based populations. This is similar to the findings of the systematic review done by van Tulder et al. [17] in 1997 such that most included studies reported a significant association between disc space narrowing and LBP. However, our review was able to provide the addition of several large

community-based studies. The included studies for both community- and occupation-based populations demonstrated substantial clinical heterogeneity (e.g., differing definitions of LBP, categorization grade of disc space narrowing, and study population). The majority of studies defined LBP as a type of chronic unspecific LBP lasting up to 1 year and defined disc space narrowing as radiographically present at a grade of 1–3, meaning at least mild disc space narrowing. Despite the clinical heterogeneity, there was little statistical heterogeneity among the studies.

Fig. 2. Pooled estimates for each radiographic feature, 95% confidence intervals, number of studies, and I2 scores (p-value) for community-based and occupation-based studies.

12

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Fig. 3. Quality scores for community-based studies, and the percentage distribution of the major types of bias that the insufficiently reported questions represented.

There may be several reasons for similar association found between community-and occupation-based populations. One reason may be the genetic influences associated with disc space narrowing [57], because genetics may pre-determine a certain degree of disc space narrowing, regardless of the external demands. Another possible explanation for the association of disc space narrowing and LBP in both community- and occupation-based populations is that disc space narrowing is due to the natural degeneration of the intervertebral disc caused by aging [58]. The natural ageing-related changes of disc space narrowing may not be influenced substantially by the biomechanical demands placed on the spine by a predominately working population. Quality and number of included studies between community-and occupation-based populations may also influence these associations. The quality of the included studies in both community-based and occupation-based populations varied substantially. However several of the studies with the highest quality scores represented the majority of the overall weight in the metaanalysis. In the occupation-based populations, due to the limited number of studies, the overall estimate might be influenced by biases introduced by some of the studies. Similar findings between disc spaces narrowing and LBP can be found with spondylosis. There is an overlap between these two radiographic feature definitions as disc space narrowing is frequently used in the classification of spondylosis (e.g., disc space narrowing and osteophytes combined). As such, it is difficult to make comparisons due to the significant overlap between them. Another difficulty is the known differences in the prevalence of degeneration between vertebral osteophytes and disc space narrowing that by combining these two into a composite definition may cloud the understanding of degeneration in the lumbar spine. A noticeable gap in this literature is the decreased number of longitudinal studies in the area of lumbar spine degeneration and LBP in general. Many factors such as the follow-up time are adequate to determine degeneration in the spine, and the potential waxing and waning nature of LBP hampers this area of research. We identified one study that longitudinally used the definition of spondylosis as a predictor of LBP amongst a Japanese

population [59]. This study identified spondylosis (K–L Z3) as a significant predictor of LBP. Given the large-scale impact that LBP has on pain and function and the potential role degeneration in the lumbar spine may contribute to this more epidemiological research and research on interventions is needed in this area. In contrast to the similar associations found between community- and occupation-based populations with disc space narrowing, the association between spondylolisthesis and LBP was significantly stronger among occupation-based populations when compared to community-based populations. There are several possible reasons for this difference. One might be the limited number of studies and subjects in the occupation-based populations, and that the definition of spondylolisthesis (not reported in most of the occupationbased populations) differed between the community- and occupation-based populations. Second, and similar to the results for disc space narrowing, the studies investigating spondylolisthesis also presented with significant clinical heterogeneity, which may influence our pooled study estimates. Two of the three studies that investigated spondylolisthesis in an occupation-based population used army recruits from Israel. These two studies combined represented close to 80% of the information (i.e., weight) of the pooled study estimate. This population and the occupational demands differ greatly from the last study that investigated lumberjacks from Finland. Third, the amount of physical training, bending, rotation, and load on the lumbar spine that these recruits undergo may influence spondylolisthesis when compared to communitybased participants. Another possible reason for the differences may be related to individual study quality as the studies with the majority of information also had the poorest study quality, which might introduce bias. Our results for community-based populations are consistent to the findings of van Tulder et al [17]. Their results indicated that spondylolisthesis did not seem to be associated with LBP. However, they investigated spondylolisthesis together with spondylolysis. Our analysis was to investigate a degenerative spondylolisthesis, and it is to our knowledge the first systematic review that investigates this particular type of spondylolisthesis in both community- and occupation-based populations.

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Fig. 4. Quality scores for occupation-based studies, and the percentage distribution of the major types of bias that the insufficiently reported questions represented.

Osteophytes, endplate sclerosis, and facet joint osteoarthritis were not significantly associated with LBP. Reasons for the weak association between osteophytes and LBP may be due to the natural occurrence of osteophytes with increasing age and its high prevalence [60]. Similar reasons can be hypothesized regarding endplate sclerosis. It too has been thought to be associated with increasing age [61] and is often encompassed in the definition of other radiographic features. Another reason might be due to the lack of adjustment for the presence of concomitant radiographic features in multivariable analysis. In addition, facet joint osteoarthritis was not significantly associated with LBP. These results may derive from the limited number of studies, which again might be due to the difficult nature of investigating facet joint osteoarthritis using plain film radiography. Plain film radiography is admittedly not the most optimal imaging technique to assess degeneration at the facet joint. Both CT scan and MRI are superior imaging techniques to assess the presence and severity of FOA [62]. In addition to the limited number of studies investigating facet joint osteoarthritis, the included studies showed significant statistical heterogeneity. Despite this, our results are similar to other studies that have investigated this topic using computed tomography (CT) and magnetic resonance imaging (MRI) [63,64]. Similar to the previous review by van Tulder et al. [17], the methodological quality of the included studies varied greatly. The most commonly identified bias was information bias; assuming a non-differential effect, our pooled estimates would be lower than expected. Information bias may have been identified for several reasons. Questions were marked as not sufficiently reported if the studies did not, or only moderately reported important aspects such as definition of LBP, categorization grade of radiographic features, which radiographic atlas was used, or other questions pertaining to the validity and reliability of measurements. Since our primary results regarding the association between disc space narrowing and LBP as well as spondylolisthesis and LBP demonstrated no statistical heterogeneity, we did not explore individual study quality as a potential influence of the pooled study estimates. Plain film radiography has been described by clinical guidelines as a reasonable first option screening tool for patients with LBP

[19]. However, these guidelines do not specify the clinical significance of specific radiographic features that are commonly evaluated in patients with LBP. Increasing evidence exists that these radiographic features have different pathophysiological processes of degeneration such that they differ in their relationship with peripheral joint osteoarthritis (i.e., knee, hip, and hand) and differ by race and gender [13]. Our results indicated that there are similarities and differences between community-based and occupational-based populations in specific radiographic features, disc space narrowing, and spondylolisthesis, respectively. These findings collectively can be used to better understand which radiographic features are informative such that more specific guidelines and algorithms of decision making can be developed. Therefore, lumbar spine plain film radiography can be better utlized in clinical care decisions. Our study is not without limitations. Most notably, the clinical heterogeneity across the studies was significant, including varying definitions of LBP and different categorization grades of radiographic features. The varying definitions used for LBP has hampered drawing comparisons across studies. Although there were a variety of different LBP definitions, nonspecific LBP was a common clinical definition. Another limiting factor in this study is the limited number of occupation-based populations. The limited number of occupation-based populations may have resulted in limited power to detect differences with community-based populations. However, we did find a statistical difference with spondylolisthesis, and the similarities found between community- and occupation-based populations can be reasonably explained by previous literature. There are known differences in disc space narrowing and facet joint osteoarthritis in relation to gender and race, respectively. However, we were unable to stratify results by these known variables as many of the included studies did not report these stratified estimates. We were unable to account for known confounding factors in the unadjusted estimates in the pooled analysis, which may influence our estimates [15,41,47]. Further, in some studies where adjusted estimates are reported, the confounding variables in the models varied. We attempted to assess this limiting factor by stratifying pooled results by adjusted and unadjusted pooled estimates

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where feasible (e.g., disc space narrowing, and osteophytes), but no significant differences were found between the two pooled estimates. Lastly, a possible limiting factor is that we searched only for articles in the English language. This might have led to the exclusion of some relevant studies. To our knowledge, this is the most up-to-date and comprehensive search with a meta-analysis of results. Our systematic review and meta-analysis indicate that disc space narrowing is significantly associated with LBP and is similar in both community-based and occupation-based populations. Our results further indicate that there is a significant difference between the association of spondylolisthesis and LBP in community-based and occupationbased populations. Spondylolisthesis may contribute a specific cause for LBP, which is influenced by external physical demands placed on the spine.

Appendix A. Supporting Information Supplementary material cited in this article is available online at doi:10.1016/j.semarthrit.2014.10.006.

References [1] Balagué F, Mannion AF, Pellisé F, Cedraschi C. Non-specific low back pain. Lancet 2012;379:482–91. [2] Macfarlane GJ, Beasley M, Jones EA, Prescott GJ, Docking R, Keeley P, et al. The prevalence and management of low back pain across adulthood: results from a population-based cross-sectional study (the MUSICIAN study). Pain 2012;153:27–32. [3] Hanney WJ, Kolber MJ, Beekhuizen KS. Implications for physical activity in the population with low back pain. Am J Lifestyle Med 2009;3:63–70. [4] Katz JN. Lumbar disc disorders and low-back pain: socioeconomic factors and consequences. J Bone Joint Surg Am 2006;88(Suppl. 2):21–4. [5] Werner EL, Indahl A. Kunnskap, praksis og holdninger til rygglidelser hos leger, fysioterapeuter og kiropraktorer. Tidsskr Nor Lægeforen 2005;125: 1794–7. [6] Oksuz E. Prevalence, risk factors, and preference-based health states of low back pain in a Turkish population. Spine (Phila Pa 1976) 2006;31:E968–72. [7] Taylor JB, Goode AP, George SZ, Cook CE. Incidence and risk factors for firsttime incident low back pain: a systematic review and meta-analysis. Spine J 2014. [8] Heneweer H, Staes F, Aufdemkampe G, Rijn M, Vanhees L. Physical activity and low back pain: a systematic review of recent literature. Eur Spine J 2011;20:826–45. [9] Videman, Leppävuori J, Kaprio J, Battié MC, Gibbons LE, Peltonen L, et al. 1998 Volvo Award Winner in Basic Science Studies: intragenic polymorphisms of the vitamin D receptor gene associated with intervertebral disc degeneration. Spine 1998;23:2477–85. [10] Battié MC, Videman T, Parent E. Lumbar disc degeneration: epidemiology and genetic influences. Spine (Phila Pa 1976) 2004;29:2679–90 [10.1097/01. brs.0000146457.83240.eb.]. [11] Froom P, Froom J, Van Dyk D, Caine Y, Ribak J, Margaliot S, et al. Lytic spondylolisthesis in helicopter pilots. Aviat Space Environ Med 1984;55: 556–557. [12] Chen JC, Chan WP, Katz JN, Chang WP, Christiani DC. Occupational and personal factors associated with acquired lumbar spondylolisthesis of urban taxi drivers. Occup Environ Med 2004;61:992–8. [13] Goode AP, Carey TS, Jordan JM. Low back pain and lumbar spine osteoarthritis: how are they related? Curr Rheumatol Rep 2012;15:305. [14] Pye SR, Reid DM, Smith R, Adams JE, Nelson K, Silman AJ, et al. Radiographic features of lumbar disc degeneration and self-reported back pain. J Rheumatol 2004;31:753–8. [15] de Schepper EI, Damen J, van Meurs JB, Ginai AZ, Popham M, Hofman A, et al. The association between lumbar disc degeneration and low back pain: the influence of age, gender, and individual radiographic features. Spine (Phila Pa 1976) 2010;35:531–6. [16] Denard PJ, Holton KF, Miller J, Fink HA, Kado DM, Marshall LM, et al. Back pain, neurogenic symptoms, and physical function in relation to spondylolisthesis among elderly men. Spine J 2010;10:865–73. [17] van Tulder MW, Assendelft WJ, Koes BW, Bouter LM. Spinal radiographic findings and nonspecific low back pain: a systematic review of observational studies. Spine 1997;22:427–34. [18] Freburger JK, Holmes GM, Agans RP, Jackman AM, Darter JD, Wallace AS, et al. The rising prevalence of chronic low back pain. Arch Intern Med 2009;169:251–8.

[19] Chou R, Qaseem A, Snow V, Casey D, Cross JT Jr., Shekelle P, et al. Diagnosis and treatment of low back pain: a joint clinical practice guideline from the American College of Physicians and the American Pain Society. Ann Intern Med 2007;147:478–91. [20] Jarvik JG, Deyo RA. Diagnostic evaluation of low back pain with emphasis on imaging. Ann Intern Med 2002;137:586–97. [21] Smith-Bindman R, Miglioretti DL, Larson EB. Rising use of diagnostic medical imaging in a large integrated health system. Health Aff 2008;27:1491–502. [22] Manchikanti L, Singh V, Pampati V, Smith HS, Hirsch JA. Analysis of growth of interventional techniques in managing chronic pain in the Medicare population: a 10-year evaluation from 1997 to 2006. Pain Physician 2009;12:9–34. [23] Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Br Med J 2009:339. [24] Cinahl. http://www.ebscohost.com/biomedical-libraries/the-cinahl-database; [accessed 18.07.13]. [25] EndNote. Philadelphia, PA. [26] Viswanathan M, Berkman ND. Development of the RTI item bank on risk of bias and precision of observational studies. J Clin Epidemiol 2012;65:163–78. [27] DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986;7:177–88. [28] Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med 2002;21:1539–58. [29] Poole C. Low P-values or narrow confidence intervals: which are more durable? Epidemiology 2001;12:291–4. [30] Sterne JA, Gavaghan D, Egger M. Publication and related bias in meta-analysis: power of statistical tests and prevalence in the literature. J Clin Epidemiol 2000;53:1119–29. [31] StataCorp College Station TX, Stata Statistical Software: Release 12. College Station, TX: StataCorp LP; 2011. [32] Biering-Sorensen F, Hansen FR, Schroll M, Runeborg O. The relation of spinal X-ray to low-back pain and physical activity among 60-year-old men and women. Spine 1985;10:445–51. [33] Chaiwanichsiri D, Jiamworakul A, Jitapunkul S. Lumbar disc degeneration in Thai elderly: a population-based study. J Med Assoc Thai 2007;90:2477–81. [34] Cho NH, Jung YO, Lim SH, Chung CK, Kim HA. The prevalence and risk factors of low back pain in rural community residents of Korea. Spine 2012;37:2001–10. [35] Frymoyer JW, Newberg A, Pope MH, Wilder DG, Clements J, MacPherson B. Spine radiographs in patients with low-back pain. An epidemiological study in men. J Bone Joint Surg Am 1984;66:1048–55. [36] Hicks GE, Morone N, Weiner DK. Degenerative lumbar disc and facet disease in older adults: prevalence and clinical correlates. Spine (Phila Pa 1976) 2009;34:1301–6. [37] Horikawa K, Kasai Y, Yamakawa T, Sudo A, Uchida A. Prevalence of osteoarthritis, osteoporotic vertebral fractures, and spondylolisthesis among the elderly in a Japanese village. J Orthop Surg (Hong Kong) 2006;14:9–12. [38] Inaoka M, Yamazaki Y, Hosono N, Tada K, Yonenobu K. Radiographic analysis of lumbar spine for low-back pain in the general population. Arch Orthop Trauma Surg 2000;120:380–5. [39] Lawrence JS. Disc degeneration. Its frequency and relationship to symptoms. Ann Rheum Dis 1969;28:121–38. [40] Leboeuf C, Kimber D, White K. Prevalence of spondylolisthesis, transitional anomalies and low intercrestal line in a chiropractic patient population. J Manipulative Physiol Ther 1989;12:200–4. [41] Muraki S, Akune T, Oka H, Ishimoto Y, Nagata K, Yoshida M, et al. Incidence and risk factors for radiographic lumbar spondylosis: the road study. Osteoarthritis Cartilage 2012;19:S214. [42] Muraki S, Oka H, Akune T, Mabuchi A, En-yo Y, Yoshida M, et al. Prevalence of radiographic lumbar spondylosis and its association with low back pain in elderly subjects of population-based cohorts: the ROAD study. Ann Rheum Dis 2009;68:1401–6. [43] Vogt MT, Rubin D, Valentin RS, Palermo L, Donaldson WF 3rd, Nevitt M, et al. Lumbar olisthesis and lower back symptoms in elderly white women. The Study of Osteoporotic Fractures. Spine (Phila Pa 1976) 1998;23:2640–7. [44] Vogt MT, Rubin DA, Palermo L, Christianson L, Kang JD, Nevitt MC, et al. Lumbar spine listhesis in older African American women. Spine J 2003;3:255–61. [45] Wang YX, Griffith JF, Zeng XJ, Deng M, Kwok AW, Leung JC, et al. Prevalence and sex difference of lumbar disc space narrowing in elderly chinese men and women: osteoporotic fractures in men (Hong Kong) and osteoporotic fractures in women (Hong Kong) studies. Arthritis Rheum 2013;65:1004–10. [46] Witt I, Vestergaard A, Rosenklint A. A comparative analysis of X-ray findings of the lumbar spine in patients with and without lumbar pain. Spine 1984;9:298–300. [47] Goode AP, Marshall SW, Renner JB, Carey TS, Kraus VB, Irwin DE, et al. Lumbar spine radiographic features and demographic, clinical, and radiographic knee, hip, and hand osteoarthritis. Arthritis Care Res (Hoboken) 2012;64:1536–44. [48] He LC, Wang YX, Gong JS, Griffith JF, Zeng XJ, Kwok AW, et al. Prevalence and risk factors of lumbar spondylolisthesis in elderly Chinese men and women. Eur Radiol 2014;24:441–8. [49] Horal J. The clinical appearance of low back disorders in the city of Gothenburg, Sweden. Comparisons of incapacitated probands with matched controls. Acta Orthop Scand Suppl 1969;118:1–109. [50] Symmons DP, van Hemert AM, Vandenbroucke JP, Valkenburg HA. A longitudinal study of back pain and radiological changes in the lumbar spines of

J. Raastad et al. / Seminars in Arthritis and Rheumatism ] (2015) ]]]–]]]

[51] [52]

[53]

[54]

[55]

[56] [57]

middle aged women. II. Radiographic findings. Ann Rheum Dis 1991;50:162–6. Libson E, Bloom RA, Dinari G. Symptomatic and asymptomatic spondylolysis and spondylolisthesis in young adults. Int Orthop 1982;6:259–61. Nemoto O, Kitada A, Naitou S, Tsuda Y, Matsukawa K, Ukegawa Y. A longitudinal study for incidence of low back pain and radiological changes of lumbar spine in asymptomatic Japanese military young adults. Eur Spine J 2013;22:453–8. Riihimaki H, Wickstrom G, Hanninen K, Mattsson T, Waris P, Zitting A. Radiographically detectable lumbar degenerative changes as risk indicators of back pain. A cross-sectional epidemiologic study of concrete reinforcement workers and house painters. Scand J Work Environ Health 1989;15:280–5. Steinberg EL, Luger E, Arbel R, Menachem A, Dekel S. A comparative roentgenographic analysis of the lumbar spine in male army recruits with and without lower back pain. Clin Radiol 2003;58:985–9. Wiikeri M, Nummi J, Riihimaki H, Wickstrom. Radiologically detectable lumbar disc degeneration in concrete reinforcement workers. Scand J Work Environ Health 1978;4(Suppl. 1):47–53. Sairanen E, Brüshaber L, Kaskinen M. Felling work, low-back pain and osteoarthritis. Scand J Work Environ Health 1981;7:18–30. Battié MC, Videman T, Parent E. Lumbar disc degeneration: epidemiology and genetic influences. Spine (Phila Pa 1976) 2004;29:2679–90.

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[58] Antoniou J, Steffen T, Nelson F, Winterbottom N, Hollander AP, Poole RA, et al. The human lumbar intervertebral disc: evidence for changes in the biosynthesis and denaturation of the extracellular matrix with growth, maturation, ageing, and degeneration. J Clin Invest 1996;98: 996–1003. [59] Muraki S, Akune T, Oka H, Ishimoto Y, Nagata K, Yoshida M, et al. Incidence and risk factors for radiographic lumbar spondylosis and lower back pain in Japanese men and women: the ROAD study. Osteoarthritis Cartilage 2012;20:712–8. [60] Snodgrass JJ. Sex differences and aging of the vertebral column. J Forensic Sci 2004;49:458–63. [61] Shao Z, Rompe G, Schiltenwolf M. Radiographic changes in the lumbar intervertebral discs and lumbar vertebrae with age. Spine 2002;27:263–8. [62] Kalichman L, Hunter DJ. Lumbar facet joint osteoarthritis: a review. Semin Arthritis Rheum 2007;37:69–80. [63] Endean A, Palmer KT, Coggon D. Potential of MRI findings to refine case definition for mechanical low back pain in epidemiological studies: a systematic review. Spine 2011;36:160. [64] Kalichman L, Li L, Kim D, Guermazi A, Berkin V, O’Donnell CJ, et al. Facet joint osteoarthritis and low back pain in the community-based population. Spine 2008;33:2560.