Risk factors for progression of lumbar spine disc degeneration: The Chingford Study
Few data exist concerning the natural history of lumbar spine disc degeneration and associated risk factors. We therefore undertook this study to examine the radiographic progression of lumbar spine disc degeneration over the course of 9 years in a population-based inception cohort of women from the Chingford Study.
Seven hundred ninety-six paired lumbar spine radiographs were read by a single reader for anterior osteophytes (AO) and disc space narrowing (DSN) using the Lane atlas at each lumbar disc space (L1–5). Disc degeneration was defined using thresholds of AO and DSN grade 1+ in one or more vertebrae (L1–5) within a subject. Progression was defined as an increase in grade in an affected year-1 vertebra. Potential risk factors were assessed using odds ratios and 95% confidence intervals adjusted for age, body mass index (BMI), and other potential confounders in logistic regression models using the STATA statistical package.
The mean ± SD age at baseline was 53.8 ± 6.0 years, and mean ± SD BMI was 25.4 ± 4.1 kg/m2. Progression rates for AO and DSN were 4% per annum and 3% per annum, respectively. Progression of DSN was predicted by age, back pain, and radiographic hip and knee osteoarthritis (OA). Progression of AO was predicted by age and radiographic hip OA, with borderline significance for BMI >30 kg/m2. No significant effects were seen for smoking, physical activity, hormone replacement therapy use, multiparity, or hand OA.
This is the first population-based longitudinal study to assess progression of the individual radiographic features of AO and DSN in lumbar spine disc degeneration. We demonstrated progression rates of 3–4% per annum, with important risk factors for progression, including age, back pain, and radiographic OA at the hip and knee.
Lumbar spine disc degeneration is characterized by disc space narrowing (DSN) and the presence of anterior vertebral osteophytes (AO). There is no consensus as to whether this is a form of osteoarthritis (OA) or a separate phenomenon, although lumbar spine disc degeneration is often labeled spinal OA and included in studies as a component of radiographic OA (1–3). There is a marked paucity of epidemiologic and population-based data on disc degeneration. Investigators in cross-sectional studies have reported similar prevalence rates increasing with age (2, 4–6). Ethnic and sex differences have been demonstrated in some studies (2), and two recent magnetic resonance imaging (MRI) studies have shown the importance of genetic factors (7, 8).
Investigators in a number of studies have reported risk factor associations for prevalent disc degeneration. These risk factors include body mass index (BMI), back pain, occupational exposures, and heavy physical activity; however, the results are inconsistent (2, 5, 9, 10). No clear association has been demonstrated with smoking, alcohol consumption, and hormone replacement therapy use. These results are likely to be limited by potential biases related to selection and consequences of the disease on behavior. The other major limitation with prevalence data is that most people have some degree of radiographic disease of the spine, even at young ages. It makes more sense to study lumbar spine deterioration longitudinally. Investigators in two previous longitudinal studies have examined deterioration of disc degeneration: the first was conducted in a select cohort of women with preexisting back pain, and the second was conducted in a cohort of 35 long-distance runners (3, 11).
In the present prospective population-based study, we have determined the rates and risk factors for progressive radiographic disc degeneration. We have also explored the relationship of degeneration with the presence of radiographic OA at other sites.
SUBJECTS AND METHODS
The Chingford Study population, established in 1988, is a well-described prospective longitudinal cohort of 1,003 women seen annually and described in detail previously (12–14). The original response rate of the sample was 78%. After 9-year followup, 821 women remained for examination, and 796 paired radiographs were available. All the women lived within 5 miles of the general practice, and 98% were white. Women from this practice are similar to women in the UK general population in terms of weight, height, and smoking characteristics (15). The area is predominantly middle class, but with a range of all social groups. A socioeconomic profile was performed using the ACORN classification system, which is based on each subject's postcode and residence (CACI International, London, UK). These codes were linked to 1 of 4 socioeconomic categories. The majority of the women (42%) belonged to group CI (middle to lower middle class, white-collar workers), 32% were in group A/B (professional workers), 17% were in group C2 (manual/skilled [blue-collar] workers), and 8% were in group D/E (manual/nonskilled workers). Each woman was asked to undergo a radiographic examination of hands, knees, hips, and thoracolumbar spine. Local ethics committee approval was obtained for both the original study and the 9-year followup.
All women were given a nurse-administered standardized questionnaire. The presence of back pain, walking distance undertaken weekly, sporting activity, and occupation at baseline were obtained from their answers to the questionnaire. Levels of physical activity were expressed as binary outcomes for analysis: walking <5 miles/week versus ≥5 miles/week, sedentary occupation versus >50% active during a day, and sporting activity <2 hours/week versus ≥2 hours/week. This enabled us to compare women who undertook low levels of physical activity with those who undertook high levels of physical activity as previously reported (16). Back pain was defined as pain lasting ≥7 consecutive days at any time point in the subject's life, excluding pain occurring only in pregnancy, during menstrual periods, or during the course of a feverish illness. Height was recorded in meters and weight in kg following physical examination. BMI was calculated as weight (kg)/height (m2) and expressed as World Health Organization BMI class groups.
Lateral lumbar spine radiographs at years 1 and 9 were taken centered on the L3 vertebrae with the subjects in the left lateral recumbent position by the same radiographer at both time points. A single trained observer (GH) blinded to patient identity and chronologic order read all radiographs. Each lateral lumbar spine radiograph was graded 0–3 for the individual features of DSN and AO formation, using the semiquantitative method reported by Lane et al, summarized as grade 0 = normal, grade 1 = mild, grade 2 = moderate, and grade 3 = severe (17). Within-observer variation was assessed by test-retest analysis of 40 randomly selected radiographs from the study. Good within-observer reproducibility (κ = 0.78–0.89) was found.
Definitions of progression were based on radiographic assessments. Disc degeneration was defined using thresholds of AO and DSN grade 1+ in one or more vertebrae (L1–5) within a subject. Progression was defined as an increase in grade in an affected year-1 vertebra.
Grading assessments of baseline hip, knee, and hand radiographs were available to assess the relationship with OA at other sites. OA of the hand and knee was graded according to the Kellgren/Lawrence (K/L) scale, using the figures and legends of the original atlas (18). OA of the hip was graded using the modification of the K/L scale proposed by Croft et al (19). Thus, the presence of definite osteophytes at any site resulted in a score of 2, while the definite presence of both osteophytes and joint space narrowing resulted in a score of 3. A millimeter reading of the narrowest hip joint space was also performed. Five groups were available for analysis: 2 knee joints, 2 hip joints, 2 carpometacarpal (CMC) joints, 10 distal interphalangeal (DIP) joints, and 8 proximal interphalangeal (PIP) joints. OA was defined as the presence of K/L grade 2+ in at least 1 joint of each group for hip, knee, and CMC joints, and in at least 2 joints for DIP and PIP joints. Hip joint space narrowing was defined as ≤2.5 mm. A single trained observer (DJH) read all films. The within-observer reproducibility of radiographic assessment at these joints has been shown to be sufficient for epidemiologic use (within-observer κ > 0.75) (20, 21).
The influence of baseline risk factors on progression in individuals was examined by logistic regression. This analysis compared subjects with progressive degeneration and those with nonprogressive degeneration adjusting for age and BMI. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were derived for AO and DSN adjusting for age and BMI. Other potential risk factors, including occupation, walking, sports, smoking status, hormone replacement therapy use, back pain, multiparity, and radiographic OA of the hips, knees, and hands, were also examined in logistic regression models. The STATA statistical package (Stata Corporation, College Station, TX) was used for all analyses.
Of the 1,353 women invited to take part in the study, 1,003 were examined at year 1 and 821 at year 9. Baseline radiographs of 25 women could not be located, and therefore 796 paired lumbar spine films (79% of the original sample) were available for analysis. The baseline characteristics of those women who were not available for analysis at year 9 were no different from those of women who remained in the study (data not shown).
The main characteristics at baseline of the 796 women with paired films are shown in Table 1. Their mean ± SD ages were 53.8 ± 6.0 years at entry and 61.6 ± 5.9 years at followup. Back pain lasting for more than 7 consecutive days had been experienced by 411 women (52%) during their lifetimes. Compared with nonprogressors, women with progression of DSN were significantly older, heavier by 1.3 kg (P = 0.2), more likely to have reported back pain at baseline (67% versus 51%), and twice as likely to have hip joint space narrowing and knee OA. Women with progression of AO were also significantly older than nonprogressors, had a 2-fold increase in the presence of hip OA, and had a significant increase in the presence of radiographic hand OA as defined by a K/L grade of 2+ in at least 1 CMC joint; however, they did not report more back pain at baseline (51% versus 52%) (data not shown). Those women who reported back pain at baseline were significantly heavier (67.4 kg versus 65.6 kg) and taller (162.4 cm versus 160.9 cm) at baseline than those who reported no back pain. However, there was no difference in mean BMI between the groups.
Table 1. Baseline characteristics of women with or without progression of disc space narrowing (DSN) on paired radiographs*
|Age, mean ± SD years||53.8 ± 6.0||55.4 ± 5.8||54.3 ± 5.8||0.04|
|Height, mean ± SD cm||161.7 ± 6.0||162.3 ± 6.4||161.6 ± 5.8||0.2|
|Weight, mean ± SD kg||66.5 ± 11.5||68.3 ± 11.2||67.0 ± 11.1||0.2|
|BMI, mean ± SD kg/m2||25.4 ± 4.1||25.9 ± 4.0||25.6 ± 3.9||0.4|
|Current HRT||60 (7.5)||11 (7.4)||32 (8.7)||0.77|
|Multiparity||248 (31.2)||50 (33.8)||101 (27.6)||0.2|
|Current smoker||175 (22.0)||35 (23.6)||77 (21.0)||0.6|
|Walking ≥5 miles/week||386 (48.5)||78 (52.7)||160 (43.7)||0.07|
|Occupation with ≥50% activity||672 (84.4)||127 (85.8)||308 (84.2)||0.7|
|Sporting activity ≥2 hours/week||164 (20.6)||34 (23.0)||64 (17.5)||0.16|
|Back pain more than once a week||411 (51.6)||99 (66.9)||186 (50.8)||0.001|
|Radiographic knee OA||105 (13.2)||34 (23.0)||41 (11.2)||0.000|
|Radiographic hip JSN||60 (7.5)||22 (14.9)||23 (6.3)||0.001|
|Radiographic hip OA||101 (12.7)||37 (25.0)||58 (15.8)||0.01|
|Radiographic CMC joint OA||125 (15.7)||28 (18.9)||64 (17.5)||0.9|
|Radiographic DIP joint OA||107 (13.4)||27 (18.2)||56 (15.3)||0.36|
|Radiographic PIP joint OA||32 (4.0)||9 (6.1)||13 (3.6)||0.2|
Prevalent radiographic AO grade 1+ was demonstrated in 727 of 796 women (91%) at year 1. Thirteen of these 727 women (1.8%) had an AO final grade score of 0 in an initially affected vertebra and were therefore excluded from the analysis. Therefore, for AO grade 1+ progression analysis, 714 paired films were analyzed. Prevalent radiographic DSN grade 1+ was demonstrated in 538 of 796 women (68%) at year 1. Twenty-four of these 538 women (4.5%) had a DSN final grade score of 0 in an initially affected vertebra and were therefore excluded from the analysis. Therefore, for DSN grade 1+ progression analysis, 514 paired films were analyzed.
Radiographic AO progression was demonstrated in 248 of 714 women (35%), or ∼4% per annum. Peak AO progression occurred at L1/2 and L2/3 (22%). One hundred forty-eight of 514 women (29%) demonstrated radiographic DSN progression (∼3% per annum). Peak DSN progression occurred at L4/5 at a rate of 27%.
Baseline risk factors in those with progressive disease were examined (Table 2). For progression to DSN grade 1+, baseline back pain (OR 2.1 [95% CI 1.4–3.2]), hip joint space narrowing (OR 2.6 [95% CI 1.4–4.8]), hip OA (OR 1.8 [95% CI 1.1–2.9]), and knee OA (OR 2.3 [95% CI 1.3–3.8]) all doubled the risk. The presence of hip OA (OR 1.5 [95% CI 1.0–2.3]) predicted progression to AO grade 1+, while BMI >30 kg/m2 showed a positive but nonsignificant association (Table 2). The hand variables (CMC, DIP, and PIP joint OA), smoking status, hormone replacement therapy use, multiparity, and physical activity (walking, occupation, and sporting activity) did not significantly predict AO or DSN progression.
Table 2. Baseline risk factors for progression of DSN and anterior osteophytes (AO)*
|Age, years|| || |
| 50–54.9||1.2 (0.7–2.1)||1.0 (0.6–1.6)|
| 55–59.9||1.5 (0.9–2.7)||1.6 (1.0–2.5)|
| >60||1.7 (1.0–3.0)||1.7 (1.1–2.6)|
|Weight, kg||1.01 (0.99–1.03)||1.01 (0.99–1.02)|
|Height, cm||1.03 (0.99–1.06)||1.02 (0.99–1.04)|
|BMI, kg/m2|| || |
| 25–29.9||1.0 (0.7–1.6)||1.1 (0.8–1.5)|
| >30||1.3 (0.7–2.3)||1.5 (0.9–2.4)|
|Knee OA, K/L grade 2+||2.3 (1.3–3.8)||1.2 (0.8–1.9)|
|Hip OA, K/L grade 2+||1.8 (1.1–2.9)||1.5 (1.0–2.3)|
|Hip JSN||2.6 (1.4–4.8)||1.3 (0.7–2.3)|
|CMC joint OA, K/L grade 2+||0.9 (0.5–1.4)||1.4 (0.9–2.1)|
|DIP joint OA, K/L grade 2+||1.0 (0.6–1.8)||1.1 (0.7–21.8)|
|PIP joint OA, K/L grade 2+||1.5 (0.6–3.7)||1.7 (0.8–3.7)|
|Multiparity||1.3 (0.9–2.0)||1.1 (0.7–2.3)|
|HRT|| || |
| Ever||1.0 (0.4–2.9)||1.5 (0.7–3.1)|
| Current||0.9 (0.4–1.8)||0.8 (0.4–1.5)|
|Back pain||2.1 (1.4–3.2)||1.0 (0.7–1.4)|
|Walking||1.4 (0.9–2.1)||1.1 (0.8–1.5)|
|Sporting activity||1.4 (0.9–2.3)||0.8 (0.5–1.1)|
|Occupation||1.0 (0.6–1.8)||0.7 (0.4–1.1)|
In this population-based prospective study of lumbar spine disc degeneration, we demonstrated progression rates of 3% per annum for DSN and 4% for AO. Our prevalence rates are highly age- and definition-dependent but are comparable with previous prevalence data (60–80% of lumbar vertebrae with K/L grade 2+ in men by age 65, with slightly lower rates in women [2, 4–6]). The increasing prevalence of intervertebral disc degeneration with age was suggested by one study to be feature specific (9). In a cross-sectional study of 292 men, Frymoyer et al found a relationship between increasing age and AO presence, but not DSN presence (9). Our results based on larger numbers contradicted this, showing clear longitudinal relationships of both AO and DSN with age.
Most previous studies have been cross-sectional with major limitations. The only two previous longitudinal studies were a major advance, but they were not strictly population based, did not separate the individual features of AO and DSN, and had only limited baseline risk factor data. Symmons et al examined radiographic changes in the lumbar spines of Dutch women over the course of 9 years (11). Two groups selected from a larger population survey with a response rate of ∼64% were divided into women with back pain at baseline (n = 236) and those without (n = 241). Using the global method of Kellgren and Lawrence, Symmons et al reported that BMI was predictive of, and multiparity protective against, incident degeneration, but they could not find any predictors of deterioration. In a 5-year longitudinal study of 35 runners and 38 controls (men and women) selected from a larger cohort, Lane et al reported the risk of OA associated with running and aging (3). A summation score for spurs (graded 0–3) was made for L1–4 for which progression rates of 16% were reported, predicted by age and baseline radiographic score (3).
We examined risk factors that have previously been shown (or hypothesized) to have an association with lumbar spine disc degeneration. Therefore, we examined BMI, smoking status, hormone replacement therapy use, back pain, physical activity, multiparity, and OA at other sites (1–2, 5, 11, 22, 23).
Obesity has been suggested as a risk factor for disc degeneration (2, 5, 11, 22, 24, 25). While higher BMI showed a trend toward predicting progression for DSN and AO, the results did not reach statistical significance. There was no significant effect of height or weight separately as continuous variables or quartiles (data not shown).
Back pain has not historically been found to be a risk factor for disc degeneration with any consistency, perhaps reflecting methodologic problems (5, 10, 11, 14). Previous studies have demonstrated an association between back pain and the presence of lumbar spine vertebral osteophytes in men, but not in women (5, 11). We found a strong association of back pain with progressive DSN, but not with progressive AO. The use of individual features rather than the global Kellgren and Lawrence system may have allowed us to isolate the true association with back pain and identify it as a relationship with DSN. Disc prolapse as the disc space narrows, with impingement of nerve roots, may be responsible for some of the symptoms. Alternatively, when DSN occurs, there is posterior displacement of the vertebral body and subsequent subluxation of the apophyseal joint that may lead to OA at this site, and therefore DSN may be a surrogate for associated facet joint OA pain (26).
In our population of women, we did not find an association of physical activity and occupational exposures with progressive disc degeneration. In cross-sectional studies, occupational exposure has previously been reported to have an association with disc degeneration in men (5, 27–29). The small numbers of women in heavily physical occupations may have limited our ability to detect a small effect of occupation, if it exists. In regard to levels of physical activity, we did not show an association with walking or with the numbers of hours spent per week in sporting activities. Similar negative reports come from cross-sectional studies and from Lane et al, who found no increased risk of lumbar osteophytes due to regular running in their small longitudinal study of runners (3, 5).
Hormonal factors may affect susceptibility to OA (30). Multiparity has been suggested to be protective against incident disc degeneration (11). We did not, however, find any significant association with hormone replacement therapy use or multiparity. MRI data in an identical-twin study on lumbar spine disc degeneration demonstrated an association between degeneration and smoking (31). However, we found no such association, although this could reflect different pathology seen in MRI studies.
The likelihood of progression of knee OA is increased in those subjects with OA at other sites (32, 33). Previously, the cross-sectional prevalence of disc degeneration has been reported to be higher in subjects with generalized OA at other sites, and in women with Heberden's nodes (1, 4, 23). We found no significant association between baseline radiographic CMC, DIP, or PIP joint OA and the risk of progressive disc degeneration. However, only a small number of women in our cohort had DIP joint OA, and even fewer had PIP joint OA (n = 32); therefore, a small association may have been missed. Nevertheless, hip joint space narrowing (<2.5 mm) and hip and knee OA (K/L grade 2+) were associated with DSN progression. For progression of AO, the associations were weaker overall, possibly suggesting different pathologic processes initiating and perpetuating deterioration of these features.
A recent family-based study has suggested a genetic relationship between generalized OA and disc degeneration, which may explain concordance at different sites (1). The association of knee OA with DSN may suggest a common mechanism through obesity, although it remained after adjustment. The clustering of risk factors and OA at other sites suggests that disc degeneration should be treated as part of the spectrum of OA diseases rather than as a distinct isolated entity.
The study has certain limitations. The rates we found may only apply to white women (2). We used a grade 1+ definition for progression, in keeping with traditional definitions of progression at other joint sites (34). The definitions of progression are problematic, however, given the lack of standard accepted or validated definitions and the high prevalence rates of grade 1 individual features, particularly osteophytes. The numbers of progressors for a grade 2+ definition of progression were too small to analyze. Similarly, the numbers of progressors for a grade 1+ definition at more than one vertebral level were too small to analyze.
Given the multilevel nature of disc degeneration, we performed a multivariate analysis using the generalized estimating equation, which permitted the addition of one or more affected vertebrae over time in an individual subject, allowing all information to be used and thus maximizing the power of our study. This analysis strengthened the relationship of the predictors of progression of lumbar spine disc degeneration (data not shown). Although we tested a number of risk factors, we chose putative risk factors that we believed were biologically plausible as causative agents and that had previously been examined in cross-sectional prevalence studies. We were also unable to assess different categories of back pain severity, since we only had the single definition at baseline. The relationship of symptoms with radiographic findings would have been even stronger if we had selected a group with more severe disease.
Facet joints were not examined, since unfortunately they are not easily or consistently visualized on lateral lumbar spine radiographs. We did not grade or examine for the presence of spondylolisthesis in our subjects. Low-grade spondylolisthesis (<25% slip) occurs in 5–10% of the population, has no known relationship to the development of lumbar spine disc degeneration, and rarely progresses in adulthood. The presence of spondylolisthesis may have influenced the relationship between the presence of DSN and back pain in our subjects; however, the reported evidence for a relationship between spondylolisthesis and low back pain is weak.
In summary, this is the first population-based longitudinal study to assess the individual features of AO and DSN in lumbar spine disc degeneration. Disc degeneration occurs at rates of 3–4% per annum. Age, back pain, and radiographic hip and knee OA all predicted progression. The associations were generally stronger for DSN than for AO. The explanation for the differences in risk factors for the individual features may shed light on the pathophysiology of lumbar spine disc degeneration. Greater understanding of the clinical epidemiology of the disorder and its relationship with OA at other sites should promote the disease from relative research obscurity and raise its potential for study as an outcome measure, especially with regard to future therapeutic cartilage- and bone-modifying agents.
We thank the staff and patients of Highams Park Medical Partnership and Chingford Hospital. We also thank Maxine Daniels and Tina Worthy for assistance with data collection.