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Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. Acknowledgements
  9. REFERENCES

Objective

We conducted a cross-sectional study to describe the prevalence of tibiofemoral joint space narrowing (JSN) in medial and lateral compartments and assess whether it differs by sex and ethnic groups, and, if it does, to what extent such a difference is accounted for by knee malalignment.

Methods

The Multicenter Osteoarthritis Study is an observational study of persons ages 50–79 years with either symptomatic knee osteoarthritis or high risk of disease. Knee radiographs were assessed for JSN in each tibiofemoral compartment. Mechanical axis angle was measured using full-extremity films. We compared the proportion of knees with medial compartment JSN and with lateral JSN between men and women, as well as between whites and African Americans, using a logistic regression model adjusting for covariates (race or sex and body mass index, age, education, and clinic site). We used generalized estimating equations to account for correlation between 2 knees within a person.

Results

Of 5,202 knees (2,652 subjects), 1,532 (29.5%) had medial JSN and 427 (8.2%) had lateral JSN. Lateral JSN was more prevalent in the knees of women than in men (odds ratio [OR] 1.9, 95% confidence interval [95% CI] 1.5–2.4) and was also higher in the knees of African Americans than in whites (OR 2.4, 95% CI 1.7–3.3). Further adjustment for malalignment attenuated the OR for sex but not the OR for race.

Conclusion

Women and African Americans are more likely to have lateral JSN than men and whites, respectively. Valgus malalignment may contribute to the higher prevalence in women.


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. Acknowledgements
  9. REFERENCES

Knee osteoarthritis (OA) is one of the most common causes of pain and disability in the elderly (1–4). Approximately 12% of US adults age >60 years experience symptomatic knee OA, and prevalence of knee OA is increasing due to both aging and obesity (5). Overall, tibiofemoral knee OA is more commonly seen in the medial than lateral compartment, possibly because of heavier loading in the former (6). Joint space narrowing (JSN) is an important compartment-specific manifestation of knee OA with demonstrated associations with important clinical outcomes including pain (7).

Numerous studies have reported that the prevalence of OA in different joints and clinical manifestations vary in sex and ethnic groups. For example, the prevalence of radiographic and symptomatic OA in hands, knees, and hips was higher in women than in men age >45 years (8), and African Americans were more likely to have radiographic knee OA than non-Hispanic whites (5). A few studies also found that the prevalence of OA in the different compartments of a specific joint differed between ethnic groups. Braga et al reported a higher likelihood of radiographic findings of lateral sclerosis and lateral JSN in African Americans than in whites (9, 10). Data from the Framingham and Beijing Osteoarthritis Studies also demonstrated that among individuals with radiographic tibiofemoral OA, the proportion of knees with lateral compartment OA was much higher in the Chinese than in whites (11). The reasons for these differences in OA prevalence between sex and racial groups are not clearly understood.

Knee malalignment is strongly associated with an increased risk of OA progression. Biomechanical evidence demonstrates that varus malalignment increases force through the medial compartment, whereas valgus malalignment places a greater proportion of the force through the lateral compartment of the knee (12). If the prevalence of knee malalignment varied between sex and racial groups, it could lead to different patterns of OA in different compartments of the knee. To date, only a few studies have tested this hypothesis. The results are conflicting. Among individuals without knee OA, Harvey et al have reported that Chinese persons have a more valgus mean distal femur alignment than whites (13). Braga et al found no difference by race in knee alignment between African Americans and whites using anatomic angle (14, 15).

We hypothesized that there is a higher prevalence of lateral compartment JSN in women than in men and in African Americans than in whites. Secondarily, we hypothesized that differences by sex and race in malalignment prevalence would explain in part the observed differences in JSN prevalence. Using the data collected from the Multicenter Osteoarthritis (MOST) Study, we compared the prevalence of radiographic OA feature JSN in the medial and lateral knee compartments between men and women, as well as between whites and African Americans, and examined to what extent such difference in prevalence was accounted for by prevalence of knee malalignment.

Significance & Innovations

  • We used a large, well-characterized multicenter osteoarthritis (OA) cohort to elucidate knee joint space narrowing compartment patterns by sex and race.

  • We identified differences in lateral compartment disease, a relatively understudied component of knee OA.

  • We explored in detail the contribution of alignment to observed differences by sex and race in patterns in knee OA using mechanical axis measures obtained from long-extremity films.

  • Understanding variations in patterns of knee OA by sex and by race may enable the identification of previously neglected subsets of patients who may have different risks for functional outcomes or arthroplasty than the general population of persons with OA.

PATIENTS AND METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. Acknowledgements
  9. REFERENCES

The MOST study is an observational study of risk factors for individuals who either had or were at high risk of knee OA due to obesity, knee pain, aching or stiffness on most of the previous 30 days, a history of knee injury, or a history of knee surgery. A total of 3,026 subjects, ages 50–79 years at enrollment, were recruited from 2 US communities: Birmingham, Alabama, and Iowa City, Iowa. A detailed description of the study population has been published previously (16).

At the clinic visit, subjects were queried about social demographic information, including age, sex, and ethnic origin. Race was assessed at baseline by the question “what is your racial background?” with potential answers being “white or Caucasian, black or African American, Asian, American Indian or Alaskan native, Hawaiian or other Pacific islander, more than one race, other, don't know.” Information about knee injury was collected by self-report using the question asked at baseline for each knee, “Have you ever injured your knee badly enough to limit your ability to walk for at least two days?”

Participants in the MOST study had baseline bilateral weight-bearing, fixed flexion posteroanterior (PA) and lateral radiographs collected (17). The knee radiographs were scored by 2 readers (1 rheumatologist and 1 musculoskeletal radiologist). The medial and lateral tibiofemoral compartment were scored for maximal JSN grade on a semiquantitative scale based on the Osteoarthritis Research International Radiographic Atlas (range 0–3, where 0 = normal, 1 = mild, 2 = moderate, and 3 = severe) (17, 18). The weighted kappa for interrater reliability for medial JSN was κ = 0.81 on the PA view and κ = 0.78 on the lateral view. The weighted kappa for interrater reliability for lateral JSN was 0.86 on the PA view and 0.84 on the lateral view.

Knees were further divided into 4 groups according to the presence of JSN at a specific compartment: 1) isolated medial compartment JSN, where JSN was >0 in the medial compartment only, 2) isolated lateral compartment JSN, where JSN was >0 in the lateral compartment only, 3) mixed medial and lateral compartment JSN, where JSN was >0 in both the lateral and medial compartments, and 4) no JSN, where JSN = 0 in both the medial and lateral compartments. In this analysis, “lateral JSN” refers to the combination of isolated lateral compartment JSN and mixed medial and lateral JSN, whereas “medial JSN” refers to the combination of isolated medial compartment JSN and mixed medial and lateral JSN. Thus, our main analysis examines lateral JSN irrespective of medial JSN presence and medial JSN irrespective of lateral JSN presence. We also defined a group of subjects with both medial and lateral compartment JSN and referred to it as a “bicompartmental” JSN.

Knee malalignment was assessed using long-extremity films in the MOST study. A knee was defined as having valgus malalignment if its mechanical axis was >181°, neutral malalignment if its mechanical axis was between 179° and 181°, and varus malalignment if its mechanical axis was <179°. The intraclass correlation coefficient for assessment of mechanical axis was 0.95 with P < 0.001 (19).

We calculated the sex-specific prevalence of compartment-specific JSN (i.e., medial and lateral JSN) for whites and African Americans, separately. We compared the prevalence of compartment-specific JSN between sex and between racial groups using a logistic regression model. Variables included in the multivariable logistic regression models were sex, race, age, body mass index (BMI), education, prior injury to knee, and clinic site. We used generalized estimating equations to account for the correlation between knees within a person. Finally, we assessed whether differences in the prevalence of lateral compartment JSN between sex and racial groups could be explained by knee mechanical axis by entering knee alignment into the regression model.

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. Acknowledgements
  9. REFERENCES

Of 3,026 participants at baseline visit, 2,981 (98.5%) were either white or African American. We excluded 850 knees that had either total knee replacement or missing data on JSN, knee alignment, history of knee injury, or BMI, leaving 2,652 subjects (5,202 knees) in the final analysis.

The characteristics of the subjects are presented in Table 1. Compared with women, men had a higher percentage of college education and history of knee injury, and a lower prevalence of valgus alignment. Overall, whites were older, had a lower BMI, and had a higher percentage of college education, as well as a lower prevalence of valgus alignment than African Americans.

Table 1. Characteristics of subjects (n = 2,652)*
 Men (n = 1,066)Women (n = 1,586)PAfrican American (n = 371)White (n = 2,281)P
  • *

    BMI = body mass index.

  • Knee alignment is a knee-based measurement, assuming 2 knees per person.

Age, mean ± SD years62.3 ± 8.262.6 ± 7.90.32759.5 ± 7.963.0 ± 7.9< 0.001
BMI, mean ± SD kg/m230.3 ± 5.030.7 ± 6.20.15433.0 ± 6.430.1 ± 5.5< 0.001
Education, %      
 High school or less27.029.5 33.227.8 
 Some college22.329.1< 0.00131.525.5< 0.001
 College graduate or higher50.7741.4 35.346.7 
Knee injury, %31.521.0< 0.00120.526.00.004
Knee alignment, % degrees      
  Varus <17960.040.3 51.147.8 
  Neutral 179–18130.835.0< 0.00128.734.00.016
  Valgus >1819.224.7 20.218.2

As shown in Table 2, women had a higher prevalence of lateral compartment JSN than men in both African Americans and whites, although the difference did not reach significance among African Americans. Women also had a higher prevalence of medial compartment JSN than men in African Americans; among whites, men had a higher prevalence of medial compartment JSN. African Americans had a higher prevalence of lateral compartment JSN than did whites, in both women and men.

Table 2. Frequency (no.) and prevalence (%) of compartment-specific JSN by sex and race (n = 5,202)*
JSN statusAfrican AmericanWhiteMen vs. women, PAfrican American vs. white, P
MenWomenMenWomenAfrican AmericanWhitesMenWomen
  • *

    Medial joint space narrowing (JSN) and lateral JSN both include bicompartmental JSN.

Knees, total no.2564661,8362,644    
JSN, no. (%)        
 Medial69 (27.0)170 (36.5)572 (31.1)721 (27.3)0.0430.0240.2950.001
 Lateral32 (12.5)78 (16.8)89 (4.8)228 (8.6)0.184< 0.001< 0.001< 0.001
Bicompartmental JSN, no. (%)12 (4.7)32 (6.9)30 (1.6)45 (1.7)0.3250.8640.010< 0.001
No JSN, no. (%)167 (65.2)250 (53.6)1,205 (65.6)1,740 (65.8)0.0160.9900.902< 0.001

Adjusting for potential confounding factors other than malalignment, the prevalence of lateral JSN was significantly higher in women than in men (Table 3). However, after adding knee alignment into the regression model, the magnitude of this effect was attenuated and the association became statistically insignificant. In contrast, for medial JSN, adding knee alignment into the regression model not only changed the direction of association but also made it statistically significant. The association between sex and bicompartmental JSN was insignificant irrespective of adjustment (Table 3).

Table 3. Association between sex and compartment-specific disease*
CompartmentCrudeAge, race, BMI, injury, education, clinic siteAge, race, BMI, injury, education, clinic site, alignment
OR (95% CI)OR (95% CI)POR (95% CI)P
  • *

    Reference group is men. Medial joint space narrowing (JSN) and lateral JSN both include bicompartmental JSN. BMI = body mass index; OR = odds ratio; 95% CI = 95% confidence interval.

Lateral JSN1.8 (1.4–2.3)1.9 (1.5–2.4)< 0.0011.1 (0.9–1.5)0.402
Medial JSN0.9 (0.8–1.1)0.9 (0.8–1.0)0.1741.3 (1.1–1.5)0.002
Bicompartmental JSN1.2 (0.8–1.9)1.2 (0.8–1.9)0.3721.1 (0.7–1.8)0.622

As shown in Table 4, prevalence of lateral JSN in African Americans was much higher than in whites. Further adjustment for knee malalignment did not change the magnitude of the association materially. On the other hand, no association was found between race and the prevalence of medial JSN, and adjustment for knee malalignment did not change the effect estimate at all. African Americans were far more likely to manifest bicompartmental JSN than were whites, and again this association was not altered by adjusting for alignment.

Table 4. Association between race and compartment-specific disease*
CompartmentCrudeAge, sex, BMI, injury, education, clinic siteAge, sex, BMI, injury, education, clinic site, alignment
OR (95% CI)OR (95% CI)POR (95% CI)P
  • *

    Reference group is whites. Medial joint space narrowing (JSN) and lateral JSN both include bicompartmental JSN. BMI = body mass index; OR = odds ratio; 95% CI = 95% confidence interval.

Lateral JSN2.3 (1.8–3.1)2.4 (1.7–3.3)< 0.0012.6 (1.8–3.7)< 0.001
Medial JSN1.2 (1.0–1.5)1.2 (1.0–1.6)0.0971.2 (0.9–1.5)0.289
Bicompartmental JSN3.8 (2.4–5.9)3.6 (2.1–6.0)< 0.0013.6 (2.1–6.0)< 0.001

When we examined the distribution of malalignment among subjects without tibiofemoral radiographic OA (TFROA), women were more likely to have valgus malalignment than men, but no difference was observed between African Americans and whites. Among the knees without TFROA (Kellgren/Lawrence grade ≤2), the prevalence of varus malalignment was higher in men and African Americans than in women and whites, respectively (Table 5).

Table 5. Malalignment by sex and race among those without tibiofemoral radiographic osteoarthritis*
KneesMalalignment
VarusValgus
  • *

    Values are the number (percentage) unless indicated otherwise.

Sex  
 Men (n = 1,372)707 (51.5)137 (10.0)
 Women (n = 1,990)631 (31.7)495 (24.9)
 P< 0.001< 0.001
Race  
 White (n = 2,945)1,151 (39.1)553 (18.8)
 African American (n = 417)187 (44.8)79 (18.9)
 P0.0910.986

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. Acknowledgements
  9. REFERENCES

We found that the prevalence of lateral knee JSN is higher in women than in men, and higher in African Americans than in whites. After adjusting for alignment, this difference disappeared between men and women but remained significant between whites and African Americans. This finding suggests that alignment may be an important factor in the etiology of lateral JSN, but that factors other than alignment may account for observed differences by race. Also, the prevalence of bicompartmental disease is much higher in African Americans than in whites, but no difference was observed between sexes; thus, the findings for bicompartmental disease bear similarities to the findings for lateral compartment JSN, suggesting that those relationships may be driven by the lateral JSN component of the mixed disease. It should be noted also that the group with bicompartmental disease is actually quite small and does not drive the results for lateral JSN. In fact, bicompartmental disease may represent a later stage and more severe lateral compartment disease.

The examination of patterns of joint involvement in OA may have clinical relevance. First, understanding these patterns gives insight into the potential pathologic mechanisms that underlie the development of the condition in general. If these patterns vary by sex or by race, this affords an opportunity to begin to understand the risk factors for OA in different populations. Furthermore, exploration of these variations may enable the identification of previously neglected subsets of patients who may have different risks for functional outcomes or arthroplasty than the general population of persons with OA. Since past OA studies have primarily focused on medial compartment disease, risk factors for lateral compartment OA have been relatively understudied.

Research on the variation in compartment of JSN by sex is limited. Weidow et al reported that lateral OA of the knee was associated with a wider pelvis and shorter femoral neck (20) than in women with medial compartment disease. Although these measures are not exactly equivalent to knee alignment, it is possible that changes in the geometry of the pelvis and femoral neck may affect knee alignment. Our findings suggest that, at least in women in the subgroup with lateral compartment OA, alignment may also play a role.

We found that the prevalence of malalignment of the knee differs in sex and racial groups among individuals without radiographic OA. Nelson et al noted no difference in valgus knee malalignment by race in the Johnston County cohort using anatomic axis measurement, and our findings using mechanical axis confirm this (15). Our findings that the prevalence of valgus malalignment is much higher in women and that adjustment for valgus malalignment removed the difference in prevalence of lateral compartment JSN between men and women suggests that, at least in some groups, valgus malalignment plays a role in lateral compartment knee OA. The presence of varus malalignment is higher among men and adjustment for malalignment revealed significantly greater odds of medial compartment JSN in women as compared with men. This may suggest that malalignment also plays a role in medial compartment knee OA in some groups.

Sharma et al found that in the MOST cohort varus but not valgus alignment was associated with incident knee OA, and also that varus alignment was associated with risk of progression of medial OA and valgus alignment with risk of lateral progression (21). Our finding that adjusting for valgus malalignment did not reduce the difference in prevalence of lateral JSN between African Americans and whites is interesting in this light: the 2 analyses parallel along the concept that valgus malalignment does not predispose to lateral compartment OA, but may contribute to a “vicious circle” of OA progression in the lateral compartment. If this is the case, then our finding that adjusting for malalignment makes insignificant the differences between men and women most likely represents a manifestation of this circle of disease progression, rather than a cause of the higher prevalence of lateral compartment OA in women. However, the higher prevalence of valgus malalignment in women without TFROA argues for an etiologic role in that group.

Mazzuca et al reported that the incident radiographic knee OA in African Americans was 3-fold greater than whites but did not evaluate compartmental differences (22). Some potential reasons for increased prevalence of lateral JSN in African Americans compared with whites include differences in life activity, hormonal or neuronal differences, and bone developmental differences in the hip or knee shape. Felson et al commented that the difference in compartment-specific prevalence of knee OA between the Chinese population and whites may suggest “…fundamentally different etiologies [for knee OA] in different cultures” (11). In the present study, although certainly cultural differences may exist between whites and African Americans within the US, these differences are likely to be very minor compared with the differences between persons living in Beijing, China, and Framingham, Massachusetts. However, there may be differences by race in the type of labor done that we could not correct for directly, but which adjusting for education partly corrects.

Although our findings do not support a role for valgus malalignment in explaining differences in prevalence of lateral compartment OA by race, it is important to emphasize that these measurements are of static alignment. Dynamic alignment is by definition different in either kind or degree from static alignment in a knee. Chang et al found that African Americans in the Osteoarthritis Initiative Study had significantly greater odds of valgus thrust, both in those with and in those without knee OA (23). Increased frequency of valgus thrust in African Americans may represent a partial explanation for the differences in lateral compartment JSN by race that we have identified in the MOST study. Although somewhat different in approach, the findings of Chang et al (23) and the present paper are consistent, mutually supportive, and reinforcing.

Several characteristics of this study are worth noting: the radiologic studies in the MOST study are well performed, standardized radiographs were taken and were read across all racial/ethnic strata, and the readings have excellent reliability. Mechanical axis was measured using full-extremity films, rather than anatomic axis. Finally, the number of subjects in both the African American group and white group is large enough that findings from this study are unlikely to be due to random error.

However, this study has limitations. Misclassification of compartment JSN, especially the mixed lateral and medial compartment JSN, could occur. However, there is also likely to be misclassification due to the relative insensitivity of the ordinal JSN measure to true differences in the joint space, and this may have biased our results and weakened the observed associations. Also, these are cross-sectional data, not longitudinal, so the full picture of the lateral compartment JSN knee OA over time might not be demonstrated. Finally, there may also be misclassification error of race by self-report.

In summary, the prevalence of medial and lateral compartment JSN varies by sex and between African Americans and whites. This difference by sex is partly accounted for by a difference in prevalence of knee malalignment between comparison groups, but racial group differences are not altered by adding malalignment into the model. Longitudinal studies are needed to elucidate the role of lateral compartment disease in the development and worsening of knee OA.

AUTHOR CONTRIBUTIONS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. Acknowledgements
  9. REFERENCES

All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be submitted for publication. Dr. Wise had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study conception and design. Wise, Lane, Hietpas, Nevitt, Zhang.

Acquisition of data. Felson, Hietpas, Nevitt, Torner, Lewis, Zhang.

Analysis and interpretation of data. Wise, Niu, Yang, Lane, Harvey, Felson, Nevitt, Sharma, Zhang.

Acknowledgements

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. Acknowledgements
  9. REFERENCES

The authors would like to thank the MOST study participants.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. Acknowledgements
  9. REFERENCES
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