Osteoarthritis (OA) is the most common arthropathy worldwide, and a major cause of disability and impairment in quality of life. It is a chronic, slowly progressive arthropathy; hence, longitudinal studies evaluating its natural history are lengthy, costly, and often impractical to perform. Although several factors have been associated with incident OA and with OA disease severity, it has been difficult to establish both their sequence of onset and whether they are causally involved in OA pathophysiology.
The role of biomechanics has been an important area of investigation in OA, especially dynamic joint loading during physiologic activity (1). The peak external knee adduction moment, a validated gait parameter that reflects the load at the medial compartment of the knee (2), has been associated with pain, radiographic severity, and progression of knee OA (3–5). Although one study demonstrated that high adduction moments preceded the onset of knee pain symptoms (5), most of the other studies conducted to date have evaluated the relationship between dynamic joint loads and already established OA; it has not yet been clearly shown that elevated peak dynamic loads precede the development of symptomatic knee OA.
In addition to gait analyses and dynamic loading, complementary information is provided by assessing subchondral areal bone mineral density (BMD) (gm/cm2) at the tibial plateau, which reflects load history across the joint (6–9), and can be assessed noninvasively using dual x-ray absorptiometry (DXA).
We previously observed that in patients with end-stage unilateral OA of the hip, advanced OA more frequently develops in the contralateral knee (which is on the opposite side of the body from the affected hip) than the ipsilateral knee (10); moreover, we also reported that the contralateral knee was subjected to substantially higher peak dynamic loads than the ipsilateral knee, and that these asymmetries remained constant several years after hip replacement (11). These previous observations in unilateral hip OA, in which the contralateral knee is known to be at elevated risk for developing OA relative to the ipsilateral knee, suggest a unique model to study factors involved in the pathogenesis of early (presymptomatic) knee OA.
Using that model (Figure 1), we evaluated dynamic joint loading and proximal tibial BMD in patients who have unilateral hip OA but do not have OA symptoms in the knees, in order to test the hypothesis that they have elevated dynamic loads and increased tibial BMD at the contralateral knee compared to the ipsilateral knee. This would demonstrate that these loading asymmetries are present during an early presymptomatic state.
Figure 1. Unilateral hip osteoarthritis (OA) study model. The knee contralateral to the affected hip was observed to have higher dynamic joint loads and higher medial tibial bone mineral density compared to the ipsilateral knee.
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- PATIENTS AND METHODS
- AUTHOR CONTRIBUTIONS
Of the 124 patients screened, 62 met the inclusion criteria and completed the study. Figure 1 illustrates the unilateral hip OA model, to relate the ipsilateral and contralateral associations with the results of this study. General patient demographic and baseline characteristics are summarized in Table 1. The mean ± SD age of the patients was 62 ± 11 years. There were 26 men and 36 women. Complete WOMAC data were missing for 1 patient. The mean ± SD baseline pain scores (adjusted to a 100-mm scale) were higher for the ipsilateral knee compared to the contralateral knee, but were extremely low in both cases (10 ± 18 mm and 5 ± 8 mm, respectively; P = 0.006).
Table 1. Characteristics of the 62 patients with unilateral hip osteoarthritis*
|Age, years||62 ± 11|
|Sex, no. male/female||26/36|
|BMI, kg/m2||28 ± 5|
|WOMAC pain VAS, 0–100 mm|| |
| Affected hip||37 ± 24|
| Unaffected hip||6 ± 11|
| Ipsilateral knee||10 ± 18|
| Contralateral knee||5 ± 8|
|WOMAC stiffness VAS, 0–100 mm|| |
| Affected hip||42 ± 29|
| Unaffected hip||9 ± 17|
| Ipsilateral knee||12 ± 18|
| Contralateral knee||7 ± 14|
|K/L grade (0–4), no. of patients|| |
| Affected hip|| |
| Unaffected hip|| |
| Ipsilateral knee|| |
| Contralateral knee|| |
Appropriate gait data for analyses were available for 58 patients. Gait data from 3 of the patients were excluded due to malfunction of the gait analysis equipment during the examination. Bone mineral density of the knees bilaterally was evaluated in 55 patients.
Gait results from the ipsilateral and contralateral limbs are summarized in Table 2. As expected, dynamic hip range of motion was significantly greater at the contralateral hip compared to the affected hip (P < 0.001). Peak hip moments, including the peak hip flexion (P = 0.003), adduction (P = 0.018), internal rotation (P < 0.001), and external rotation moments (P = 0.037) were significantly higher at the contralateral unaffected hip compared to the ipsilateral osteoarthritic hip.
Table 2. Gait characteristics and bone density in individual limbs*
|Characteristic||Ipsilateral (affected hip) limb||Contralateral (unaffected hip) limb|
|Flexion–extension ROM, degrees|| || |
| Hip ROM||21 ± 8||29 ± 6†|
| Knee ROM||60 ± 6||62 ± 4|
|Peak moments, %BW × height|| || |
| Hip flexion||4.75 ± 1.49||5.66 ± 2.09†|
| Hip adduction||3.06 ± 0.98||3.36 ± 0.94†|
| Hip internal rotation||0.45 ± 0.25||0.57 ± 0.23†|
| Hip external rotation||0.37 ± 0.26||0.46 ± 0.22†|
| Knee flexion||1.43 ± 0.97||1.79 ± 1.26|
| Knee adduction||2.23 ± 0.81||2.46 ± 0.71†|
|Knee compartmental loads, × BW|| || |
| Medial compartment load||1.96 ± 0.63||2.23 ± 0.52†|
| Lateral compartment load||1.23 ± 0.35||1.41 ± 0.48†|
|Bone mineral density, gm/cm2|| || |
| Medial tibial plateau||0.854 ± 0.206||0.897 ± 0.208†|
| Lateral tibial plateau||0.726 ± 0.190||0.744 ± 0.195|
In the knees, both primary gait outcome measures, the peak external knee adduction moment (P = 0.029) and the total medial compartment knee load (P = 0.003), were significantly higher at the contralateral knee relative to the ipsilateral knee, as was the lateral compartment load (P = 0.008). Additionally, the peak knee flexion moment appeared to be higher at the contralateral knee, but this did not reach statistical significance (P = 0.052).
Medial tibial plateau BMD was significantly higher at the contralateral knee relative to the ipsilateral knee (P = 0.033). However, there were no significant differences at the lateral tibial plateau (P = 0.469) (Table 2).
Bivariate correlations between contralateral:ipsilateral knee dynamic loading and BMD revealed that the ratio of contralateral:ipsilateral medial compartment knee BMD was directly correlated with contralateral:ipsilateral peak external knee adduction moment (ρ = 0.287, P = 0.036) and contralateral:ipsilateral knee medial compartment load (ρ = 0.351, P = 0.009).
Considering that radiographic changes at the contralateral hip in some patients were graded 3 on the K/L scale, despite minimal clinical symptoms of pain, a separate analysis was performed, excluding these participants. The asymmetry between the contralateral knee and ipsilateral knee medial tibial BMD remained significant (in 47 patients, mean ± SD 0.892 ± 0.199 gm/cm2 versus 0.845 ± 0.212 gm/cm2, respectively; P = 0.030). The asymmetry in the peak external knee adduction moment remained, but lost significance (in 46 patients, mean ± SD 2.39 ± 0.69 %BW*ht versus 2.18 ± 0.75 %BW*ht; P = 0.075). The correlation between contralateral:ipsilateral medial compartment knee BMD and peak external knee adduction moment (ρ = 0.406, P = 0.006) and contralateral:ipsilateral knee medial compartment load (ρ = 0.454, P = 0.002) strengthened and remained significant.
Similarly, an analysis that excluded knees with a K/L grade of 2 or 3 was performed. Once again, the asymmetry between the contralateral knee and ipsilateral knee medial tibial BMD remained significant (in 35 patients, 0.901 ± 0.217 gm/cm2 versus 0.851 ± 0.218 gm/cm2, respectively; P = 0.05). The asymmetry in the peak external knee adduction moment remained, but lost significance (in 36 patients, 2.51 ± 0.73 %BW*ht versus 2.31 ± 0.69 %BW*ht; P = 0.109). The correlation between contralateral:ipsilateral medial compartment knee BMD and the peak external knee adduction moment lost significance (ρ = 0.310, P = 0.079); however, the correlation with the contralateral:ipsilateral knee medial compartment load remained significant (ρ = 0.452, P = 0.008).
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- PATIENTS AND METHODS
- AUTHOR CONTRIBUTIONS
This study demonstrates that, in unilateral hip OA, the contralateral knee is subjected to significantly higher dynamic joint loading, as assessed by peak external knee adduction moment and by total medial compartment loads, relative to the ipsilateral knee. Importantly, this asymmetry of knee loading is observable even when knees are asymptomatic and have no clinical evidence of OA. Moreover, the significant asymmetries observed in the proximal tibial BMD of the contralateral versus ipsilateral knees also provide evidence of substantially altered load history in the knees. This study, along with data from our previous study demonstrating asymmetric progression of knee OA in those with unilateral hip OA (10), provides support for the notion that alterations in dynamic joint loading may precede the onset of symptomatic knee OA in humans. In addition, our findings support the idea of a relationship between dynamic loading and measures of load history in OA.
In a study of adults from the general population, Amin and colleagues demonstrated that the development of new chronic knee pain over 3–4 years was associated with significantly higher baseline knee adduction moments, compared to those who did not develop pain (5). The results of the current study provide further support to the notion that high dynamic loads may precede knee pain symptoms.
The asymmetry in knee loading in unilateral hip OA was first described in a population with end-stage hip disease (in patients awaiting total hip replacement) and interestingly, was shown to persist for up to 2 years, even after hip replacement and complete resolution of hip pain (11). The current study demonstrates that loading asymmetries at the knees begins early in the disease course of hip OA, suggesting that the relative overload of the contralateral knee that places it at higher risk of developing advanced OA is likely already established years before the progression of hip OA to end-stage disease. These results may have implications for interventional treatments that target unilateral hip OA in order to prevent or minimize these asymmetries early in the disease course.
Increased loading was observed in both the contralateral hip and the contralateral knee, which is presumably related to a pain response in the ipsilateral limb. This pain–loading relationship, which was previously demonstrated in knee OA to actually show increased loading at the affected joint after analgesic treatment for pain (3, 25), complicates the interpretation and evaluation of the relationship between loading and disease. Whereas loading and disease severity are directly related, pain (the principal symptom of OA) may actually result in decreased loading. In contrast, a unique aspect of this study, and of the unilateral hip OA model, is the ability to assess the knees without the confounding influence of localized knee pain.
The asymmetries noted in the subchondral BMD of the proximal tibiae, which reflected those observed in medial knee loads, provide evidence of the structural consequences of loading alterations, particularly since the relative loading and bone density asymmetries were directly associated. Although the relationship between dynamic knee loading and tibial BMD has previously been reported (6, 26), the observation of asymmetric BMDs reflecting asymmetric knee loading and asymmetric risk of progressive knee OA is novel. Interestingly, this is consistent with previous reports on OA of the hip, which suggested that increased hip BMD was associated with an increased risk of disease progression (27).
It should be noted that, while the knees of our study participants were explicitly asymptomatic, several were found to have radiographic evidence of OA. Because radiographic OA is almost universal in the age group studied, these subjects are likely more representative of a “normal” population than if those with radiographic OA had been completely excluded. It is for this reason that this study utilized a more clinically relevant definition of OA than one based purely on structural degeneration. In addition, it has previously been demonstrated that individuals who are asymptomatic, but have K/L grade 2 radiographic disease, are biomechanically indistinguishable from normal subjects who have no structural degeneration (28), whereas those who have K/L grade 2 radiographic knee OA and OA symptoms have significantly elevated peak adduction moments. This suggests that those with clinically evident OA are fundamentally different from those without clinical OA.
It should also be noted that increased loading at the contralateral knee and hip in this model of unilateral hip OA is in comparison to the ipsilateral side. It is not necessarily that the loading at the contralateral side is higher than that in a “normal” population. Nevertheless, the important concept is that this comparative asymmetry in loading precedes the corresponding asymmetric progression of knee OA in this group.
This study provides some evidence that in the contralateral knees of patients with unilateral hip OA, which are at high risk of developing progressive symptomatic OA, loading and structural asymmetries appear early in the disease course, while the knees are still asymptomatic. Thus, this model suggests that these early biomechanical asymmetries may have corresponding long-term consequences, providing further evidence of a role of loading in OA progression.
- Top of page
- PATIENTS AND METHODS
- AUTHOR CONTRIBUTIONS
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 published. Dr. Shakoor 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. Shakoor, Thorp, Block.
Acquisition of data. Shakoor, Dua, Thorp, Mikolaitis, Wimmer, Foucher.
Analysis and interpretation of data. Shakoor, Dua, Thorp, Wimmer, Fogg.