Association of leg-length inequality with knee osteoarthritis: a cohort study.
Context Unequal leg length is common and may play a role in a variety of musculoskeletal conditions, including osteoarthritis of the knee. Previous studies of leg-length inequality and osteoarthritis have been small and cross-sectional and have often focused on biomechanical rather than clinical outcomes. Contribution This study used radiography to evaluate leg length in 3026 adults. After following participants for 30 months, the researchers found leg-length inequality of 1 cm or more to be associated with prevalent, incident, symptomatic, and progressive knee osteoarthritis that was strongest in the shorter leg. Implication Future studies should evaluate whether leg-length inequality is a modifiable risk factor for knee osteoarthritis. The Editors Leg-length inequality, defined as a difference in lengths of the 2 legs, is very common, occurring in up to 70% of the population (1). Leg-length inequality may be caused by trauma or mild developmental abnormalities, with onset in birth or childhood. It has been implicated as a cause of several conditions, including low back pain; trochanteric bursitis; osteoarthritis of the hip and knee; knee pain; and running injuries, such as Achilles rupture (210). Various imaging techniques have been used to measure leg-length inequality. Radiography is the gold standard for measurement, with accepted methods including full-limb radiography, scanography (3 separate exposures of the hip, knee, and ankle), and computerized digital radiography (11). In addition, magnetic resonance imaging and computed tomography can be used but are costly. Although susceptible to parallax error, full-limb radiography, with measurement from the femoral head to the ankle, is the most commonly used method (12). Studies of leg-length inequality have mostly been small, uncontrolled, and cross-sectional, and some have used artificially induced leg-length inequality (shoe inserts) to study the effects of this disorder on biomechanical asymmetry during motion. Bhave and colleagues (13) reported that leg-length inequality causes increased ground-reaction forces in the longer leg. Because it has to come from a higher level to reach the ground during walking, a shorter leg would probably also incur an increased ground-reaction force compared with legs that are equal in length. Therefore, compared with legs of equal length, both shorter and longer legs may subject the knee to increased biomechanical loading and may increase the risk for osteoarthritis of the knee. However, we are not aware of any longitudinal study assessing risk. Few studies have specifically evaluated the association between leg-length inequality and knee osteoarthritis. Because articular cartilage is lost with the development of knee osteoarthritis, leg-length inequality can develop as a consequence of disease. A longitudinal study is needed to evaluate causal effects. Any study of leg-length inequality and knee osteoarthritis should control for alignment, because severe angular deformity from malalignment increases risk for knee osteoarthritis and, if present in only 1 leg, could cause leg-length inequality. In studies of leg-length inequality as a risk factor for other musculoskeletal disorders, such as low back pain or trochanteric bursitis, no definitive effect of inequality has been noted and no specific threshold has been determined (3, 4, 7, 9, 10, 14). We studied the relationship between leg-length inequality and knee osteoarthritis in the MOST (Multicenter Osteoarthritis Study). The goals of MOST are to characterize risk factors for knee osteoarthritis progression and incidence. Our study had 2 objectives: to describe the cross-sectional relationship between leg-length inequality by radiographic measurement and prevalent knee osteoarthritis, and to examine the relationship between leg-length inequality and both incident and progressive knee osteoarthritis. Although clinical intervention is generally targeted when leg-length inequality is 2 cm or more, this value either is arbitrary or is based on small casecontrol studies (6). Therefore, in these 2 objectives, we wished to explore multiple definitions of leg-length inequality to determine whether a more appropriate clinical cutoff value exists. Methods The MOST is a multicenter, longitudinal, community-based study of 3026 participants aged 50 to 79 years with knee osteoarthritis or with high risk for knee osteoarthritis due to knee pain, obesity, knee injury, or knee surgery. At baseline, the parent study collected demographic information (age, sex, height, weight, and body mass index), full-limb radiographs, and standard knee radiographs. Participants were reassessed at a 30-month follow-up visit. Written informed consent was obtained before participation at each visit, as approved by the institutional review boards of the participating institutions (15). Trained technologists measured leg length with full-limb radiography. We defined leg length as the distance from the center of the femoral head to the tibial mid-plafond point (Figure 1, A). The mid-plafond point is the most distal portion of the tibia directly over the talar dome and does not include the ankle joint. We determined reliability of leg-length measurement by using intrarater and interrater testretest measurements performed on 10% of the films, which were reread by readers blinded to initial results. We also determined alignment by measuring the mechanical axis on the full-limb films; the mechanical axis was measured in degrees from the intersection of lines drawn from the above 2 points through the tibial spines (Figure 1, B). We scored standard fixed-flexion and lateral weight-bearing knee radiographs for osteophytes and joint-space narrowing by using the Osteoarthritis Research Society International atlas and the Kellgren and Lawrence grading system (16, 17). Figure 1. Diagram of a bilateral standing full-limb radiograph. A. Measurements of leg-length inequality. B. Mechanical axis alignment. Of participants studied at baseline, 89.6% had 30-month follow-up clinical visits. Although knee radiography was redone at the 30-month follow-up visit to permit assessment of change in radiographic features of osteoarthritis, full-limb radiography was not. Definition of Variables The primary exposure variable was leg-length inequality, calculated from the measurements taken on the full-limb radiographs at baseline. We maintained a leg-specific definition, allowing a knee-based analysis to determine whether the shorter or the longer leg was at higher risk (see Statistical Analysis). Initially, we defined clinically significant leg-length inequality as a difference of 1 cm or more, creating a dichotomous variable (presence or absence of leg-length inequality). We conducted additional analyses by using a leg-length inequality cutoff value of 2 cm or more. We conducted exploratory analyses to determine whether there was an important threshold value of leg-length inequality above which knee osteoarthritis was more likely. We did this by stratifying leg-length inequality into 4 categories: less than 0.5 cm (reference group), 0.5 cm to less than 1 cm, 1 cm to less than 2 cm, and 2 cm or more. Radiographic Definitions of Knee Osteoarthritis We defined prevalent radiographic knee osteoarthritis by using the standard radiographic definition of Kellgren and Lawrence grade 2 or greater (18). In knees with a Kellgren and Lawrence grade less than 2 at baseline, we defined incident knee osteoarthritis as the presence at the 30-month visit of Kellgren and Lawrence grade 2 or greater or new total knee replacement. We defined radiographic knee osteoarthritis progression as an increase in joint-space narrowing score from baseline to the 30-month follow-up or as a new total knee replacement not present at the baseline visit. We chose this definition because progression measured by the Kellgren and Lawrence score is not sensitive to some obvious examples of progression (19). Symptomatic Definitions of Knee Osteoarthritis We defined symptomatic osteoarthritis in accordance with the convention used in MOST analyses (20, 21). We considered a knee to have symptomatic osteoarthritis if radiographic osteoarthritis was present in either or both of the tibiofemoral or patellofemoral compartments (22) and the knee was consistently painful. We defined consistently painful as a response of yes to the question, Do you have knee pain in or around the knee on most days in the past 30 days? at both the telephone call and clinical visit, which were fewer than 30 days apart. We identified prevalent symptomatic osteoarthritis in participants who met this definition at baseline. We identified incident symptomatic osteoarthritis in participants who did not have consistent knee pain and radiographic osteoarthritis at baseline but developed that combination at 30 months. Statistical Analysis We calculated means (SDs) for study participant characteristics. We determined the association of leg-length inequality with prevalent, incident, and progressive knee osteoarthritis by using logistic regression models with generalized estimating equations (23) to account for correlation between knees in a participant. We used baseline visit data to adjust all analyses for the following potential confounders: age, sex, body height, body mass index, and alignment. Alignment is particularly important because, as a potential confounder, it has been associated with progression of knee osteoarthritis in previous studies (24). We measured alignment in degrees as a continuous variable. In our statistical models, we explored the relationship between alignment and our outcomes. Because of the shape of the distribution for the alignment variable, we used a categorical definition of alignment with the following strata: varus (178 degrees), neutral (179 to 181 degrees), and valgus (182 degrees). We ran models controlling for alignment difference (defined as the difference in degrees betwe