Meniscectomy of the knee is associated with a high risk of radiographic knee osteoarthritis (OA) and knee disability at long-term followup (1–5). The OA disease process that commonly follows such injury and intervention is suggested to depend on local biomechanical factors associated with the acute trauma and chronic overload on the joint cartilage generated by the loss of meniscal tissue, and may be further influenced by other risk factors such as obesity. However, recent evidence suggests that the risk of developing symptomatic or radiographic OA following a meniscal tear remains high, even if a limited meniscal resection has been performed (6, 7). These results raise the question as to whether, in addition to knee trauma and loss of meniscal function, an endogenous susceptibility to OA in the individual may contribute to the risk of meniscal tears and OA (8). Importantly, this would provide an example of interaction between heredity and environment for a common and genetically complex disease.
In support of this hypothesis, a single previous study published in 1983 investigated the relationship between radiographic hand OA and radiographic knee OA in individuals who had undergone meniscectomy, and found that the presence of hand OA was associated with a higher frequency of radiographic knee OA (9). Polyarticular hand OA has been suggested as a marker for generalized primary OA and shows marked heritability (10–15). Further studies on the association between hand OA and OA of the knee following meniscectomy might thus provide valuable information.
To evaluate the hypothesis that there is interaction between hereditary and environmental risk factors, we have studied a well-defined and carefully examined cohort of patients who were treated with meniscal surgery but did not have major ligament injuries in either knee; this cohort was examined within a narrow range of time after surgery and the loss to followup was only 20%. The primary objective was to examine the influence of radiographic hand OA on radiographic OA in the operated index knees as well as in the contralateral knees.
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We found that the presence of radiographic hand OA is associated with an increased frequency of radiographic knee OA after meniscectomy. Patients with hand OA at an age younger than 50 years already have more advanced radiographic knee changes than do patients in the same age category whose hands are healthy. These findings support previous evidence of the influence of endogenous factors on the risk of OA after meniscal lesions and meniscectomy.
Several epidemiologic studies have shown an association between OA of the hand and OA of the knee in community-based study populations, suggesting that hand OA is often part of a more generalized OA (22–24). Hand OA has a significant heredity, indicating the presence of a genetic risk factor (13, 15). The only previous study investigating an association between hand OA and knee OA in individuals who had undergone meniscectomy, as a human model of isolated joint damage, was in 1983 (9). That study was the first to suggest an interaction between local joint injury and systemic factors in OA. Thus, the classic view of secondary OA may be incorrect and any distinction from primary OA may not be as clear as previously thought. Some limitations associated with the previous study provided a rationale for the present investigation. The previous study involved a heterogeneous study group with regard to injury type and extent, a wide range of time since surgery, and a high dropout rate, and evaluation of radiographic severity was confounded by disease prevalence. Furthermore, the type of meniscal tear was not evaluated and the radiographic criteria used to consider a joint diseased were difficult to interpret.
In the present study, we confirmed the association between radiographic hand OA and radiographic knee OA after meniscal injury, for both the operated knee and the nonoperated knee. These findings provide additional support for an interaction between genetic and environmental factors in OA. We also confirmed a strong association between degenerative meniscal tears and radiographic OA in the operated knee. We have previously reported that degenerative meniscal tears are associated with a worse long-term patient-relevant knee outcome in individuals after limited meniscal resection (7), and this type of tear has also been associated with radiographic OA and with combined radiographic and symptomatic OA, i.e., clinical OA (5). Meniscal degenerative pathology has been correlated with degenerative cartilage changes (25), and meniscal tears have been found to be highly prevalent in OA of the knee but lack a clear effect on the patient's symptoms and functional status (26). We therefore hypothesize that the meniscal tear itself may, in some individuals, indicate the presence of incipient OA, a disease involving changes not only in joint cartilage, but also in the whole joint (27). This type of tear could be caused by the degenerated tissue's decreased ability to withstand loads and force transmissions during knee joint movement, and may develop spontaneously or in conjunction with minor knee trauma. Thus, patients with these types of meniscal symptoms and who undergo surgery due to degenerative tears may provide a subpopulation enriched in individuals with an inherited tendency to develop OA.
It was suggested that, in addition to an increased frequency of knee OA, the severity of the radiographic changes was greater if hand OA was present (9). This previous suggestion was based on data from all knees, regardless of whether or not they were considered osteoarthritic. In order to compare the disease severity, patients who are not classified as having the disease, or, alternatively, patients without any radiographic sign of the disease, should be excluded from analysis; otherwise, the result would be influenced by the disease prevalence. Due to the small number of patients in both the previous and present study, an accurate estimation of the association between disease severity and hand OA is difficult. In the present study, we could not confirm a generally increased disease severity if radiographic hand OA was present, when taking into account the age difference between the groups. However, our results do indicate that patients with radiographic hand OA at an early age may have both more frequent and more severe radiographic knee changes than that seen in patients with no hand OA in the corresponding age category, which further supports the possibility of an influence by a genetic risk factor.
The present study has the limitations inherent in any retrospective cohort study. The surgical records were not standardized, but were usually detailed and easily interpreted by the investigators. The radiologist's written statement from the preoperative examination was used to exclude patients with knee OA at the time of surgery. In 16 cases (9%), the preoperative radiographic statement or films were not available, and therefore individual patients with radiographic knee OA present already at baseline may have been included. We excluded patients with cruciate ligament injury in any knee, thereby creating a homogeneous study cohort with regard to the environmental risk factor. Exclusion of subjects with this injury may have increased the proportion of degenerative meniscal tears in the study population. The OA classification was based on separate readings of JSN and osteophytes, in accordance with the atlas from OARSI scoring method (20), and the cutoff value for individual knee OA and hand joint OA approximated a Kellgren/Lawrence grade ≥2 (21). Thus, we did not classify a single grade 1 osteophyte or grade 1 JSN alone as radiographic OA, but we did recognize that a grade 1 osteophyte may represent emergent disease (28, 29). We based our definition of radiographic hand OA on polyarticular unilateral involvement in a typical pattern, or bilateral symmetric hand OA, thus eliminating patients with possible secondary hand OA. The small number of patients limits the statistical power of some of the analyses, especially for the nonoperated contralateral knees.
In conclusion, we report that the presence of radiographic hand OA is associated with an increased frequency of radiographic knee OA after meniscectomy. It would appear from present and previously reported results that there is an interaction between hereditary and environmental factors, and not only knee trauma, that leads to meniscal tears and meniscal surgery. A degenerative tear may be regarded as an early signal of susceptibility to osteoarthritic disease. Consequently, we consider the widely accepted classification of knee OA after meniscectomy as secondary OA to be misleading. The relative importance of genetics, knee trauma, and surgery in the initiation and progression of OA after meniscal tears remains to be further explored.