Bilateral lateral radiographic knee osteoarthritis. The 37-year old male patient has undergone subtotal meniscectomy of the lateral meniscus of his right knee 15 years earlier, followed by repeated meniscal resections also of the lateral meniscus in the left knee. The radiographs show osteophyte formation and joint space narrowing in the lateral compartment of both knees. 

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... al. 2003) (Figure 10). 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 published in the early 1980s (Doherty et al. 1983). This study was the fi rst to suggest an interaction between local joint injury and systemic factors in OA. Thus, the classic view of secondary OA may be incorrect and the distinction from primary OA not as clear as previously thought. However, the report has drawn relatively little attention, at least in the orthopedic community. Some limitations associated with the study pro- vided a rationale for the present investigation: a heterogeneous study group with regard to injury type and extent, a wide range of time since surgery, a high dropout rate, and evaluation of radiographic severity being confounded by disease prevalence. Furthermore, the type of meniscal tear was not evaluated and the radiographic criteria used to consider a diseased joint are diffi cult to interpret. In the present study (Paper III), I confi rm the association between radiographic hand OA and radiographic knee OA after meniscal injury, for both the operated and the nonoperated knee (Table 5). A degenerative type of meniscal tear was more frequently found at index surgery in patients with radiographic hand OA (Table 6). Furthermore, patients with bilateral radiographic knee OA had radiographic hand OA more frequently than did patients with unilateral disease (61% vs. 35% p = 0.01). These fi ndings provide additional support for an interaction between genetic and environmental risk factors for OA. As a consequence, degenerative joint disease after meniscectomy should not be considered to be a single entity or secondary OA only. Many patients undergoing meniscal surgery seem to carry an inherited OA tendency, and the meniscal tear merely represents the fi rst “signal” feature of the disorder. Despite the impact of endogenous risk factors for the development and progression of knee OA in patients who have undergone meniscectomy, there are important biomechanical aspects that need to be addressed. To my knowledge, the fourth study of this thesis is the fi rst, using large subject numbers, to show that partial meniscal resection induces less structural tibiofemoral changes related to OA than does total meniscectomy (Table 7). However, the frequency of symptomatic radiographic knee OA was not substantially lowered (Table 8), confi rming that radiographic changes and clinical symptoms do not necessarily go hand in hand (Lethbridge- Cejku et al. 1995, Hannan et al. 2000). As suggested by reports from Tapper and Hoover and some other investigators the preservation of an intact peripheral rim of the meniscus may produce better long-term results (Tapper and Hoover 1969, Northmore-Ball et al. 1983, Chatain et al. 2001, Andersson-Molina et al. 2002). If a substantial portion of the circumferentially oriented matrix fi bers is intact, hoop tension may still develop, which counteracts meniscal extrusion when the knee is loaded. Substantial function of the residual meniscus in shock absorption and load transmission may thus remain. Any form of meniscal lesion or resection disrupting the circumferential continu- ity of the meniscus would compromise the major meniscal functions. However, most reports of partial meniscectomy, including the only prospective study (Hede et al. 1992), have failed to demonstrate, or presented only very limited evidence, of a lower frequency of radiographic knee OA or functional improve- ments (Faunø and Nielsen 1992, Neyret et al. 1993, Burks et al. 1997, Higuchi et al. 2000, Andersson-Molina et al. 2002). In addition to the limitations associated with the reports after total meniscectomy, previous studies may have been affected by the use of short follow-up times, lack of adjustment for BMI, low patient numbers, and the patient-relevant outcome has been inadequately evaluated. Furthermore, the extent of meniscal resection is not an independent vari- able but is infl uenced by the extent and type of the meniscal tear. Although there appears to be some benefi t by preserving meniscal tissue, a dramatically reduced frequency of knee OA seems not to be the case, judging by today’s evidence. The reason may be that many of the patients operated on already have incipient OA, as proposed in this thesis. The surgical intervention simply removes some of the evidence of the disorder, while the OA joint degradation proceeds. The worse outcome after lateral meniscectomy (Table 7) (Paper IV) is in accordance with other reports (Johnson et al. 1974, Allen et al. 1984, Jørgensen et al. 1987, Hede et al. 1992b, McNicholas et al. 2000, Chatain et al. 2003). The lateral meniscus has been reported to carry higher load in the knee compared with the medial meniscus. Conse- quently, the loss of the lateral meniscus results in more cartilage contact stress, which may further facilitate the OA process (Figure 11) (Walker and Erkman 1975, Seedhom and Hargreaves 1979). I found an association between obesity and the presence of both radiographic knee OA and symptomatic radiographic knee OA (Table 7, 8) (Paper IV), consistent with previous reports (Spector et al. 1994, Manninen et al. 1996, Felson et al. 1997b, Gelber et al. 1999). I cannot rule out the possibil- ity that some individuals in the material could fi rst have developed OA and then became sedentary and obese. However, using retrospective estimates of weight, made by the subjects, I did not fi nd such a cause and effect. Therefore, to encourage weight loss, is one of the most important recommenda- tions to give obese patients at high risk of OA (Felson et al. 1992). The link between obesity and OA is not entirely clear. The association between obesity and hand OA (Carman et al. 1994), and the high risk of knee OA predominantly among women with high BMI (Felson et al. 1997b), suggest that increased cartilage stress in obese subjects may not be the only explanation. In the Framingham Study high knee load at work and leisure has been reported to be a factor of signifi cance in the development of incident radiographic or symptomatic knee OA (McAlindon et al. 1999). I did not fi nd such an association in my material (Paper IV). However, methodologi- cal issues (diffi culty for subjects to estimate knee load retrospectively) may have contributed to the result. Previous reports have found a limited correlation between radiographic signs of OA and patient- relevant outcome (Lethbridge-Cejku et al. 1995, Creamer et al. 2000, Hannan et al. 2000), but little is known of how large the proportion is of patients with asymptomatic radiographic disease. I used the patient’s self-report in the KOOS to establish a clinically relevant cutoff, in order to defi ne symptomatic subjects. In the material nearly half of the patients defi ned as having radiographic knee OA were classifi ed as asymptomatic (Figure 12). Even though advanced features of OA were noted on the knee radiographs of several of these subjects, the disease was silent and did not infl uence the knee function, as assessed by the KOOS. Furthermore, almost half of the patients who were symptomatic did not have radiographic knee OA. Several other causes than radiographic tibiofemoral or patellofemoral OA could explain knee complaints, but many patients are likely to suffer from symptoms of early-stage knee OA, even though defi nite features on conventional radiographs are absent (Lachance et al. 2002). Therefore, one of the challenges of future research will be to validate and standardize the criteria for “pre-radiographic” osteoarthritic disease (Figure 13). Present study (Paper IV) corroborates Lager- gren’s fi nding that female sex was a risk factor for knee OA after meniscectomy (Lagergren 1943). In community based studies women are more prone to develop radiographic knee OA than are men (van Saase et al. 1989, Felson et al. 1997b). The strongest association in my material was obtained for symptomatic radiographic knee OA (Table 8). The cause of more symptoms in women is unclear but may involve muscular, neurophysiological, and psychosocial factors (McAlindon et al. 1993, O’Reilly et al. 1998, Creamer et al. 1999). With the introduction of arthroscopy, it may be that the indications for meniscal surgery have been lib- eralized. The low risk of complications and quick patient recovery have made the arthroscopic technique an attractive alternative to investigating and treating “meniscal” pain also in the older patient population. In my material, I have noticed an increase in the patient age at surgery with time, and consequently a gradual increase in the proportion of degenerative meniscal tears operated on. Furthermore, the increased use of diagnostic MRI, which very likely visualizes a meniscal tear, irrespective of whether the patient is symptomatic or not, contributes to a delicate situation for the arthroscopist (Bhattacharyya et al. 2003). It may be diffi cult not to operate even stable tears, if knee symptoms are present. Bearing in mind that the central 2/3 of the meniscus lack innervation, it may be diffi cult to discriminate between symptoms caused by a meniscal tear and symptoms of early-stage OA. The osteoarthritic disease process (and symptoms) may start at a much younger age than previously thought. The etiology of pain in OA is still unclear, but recent fi ndings suggest that bone marrow lesions on MRI or soft tissue involvement are important factors (Felson et al. 2001, Hill et al. 2001). If the degenerative meniscal lesion is regarded as representing incipient OA, it is not surprising that surgical intervention directed to the meniscus has little or no infl uence on long-term patient-relevant and radiographic outcome (Moseley et al. 2002, Bhattacharyya et al. 2003, Dervin et al. 2003). There is no evidence that leaving a degenerative tear causes OA or increases progression (Fahmy et ...