Genetic and developmental factors include dysplastic lateral femoral condyle, spontaneous osteonecrosis and metabolic disorders. Where early OA develops in association with known genetic or developmental risk factors and no clear external factor such as trauma, the assumption would be that the cause was intrinsic and unrelated to occupation. There is no identified risk of increased knee OA in association with hypermobility syndromes.
Major risk factors include obesity and varus or valgus malalignment. Where early knee OA develops in association with obesity or malalignment without any clear significant traumatic event, the cause is most likely to be intrinsic to the person rather than due to occupational activity. Where there is a history of trauma to one knee, but OA has developed equally in both knees, and there is evidence of more widespread OA, the cause is most likely to be intrinsic to the person rather than due to occupational activity. Careful pre-employment selection is important in minimising the likelihood of employees in physically demanding roles developing early knee OA.
Growth factor and obesity. A large case-control study of 2018 cases of severe symptomatic and radiographic knee and hip OA and 967 controls were studied. Transforming growth factor beta 1 (TGFβ1) gene polymorphisms interact with being overweight to influence the risk of large joint OA (Muthuri et al., 2013).
Patello-femoral osteoarthritis (PF OA) and varus-valgus alignment. In 292 knee OA patients, fluoroscopy confirmed radiographs showed lateral PF OA was more common than medial PF OA (p<0.0001). Forty-three of 75 knees with lateral PF OA had valgus malalignment compared with only 5 of 21 patients with medial PF OA (p= 0.0066). Conversely, varus malalignment was more likely in the medial PF OA group. Knees with isolated PF OA were more likely to have valgus malalignment than those with isolated tibio-fibular (TF) OA (p=0.0002), as were knees with mixed PF-TF OA (p – 0.0006) (Elahi et al., 2000).
Q-angle influences on patello-femoral force and potential dislocation. Six cadaver knees were tested in normal alignment and varied Q-angle. Increasing the Q-angle significantly shifted the patella laterally, tilted the patella medially and rotated the patella medially. Decreasing the Q-angle significantly tilted the patella laterally, rotated the tibia externally and increased the tibio-femoral varus orientation. An increase in Q-angle could lead to lateral patellar dislocation or increased lateral patello-femoral contact pressures. A Q-angle decrease may not shift the patella medially but could increase the medial tibiofemoral contact pressure by increasing the varus orientation (Mizuno et al., 2001).
Axial lower limb alignment. One hundred and sixty seven symptomatic osteoarthritis patients were compared with 119 healthy adult volunteers. Overall alignment in healthy adults was principally determined by distal femoral valgus (condylar hip angle) and proximal tibial-plateau varus (plateau-ankle angle). The angle between the joint surfaces of the condylar plateau was relatively constant. In osteoarthritis, disease associated differences included condylar-plateau angles that were divergent, accentuated medial convergence in varus osteoarthritis and lateral convergence in valgus osteoarthritis. In varus osteoarthritis there was abnormal femoral geometry but tibial surface geometry was the same. The opposite was found in valgus osteoarthritis. These abnormal knee geometries may pre-exist and predispose to osteoarthritis but they may also change as disease progresses (Cooke et al., 1997).
Systematic review of knee malalignment and risk of knee osteoarthritis. There was limited evidence for an association between knee malalignment and incident knee OA and strong evidence that knee malalignment was an independent risk factor for progression of radiographic knee OA. There was a further relationship between varus and valgus alignment and structural progression of knee OA (Tanamas et al., 2009).
Self-reported malalignment in early adult life is associated with a significant increased risk of knee OA. Seventy two percent of 3022 participants in a case-control database responded to a questionnaire on knee and foot alignment at ages 20-29 years. Increased risk of isolated knee OA occurred with early adult varus (adjusted OR 5.16, 95% CI 2.87-9.41). The positive association between knee OA and toe-in foot was explained by varus knee. There was an increased risk of combined knee and hip OA from varus (adjusted OR 4.52, 95% CI 2.39-8.53) and valgus knees (adjusted OR 3.07, 95% CI 0.99-9.54). Varus knee was associated with risk of medial tibio-femoral OA, whereas valgus knee was associated with risk of lateral tibio-femoral and lateral patella-femoral OA. Toe-out foot was associated with reduced medial patello-femoral OA. For knee OA, a multiplicative interaction analysis between occupational risks and varus/valgus yielded an OR (int) of 3.20 (95% CI 1.08-9.49). The conclusion was that constitutional alignment of the leg in terms of varus or valgus knee or foot rotation may be a significant factor in determining development and distribution of knee OA (McWilliams et al., 2010).
Risk factors associated with early knee structural changes. MRI changes are far more common than radiographic changes, and a cascade of joint structure changes are seen starting with subchondral bone expansion, bone marrow lesions, meniscal tears and extrusion followed by cartilage defects and ultimately but not inevitably cartilage loss and radiographic osteoarthritis. These early changes are associated with smoking, lipids, leptin, vitamin D deficiency and inflammation (Ding et al., 2010).
Interaction between hereditary and environmental risk factors: there is a significant increased risk of radiographic knee OA after meniscectomy where there is contralateral knee OA and hand OA. One hundred and seventy patients mean age 54 years (range 33-87) were identified an average of 20 years (range 17-22 years) after isolated meniscectomy. Radiographic hand OA was present in 57 patients (34%), knee OA in 105 patients (62%), within 94 index knees (55%) and 47 contralateral knees (28%). Odds ratio for OA with hand OA in the index knee was 3.0 (95% CI 1.2-7.5), and in the non-operated contralateral knee OR 3.5 (95% CI 1.0-12.2) (Englund et al., 2004).
No evidence of increased prevalence of knee OA in hypermobility syndromes. Two study populations investigating genetic disease were assessed for Beighton score and hand, knee and hip radiographic OA. Hypermobility was associated with a decreased prevalence of knee OA (P=0.02, when adjusted for age and BMI P=0.07). A number of previous studies were reviewed, some showing reduced risk of radiographic knee OA and some showing increased risk. Other factors may be involved including hypermobile individuals moderating activity due to pain or joint instability (Chen et al., 2008).
CHEN, H. C., SHAH, S. H., LI, Y. J., STABLER, T. V., JORDAN, J. M. & KRAUS, V. B. 2008. Inverse association of general joint hypermobility with hand and knee osteoarthritis and serum cartilage oligomeric matrix protein levels. Arthritis Rheum, 58, 3854-64.
COOKE, D., SCUDAMORE, A., LI, J., WYSS, U., BRYANT, T. & COSTIGAN, P. 1997. Axial lower-limb alignment: comparison of knee geometry in normal volunteers and osteoarthritis patients. Osteoarthritis Cartilage, 5, 39-47.
DING, C., JONES, G., WLUKA, A. E. & CICUTTINI, F. 2010. What can we learn about osteoarthritis by studying a healthy person against a person with early onset of disease? Curr Opin Rheumatol, 22, 520-7.
ELAHI, S., CAHUE, S., FELSON, D. T., ENGELMAN, L. & SHARMA, L. 2000. The association between varus-valgus alignment and patellofemoral osteoarthritis. Arthritis Rheum, 43, 1874-80.
ENGLUND, M., PARADOWSKI, P. T. & LOHMANDER, L. S. 2004. Association of radiographic hand osteoarthritis with radiographic knee osteoarthritis after meniscectomy. Arthritis Rheum, 50, 469-75.
MCWILLIAMS, D. F., DOHERTY, S., MACIEWICZ, R. A., MUIR, K. R., ZHANG, W. & DOHERTY, M. 2010. Self-reported knee and foot alignments in early adult life and risk of osteoarthritis. Arthritis Care Res (Hoboken), 62, 489-95.
MIZUNO, Y., KUMAGAI, M., MATTESSICH, S. M., ELIAS, J. J., RAMRATTAN, N., COSGAREA, A. J. & CHAO, E. Y. 2001. Q-angle influences tibiofemoral and patellofemoral kinematics. J Orthop Res, 19, 834-40.
MUTHURI, S. G., DOHERTY, S., ZHANG, W., MACIEWICZ, R. A., MUIR, K. R. & DOHERTY, M. 2013. Gene-environment interaction between body mass index and transforming growth factor beta 1 (TGFbeta1) gene in knee and hip osteoarthritis. Arthritis Res Ther, 15, R52.
TANAMAS, S., HANNA, F. S., CICUTTINI, F. M., WLUKA, A. E., BERRY, P. & URQUHART, D. M. 2009. Does knee malalignment increase the risk of development and progression of knee osteoarthritis? A systematic review. Arthritis Rheum, 61, 459-67.