Our findings from a population-based prospective cohort study suggest that men and women in manual occupations are at an increased risk of kOA, and that men exposed to lifting or kneeling at work in later adulthood may have a higher risk of kOA. Higher BMI was consistently associated with an elevated risk of kOA. Lastly, there was some evidence of a multiplicative interaction between BMI and lifting in men such that the positive association between BMI and kOA was strongest in those likely to be exposed to regular lifting of 25 kg at age 43, and in women, where BMI conferred a higher odds ratio for kOA among the most-active women, and conversely there was a protective association of higher activity among women with lower levels of BMI.
Our study has several strengths, namely we were able to examine associations gathered at three stages in adulthood using prospective data, which should minimise recall bias. In addition, symptomatic cases of kOA were determined via a standardised clinical examination. We also examined this relationship in a younger population which may be less prone to comorbidities that would bias our findings. And unlike other studies , we included ‘homemakers’ (women not in paid employment) in our analyses. Finally, while our results may suffer from bias due to loss to follow-up (e.g., loss of contact, emigration, survey-wave refusal, permanent refusal, death), it is difficult to conceive of a mechanism that would radically alter the associations between exposures and outcome considered here among those lost to follow up. Further, the sample at age 53 remained largely representative of a similarly-aged UK-born population [36, 37], and as such the nature and level of the exposures studied should be generalizable to the wider UK population of similar age.
A few limitations should also be noted. While a standardized clinical examination protocol was used, it is possible that observer error was introduced into the examination, possibly leading to systematic miss-classification of kOA cases. In addition, our cases are prevalent rather than incident since they were obtained by a screening only at age 53. As such, we cannot exclude the possibility that the exposures post-dated the onset of disease, although this is unlikely for exposures at ages 36 and 43 given the reported age-related incidence of kOA rises steeply after age 50 [38, 39]. Unknown is whether individuals exited their occupation and entered into less physically-demanding work due to physically limiting health conditions. Our attempt to examine this was limited due to the small-sample size of individuals with the same occupational exposure across time. And while there were benefits to drawing upon an existing job-exposure matrix, developed specifically to examine knee-risk exposure from occupational activity, the accuracy of a job-exposure matrix is limited by the specificity of the occupational categories upon which it is based. If the occupational categories are broad, as is normally the case in general population-based studies, there will be heterogeneity of exposure within occupational categories, and not all individuals within a group will be accurately classified. Compared to methods that ascertain individual-level exposure, some additional measurement error is likely from this group-based approach. Therefore, possible errors in case ascertainment and assignment of exposure may have obscured the associations with risk factors in this study, especially given the previous support for occupational activities as a risk factor for kOA [6, 7, 18, 19]. Our results may not be generalizable to current or future populations given the changing BMI landscape and occupational activity levels.
The greater observed odds of kOA among those in manual occupations may be due to the aggregate exposure to a range of higher risk activities undertaken by those in manual occupations. This is supported in our study by the suggestive associations between lifting and kneeling and kOA in men and the protective association between sitting at work and kOA in women, which agrees with previous research showing a link between physically arduous activities at work and kOA [6, 18, 26]. While our finding that sitting at work may offer protection from kOA in women has been shown before , it seems unlikely that sitting is the causal factor that reduces the risk of kOA. Rather this more likely reflects the fact that individuals who sit more at work are less-often exposed to strenuous occupational activity that increases the risk of kOA through higher mechanical loads [19, 40, 41].
Our finding of a multiplicative interaction between lifting and BMI in men is supported by a previous case–control study , although not by another prospective study . However, it is important to note that out of 30 interaction tests that we performed, only two were statistically significant at the 5% level and not all tests can be considered as independent. It is thus possible that these two reflect chance rather than any true underlying multiplicative interaction between exposure to activity and BMI. McWilliams et al.  noted in a recent meta-analysis examining occupational risk factors for kOA that there was evidence of publication bias, such that cross-sectional and case–control studies more often report greater risk of kOA from occupational activity than do prospective or longitudinal studies. However both interactions were evident at age 43 and if we ignore the age 53 results as being most likely to be biased towards the null due to healthy worker and reverse causality bias (i.e., individuals self-selecting out of physically demanding occupations and subsequently gaining weight), then this would suggest that an individual has less sensitivity, in terms of kOA risk, to exposure to higher levels of BMI and activity in younger adulthood (interactions were also not observed at age 26 – results not shown).
The evidence for a combination of independent multiplicative effects for BMI and activity seen in our study and in particular the absence of any negative interactions emphasizes the potential public health importance of joint exposure to high BMI and high activity stressors. Any evidence for a positive interaction would add to the public health importance of these exposures. Our findings with regard to these possible synergistic effects on kOA require further investigation. Large-scale prospective studies are required to further investigate these relationships. Individual-level, direct measures of occupational activities should be used to characterize the population with greater resolution and examine the extreme ends of the activity spectrum. For example, one study suggests a non-linear pattern - only those with the very heaviest exposure to physical activity at work are at risk of kOA . Future prospective studies would also do well to incorporate clinical and radiographic assessment of kOA at multiple time-points past age 40 to better determine incident and prevalent cases.