An Exploration of Risk Factors, Modifiers for Knee OA
Of the 2957 participants with a clinical knee examination, 302 (10.2%) were classified with kOA (Table 1). In general, participants' BMI increased as they got older, from 24.1 (SD: 3.7) at 36y to 25.4 (4.2) and 27.4 (4.0) at 43y and 53y, respectively. Most self-reported good health at 53y and 22.8% reported ever having a knee injury. Nearly 36% of participants had educational qualifications of 'A- levels' or higher and 35% had a household income of £25,000 or more.
Around a third of participants were employed in a 'manual' occupation at each time-point (Table 2). Lifting and kneeling occupational activities were more common than climbing or walking, and approximately 70% of participants were in occupations which involved sitting for ≥ two hours/day. The prevalence of occupational activity exposures remained relatively stable with age, except for kneeling which decreased with age. The majority of participants had low-levels of leisure-time physical activity and the prevalence of inactivity increased with age. Compared with women, men had a higher mean BMI, more reports of knee injuries, and were more likely to engage in lifting and kneeling at work at ages 36 and 43. In comparison, women had a higher prevalence of kOA, disabling/life-threatening health conditions, family history of arthritis, and were more likely to be inactive at ages 36 and 43 and to be in occupations involving sitting.
An examination of the unadjusted distributions of BMI by activity (Additional file 1: Table S2) indicated that individuals in non-manual occupations consistently had higher BMI while those in manual occupations had a lower BMI at ages 36, 43 and 53. Associations between BMI and occupational activities were observed for various activities (e.g., lifting, kneeling, sitting and exercise), but these were generally small and inconsistent. There was a wide range of BMI scores within each stratum of physical activity, indicating there was a necessary amount variation in BMI needed to further examine whether physical activity modifies the association between BMI and kOA.
In models containing both BMI and each activity domain: BMI was generally positively associated with kOA, such that for every z-score increase in BMI, the odds of kOA increased by an approximate factor of 1.4 (OR range 1.40–1.47), and men in manual occupations had a 2-fold increase in odds of kOA when compared to those in non-manual occupations (95% CI: 1.19, 3.49). There was a weak suggestion that men who were exposed to lifting or kneeling at work at age 53 had a higher risk of kOA. There was no evidence for an association with any of the other occupational exposures, or leisure activity at any ages (Table 3).
We found no evidence of a multiplicative interaction between BMI and occupational status, occupational exposure to kneeling/bending and sitting, or leisure activity influencing the risk of kOA among men at ages 36, 43, or 53 (Table 3). The only evidence of an interaction between activity and BMI in men occurred between occupational lifting and BMI (p = 0.011) at 43y (Table 3). The effect of BMI (per z-score) on kOA within stratum of lifting indicated that BMI conferred greater odds of kOA for men employed in occupations that were 'highly likely' to involve lifting (OR: 3.55, 95% CI: 1.72–7.33), while there was no effect of BMI on risk of kOA observed among men 'unlikely' or 'somewhat likely' to lift (Figure 1A). Comparing occupations 'highly likely' to lift versus those 'somewhat likely' to lift, we interpreted the interaction in terms of the effect of lifting on risk of kOA at the three levels of BMI (−1SD, 0SD, and +1SD). Results suggested that an inverse association of lower odds for kOA comparing occupations 'highly likely' to lift versus those 'somewhat likely' to lift, was only present among those with lower BMI (−1SD - OR: 0.14, 95% CI: 0.03–0.60; 0SD - OR: 0.30, 95% CI: 0.11–0.84; +1SD – OR: 0.93, 95% CI: 0.41–2.13) (Figure 1B).
(Enlarge Image)
Figure 1.
Results for interaction between BMI and activity exposure. A - Occupational Exposure to Lifting among men; B – BMI level (SD) among men; C – Leisure-time activity exposure among women; D – BMI level (SD) among women.
In models containing both BMI and each activity domain: BMI was generally positively associated with kOA (OR ~ 1.8; OR range 1.49–1.92), there was a suggestion of a reduced risk of kOA for women 'highly likely' to sit compared to those in occupations 'somewhat likely' to sit 2 or more hours per day at age 36 (OR: 0.56, 95% CI: 0.33–0.94) and at age 43 (OR: 0.57,95% CI: 0.36–0.89), and women in manual occupations at ages 36 and 53 had an approximate 85% increase in odds of kOA when compared to those in non-manual occupations. There was no evidence for an association between any of the other domains of activity and kOA in women.
There was no evidence of a multiplicative interaction between BMI and any of the occupational exposures among women (Table 4). However, there was evidence of an interaction between BMI and leisure activity (p = 0.005) at age 43 (Table 4), such that BMI conferred greater odds of kOA as levels of reported activity increased. For every increase per z-score of BMI, the odds of kOA increased by an approximate factor of 1.59 (95% CI: 1.26–2.00) for 'inactive' women, 1.70 (95% CI: 1.14–2.55) for 'less active' women, and 4.44 (95% CI: 2.26–8.36) for 'most active' women (Figure 1C). Comparing activity levels 'most active' versus those 'less active', we interpreted the interaction in terms of the effect of leisure activity on risk of kOA at the three levels of BMI (−1SD, 0SD, and +1SD). Results suggested that 'most active' women had the most benefit in terms of reduced risk of kOA when compared to those 'less active' women if they had lower levels of BMI (−1SD - OR: 0.14, 95% CI: 0.04–0.48 and 0SD - OR: 0.36, 95% CI: 0.18–0.73; +1SD – OR: 0.93, 95% CI: 0.44–1.98) (Figure 1D).
Table 5 shows the estimated additive risk of kOA from combinations of exposure to high BMI and manual occupation with kOA. It illustrates that joint exposure to both may carry an extra additive risk despite the absence of an interaction in the logistic regression model.
Only 237 men and 144 women had the same occupational activity exposure at ages 36, 43 and 53 and the number individuals with kOA was very small (men: n = 15; women: n = 15). This resulted in reduced analytic power to detect any associations with occupational activity or leisure activity. Qualitatively, however, the results in terms of main effects of BMI and activity exposures were similar.
Results
Of the 2957 participants with a clinical knee examination, 302 (10.2%) were classified with kOA (Table 1). In general, participants' BMI increased as they got older, from 24.1 (SD: 3.7) at 36y to 25.4 (4.2) and 27.4 (4.0) at 43y and 53y, respectively. Most self-reported good health at 53y and 22.8% reported ever having a knee injury. Nearly 36% of participants had educational qualifications of 'A- levels' or higher and 35% had a household income of £25,000 or more.
Around a third of participants were employed in a 'manual' occupation at each time-point (Table 2). Lifting and kneeling occupational activities were more common than climbing or walking, and approximately 70% of participants were in occupations which involved sitting for ≥ two hours/day. The prevalence of occupational activity exposures remained relatively stable with age, except for kneeling which decreased with age. The majority of participants had low-levels of leisure-time physical activity and the prevalence of inactivity increased with age. Compared with women, men had a higher mean BMI, more reports of knee injuries, and were more likely to engage in lifting and kneeling at work at ages 36 and 43. In comparison, women had a higher prevalence of kOA, disabling/life-threatening health conditions, family history of arthritis, and were more likely to be inactive at ages 36 and 43 and to be in occupations involving sitting.
An examination of the unadjusted distributions of BMI by activity (Additional file 1: Table S2) indicated that individuals in non-manual occupations consistently had higher BMI while those in manual occupations had a lower BMI at ages 36, 43 and 53. Associations between BMI and occupational activities were observed for various activities (e.g., lifting, kneeling, sitting and exercise), but these were generally small and inconsistent. There was a wide range of BMI scores within each stratum of physical activity, indicating there was a necessary amount variation in BMI needed to further examine whether physical activity modifies the association between BMI and kOA.
Associations in Men
In models containing both BMI and each activity domain: BMI was generally positively associated with kOA, such that for every z-score increase in BMI, the odds of kOA increased by an approximate factor of 1.4 (OR range 1.40–1.47), and men in manual occupations had a 2-fold increase in odds of kOA when compared to those in non-manual occupations (95% CI: 1.19, 3.49). There was a weak suggestion that men who were exposed to lifting or kneeling at work at age 53 had a higher risk of kOA. There was no evidence for an association with any of the other occupational exposures, or leisure activity at any ages (Table 3).
We found no evidence of a multiplicative interaction between BMI and occupational status, occupational exposure to kneeling/bending and sitting, or leisure activity influencing the risk of kOA among men at ages 36, 43, or 53 (Table 3). The only evidence of an interaction between activity and BMI in men occurred between occupational lifting and BMI (p = 0.011) at 43y (Table 3). The effect of BMI (per z-score) on kOA within stratum of lifting indicated that BMI conferred greater odds of kOA for men employed in occupations that were 'highly likely' to involve lifting (OR: 3.55, 95% CI: 1.72–7.33), while there was no effect of BMI on risk of kOA observed among men 'unlikely' or 'somewhat likely' to lift (Figure 1A). Comparing occupations 'highly likely' to lift versus those 'somewhat likely' to lift, we interpreted the interaction in terms of the effect of lifting on risk of kOA at the three levels of BMI (−1SD, 0SD, and +1SD). Results suggested that an inverse association of lower odds for kOA comparing occupations 'highly likely' to lift versus those 'somewhat likely' to lift, was only present among those with lower BMI (−1SD - OR: 0.14, 95% CI: 0.03–0.60; 0SD - OR: 0.30, 95% CI: 0.11–0.84; +1SD – OR: 0.93, 95% CI: 0.41–2.13) (Figure 1B).
(Enlarge Image)
Figure 1.
Results for interaction between BMI and activity exposure. A - Occupational Exposure to Lifting among men; B – BMI level (SD) among men; C – Leisure-time activity exposure among women; D – BMI level (SD) among women.
Associations in Women
In models containing both BMI and each activity domain: BMI was generally positively associated with kOA (OR ~ 1.8; OR range 1.49–1.92), there was a suggestion of a reduced risk of kOA for women 'highly likely' to sit compared to those in occupations 'somewhat likely' to sit 2 or more hours per day at age 36 (OR: 0.56, 95% CI: 0.33–0.94) and at age 43 (OR: 0.57,95% CI: 0.36–0.89), and women in manual occupations at ages 36 and 53 had an approximate 85% increase in odds of kOA when compared to those in non-manual occupations. There was no evidence for an association between any of the other domains of activity and kOA in women.
There was no evidence of a multiplicative interaction between BMI and any of the occupational exposures among women (Table 4). However, there was evidence of an interaction between BMI and leisure activity (p = 0.005) at age 43 (Table 4), such that BMI conferred greater odds of kOA as levels of reported activity increased. For every increase per z-score of BMI, the odds of kOA increased by an approximate factor of 1.59 (95% CI: 1.26–2.00) for 'inactive' women, 1.70 (95% CI: 1.14–2.55) for 'less active' women, and 4.44 (95% CI: 2.26–8.36) for 'most active' women (Figure 1C). Comparing activity levels 'most active' versus those 'less active', we interpreted the interaction in terms of the effect of leisure activity on risk of kOA at the three levels of BMI (−1SD, 0SD, and +1SD). Results suggested that 'most active' women had the most benefit in terms of reduced risk of kOA when compared to those 'less active' women if they had lower levels of BMI (−1SD - OR: 0.14, 95% CI: 0.04–0.48 and 0SD - OR: 0.36, 95% CI: 0.18–0.73; +1SD – OR: 0.93, 95% CI: 0.44–1.98) (Figure 1D).
Absolute Risk
Table 5 shows the estimated additive risk of kOA from combinations of exposure to high BMI and manual occupation with kOA. It illustrates that joint exposure to both may carry an extra additive risk despite the absence of an interaction in the logistic regression model.
Sensitivity Analysis on Selection
Only 237 men and 144 women had the same occupational activity exposure at ages 36, 43 and 53 and the number individuals with kOA was very small (men: n = 15; women: n = 15). This resulted in reduced analytic power to detect any associations with occupational activity or leisure activity. Qualitatively, however, the results in terms of main effects of BMI and activity exposures were similar.
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