osteoarthritis ( oa ) of the major joints in the lower limb is a painful and disabling condition that accounts for an enormous healthcare burden [ 13 ] . the pathogenesis of oa is complex and thus predicting individuals in a healthy population who will progress to develop severe oa remains difficult . consequently , there is a paramount need to reliably identify high - risk population cohorts who can be targeted for future therapeutic trials , for early intervention of modifiable risk factors and for ongoing research into the complex disease process and natural history of progression of oa . there are many risk factors associated with end - stage knee oa , however few are as modifiable as body mass index ( bmi ) . there is currently a strong level of evidence correlating bmi to future radiographic oa and clinical oa of the knee [ 79 ] with a similar but weaker association with the hip . whilst the link between bmi and end - stage oa in the knee continues to be scrutinised , it is also of interest to know how temporal changes in weight affect oa risk . of the previous studies that have investigated this relationship , few have looked at change in bmi and end stage disease in a healthy community - based sample followed for almost 20  years . additionally , surgically relevant oa endpoints such as total joint arthroplasty ( tja ) have seldom been used , with many studies favouring radiographic change and clinical score severity as surrogate endpoints for oa [ 1214 ] . the present study investigated the relationship between bmi measurements at different time points and risk of end - stage oa in the knee , defined by tka . in 1989 , all women between 45 and 64  years of age who were registered at the same medical practice in chingford , north - east london were invited to join in this longitudinal prospective study . the primary focus of the study was to investigate the natural history of osteoporosis and osteoarthritis . a total of 1003 women volunteered to join the study at its commencement , representing 78% of the initially invited women . at year 19 , 733 of these women were still actively involved in yearly follow - up clinics ( 104 had died , 78 dropped out , 62 moved away , 23 did not respond and three were too ill to attend ) . the clinical characteristics of the cohort and selected group are shown in table  1 . at study baseline ( year 1 ) , each individual was measured for height and weight . also , each participant was asked to estimate their body weight from when they were aged 20 . these measurements were taken in addition to extensive medical history questionnaires , social history , sf36 forms and radiological and serological investigations . follow - up clinics were conducted annually up till year 10 of the study and annual postal questionnaires were sent thereafter . during the follow up period , tka was deemed to be due to oa where oa was listed as the primary indication . only cases where oa was listed as indication for tka were included in the study , whereas cases with other indications for tka ( rheumatoid arthritis , trauma , etc . ) were excluded . of the respondents remaining in the study at year 19 , 31 had received a tka due to oa and one had received tka due to ra . individuals who underwent more than one tka during the follow - up period were only counted once . arthroplasty records were initially gathered via patient testimony at annual follow - up clinics and then validated by verification with each individual 's general practitioner records . the tka cases were compared against a control group comprising those respondents remaining in the study at year 19 who did not have tja ( tkas and/or thas were excluded to create a more stringent control group , n  =  676 ) . bmi ( defined as weight / height ) was calculated at four time points ( recalled bmi at age 20 , measured bmi at baseline , year 5 and year 10 ) . individual bmi measurements were stratified into categories based on the world health organization ( who ) classification : underweight ( bmi <  18.50 ) , normal ( bmi 18.5024.99 ) , overweight ( bmi 2529.99 ) and obese ( bmi    30.00 ) at each time point . the changes in bmi between different time points t1 and t2 ( defined as bmit1,t2  =  bmi at t2    bmi at t1 , where t2  > approval for this study was granted by the redbridge and waltham forest ethics committee and all patients were consenting volunteers who freely donated their time . the baseline clinical characteristics of the respondents at year 19 ( case and control groups ) were compared against the non - respondents using the mann whitney test , two tailed unpaired t - test with unequal variances and the fisher 's exact test for non - normal , normal and categorical data respectively ( results discussed but not shown ) . the same was done when comparing tka cases against the control group ( shown in table  1 ) . the correlation of bmi at different time points was assessed using the spearman correlation matrix . this produced high values ( >  80% ) between pairs of measured bmi at baseline , year 5 , year 10 , suggesting that an overall model incorporating multiple time points would be unsuitable . therefore the value of bmi as a predictor at each individual time point rather than collectively was reviewed . logistic regression , adjusted for age at baseline and smoking (  never  or  ever  ) was performed using tka by year 19 as the outcome and bmi ( for each time point or bmit1,t2 ) as the exposure . using 90% power at the 5% significance level , the detectable departure from the mean of baseline bmi was 0.65  kg / m . stata se v10 , statcorp , college station , tx , usa and matlab r2010a , the mathworks , natick , ma , usa was used for the analyses . the baseline clinical characteristics of case control respondents used in this study ( n  =  707 ) were compared to the non - respondents ( n  =  296 ) . the respondents were younger than than the non - respondents on entry to the study ( median age 53 versus 57  years , p  <  0.0005 ) , had a lower bmi ( median bmi 24.7 versus 25.3  kg / m , p  =  0.026 ) and had less smokers in their group ( 43.4% versus 52.7% , p  =  0.004 ) . when compared against the controls , the women who underwent tka ( cases group ) during the follow - up period had significantly elevated bmi measurements at baseline ( median 26.5 versus 24.5  kg / m , p  =  0.005 ) and year 5 ( median 27.4 versus 25.5  kg / m , p  =  0.022 ) as shown in table  1 . they did not however have an increased self reported bmi at age 20 compared to controls ( median 21.6 versus 21.4  kg / m , p  =  0.251 ) . the risk ( percentage of patients ) of tka was calculated for each who category at age 20 , study baseline , year 5 and 10 ( fig .  1 ) . there was an increase in risk of tka with increased bmi at baseline , but this was attenuated at years 5 and 10 . logistic regression analyses using tka as the outcome and bmi as the univariate exposure ( bmi at age 20 , baseline , year 5 , year 10 and bmi changes bmia20,y1 , bmiy1,y5 , bmiy5,y10 , bmiy1,y10 ) revealed that the significant predictors of tka were bmi at baseline with an or(95% ci ) of 1.105 ( 1.018 , 1.198 ) , p  =  0.017 and bmi at year 5 , 1.086 ( 1.003 , 1.175 ) , p  =  0.042 . when adjusted for baseline age and smoking , the bmi at baseline was the only significant predictor 1.100 ( 1.013 , 1.195 ) , p  =  0.024 . the association with bmi at year 5 was of borderline statistical significance 1.082 ( 0.998 , 1.173 ) , p  =  0.056 . no other significant values were found for predicting tka , although all or 's were greater than 1 , as shown in fig . 2 . repeating the regression analyses using bmi who categories ( underweight , normal , overweight , obese ) as the univariate exposure and adjusting for age and smoking revealed the categories at baseline to be the only significantly predictor of tka , 1.867 ( 1.150 , 3.030 ) , p  =  0.012 . this longitudinal , population based study of women aged between 45 and 65  years of age at baseline demonstrated that both baseline and year 5 bmi were significantly associated with an elevated risk of tka over the follow - up period . when adjusted for baseline age and smoking , the results showed a single unit increase in bmi at baseline was associated with a 10.0% rise in the risk of tka by year 19 . these results are consistent with several other large studies that have demonstrated the positive relationship between obesity and risk of radiographic knee oa . initially used radiographic data from a small subgroup ( n  =  58 ) of this same population cohort and demonstrated that bmi had a strong effect on the risk of incidence and progression of radiographic oa . again using this same population , hart et al . examined paired knee radiographs with a 4  year follow - up between imaging and found those individuals in the upper bmi tertile had an odds ratio of 2.38 for developing radiographic knee oa . these results have been further strengthened by several larger population - based cohort studies that demonstrate the positive relationship between bmi and incidence of radiographic knee .   recently demonstrated the strong relationship between bmi and knee oa in a study similar to the present investigation using tka as an outcome measure for severe disease . this study demonstrates that bmi in middle age is the strongest predictor of the need for tka with diminishing risks associated with bmi assessed at later time points . change in bmi between various time points however , showed no significant association with the risk of tka at year 19 . the majority of previous studies have only examined bmi at one time point as an explanatory variable   and thus to our knowledge the present study , by comparing longitudinal changes in bmi to future oa outcome data , is unique . the results suggest that interventions targeting weight loss may have to be targeted prior to middle age , if the risk of severe knee oa and tka is to be minimised . this is a unique , long - term population based study with multiple measures of bmi and tja in the same population . tja is a surrogate measure of severe oa in the knee and hip , however it is a surgical end - point with good clinical relevance to both patient and practitioner . it should be noted that the uk has a taxpayer - funded public health system , and thus all individuals in the present study have more - or - less equal access to tja with no personal expense . despite the relative equity in tja access , have shown that patient willingness to consider tja is the primary determinant in the time taken to the receipt of a first tja . willingness is in turn affected by level of patient education , meaning that individual 's use of a tax payer - funded tja service is probably still influenced by socioeconomic status . other limitations of the data include loss to follow up , the single sex of the cohort , the mono - ethnicity and the subjectively reported weight at age 20 . whilst there does not appear to be a systemic misreporting of data , we acknowledge that this measurement may be under reported . in conclusion , we found an increasing risk of tka due to severe oa with bmi at baseline and at year 5 . our data suggest that weight loss interventions for the prevention of severe knee oa may have to be targeted in early middle age for optimal effect . all authors declare that they do not have any conflict of interest relating to this paper .
the evidence linking body mass index ( bmi ) to severe oa shows a strong association in the knee . 
 there are limited data exploring the effect of bmi on the risk of joint arthroplasty in a healthy population with long periods of follow up . 
 we compared the self - reported bmi at age 20 , measured bmi at baseline , year 5 and year 10 with the year 19 risk of total knee arthroplasty ( tka ) in a well - described , population based cohort of healthy women . 
 a total of 733 women attended the 19th year visit , of whom 31 underwent tka and 676 were used as a control group after 26 were removed for having hip arthoplasty.using logistic regression , an increase in 1 unit of bmi at baseline was associated with a 10.5% increased risk of tka ( p  =  0.017 ) and at year 5 the increased risk is 8.6% ( p  =  0.042 ) . when adjusted for baseline age and smoking , 
 baseline bmi was the only significant predictor of tka at 10.0% with p  =  0.024 . 
 there was no significant association at 10  years or for change in bmi over time.in this prospective , population based study , bmi predicted the risk of tka for oa . 
 the risk was greatest at baseline when the patients were in middle age suggesting that this is the most important time to target weight reduction interventions .