Abstract
Multiple factors can help predict knee osteoarthritis (OA) patients from healthy individuals, including age, sex, and BMI, and possibly metabolite levels. Using plasma from individuals with primary OA undergoing total knee replacement and healthy volunteers, we measured lysophosphatidylcholine (lysoPC) and phosphatidylcholine (PC) analogues by metabolomics. Populations were stratified on demographic factors and lysoPC and PC analogue signatures were determined by univariate receiver-operator curve (AUC) analysis. Using signatures, multivariate classification modeling was performed using various algorithms to select the most consistent method as measured by AUC differences between resampled training and test sets. Lists of metabolites indicative of OA [AUC > 0.5] were identified for each stratum. The signature from males age > 50 years old encompassed the majority of identified metabolites, suggesting lysoPCs and PCs are dominant indicators of OA in older males. Principal component regression with logistic regression was the most consistent multivariate classification algorithm tested. Using this algorithm, classification of older males had fair power to classify OA patients from healthy individuals. Thus, individual levels of lysoPC and PC analogues may be indicative of individuals with OA in older populations, particularly males. Our metabolite signature modeling method is likely to increase classification power in validation cohorts.
Highlights
Commencing at age 50, there is a steep increase in the incidence of symptomatic osteoarthritis (OA) and the number of individuals undergoing total knee replacement (TKR) [1,2,3]
In addition to the amino acid arginine [6], select lysophosphatidylcholine to phosphatidylcholine (PC) analogue ratios are altered in plasma from patients with OA compared to healthy adult volunteers (HV) and the ratio of total lysoPCs to PCs are predictive of TKR in 10 years follow-up [7]
Since age was significantly different, our study focused on individuals over 50 years old. This reduced the mean difference in age between OA and HV to 4.5 years compared to 13.6 years in the entire cohort (Table 1)
Summary
Commencing at age 50, there is a steep increase in the incidence of symptomatic osteoarthritis (OA) and the number of individuals undergoing total knee replacement (TKR) [1,2,3]. In addition to the amino acid arginine [6], select lysophosphatidylcholine (lysoPC) to phosphatidylcholine (PC) analogue ratios are altered in plasma from patients with OA compared to healthy adult volunteers (HV) and the ratio of total lysoPCs to PCs are predictive of TKR in 10 years follow-up [7]. It is unclear, if a signature of individual metabolite levels, of lysoPC or PC analogues, in a combined signature, is capable of classifying OA from healthy individuals. Optimal methods to help improve predictive metabolite selection and prediction modeling in cross-sectional cohorts to aid in successful prediction in external validation cohorts have not been investigated
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