Metabolomic Profile Predicts Risk for Sustained Knee Pain After TKA in Osteoarthritis

Using independent cohorts, researchers conducted a meta-analysis of metabolomics on knee pain in primary osteoarthritis.

One metabolite and 3 metabolite ratios corresponded to sustained knee pain 1 year after total knee arthroplasty (TKA) among patients with primary knee osteoarthritis (OA), according to study findings published in Rheumatology (Oxford).

Researchers conducted a dual cohort study among patients with primary knee OA. They analyzed the association between preoperative metabolomics and sustained knee pain caused by primary knee OA.

The pain subscale from the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was used 1 year after TKA for primary knee OA. Fasting preoperative blood samples were collected to perform metabolomic profiling.

A total of 430 and 495 individuals with knee OA were included in the study from each of the 2 independent cohorts. The metabolite phosphatidylcholine diacyl (PC aa) C28:1 (odds ratio [OR], 0.66; P =.00026) and 3 metabolite ratios all significantly correlated with sustained knee pain on the WOMAC pain subscale. The 3 metabolite ratios included PC aa C32:0 to PC aa C28:1 (OR, 1.59; P <.00002), PC aa C28:1 to PC aa C32:0 (OR, 0.60; P <.00002), and tetradecadienylcarnitine C14:2 to sphingomyelin C20:2 (OR, 1.59; P <.00002).

The researchers hypothesized that sustained knee pain in patients with primary knee OA might result from dysregulation of PC lipid metabolism, which has previously been found to contribute to chronic inflammation, neuropathic pain, and possibly central sensitization.

Study limitations included lack of generalizability to ethnic groups outside of those of European descent and the need for different reference ranges for men and women when using the identified metabolite and ratios to predict risk for sustained knee pain.

“Though further investigations are needed, our results provide potential predictive biomarkers and drug targets that could serve as a marker for poor response and be modified pre-operatively to improve knee pain and surgical response to TKA,” the study authors concluded. “These findings suggest potential roles for inflammation, oxidative stress, pain sensitization, and altered lipid metabolism… [in sustained knee pain due to primary knee OA].”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Costello CA, Rockel JS, Liu M, et al. Individual participant data meta-analysis of metabolomics on sustained knee pain in primary osteoarthritis patients. Rheumatology (Oxford). Published online September 19, 2022. doi:10.1093/rheumatology/keac545