Background/Purpose: Fibulin3 is highly expressed in osteoarthritic cartilage and inhibits angiogenesis and chondrocyte differentiation. It has been demonstrated to interact with the tissue inhibitor of metalloprotease (TIMP)-3, which is a matrix bound inhibitor of matrix metalloproteinases (MMPs) and stimulates the expression of TIMP-1 and TIMP-3, but inhibits the expression and activities of MMP-2, MMP-3, and MMP-9. In the present study, the association between three Fibulin3 peptides identified by proteomics and the incidence of radiographic and clinical knee osteoarthritis (OA) in middle-aged overweight and obese women, free of radiographic and symptomatic knee OA at baseline was tested.

Methods: Women between 50 and 60 years, with a BMI ≥ 27 kg/m², free of knee OA were recruited through their general practitioner. At baseline, physical examination including serum collection was performed and radiographs and questionnaires on knee complaints were obtained. Using binary logistic regression, the association between baseline concentration of Fibulin (Fib)3-1, Fib3-2 and Fib3-3 and incidence of clinical and radiographic knee OA after 30 months of follow-up was tested, adjusting for age, BMI, and other potential covariates that were identified in multivariable regression analyses.

Results: Baseline serum samples and follow-up measurements were available for 242 women. Mean age was 55.9 ± 3.2 years, mean BMI was 31.6 ± 3.6 kg/m² and 70% was postmenopausal. All subjects were free of clinical and radiographic knee OA at baseline, but 24% had a unilateral K&L score of 1 and 33% bilaterally. Mild symptoms were present in 24% and 17% of the subjects, uni- and bilaterally respectively. Baseline concentrations of all Fib3 fragments were log-transformed for a normal distribution and z-transformed for uniformity reasons. Correlation coefficients for the baseline concentrations of the three Fib3 fragments ranged from 0.13 to 0.58. Neither of the concentrations of the three Fib3 fragments were associated with incidence of medial or lateral joint space narrowing ≥ 1.0 mm. or incidence of K&L grade 2. All three Fib3 fragments were associated with incidence of the clinical and radiographic ACR-criteria and Fib3-1 and Fib3-3 also with chronic pain at follow-up. When adjusted for the other Fib3 peptide concentrations, only Fib3-1 was significantly associated to the incidence of the ACR criteria (OR 2.5 [1.0-6.2]) and chronic pain at follow-up (OR 2.6 [1.1-5.9]).

Conclusion: Baseline Fibulin3 concentrations are associated to the incidence of clinical knee OA among middle-aged overweight and obese women. Therewith, they meet the criteria of a prognostic biomarker according to the BIPED biomarker classification for OA. Further validation of the Fibulin3 fragments seems warranted in order to better distinguish subgroups of individuals at increased risk for knee OA development.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/baseline-fibulin3-concentrations-are-associated-with-incidence-of-clinical-knee-oa-after-30-months-in-overweight-and-obese-women/