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Jeffrey B. Driban

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Jeffrey B. Driban and R. Mark Laursen

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Jeffrey B. Driban, Easwaran Balasubramanian, Mamta Amin, Michael R. Sitler, Marvin C. Ziskin and Mary F. Barbe

Context:

Joint trauma is a risk factor for osteoarthritis (OA), which is becoming an increasingly important orthopedic concern for athletes and nonathletes alike. For advances in OA prevention, diagnosis, and treatment to occur, a greater understanding of the biochemical environment of the affected joint is needed.

Objective:

To demonstrate the potential of a biochemical technique to enhance our understanding of and diagnostic capabilities for osteoarthritis.

Design:

Cross-sectional.

Setting:

Outpatient orthopedic practice.

Participants:

8 subjects: 4 OA-knee participants (65 ± 6 y of age) and 4 normal-knee participants (54 ± 10 y) with no history of knee OA based on bilateral standing radiographs.

Intervention:

The independent variable was group (OA knee, normal knee).

Main Outcome Measures:

16 knee synovial-protein concentrations categorized as follows: 4 as pro-inflammatory, or catabolic, cytokines; 5 as anti-inflammatory, or protective, cytokines; 3 as catabolic enzymes; 2 as tissue inhibitors of metalloproteinases [TIMPs]; and 2 as adipokines.

Results:

Two anti-inflammatory cytokines (interleukin [IL]-13 and osteoprotegerin) and a pro-inflammatory cytokine (IL-1β) were significantly lower in the OA knees. Two catabolic enzymes (matrix metalloproteinase [MMP]-2 and MMP-3) were significantly elevated in OA knees. TIMP-2, an inhibitor of MMPs, was significantly elevated in OA knees.

Conclusions:

Six of the 16 synovial-fluid proteins were significantly different between OA knees and normal knees in this study. Future research using a similar multiplex ELISA approach or other proteomic techniques may enable researchers and clinicians to develop more accurate biochemical profiles of synovial fluid to help diagnose OA, identify subsets of OA or individual characteristics, guide clinical decisions, and identify patients at risk for OA after knee injury.

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Jamie L. Mansell, Ryan T. Tierney, Jeffrey B. Driban, Shannon M. Clegg, Michael J. Higgins, Anurag K. Mishra and Evgeny Krynetskiy

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Jeffrey B. Driban, Nicole Cattano, Easwaran Balasubramanian, Michael R. Sitler, Mamta Amin, Joseph Glutting and Mary F. Barbe

Context: To better understand why a knee develops osteoarthritis after joint trauma we need to assess the local biochemical changes. Unfortunately, it is challenging to obtain synovial fluid from a knee with no effusion. Objective: To describe the authors' protocol for aspirating synovial fluid from noneffused knees. Second, they demonstrate the validity of this method by evaluating the relationships between normalized and raw biomarker concentrations among knees with effusion (undergoing a traditional aspiration) and without effusion (requiring a saline-assisted aspiration). Design: Validation study based on secondary analyses from 2 cohort studies. Setting: Outpatient orthopedic clinic and basic-science laboratory. Participants: Participants had moderate to severe radiographic knee osteoarthritis (n = 15 with and 11 without effusion) and no osteoarthritis or effusion (n = 4). Interventions: The same orthopedic surgeon performed all synovial-fluid joint aspirations, including saline-assisted aspirations. Main Outcome Measures: The authors used multiplex enzyme-linked immunosorbent assays to determine 7 synovial-fluid biomarker concentrations. They then calculated correlations between raw and normalized (to total synovial-fluid protein content) biomarker concentrations. Results: The authors excluded 1 sample collected with a saline-assisted aspiration because it contained blood. Normalized biomarker concentrations had positive associations with raw biomarker concentrations (r = .77-99), with the exception of interleukin-13 and interleukin-1Β among knees that underwent a saline-assisted aspiration. Excluding interleukin-1Β, associations between normalized and raw biomarker concentrations were consistent between knees that had a saline-assisted or traditional aspiration. Conclusions:Saline-assisted aspiration is a valid technique for assessing the local biochemical changes in knees without effusion.