The following is a summary of the “Potential surrogate outcomes in individuals at high risk for incident knee osteoarthritis,” published in the March 2023 issue of Osteoarthritis and Cartilage by Runhaar, et al.
The goal of this research was to investigate the feasibility of using short-term changes in clinical and imaging biomarkers as surrogate outcomes for long-term clinical knee OA incidence. Women in their mid-30s who were overweight or obese but otherwise healthy were enlisted for the study by contacting their primary care physicians. Questionnaires, physical examinations, radiographs, and Magnetic Resonance Imaging (MRI) scans were acquired at baseline, 2.5 years, and 6.5 years. To do this, they calculated the proportion of knees with changes in medial knee alignment, chronic knee pain, radiographic osteophytes, and cartilage defects, bone marrow lesions, osteophytes, and effusion/synovitis, as well as the proportion of knees with a minimal clinically important difference in knee pain severity, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain/stiffness/function, and joint space narrowing.
After 6.5 years, the correlation between these possible surrogate outcomes and incident clinical knee OA, defined using the combined ACR-criteria, was calculated. Each outcome was defined as a change in the population of 10% in either direction over a period of 2.5 years. Over a 2.5-year period, most pre-defined potential surrogate outcomes showed 10% population-level change; however, only worsening of TF cartilage defects, worsening of TF osteophytes on MRI, and an increase in pain severity were significantly associated with greater clinical knee OA incidence after 6.5 years.
The specificity and negative predictive value of these possible surrogate outcomes were 89-91%, while their sensitivity and positive predictive value were only 20%-28%. Surrogate outcomes for the development of long-term OA include the worsening of MRI-detected TF cartilage defects and TF osteophytes, as well as an increase in the degree of TF pain. To be useful in future preventive studies, however, these characteristics likely need to have stronger positive predictive values.