Senolytic Drugs Attenuate Osteoarthritis-Related Articular Cartilage Degeneration: A Clinical Trial

Serum C-reactive protein (CRP) level measured on ELISA. The enzyme linked immunoassay (ELISA) is a laboratory technique that detects certain antigens in the blood. ELISA was used to detect the level of CRP in the blood. The liver releases CRP into blood in response to inflammation. All post-intervention group comparisons were adjusted for the baseline value as a covariate.

Serum cartilage oligomeric matrix protein (COMP) level measured on ELISA. All post-intervention group comparisons were adjusted for the baseline value as a covariate.

The 6 minute walk test (6MWT) assesses distance (in meters) walked over 6 minutes as a sub-maximal test of aerobic capacity, exercise tolerance and endurance. The score range for healthy adults is 400-700 m, depending on age and sex. Shorter distances indicate increased impairment. All post-intervention group comparisons were adjusted for the baseline value as a covariate.

The Timed Up and Go (TUG) test measures how long it takes (in seconds) to stand up, walk a distance of 10 feet, turn, walk back, and sit down again. < 10 seconds is considered normal. Longer times indicate poorer function. All post-intervention group comparisons were adjusted for the baseline value as a covariate.

fast 4-meter walk test (4MW). The 4MW was assessed at the fastest safe speed for each participant. This test assesses the capacity for performance of certain activities (e.g., crossing a street before the light changes). Units are m/s, and slower speeds indicate greater impairment. All post-intervention group comparisons were adjusted for the baseline value as a covariate.

Peak knee adduction moment (KAM) during stance phase of gait in the affected leg, determined using video-motion analysis and force plate data. Values are normalized by mass*height of participant. Higher KAM has been associated with more rapid osteoarthritis progression. All post-intervention group comparisons were adjusted for the baseline value as a covariate.

The Stair-Climbing Test assesses the time required (in seconds) to ascend and descend a standard flight of 10 stairs. Longer times indicate poorer physical function. Stairs require greater knee extensor force than gait, so this test may be more sensitive to osteoarthritis pain and function than walking tests. All post-intervention group comparisons were adjusted for the baseline value as a covariate.

This test utilizes an isokinetic dynamometer to assess the peak knee extension torque that can be produced by the affected leg at a constant rate of knee extension (60 degrees/s). The resulting measure is normalized by body mass and reported with units Newton-meters (Nm). Increased torque over time would indicate improved muscle strength and/or decreased joint pain. All post-intervention group comparisons were adjusted for the baseline value as a covariate.

Numeric Rating Scale (NRS) reporting 'pain today'. Scale of 0-10 with 0 representing 'no pain' and 10 representing 'severe pain'. All post-intervention group comparisons were adjusted for the baseline value as a covariate.

Western Ontario and McMaster Universities Arthritis Index (WOMAC) - total score. Scores range from 0 to 96 for the total WOMAC where 0 represents the best health status and 96 the worst possible status. The higher the score, the poorer the function. All post-intervention group comparisons were adjusted for the baseline value as a covariate.

Mean T2 relaxation times were determined across 4 subregions: central medial femur (CMF), central lateral femur (CLF), central medial tibia (CMT), and central lateral tibia (CLT). All post-intervention group comparisons were adjusted for the baseline value as a covariate. The mean T2 changes over time for all subregions were listed in rank order from most positive (indicating worsened cartilage condition over time) to most negative (indicating improved cartilage condition over time). These unitless rankings were used in a Sum of Ranks statistical analysis to compare cartilage changes across different knee joint regions without assuming normality (as appropriate for MRI data). There are no published standards for what would be considered a clinically significant effect for sum-of-ranks cartilage T2 data, so it was assumed that a statistically significant difference would imply clinical significance as well.

Patients will be allowed to receive a steroid injection and still participate in the study. All participants that undergo alternative therapy (e.g. total knee arthroplasty or biologic injection) will be recorded, and proportions will be compared between groups.