We tested whether inhibiting mechanically-responsive articular chondrocyte mitochondria after severe traumatic injury and preventing oxidative damage represent a viable paradigm for posttraumatic osteoarthritis (PTOA) prevention. We used a porcine hock intra-articular fracture (IAF) model well suited to human-like surgical techniques and with excellent anatomic similarities to human ankles. After IAF, amobarbital or N-acetylcysteine (NAC) was injected to inhibit chondrocyte electron transport or downstream oxidative stress, respectively. Effects were confirmed via spectrophotometric enzyme assays or glutathione/glutathione disulfide assays and immunohistochemical measures of oxidative stress. Amobarbital or NAC delivered after IAF provided substantial protection against PTOA at 6 months, including maintenance of proteoglycan content, decreased histological disease scores, and normalized chondrocyte metabolic function. These data support the therapeutic potential of targeting chondrocyte metabolism after injury and suggest a strong role for mitochondria in mediating PTOA.
Hip dysplasia is known to lead to premature osteoarthritis. Computational models of joint mechanics have documented elevated contact stresses in dysplastic hips, but elevated stress has not been directly associated with regional cartilage degeneration. The purpose of this study was to determine if a relationship exists between elevated contact stress and intra‐articular cartilage damage in patients with symptomatic dysplasia and femoroacetabular impingement. Discrete element analysis was used to compute hip contact stresses during the stance phase of walking gait for 15 patients diagnosed with acetabular dysplasia and femoral head‐neck offset deformity. Contact stresses were summed over the duration of the walking gait cycle and then scaled by patient age to obtain a measure of chronic cartilage contact stress exposure. Linear regression analysis was used to evaluate the relationship between contact stress exposure and cartilage damage in each of six acetabular subregions that had been evaluated arthroscopically for cartilage damage at the time of surgical intervention. A significant correlation (R2 = 0.423, p < 0.001) was identified between chondromalacia grade and chronic stress‐time exposure above both a 1 MPa damage threshold and a 2 MPa‐years accumulated damage threshold. Furthermore, an over‐exposure threshold of 15% regional contact area exceeding the 1 and 2 MPa‐years threshold values resulted in correct identification of cartilage damage in 83.3% (55/66) of the acetabular subregions loaded during gait. These results suggest corrective surgery to alleviate impingement and reduce chronic contact stress exposures below these damage‐inducing thresholds could mitigate further cartilage damage in patients with hip dysplasia.
Evaluation of abnormalities in joint contact stress that develop after inaccurate reduction of an acetabular fracture may provide a potential means for predicting the risk of developing post-traumatic osteoarthritis. Discrete element analysis (DEA) is a computational technique for calculating intra-articular contact stress distributions in a fraction of the time required to obtain the same information using the more commonly employed finite element analysis technique. The goal of this work was to validate the accuracy of DEA-computed contact stress against physical measurements of contact stress made in cadaveric hips using Tekscan sensors. Four static loading tests in a variety of poses from heel-strike to toe-off were performed in two different cadaveric hip specimens with the acetabulum intact and again with an intentionally malreduced posterior wall acetabular fracture. DEA-computed contact stress was compared on a point-by-point basis to stress measured from the physical experiments. There was good agreement between computed and measured contact stress over the entire contact area (correlation coefficients ranged from 0.88 to 0.99). DEA-computed peak contact stress was within an average of 0.5 MPa (range 0.2-0.8 MPa) of the Tekscan peak stress for intact hips, and within an average of 0.6 MPa (range 0-1.6 MPa) for fractured cases. DEA-computed contact areas were within an average of 33% of the Tekscan-measured areas (range: 1.4-60%). These results indicate that the DEA methodology is a valid method for accurately estimating contact stress in both intact and fractured hips.
Background Acceptance and commitment therapy (ACT) is a pragmatic approach to help individuals decrease avoidable pain. Objective This study aims to evaluate the effects of ACT delivered via an automated mobile messaging robot on postoperative opioid use and patient-reported outcomes (PROs) in patients with orthopedic trauma who underwent operative intervention for their injuries. Methods Adult patients presenting to a level 1 trauma center who underwent operative fixation of a traumatic upper or lower extremity fracture and who used mobile phone text messaging were eligible for the study. Patients were randomized in a 1:1 ratio to either the intervention group, who received twice-daily mobile phone messages communicating an ACT-based intervention for the first 2 weeks after surgery, or the control group, who received no messages. Baseline PROs were completed. Two weeks after the operative intervention, follow-up was performed in the form of an opioid medication pill count and postoperative administration of PROs. The mean number of opioid tablets used by patients was calculated and compared between groups. The mean PRO scores were also compared between the groups. Results A total of 82 subjects were enrolled in the study. Of the 82 participants, 76 (38 ACT and 38 controls) completed the study. No differences between groups in demographic factors were identified. The intervention group used an average of 26.1 (SD 21.4) opioid tablets, whereas the control group used 41.1 (SD 22.0) tablets, resulting in 36.5% ([41.1-26.1]/41.1) less tablets used by subjects receiving the mobile phone–based ACT intervention (P=.004). The intervention group subjects reported a lower postoperative Patient-Reported Outcome Measure Information System Pain Intensity score (mean 45.9, SD 7.2) than control group subjects (mean 49.7, SD 8.8; P=.04). Conclusions In this study, the delivery of an ACT-based intervention via an automated mobile messaging robot in the acute postoperative period decreased opioid use in selected patients with orthopedic trauma. Participants receiving the ACT-based intervention also reported lower pain intensity after 2 weeks, although this may not represent a clinically important difference. Trial Registration ClinicalTrials.gov NCT03991546; https://clinicaltrials.gov/ct2/show/NCT03991546
Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.
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