Donald D. Anderson

Post‐traumatic osteoarthritis: Improved understanding and opportunities for early intervention

Even with current treatments of acute joint injuries, more than 40% of people who suffer significant ligament or meniscus tears, or articular surface injuries, will develop osteoarthritis (OA). Correspondingly, 12% or more of all patients with lower extremity OA have a history of joint injury. Recent research suggests that acute joint damage that occurs at the time of an injury initiates a sequence of events that can lead to progressive articular surface damage. New molecular interventions, combined with evolving surgical methods, aim to minimize or prevent progressive tissue damage triggered by joint injury. Seizing the potential for progress in the treatment of joint injuries to forestall OA will depend on advances in (1) quantitative methods of assessing the injury severity, including both structural damage and biologic responses, (2) understanding of the pathogenesis of post‐traumatic OA, taking into account potential interactions among the different tissues and the role of post‐traumatic incongruity and instability, and (3) application of engineering and molecular research to develop new methods of treating injured joints. This paper highlights recent advances in understanding of the structural damage and the acute biological response following joint injury, and it identifies important directions for future research.

Insulin-Like Growth Factor I Accelerates Functional Recovery from Achilles Tendon Injury in a Rat Model

We studied the effects of insulin-like growth factor I on Achilles tendon healing in a rat model. Rats were randomized into groups of six each: sham surgery, transection alone, and transection plus growth factor. Postoperatively, rats treated with growth factor had a significantly smaller maximum functional deficit and a decreased time to functional recovery than rats in the untreated groups. Biomechanical testing revealed no significant differences in the measured parameters between the treated and the untreated groups after transection. To study the mechanism of action, six additional animals received an Achilles tendon injection of the inflammatory agent carrageenan alone and six received carrageenan plus growth factor. Rats treated with growth factor did not show the inflammation-induced functional deficit experienced by the control rats. Spectrometric myeloperoxidase assays on the remaining eight rats after Achilles tendon transection demonstrated no significant difference between the untreated and the growth factor-treated groups, indicating a mechanism other than neutrophil recruitment by which the growth factor limits inflammation. Histologic studies were performed on carrageenan-injected rats at postinjection day 2 and on surgically treated rats at postoperative day 15. No gross histologic differences were seen between untreated and growth factor-treated groups. This study demonstrated that via a possible antiinflammatory mechanism, insulin-like growth factor I reduces maximum functional deficit and accelerates recovery after Achilles tendon injury.

LOGISMOS—Layered Optimal Graph Image Segmentation of Multiple Objects and Surfaces: Cartilage Segmentation in the Knee Joint

A novel method for simultaneous segmentation of multiple interacting surfaces belonging to multiple interacting objects, called LOGISMOS (layered optimal graph image segmentation of multiple objects and surfaces), is reported. The approach is based on the algorithmic incorporation of multiple spatial inter-relationships in a single n-dimensional graph, followed by graph optimization that yields a globally optimal solution. The LOGISMOS methods utility and performance are demonstrated on a bone and cartilage segmentation task in the human knee joint. Although trained on only a relatively small number of nine example images, this system achieved good performance. Judged by dice similarity coefficients (DSC) using a leave-one-out test, DSC values of 0.84 0.04, 0.80 0.04 and 0.80 0.04 were obtained for the femoral, tibial, and patellar regions, respectively. These are excellent DSC values, considering the narrow-sheet character of the cartilage regions. Similarly, low signed mean cartilage thickness errors were obtained when compared to a manually-traced independent standard in 60 randomly selected 3-D MR image datasets from the Osteoarthritis Initiative database-0.11 0.24, 0.05 0.23, and 0.03 0.17 mm for the femoral, tibial, and patellar cartilage thickness, respectively. The average signed surface positioning errors for the six detected surfaces ranged from 0.04 0.12 mm to 0.16 0.22 mm. The reported LOGISMOS framework provides robust and accurate segmentation of the knee joint bone and cartilage surfaces of the femur, tibia, and patella. As a general segmentation tool, the developed framework can be applied to a broad range of multiobject multisurface segmentation problems.

Displaced intra-articular fractures of the distal radius: The effect of fracture displacement on contract stresses in a cadaver model

Contact stresses in the wrist were measured after simulating displaced fractures of the lunate fossa in the distal radius of eight human cadaver arms. Osteotomies created displaced lunate fossa fractures of 0, 1, 2, and 3 mm. Contact stresses were measured with Fuji pressure-sensitive film after loads of 100 N were applied to the wrist through wrist flexor and extensor tendons. Mean contact stresses were significantly increased with step-offs of 1 mm or more. Maximum stresses and overloaded areas were significantly increased with step-offs of 2 mm or more. As the magnitude of the fracture displacement increased, there was a shift in the focus of the maximum stresses toward the fracture line. In this model, simulated displaced die-punch fractures created alterations in both the magnitude and location of contact stresses in the wrist joint.

Baseline articular contact stress levels predict incident symptomatic knee osteoarthritis development in the MOST cohort.

We studied whether contact stress estimates from knee magnetic resonance images (MRI) predict the development of incident symptomatic tibiofemoral osteoarthritis (OA) 15 months later in an at‐risk cohort. This nested case‐control study was conducted within a cohort of 3,026 adults, age 50 to79 years. Thirty cases with incident symptomatic tibiofemoral OA by their 15 month follow‐up visit were randomly selected and matched with 30 control subjects. Symptomatic tibiofemoral OA was defined as daily knee pain/stiffness and Kellgren‐Lawrence Grade ≥2 on weight bearing, fixed‐flexion radiographs. Tibiofemoral geometry was segmented on baseline knee MRI, and contact stresses were estimated using discrete element analysis. Linear mixed models for repeated measures were used to examine the association between articular contact stress and case/control status. No significant intergroup differences were found for age, sex, BMI, weight, height, or limb alignment. However, the maximum articular contact stress was 0.54 ± 0.77 MPa (mean ± SD) higher in incident OA cases compared to that in control knees (p = 0.0007). The interaction between case‐control status and contact stress was significant above 3.20 MPa (p < 0.0001). The presence of differences in estimated contact stress 15 months prior to incidence suggests a biomechanical mechanism for symptomatic tibiofemoral OA and supports the ability to identify risk by subject‐specific biomechanical modeling.

The Roles of Mechanical Stresses in the Pathogenesis of Osteoarthritis: Implications for Treatment of Joint Injuries*

Excessive joint surface loadings, either single (acute impact event) or repetitive (cumulative contact stress), can cause the clinical syndrome of osteoarthritis (OA). Despite advances in treatment of injured joints, the risk of OA following joint injuries has not decreased in the past 50 years. Cumulative excessive articular surface contact stress that leads to OA results from posttraumatic joint incongruity and instability, and joint dysplasia, but may also cause OA in patients without known joint abnormalities. In vitro investigations show that excessive articular cartilage loading triggers release of reactive oxygen species (ROS) from mitochondria, and that these ROS cause chondrocyte death and matrix degradation. Preventing release of ROS or inhibiting their effects preserves chondrocytes and their matrix. Fibronectin fragments released from articular cartilage subjected to excessive loads also stimulate matrix degradation; inhibition of molecular pathways initiated by these fragments prevents this effect. Additionally, injured chondrocytes release alarmins that activate chondroprogentior cells in vitro that propogate and migrate to regions of damaged cartilage. These cells also release chemokines and cytokines that may contribute to inflammation that causes progressive cartilage loss. Distraction and motion of osteoarthritic human ankles can promote joint remodeling, decrease pain, and improve joint function in patients with end-stage posttraumatic OA. These advances in understanding of how altering mechanical stresses can lead to remodeling of osteoarthritic joints and how excessive stress causes loss of articular cartilage, including identification of mechanically induced mediators of cartilage loss, provide the basis for new biologic and mechanical approaches to the prevention and treatment of OA.

Subchondral bone remodeling is related to clinical improvement after joint distraction in the treatment of ankle osteoarthritis

OBJECTIVE In osteoarthritis (OA), subchondral bone changes alter the joints mechanical environment and potentially influence progression of cartilage degeneration. Joint distraction as a treatment for OA has been shown to provide pain relief and functional improvement through mechanisms that are not well understood. This study evaluated whether subchondral bone remodeling was associated with clinical improvement in OA patients treated with joint distraction. METHOD Twenty-six patients with advanced post-traumatic ankle OA were treated with joint distraction for 3 months using an Ilizarov frame in a referral center. Primary outcome measure was bone density change analyzed on computed tomography (CT) scans. Longitudinal, manually segmented CT datasets for a given patient were brought into a common spatial alignment. Changes in bone density (Hounsfield Units (HU), relative to baseline) were calculated at the weight-bearing region, extending subchondrally to a depth of 8mm. Clinical outcome was assessed using the ankle OA scale. RESULTS Baseline scans demonstrated subchondral sclerosis with local cysts. At 1 and 2 years of follow-up, an overall decrease in bone density (-23% and -21%, respectively) was observed. Interestingly, density in originally low-density (cystic) areas increased. Joint distraction resulted in a decrease in pain (from 60 to 35, scale of 100) and functional deficit (from 67 to 36). Improvements in clinical outcomes were best correlated with disappearance of low-density (cystic) areas (r=0.69). CONCLUSIONS Treatment of advanced post-traumatic ankle OA with 3 months of joint distraction resulted in bone density normalization that was associated with clinical improvement.

Biomechanical evaluation of cervical spine stabilization methods using a porcine model

Study Design. The biomechanical stability of three different methods of cervical spine stabilization was evaluated in a porcine model. Specimens were tested in flexion, extension, and axial rotation. Objectives. Our goal was to determine if posterior lateral mass plating after anterior reconstruction provided more stability compared with uncortical or bicortical anterior plate fixation after a simulated corpectomy. Summary of Background Data. Previous implant biomechanical evaluations use ligamentous and intervertebral disc disruption models under constrained and nonrepetitive loading. This study examines implant performance using a corpectomy model loaded for multiple cycles, allowing for unconstrained motion. Methods. Twenty-one porcine cervical spines were destabilized with a one-level cervical corpectomy and reconstructed with an anterior methacrylate graft. Each construct was stabilized with either an AO Morscher plate system with unicortical, self-locking screws; a Caspar plate with bicortical screws; or two posterior lateral mass plates. Testing with cyclic loads was performed on an MTS machine in flexion, extension, and axial rotation. Results. There was no statistical difference between the two anterior forms of fixation in flexion, extension, or axial rotation. Posterior lateral mass plating was significantly more stable than either anterior construct. Screw loosening was seen most frequently with bicortical Caspar plating. Conclusions. After a single-level cervical corpectomy and idealized grafting, all three surgical constructs provided stability equal to or greater than the intact condition in flexion, extension, and axial rotation. In unstable cervical spine injury patterns involving anterior disruption, this study supports the use of anterior grafting combined with posterior lateral mass plating to achieve maximum stability.

Effect of osteochondral defects on articular cartilage: Contact pressures studied in dog knees

Full thickness osteochondral defects 6 mm in diameter were created in the weight-bearing regions of the femoral condyles in 5 adult mongrel dogs to study the contact pressure changes accompanying healing. A digital imaging technique employing Fuji Prescale film mapped contact pressures following 11 months of healing for comparison with contralateral normal knees, and knees with freshly made defects. Although all defects healed uneventfully with subchondral plate reconstitution and with growth restoration of the articular surface, the repair soft tissue appeared histologically to be primarily fibrous tissue, with varying degrees of a fibrocartilaginous component. The mean and peak stresses about fresh defects were not appreciably different from those about healed defects. Neither were there substantial differences in the total cartilage area making contact, except when very low loads were applied. The results suggest that the repair tissue is of poor mechanical quality, and does not contribute appreciably to weight bearing. The cartilage adjacent to the defect did not experience high stresses; neither gross nor light microscopic evidence of degeneration appeared at 11 months. If degeneration does occur following such defects, our data suggest that it is not because of elevated contact stresses.

Motion Versus Fixed Distraction of the Joint in the Treatment of Ankle Osteoarthritis: A Prospective Randomized Controlled Trial

BACKGROUND Initial reports have shown the efficacy of fixed distraction for the treatment of ankle osteoarthritis. We hypothesized that allowing ankle motion during distraction would result in significant improvements in outcomes compared with distraction without ankle motion. METHODS We conducted a prospective randomized controlled trial comparing the outcomes for patients with advanced ankle osteoarthritis who were managed with anterior osteophyte removal and either (1) fixed ankle distraction or (2) ankle distraction permitting joint motion. Thirty-six patients were randomized to treatment with either fixed distraction or distraction with motion. The patients were followed for twenty-four months after frame removal. The Ankle Osteoarthritis Scale (AOS) was the main outcome variable. RESULTS Two years after frame removal, subjects in both groups showed significant improvement compared with the status before treatment (p < 0.02 for both groups). The motion-distraction group had significantly better AOS scores than the fixed-distraction group at twenty-six, fifty-two, and 104 weeks after frame removal (p < 0.01 at each time point). At 104 weeks, the motion-distraction group had an overall mean improvement of 56.6% in the AOS score, whereas the fixed-distraction group had a mean improvement of 22.9% (p < 0.01). CONCLUSION Distraction improved the patient-reported outcomes of treatment of ankle osteoarthritis. Adding ankle motion to distraction showed an early and sustained beneficial effect on outcome.