Prevention Of Post-traumatic Osteoarthritis Research Articles

A Surgical Model of Posttraumatic Osteoarthritis With Histological and Gait Validation.

Background:Posttraumatic osteoarthritis (PTOA) is secondary to an array of joint injuries. Animal models are useful tools for addressing the uniqueness of PTOA progression in each type of joint injury and developing strategies for PTOA prevention and treatment.Hypothesis:Intra-articular fracture induces PTOA pathology.Study Design:Descriptive laboratory study.Methods:Through a parapatellar incision, the medial tibial plateau was exposed in the left knees of 8 Sprague-Dawley rats. Osteotomy at the midpoint between the tibial crest and the outermost portion of the medial tibial plateau, including the covering articular cartilage, was performed using a surgical blade. The fractured medial tibial plateau was fixed with 2 needles transversely. The fractured knees were not immobilized. Before and after surgery, rat gait was recorded. Rats were sacrificed at week 8, and their knees were harvested for histology.Results:After intra-articular fracture, the affected limbs altered gait from baseline (week 0). In the first 2 weeks, the gait of the operated limbs featured a reduced paw print intensity and stride length but increased maximal contact and stance time. Reduction of maximal and mean print area and duty cycle (the percentage of stance phase in a step) was present from week 1 to week 5. Only print length was reduced in weeks 7 and 8. At week 8, histology of the operated knees demonstrated osteoarthritic pathology. The severity of the PTOA pathology did not correlate with the changes of print length at week 8.Conclusion:Intra-articular fracture of the medial tibial plateau effectively induced PTOA in rat knees. During PTOA development, the injured limbs demonstrated characteristic gait.Clinical Relevance:Intra-articular fracture represents severe joint injury and associates with a high rate of PTOA. This animal model, with histologic and gait validations, can be useful for future studies of PTOA prevention and early diagnosis.

Using mouse models to investigate the pathophysiology, treatment, and prevention of post-traumatic osteoarthritis.

Post-traumatic osteoarthritis (PTOA) is defined by its development after joint injury. Factors contributing to the risk of PTOA occurring, the rate of progression, and degree of associated disability in any individual, remain incompletely understood. What constitutes an "OA-inducing injury" is not defined. In line with advances in the traumatic brain injury field, we propose the scope of PTOA-inducing injuries be expanded to include not only those causing immediate structural damage and instability (Type I), but also those without initial instability/damage from moderate (Type II) or minor (Type III) loading severity. A review of the literature revealed this full spectrum of potential PTOA subtypes can be modeled in mice, with 27 Type I, 6 Type II, and 4 Type III models identified. Despite limitations due to cartilage anatomy, joint size, and bio-fluid availability, mice offer advantages as preclinical models to study PTOA, particularly genetically modified strains. Histopathology was the most common disease outcome, cartilage more frequently studied than bone or synovium, and meniscus and ligaments rarely evaluated. Other methods used to examine PTOA included gene expression, protein analysis, and imaging. Despite the major issues reported by patients being pain and biomechanical dysfunction, these were the least commonly measured outcomes in mouse models. Informative correlations of simultaneously measured disease outcomes in individual animals, was rarely done in any mouse PTOA model. This review has identified knowledge gaps that need to be addressed to increase understanding and improve prevention and management of PTOA. Preclinical mouse models play a critical role in these endeavors. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:424-439, 2017.

Factors predicting the development of early osteoarthritis following lateral tibial plateau fractures: mid-term clinical and radiographic outcomes of 73 operatively treated patients.

The indications for operative treatment of lateral tibial plateau fractures are still controversial. The objective of this study was to determine whether residual articular surface depression and valgus malalignment of plated lateral tibial plateau fractures at medium-term follow-up affect the clinical and radiographic outcomes. A chart review of patients with operatively treated (AO type B3.1) tibial plateau fractures that were admitted to our level I trauma center between 2002 and 2008 was performed. Out of 123 patients, 73 were available to participate in a clinical and radiographic follow-up examination. The mean follow-up time was 54 months. Patients were clinically assessed and completed the Lysholm knee score and Western Ontario and McMaster Universities Osteoarthritis Index. Maximal articular surface depression, radiological mechanical axis, and degree of posttraumatic osteoarthritis were evaluated from standing radiographs. Patients with valgus malalignment of 5° or greater at follow-up developed more advanced osteoarthritis (Kellgren-Lawrence grade 3-4) than patients with a normal mechanical axis (p = 0.006). Similarly, patients with articular depression greater than 2 mm at follow-up also developed more advanced osteoarthritis compared to patients with a depression of 2 mm or less (p = 0.001). The degree of valgus malalignment or articular depression had no effect on the Western Ontario and McMaster Universities Osteoarthritis Index or Lysholm scores. The postoperative articular congruity and normal mechanical axis of the lower leg after plate fixation in lateral tibial plateau fractures seem to have a role in prevention of posttraumatic osteoarthritis but does not appear to predict clinical outcome at medium-term follow-up. The role of initial dislocation and associated cartilage damage in the development of osteoarthritis following these fractures is still unknown.

MOON-AAA GCP clinical trial: early lessons from an early interventional trial in patients within 1 week after ACL tear

Posttraumatic Osteoarthritis (PTOA) often results from knee ligament injuries such as to the anterior cruciate ligament (ACL). Patients with ACL injuries are a unique population the initiation event for the development of PTOA is often known. Enrolment of these patients and the prospective collection of “early” information on this population is challenging as the majority in the USwill not be seen by a specialist until severalweeks after injury. We here describe the early lessons learned from the “Multicenter Orthopaedic Outcome Network Early-Anti-inflammatory Treatment in Patients with Acute ACL Tear and Painful Effusions” (MOON-AAA) clinical trial. This is the first US-based multicenter, randomized, good clinical practices (GCP) interventional clinical trial recording biomarker profiles, standardized X-rays as well as patient reported outcomes (PRO’s) in isolated ACL tears seen within 4 days after ACL injury. Methods: This is a GCP multicenter clinical trial enrolling patients with primary isolated ACL tears within 4 days after injury. Inclusion criteria follow the MOON -protocol (Table 1). All patients undergo aspiration of the post-injury effusion within 4 days and 10 days post-injury. Patients receive an injection with 40 mg Kenalog within 4 days, 10 days, both time points or not at all (saline injection control). Permutated block randomization into one of these four groups is done at the time point of the first aspiration. Blinding of patients and investigators is maintained throughout the study. Serum, synovial fluid and urine collection is performed at the first and second aspiration as well as at the time of ACL reconstruction. Synaflexor standardized flexion weightbearing X-rays are obtained on patients pre-operatively. Patient reported outcomes are being collected at 6 time points up to 6months post-ACL reconstruction with a focus on function and symptoms (IKDC, KOOS) activity level (Marx-score), quality of life (KOOS-QOL, SF36) and pain (VAS, KOOSpain, Catastrophizing scale, CSQ). Results: Only data from one cohort are available to date. Our practice performs w 400 ACL reconstructions annually. Pre-study data showed capture of 85.7% of all ACL injuries occurring in Fayette County: 66% of patients were seen within 30 days after ACL injury; 37% were seen by a Surgeon but 73% were seen by a Surgeon or PCP within 1 week of injury; 30% were seenwithin 4 days of injury. A total of 10 patients were eligible for enrollment in a 4 month time period. After this pre-study data changes were made to the study design including development of an “early warning system” through physician extenders in high schools and placement of additional physician extenders in the clinics to help with enrollment. These changes allowed for enrollment of 30 patients in a 7 month time period, a 220% increase in enrollment numbers from the prestudy period. 10–20% of all patients with ACL tears fulfill the inclusion criteria. Screen failures occur at a rate of 25–30% due to either accompanying injuries (n 1⁄4 6) or patient refusal (n 1⁄4 4). No patient withdrew from the study. One patient refused the second knee joint aspiration. No patient was lost to follow-up. No problems were encountered regarding the data collection, specimen storage or patient follow-up. Conclusions: ACL patients can be recruited to a PTOA prevention trial within 4 (þ 4) days after ACL injury if typical patient referral patterns are changed. Even for a highly productive ACL practice it is imperative to involve PCPs, Surgeons and outreach physician providers as stake holders into the study. Early knee joint aspirations are well tolerated and can be performed consecutively without patient withdrawals. Patients report subjectively less pain after the aspirations. Few patients refuse enrollment. Strict inclusion criteria result in a low number of eligible patients (10–20% only). A careful pre-study analysis of referral patterns, patient capture and environment is critical to perform randomized clinical trials in this patient population.

Post-traumatic osteoarthritis: from mouse models to clinical trials

Osteoarthritis (OA), the most common of all arthropathies, is a leading cause of disability and has a large (and growing) worldwide socioeconomic cost. Despite its burgeoning importance, translation of disease-modifying OA therapies from the laboratory into clinical practice has slowed. Differences between the OA models studied preclinically and the disease evaluated in human clinical trials contribute to this failure. Most animal models of OA induce disease through surgical or mechanical disruption of joint biomechanics in young individuals rather than the spontaneous development of age-associated disease. This instability-induced joint disease in animals best models the arthritis that develops in humans after an injurious event, known as post-traumatic OA (PTOA). Studies in genetically modified mice suggest that PTOA has a distinct molecular pathophysiology compared with that of spontaneous OA, which might explain the poor translation from preclinical to clinical OA therapeutic trials. This Review summarizes the latest data on potential molecular targets for PTOA prevention and modification derived from studies in genetically modified mice, and describes their validation in preclinical therapeutic trials. This article focuses on how these findings might best be translated to humans, and identifies the potential challenges to successful implementation of clinical trials of disease-modifying drugs for PTOA.

The Posterolateral Approach for the Treatment of Trimalleolar Fractures

Anatomical reduction and fixation, early functional treatment, and prevention of posttraumatic osteoarthritis are the utmost goals in the treatment of articular fractures in the lower extremity. Especially in articular fractures of the ankle, where a high load transfer is omitted through a very small area, anatomical reduction is crucial. Historically, ankle fractures with involvement of large posterolateral fragments (Volkmann triangle) were reduced by an indirect technique. This procedure may be technically demanding and can be associated with important exposure to teratogenic irradiation. Additionally, impacted articular fragments cannot be reduced, and very large fragments tend to dislocate secondarily, thus leading to bad results. An easy, safe, and fast alternative to the indirect reduction technique is the fixation under direct visual control of the posterior tibial margin. Therefore, we advocate the posterolateral approach for the reduction Volkmann triangle in complex fractures of the ankle joint. It allows stable fixation of the posterior key fragment of the tibia with its syndesmosis. Impacted articular fragments can be reduced, and by the placement of a posterior buttress plate, secondary dislocation can be avoided. By the same incision, the placement of a posterior antiglide plate to the fibula is possible, and through a simple maneuver, the approach to the medial malleolus is granted.

P-188, Anti-TNF-α AND OP-1: a novel triad in the prevention of post-traumatic osteoarthritis

P-188, Anti-TNF-α AND OP-1: a novel triad in the prevention of post-traumatic osteoarthritis

Peroneus Longus Tenodesis for Chronic Instability of the Distal Tibiofibular Syndesmosis

Reconstruction of the three-point dynamic suspension of the fibula in the fibular groove of the tibia. Elimination of pain and functional disturbances. Prevention of posttraumatic osteoarthritis. Chronic symptomatic insufficiency of the distal tibiofibular syndesmosis with widening of the mortise. Poor skin and soft tissue conditions. Advanced osteoarthritis of ankle. Reconstruction of the three most important ligaments of the distal syndesmosis complex: the anterior and posterior as well as the interosseous tibiofibular ligaments, with a halved, distally pedicled tendon of the peroneus longus tendon. Ten tenodeses (eight women, two men, average age 40 years) were done between January 1998 and December 1999. The syndesmosis insufficiency persisted after surgical treatment of eight pronation-eversion and two -abduction fractures. Average duration of follow-up 11.4 months. Using the Karlsson score, the subjective and functional assessment of all patients reached 88 out of 100 points. One patient reached only 70 points on account of a preoperatively present dysesthesia in the territory of the tibial nerve giving rise to persistent pain.

Surgical Treatment of Maisonneuve Fractures

Closed or open reduction and internal fixation of Maisonneuve fracture with the goal to restore form and function of ankle joint. Prevention of posttraumatic osteoarthritis. Proximal fibular fractures associated with rupture of the distal tibiofibular syndesmosis, the interosseous membrane, and the deltoid ligament; sometimes associated with fracture of the medial malleolus and the posterior rim of the tibia. Poor skin and soft-tissue conditions. Poor general health. Open or closed reduction and repositioning of lateral malleolus into fibular incisure of the tibia. Internal fixation with one or two temporarily inserted syndesmosis screws. Suture of syndesmosis. Treatment of associated injuries. Split below-knee cast. After wound healing closed below-knee cast for 6 weeks and walking with crutches and partial weight bearing. Removal of syndesmosis screw(s) 6–8 weeks postoperatively. Once ligamentous stability has been ascertained, increasing mobilization and weight bearing. An exact diagnosis, meticulous reduction and internal fixation as well as intensive postoperative physiotherapy will guarantee a satisfactory functional result.