animal studies

 Animal Studies

  1. Effective repair of a fresh osteochondral defect in the rabbit knee joint by

articulated joint distraction following subchondral drilling.

Kajiwara R, Ishida O, Kawasaki K, Adachi N, Yasunaga Y, Ochi M.

Journal of Orthopaedic Research. 2005; 23(4): 909-15.

Purpose: Joint distraction has been used to treat osteoarthritis and was found to delay the need for arthrodesis or joint replacement. However, there has been little basic research on articulated joint distraction for the repair of osteochondral defects. We investigated the effects of joint distraction with motion after drilling on a fresh osteochondral defect in the weight bearing area of the rabbit knee joint.

Methods: A full thickness osteochondral defect was created in the weight bearing area of both medial femoral condyles of an adult Japanese white rabbit. After drilling of the defect, the experimental knee joint was distracted for 1.5 mm using a pair of external fixators to decrease compression force. The contralateral knee joint was used as a control with no apparatus. Gross findings and histological evaluation were assessed to study morphology of the repaired cartilage.

Results: A partial repair with cartilage-like tissue was observed in the joints of the experimental group at 4 weeks. While cartilage-like tissue stained with Safranin 0 was found in the experimental group at 8 and 12 weeks, destructive changes were observed in the control joints. Morphological changes were evaluated using the histological grading scale. There was no significant difference between experimental and control groups at 4 weeks (mean 11.2 and 13.8 points, respectively). However, the mean scores of the experimental groups at 8 and 12 weeks (mean 6.8 and 7.5, respectively) were significantly better than those of the control groups at the same time points (mean 14 points each). Between the experimental groups, the scores at 8 and 12 weeks were both significantly better than those at 4 weeks.

Conclusion: A combination of subchondral drilling, joint motion and distraction by an articulated external fixator promoted repair of a fresh osteochondral defect in the weight bearing area. Although distraction for 4 weeks was not a long enough period to repair the defect, distraction for 8 and 12 weeks resulted in a good outcome.

  1. Joint distraction in treatment of osteoarthritis (II): effects on cartilage in a canine model.

van Valburg AA, van Roermund PM, Marijnissen AC, Wenting MJ, Verbout AJ, Lafeber FP, Bijlsma JW.

Osteoarthritis and Cartilage. 2000; 8(1): 1-8.

Objective: From a clinical point of view, joint distraction as a treatment for osteoarthritis (OA) of hip and ankle has been demonstrated to be very promising. Pain, joint mobility and functional ability, the most important factors for a patient with severe OA, all improved. Although radiographic joint space enlargement in a significant number of patients suggested cartilage repair, actual cartilage repair remains difficult to evaluate. Therefore the present study was initiated to evaluate the actual effects of joint distraction on cartilage.

Methods: For this purpose a canine model for OA, anterior cruciate ligament transection (ACLT) was used. Sixteen weeks after ACLT articulating Ilizarov joint distraction of the knee was carried out. Absence of mechanical contact between articular surfaces and presence of intra-articular intermittent fluid pressure, characteristics of Ilizarov joint distraction, were confirmed. Twenty-five weeks after ACLT joint tissue of the dogs was analyzed.

Results: Biochemical analysis showed that after joint distraction the abnormal cartilage proteoglycan (PG) metabolism, characteristic for OA, had changed to a level found in control joints. Moreover, a mild degree of inflammation, present after ACLT, was reduced upon joint distraction. PG-content and histological cartilage degeneration had not (yet) improved within the time of treatment.

Discussion: Results suggest that the promising clinical results of Ilizarov joint distraction in patients with OA are accompanied by changes in cartilage metabolism. A change in proteoglycan turnover, indicating normalization of overall chondrocyte function, might in the long term, with normal joint use, lead to actual repair of cartilage.

  1. Evidence of cartilage repair by joint distraction in a canine model of osteoarthritis.

Wiegant K, Intema F, van Roermund PM, Barten-van Rijbroek AD, Doornebal A, Hazewinkel HA, Lafeber FP, Mastbergen SC.

Arthritis & Rheumatology. 2015; 67(2): 465-74.

Objective. Knee osteoarthritis (OA) is a degenerative joint disorder characterized by cartilage, bone, and synovial tissue changes that lead to pain and functional impairment. Joint distraction is a treatment that provides long-term improvement in pain and function accompanied by cartilage repair, as evaluated indirectly by imaging studies and measurement of biochemical markers. The purpose of this study was to evaluate cartilage tissue repair directly by histologic and biochemical assessments after joint distraction treatment.

Methods. In 27 dogs, OA was induced in the right knee joint (groove model; surgical damage to the femoral cartilage). After 10 weeks of OA development, the animals were randomized to 1 of 3 groups. Two groups were fitted with an external fixator, which they wore for a subsequent 10 weeks (one group with and one withoutjoint distraction), and the third group had no external fixation (OA control group). Pain/function was studied by force plate analysis. Cartilage integrity and chondrocyteactivity of the surgically untouched tibial plateaus were analyzed 25 weeks after removal of the fixator.

Results. Changes in force plate analysis values between the different treatment groups were not conclusive. Features of OA were present in the OA control group, in contrast to the generally less severe damage after joint distraction. Those treated with joint distraction had lower macroscopic and histologic damage scores, higher proteoglycan content, better retention of newly formed proteoglycans, and less collagen damage. In the fixator group without distraction, similarly diminished joint damage was found, although it was less pronounced.

Conclusion. Joint distraction as a treatment of experimentally induced OA results in cartilage repair activity, which corroborates the structural observations of cartilage repair indicated by surrogate markers in humans.