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Studies on the articular cartilage and subchondral bone following unilateral medial meniscectomy in sheep

Armstrong, Sarah Jane (1993) Studies on the articular cartilage and subchondral bone following unilateral medial meniscectomy in sheep. PhD thesis, Murdoch University.

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Osteoarthritis (OA) is the most common joint disorder in humans, and may account for more disability amongst the elderly than any other disease (Felson, 1988). Human patients usually present only once the disease is relatively advanced, so in order to gain insights into possible causes, and the early pathogenesis of OA, animal models are used. The aim of this thesis was to establish unilateral medial meniscectomy in sheep as a model of early OA. It was shown that six months after meniscectomy the sheep exhibited clinical signs of OA (lameness), the articular cartilage showed typical gross, histopathological and biochemical lesions, and the subchondral bone had developed the histomorphometrical changes reported in other animal models and in clinical OA.

Having established the validity of the model, various post-surgical protocols were examined. Firstly, the changes observed in animals subjected to moderate walking exercise (24km/wk) were compared to those in unexercised sheep. It was found that although the exercise program decreased lameness it was associated with the development of more severe gross and histopathological changes in the articular cartilage and subchondral bone.

Three further trials were performed to examine the effects of administering various drugs to the meniscectomised sheep. Treatment regimes commenced three months after surgery when OA had already begun to develop. Oral tiaprofenic acid, a non-steroidal anti-inflammatory drug (NSAID), was administered daily for three months and force plate analysis of gait showed that it prevented the increase in lameness seen in untreated controls. There were few differences observed in the articular cartilage and subchondral bone when treated and untreated sheep were compared. However, tiaprofenic acid did not appear to exacerbate the osteoarthritic lesions as has been reported following treatment with certain other NSAIDs (Palmoski and Brandt, 1979; Pelletier et al, 1989).

A second trial examined the effect of lOmg intraarticular hyaluronan (HA) on meniscectomised knees. Two preparations with different molecular weights were examined. Both decreased lameness but this effect was more marked in the sheep treated with the higher molecular weight preparation. At this dose rate, neither preparation had a beneficial effect on the severity of the observed osteoarthritic lesions. Furthermore, histological cartilage damage was more severe in the group treated with the higher molecular weight HA.

The final trial compared the effects of intra-articular HA (20mg), pentosan polysulphate (PPS) and a combination of HA and PPS. At this dose rate, HA significantly decreased the severity of both the cartilage and subchondral bone changes. Intraarticular PPS had no effect on the development of osteoarthritic lesions, nor did it decrease lameness in the sheep. When used in combination, HA and PPS provided a greater improvement in gait than either drug alone, but relief of joint pain appeared to be associated with overuse of the limb and resulted in lesions in the articular cartilage as severe as those seen in saline treated control animals.

Item Type: Thesis (PhD)
Murdoch Affiliation(s): School of Veterinary Studies
Notes: Note to the author: If you would like to make your thesis openly available on Murdoch University Library's Research Repository, please contact: Thank you.
Supervisor(s): Read, Rick
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