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Early knee osteoarthrosis after meniscectomy: studies in rabbits
Linköping University, Department of Neuroscience and Locomotion, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Post-traumatic osteoarthrosis develops after intraarticular injuries. It is a disease, which affects both articular cartilage and subchondral bone, and progresses over 10-20 years. Irreversible damage has often occurred by the time clinical diagnosis is possible. More knowledge about the early phase of the disease might yield measures to detect and delay or even prevent progression. This thesis evaluates changes in articular cartilage and subchondral bone at an early stage of post-traumatic osteoarthrosis.

Simultaneous changes in articular cartilage and subchondral bone were evaluated 3 to 40 weeks post-operatively in a rabbit meniscectomy model for post-traumatic osteoarthrosis. Rabbits were meniscectomized in the right knee and sham-operated in the left knee. Osteoarthrotic cartilage changes were evaluated by histology. Changes in the subchondral bone were evaluated by histology, scintimetry and dual-energy X-ray absorptiometry (DEXA). Joint space narrowing, and its utility as diagnostic tool at early stages of osteoarthrosis, was assessed with weight-bearing radiographs. The prognostic value of transforming growth factor-ßI (TGF-ß1) and proteoglycan fragment concentrations in the joint fluid at an early stage was also assessed.

We found slight cartilage changes and an increased metabolic activity in the subchondral bone as early as 3 weeks after meniscectomy. However, sham-operated knees displayed similar changes, although to a lesser degree. Cartilage fibrillation progressed at areas of high load within the meniscectomized knee joint. The subchondral bone showed a general response such as high scintimetric activity 3 weeks after surgery, and a decreased bone mineral density at later time points. Local adaptation in areas of high load within the subchondral bone was also seen. There was an increased osteoid content at the border between the cancellous bone and the marrow cavity already 3 weeks after meniscectomy, and at 13 weeks the subchondral bone plate was thickened. This thickening of the bone plate persisted up to 40 weeks. Joint space narrowing occurred after removal of the meniscus, but weight-bearing radiographs were not sensitive enough to measure early cartilage changes. Increased concentration of TGF-ß1 in the joint fluid at 3 weeks after surgery was associated with a higher degree of histological osteoarthrotic changes at a later time point.

Simultaneous changes in both cartilage and bone were apparent already 3 weeks after surgery, indicating that both tissues are involved from a very early stage. The localisation of cartilage changes illustrates that mechanical consequences of meniscectomy play a crucial role in progression of the disease. Surgical trauma resulted in increased release of TGF-ß1 at 3 weeks after surgery. This was found to be indicative for the severity of later osteoarthrosis. Thus, factors solely associated with the surgical trauma may also be important for the progression of osteoarthrosis.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet , 2003. , 55 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 795
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-28031Local ID: 12791ISBN: 91-7373-553-1 (print)OAI: oai:DiVA.org:liu-28031DiVA: diva2:248582
Public defence
2003-06-05, Elsa Brändströms sal, Hälsouniversitet, Linköping, 13:00 (Swedish)
Opponent
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-10-10Bibliographically approved
List of papers
1. Simultaneous changes in bone mineral density and articular cartilage in a rabbit meniscectomy model of knee osteoarthrosis
Open this publication in new window or tab >>Simultaneous changes in bone mineral density and articular cartilage in a rabbit meniscectomy model of knee osteoarthrosis
2000 (English)In: Osteoarthritis and Cartilage, ISSN 1063-4584, E-ISSN 1522-9653, Vol. 8, no 3, 197-206 p.Article in journal (Refereed) Published
Abstract [en]

Objective It was hypothesized that increased bone mineral density of the medial proximal tibia would precede or coincide with the development of more severe cartilage changes after meniscectomy.

Methods In a rabbit knee model, mineral density of subchondral bone and changes of articular cartilage were monitored 13 to 40 weeks after medial meniscectomy or a sham operation.

Results Both procedures resulted in a decrease of bone mineral density, especially of the medial proximal tibia, which persisted up to 40 weeks (P< 0.02–0.0007). Meniscectomy induced cartilage changes typical for osteoarthrosis (P< 0.009), which progressed over time on the posterior aspect of the medial tibial plateau (P< 0.009), which is physiologically covered by the meniscus, but the procedure also induced iatrogenic changes which were located mainly on the anterior aspect of the concerned compartment, and which did not progress or develop to osteoarthrosis.

Conclusions The data suggest that the cartilage changes after meniscectomy in this animal model are caused by the surgical trauma, subsequent limb misuse, and altered load distribution, and initially associated by a decrease not an increase in bone mineral density of the proximal tibia. Moreover, the cartilage changes progressed without a simultaneous increase of the bone mineral density at corresponding sites.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-27749 (URN)10.1053/joca.1999.0290 (DOI)12490 (Local ID)12490 (Archive number)12490 (OAI)
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
2. Meniscectomy leads to an early increase in subchondral bone plate thickness in the rabbit knee
Open this publication in new window or tab >>Meniscectomy leads to an early increase in subchondral bone plate thickness in the rabbit knee
2003 (English)In: Acta Orthopaedica Scandinavica, ISSN 0001-6470, Vol. 74, no 4, 437-441 p.Article in journal (Refereed) Published
Abstract [en]

We evaluated morphological changes in the tibial bone after meniscectomy in a rabbit model. 15 rabbits subjected to a medial meniscectomy in the right knee and a sham-operation in the left. Histomorphometric parameters were evaluated in the subchondral bone plate and the underlying trabecular bone, 13, 25 and 40 weeks after surgery. 5 rabbits were used as unoperated controls.Meniscectomized knees had a thicker subchondral bone plate than sham-operated contralateral ones in 13 of the 15 rabbits (p= 0.01), but the trabecular bone showed no morphological differences. The meniscectomized knees of these rabbits developed mild osteoarthrosis, described elsewhere, which may have been partly due to a change in the mechanical properties of the thickened subchondral bone plate. Our findings suggest that the first bony response after meniscectomy occurs in the subchondral bone plate rather than in the trabecular bone.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-27640 (URN)10.1080/00016470310017758 (DOI)12376 (Local ID)12376 (Archive number)12376 (OAI)
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
3. Meniscectomy in the rabbit knee leads to increased bone remodelling and cartilage degeneration within three weeks
Open this publication in new window or tab >>Meniscectomy in the rabbit knee leads to increased bone remodelling and cartilage degeneration within three weeks
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Increased knowledge about the early cartilaginous and osseous responses to meniscectomy may elucidate processes behind development of osteoarthrosis. The purpose of the present study was to evaluate tibial bone and cartilage changes during the first months after meniscectomy.

Thirty-one skeletally mature New Zealand white rabbits were operated on with meniscectomy in the right knee and a sham-operation in the left knee. Another 12 rabbits were used as controls. The knee joints were evaluated 3, 6 and 12 weeks after surgery by radiolabelled bisphosphonate uptake (99mTc-HDP) and semiquantitative grading of histological changes in the subchondral bone and cartilage.

Already 3 weeks after meniscectomy, there was increased metabolic activity in the subchondral bone, and articular cartilage fibrillation. Similar changes were seen in shamoperated knees, but to a lesser extent. This appears to be caused both by the new loading situation in the joint after meniscectomy and the operative trauma.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-84496 (URN)
Available from: 2012-10-10 Created: 2012-10-10 Last updated: 2012-10-10Bibliographically approved
4. Radiographic joint space narrowing and histologic changes in a rabbit meniscectomy model of early knee osteoarthrosis
Open this publication in new window or tab >>Radiographic joint space narrowing and histologic changes in a rabbit meniscectomy model of early knee osteoarthrosis
2001 (English)In: American Journal of Sports Medicine, ISSN 0363-5465, E-ISSN 1552-3365, Vol. 29, no 2, 151-160 p.Article in journal (Refereed) Published
Abstract [en]

The purpose of this study was to compare weightbearing radiographs with histologic cartilage evaluation in a rabbit meniscectomy model of the early stage of osteoarthrosis. Fifteen rabbits had a medial meniscectomy performed in one knee and a sham operation in the other knee. Five rabbits each were sacrificed at 13, 25, and 40 weeks after surgery. Radiographic joint space width and histologic cartilage changes of the medial knee compartment were quantified. Five nonoperated knees and five knees in which the meniscus had been removed immediately before the evaluations served as control specimens. Overall, the joint space of the peripheral part of the medial knee compartment was narrower in knees operated on for meniscus removal than in sham-operated knees (P < 0.003). In the knees with the meniscus removed, more cartilage changes were seen at the joint surface area of contact on radiographs than in the sham-operated knees (P < 0.0015). Indeed, the area of contact had cartilage changes similar to those in the whole medial compartment. However, there was no correlation between the degree of histologic cartilage change and the corresponding joint space measurements. Joint space width as measured on weightbearing radiographs is reduced after meniscectomy in the rabbit, but it does not reflect the degree of cartilage damage of the loaded joint surfaces in early stages of osteoarthrosis.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25901 (URN)10342 (Local ID)10342 (Archive number)10342 (OAI)
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
5. TGF-β1 as a prognostic factor in the process of early osteoarthrosis in the rabbit knee
Open this publication in new window or tab >>TGF-β1 as a prognostic factor in the process of early osteoarthrosis in the rabbit knee
2001 (English)In: Osteoarthritis and Cartilage, ISSN 1063-4584, E-ISSN 1522-9653, Vol. 9, no 3, 195-202 p.Article in journal (Refereed) Published
Abstract [en]

Objective To assess changes in knee joint fluid concentrations of transforming growth factor-β1 (TGF-β1) and proteoglycan (PG) fragments during the early course of post-traumatic osteoarthrosis (OA) after meniscectomy in the rabbit knee, and to ascertain whether the concentrations of these substances shortly after operation could be used as prognostic markers for the OA process.

Design In 15 rabbits with medial meniscectomy in one knee and a sham operation in the other knee, synovial lavage fluid samples were taken repeatedly, before operation, every third week post-operatively until 12 weeks, thereafter every sixth week, and at death. Five rabbits each were killed at 13, 25 and 40 weeks. Synovial lavage fluid samples from five non-operated rabbits served as controls. At death, two histological scores were formed that characterized the highest (MAX) and the overall (ALL) degree of OA changes in each joint.

Results TGF-β1 and PG fragment concentrations in synovial lavage fluid correlated highly (R=0.81, P< 0.001). Both OA scores were higher in meniscectomized than controls (P< 0.05). The synovial lavage fluid concentration of TGF-β1 at 3 weeks, but no other time point, correlated to the histological scores (ALL, R=0.58; MAX, R=0.52;P< 0.001).

Conclusion Higher concentrations of TGF-β1 in synovial lavage fluid early after surgery seemed indicative for the later development of more severe OA changes in contrast to lower concentrations. The association between TGF-β1 and the changes found later in the cartilage was underlined by the high correlations between this substance and PG fragment concentrations in synovial lavage fluid at all time points.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-27601 (URN)10.1053/joca.2000.0376 (DOI)12331 (Local ID)12331 (Archive number)12331 (OAI)
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved

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