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An experimental animal model of aseptic loosening of hip prostheses in sheep to study early biochemical changes at the interface membrane.

El-Warrak AO, Olmstead M, Schneider R, Meinel L, Bettschart-Wolfisberger R, Akens MK, Auer J, von Rechenberg B - BMC Musculoskelet Disord (2004)

Bottom Line: Nitric oxide (NO) and PGE2 concentrations were higher in the 8.5 months group (P < 0.0001) compared to the 2 months group with a tendency for the unstable group to have higher concentrations.The same was true for collagenolytic activity (P = 0.05), but not for caseinolytic activity that decreased over time (P < 0.0001).The early biochemical changes may well explain the pathologic bone resorption and formation of an interface membrane as is observed in clinical cases.

View Article: PubMed Central - HTML - PubMed

Affiliation: Musculoskeletal Research Unit, Dept of Veterinary Surgery, University of Zurich, Winterthurerstr, 260, 8057 Zurich, Switzerland. warrakel@uiuc.edu

ABSTRACT

Background: Aseptic loosening of hip prosthesis as it occurs in clinical cases in human patients was attributed to wear particles of the implants, the response of the tissue dominated by macrophages and the production of inflammatory mediators and matrix degrading enzymes; however, the cascade of events initiating the process and their interaction regarding the time course is still open and discussed controversially. Therefore, the goal of this study was to establish an experimental animal model in sheep allowing to follow the cascade of early mechanical and biochemical events within the interface membrane and study the sequence of how they contribute to the pathological bone resorption necessary for aseptic loosening of the implant.

Methods: A cemented modular system (Biomedtrix) was used as a hip replacement in 24 adult Swiss Alpine sheep, with one group receiving a complete cement mantle as controls (n = 12), and the other group a cement mantle with a standardized, lateral, primary defect in the cement mantle (n = 12). Animals were followed over time for 2 and 8.5 months (n = 6 each). After sacrifice, samples from the interface membranes were harvested from five different regions of the femur and joint capsule. Explant cell cultures were performed and supernatant of cultures were tested and assayed for nitric oxide, prostaglandin E2, caseinolytic and collagenolytic activity. RNA extraction and quantification were performed for inducible nitric oxide synthase, cyclooxygenase-2, interleukin 1, and interleukin 6. Overall differences between groups and time periods and interactions thereof were calculated using a factorial analysis of variance (ANOVA).

Results: The development of an interface membrane was noticed in both groups at both time points. However, in the controls the interface membrane regressed in thickness and biological activity, while both variables increased in the experimental group with the primary cement mantle defect over time. Nitric oxide (NO) and PGE2 concentrations were higher in the 8.5 months group (P < 0.0001) compared to the 2 months group with a tendency for the unstable group to have higher concentrations. The same was true for collagenolytic activity (P = 0.05), but not for caseinolytic activity that decreased over time (P < 0.0001).

Conclusion: In this study, a primary cement mantle defect of the femoral shaft elicited biomechanical instability and biochemical changes over time in an experimental animal study in sheep, that resembled the changes described at the bone cement-interface in aseptic loosening of total hip prosthesis in humans. The early biochemical changes may well explain the pathologic bone resorption and formation of an interface membrane as is observed in clinical cases. This animal model may aid in future studies aiming at prevention of aseptic loosening of hip prosthesis and reflect some aspects of the pathogenesis involved.

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Caseinolytic activity in cell culture media of tissue from interface membranes was highest in the stable group at 2 month and decreased over time. Differences were significant for all groups.
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Figure 5: Caseinolytic activity in cell culture media of tissue from interface membranes was highest in the stable group at 2 month and decreased over time. Differences were significant for all groups.

Mentions: PGE2 analysis revealed differences in concentrations over time but just missed statistical significances (P = 0.058). If the stable groups I were compared at 2 and 8 months statistical significant differences were found (P = 0.0002), which was not the case in the group II with the primary cement mantle defect (P = 0.09). The same was true if both groups were compared at 2 (P = 0.18) and 8.5 months (P = 0.27), however, there was a tendency for the groups II with the primary cement mantle defect to show higher concentrations. As with NO, standard deviations were very high.


An experimental animal model of aseptic loosening of hip prostheses in sheep to study early biochemical changes at the interface membrane.

El-Warrak AO, Olmstead M, Schneider R, Meinel L, Bettschart-Wolfisberger R, Akens MK, Auer J, von Rechenberg B - BMC Musculoskelet Disord (2004)

Caseinolytic activity in cell culture media of tissue from interface membranes was highest in the stable group at 2 month and decreased over time. Differences were significant for all groups.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC404466&req=5

Figure 5: Caseinolytic activity in cell culture media of tissue from interface membranes was highest in the stable group at 2 month and decreased over time. Differences were significant for all groups.
Mentions: PGE2 analysis revealed differences in concentrations over time but just missed statistical significances (P = 0.058). If the stable groups I were compared at 2 and 8 months statistical significant differences were found (P = 0.0002), which was not the case in the group II with the primary cement mantle defect (P = 0.09). The same was true if both groups were compared at 2 (P = 0.18) and 8.5 months (P = 0.27), however, there was a tendency for the groups II with the primary cement mantle defect to show higher concentrations. As with NO, standard deviations were very high.

Bottom Line: Nitric oxide (NO) and PGE2 concentrations were higher in the 8.5 months group (P < 0.0001) compared to the 2 months group with a tendency for the unstable group to have higher concentrations.The same was true for collagenolytic activity (P = 0.05), but not for caseinolytic activity that decreased over time (P < 0.0001).The early biochemical changes may well explain the pathologic bone resorption and formation of an interface membrane as is observed in clinical cases.

View Article: PubMed Central - HTML - PubMed

Affiliation: Musculoskeletal Research Unit, Dept of Veterinary Surgery, University of Zurich, Winterthurerstr, 260, 8057 Zurich, Switzerland. warrakel@uiuc.edu

ABSTRACT

Background: Aseptic loosening of hip prosthesis as it occurs in clinical cases in human patients was attributed to wear particles of the implants, the response of the tissue dominated by macrophages and the production of inflammatory mediators and matrix degrading enzymes; however, the cascade of events initiating the process and their interaction regarding the time course is still open and discussed controversially. Therefore, the goal of this study was to establish an experimental animal model in sheep allowing to follow the cascade of early mechanical and biochemical events within the interface membrane and study the sequence of how they contribute to the pathological bone resorption necessary for aseptic loosening of the implant.

Methods: A cemented modular system (Biomedtrix) was used as a hip replacement in 24 adult Swiss Alpine sheep, with one group receiving a complete cement mantle as controls (n = 12), and the other group a cement mantle with a standardized, lateral, primary defect in the cement mantle (n = 12). Animals were followed over time for 2 and 8.5 months (n = 6 each). After sacrifice, samples from the interface membranes were harvested from five different regions of the femur and joint capsule. Explant cell cultures were performed and supernatant of cultures were tested and assayed for nitric oxide, prostaglandin E2, caseinolytic and collagenolytic activity. RNA extraction and quantification were performed for inducible nitric oxide synthase, cyclooxygenase-2, interleukin 1, and interleukin 6. Overall differences between groups and time periods and interactions thereof were calculated using a factorial analysis of variance (ANOVA).

Results: The development of an interface membrane was noticed in both groups at both time points. However, in the controls the interface membrane regressed in thickness and biological activity, while both variables increased in the experimental group with the primary cement mantle defect over time. Nitric oxide (NO) and PGE2 concentrations were higher in the 8.5 months group (P < 0.0001) compared to the 2 months group with a tendency for the unstable group to have higher concentrations. The same was true for collagenolytic activity (P = 0.05), but not for caseinolytic activity that decreased over time (P < 0.0001).

Conclusion: In this study, a primary cement mantle defect of the femoral shaft elicited biomechanical instability and biochemical changes over time in an experimental animal study in sheep, that resembled the changes described at the bone cement-interface in aseptic loosening of total hip prosthesis in humans. The early biochemical changes may well explain the pathologic bone resorption and formation of an interface membrane as is observed in clinical cases. This animal model may aid in future studies aiming at prevention of aseptic loosening of hip prosthesis and reflect some aspects of the pathogenesis involved.

Show MeSH
Related in: MedlinePlus