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Mechanism of bone resorption in hip prosthesis
WS4-K-2-01
ANALYSES OF BONE RESORPTION AROUND CEMENTLESS HIP PROSTHESES - - IN VlVO AND IV VITRO STUDY-KJ. Kim 1 , T. Itoh 1 , M. Kumegawa2, HE. Rubash3 1) Dept. of Orthopaedic Surgery, Tokyo Women's Medical College, Tokyo, Japan 2) Dept. of Oral Anatomy, Meikai Univ. of School of Dentistry, Saitama, Japan 3) Dept. of Orthopaedic Surgery, Univ. of Pittsburgh, PA, U.S.A. Introduction: Bone resorption and/or osteolysis around hip prostheses has been implicated with the failure of implants whether they are inserted with cement or without cement. Recent reports have indicated that wear particles, such as cement, polyethylene, and metal may play an important role in inducing bone resorbing factors from macrophages in the fibrous membrane around the prostheses. In this study, we analyzed interface membranes surrounding failed hip prostheses without cement biochemically and immunohistochemically. In addition, we performed in vitro studies to investigate what kind of wear particles could stimulate the production of bone resorbing factors from rabbit synovial cells. Materials and M e t h o d s : In vivo analvses; Membranes from sixty-four femoral components were obtained from sixty-three patients. Fifty-seven membranes were from implants that articulated with polyethylene (32 were made of cobalt alloy, and 25 were titanium alloy), and 7 were.from unipolar prosthesis that did not articulate with polyethylene. Tissue specimens were prepared for biochemical assays and immunohistochemical analyses. Biochemically, organ cultures of each specimen were assayed for collagenase, prostaglandin E 2 (PGE2), and interleukin-1 (IL-1). Immunohistochemical analyses was done for T iymphocytas, B
lymphocytas, macrophages and IL-1. /n vitro exoeriment ; Wear particles (average size was about 5 microns) were prepared as follows; polyethylene (PE), cobalt alloy (Co-C 0, titanium alloy (Ti6AI4V), pure titanium (Ti), and hydroxyapatite (HA). Conditioned media (CM) of rabbit synovial cells cultured with various wear particles were added to unfractionated rabbit bone cells on a dentin slice. The number of pits formed on the slices were counted to evaluate osteoctastic bone resorption. Results and Discussion: The membranes from implants with a polyethylene articulation released significantly higher levels of collagenase and IL-1 (p<0.05). Furthermore, membranes from implants with roentgenographic evidence of osleolysis released significantly higher levels of IL-1 compared to those from membranes without osteolysis. Immunohistochemical analyses showed that many macrophages phagocytized polyethylene and metal debris were present in the membranes from implants with a polyethylene articulation. IL-1 v~s stained on macrophages, fibroblasts, and endothelial cells. In vitro experiment showed that only CM cultured with PE particles significantly increased resorbed area on a dentin slice (p<0.05). However, recombinant IL-1 alone did not stimulate osteoclastic bone resorption. This experiment demonstrates that osteoclastic bone resorption is induced by soluble factors from the cells activated by PE debris around implants. Our results also suggest that unknown soluble factors other than IL-1 or combined effects of various cytokines may play an important role in osteoclastic bone resorption around implants.
WS4-K-2-02 MECHANISM OF BONE RESORPTION IN HIP PROSTHESIS H. Hayashi, Y. Kuroki, K. Hirakawa, Y. Imazato, ~ Hirakawm Dept. of Orthopaedic Surgery, Fujigaoka Hospital, Showa University School of Medicine, Kanagawa, Japan (INTRODUCTION) The progressive enlargement of radiolucent areas has often been observed after hip prosthesis replacement The purpose of this study is to elucidate the mechanism of radiolucent area formation. (MATERIAL & METHODS) The interface membranes and pseudo capsules were obtained from patietns at the time of surgery for revision of either cemented THA or cemenfless bipolar endprosthesis replacement. The lateral capsule was used as controL Tissue samples were divided for both histological and biochemical studies. Historogical specimens were stained with H.E., T a r t r a t e - resistant acid phosphate and immunohistochemical reagents; the latter included a n t i - macrophage antibody (CD68), and anti - T - lymphocyte antibody (MT - 1) Biochemically, Interleukin - I /~ (IL - 1 B), IL - 6, IL - 8, and Tumor Necrosis F a c t o r - a were assayed by ELISA in the supernatant of homogenized samples and organ culture media. Prostagiandin E2 was assayed by radioimmunoassay. Futhermore, radiolucent areas were classified to two types (linear type, and w o r m - eaten type), and these two groups were compared as to the biochemical and histological results. (RESULT) The levels of I L - 6 and I I - 8 in both of the supernatants of homogenized sample and organ culture media from the interface membrane of the acetabular and femoral side were higher than those from control group. Histologically, the interference membranes contained many debris (cement, High density polyethylene (HI)P), and metal) with inflammation, fibrosis, and necrosis. Smaller pieces of HDP debris wereingested by macrophages, and large fragments were surrounded by multinucleated foreign body giant cell~ Cement debris were difficult to visualize, and many of them were could be observed as large vacuolea The interface membranes of the w o r m - eaten type lesion contained more debris, macrophages, T - lymphocytes and multinucleated foreign body giant cells than the linear type lesion did. (DISCUSSION) The bone resorption surrounding the implant after hip prosthesis replacement occurs in different pathways. One pathway might be the stimulation of T - lymphocytes and macrophages by various debris and micromovements, foliowing the release of chemical mediators such as cytokine, which, in turn, activate osteoclasts to absorb bone, another possible mechanism would be the biomechanically unstable implant causing the bone necrosis directly. It appears that a single pathway is insufficient for the bone resorption surrounding implant. It is neccessary to improve the quality of the biomaterial, and to construct biomechanically stable prosthesis, at the same time.
282
ANALYSES OF BONE RESORPTION AROUND CEMENTLESS HIP PROSTHESES - - IN VlVO AND IV VITRO STUDY-KJ. Kim 1 , T. Itoh 1 , M. Kumegawa2, HE. Rubash3 1) Dept. of Orthopaedic Surgery, Tokyo Women's Medical College, Tokyo, Japan 2) Dept. of Oral Anatomy, Meikai Univ. of School of Dentistry, Saitama, Japan 3) Dept. of Orthopaedic Surgery, Univ. of Pittsburgh, PA, U.S.A. Introduction: Bone resorption and/or osteolysis around hip prostheses has been implicated with the failure of implants whether they are inserted with cement or without cement. Recent reports have indicated that wear particles, such as cement, polyethylene, and metal may play an important role in inducing bone resorbing factors from macrophages in the fibrous membrane around the prostheses. In this study, we analyzed interface membranes surrounding failed hip prostheses without cement biochemically and immunohistochemically. In addition, we performed in vitro studies to investigate what kind of wear particles could stimulate the production of bone resorbing factors from rabbit synovial cells. Materials and M e t h o d s : In vivo analvses; Membranes from sixty-four femoral components were obtained from sixty-three patients. Fifty-seven membranes were from implants that articulated with polyethylene (32 were made of cobalt alloy, and 25 were titanium alloy), and 7 were.from unipolar prosthesis that did not articulate with polyethylene. Tissue specimens were prepared for biochemical assays and immunohistochemical analyses. Biochemically, organ cultures of each specimen were assayed for collagenase, prostaglandin E 2 (PGE2), and interleukin-1 (IL-1). Immunohistochemical analyses was done for T iymphocytas, B
lymphocytas, macrophages and IL-1. /n vitro exoeriment ; Wear particles (average size was about 5 microns) were prepared as follows; polyethylene (PE), cobalt alloy (Co-C 0, titanium alloy (Ti6AI4V), pure titanium (Ti), and hydroxyapatite (HA). Conditioned media (CM) of rabbit synovial cells cultured with various wear particles were added to unfractionated rabbit bone cells on a dentin slice. The number of pits formed on the slices were counted to evaluate osteoctastic bone resorption. Results and Discussion: The membranes from implants with a polyethylene articulation released significantly higher levels of collagenase and IL-1 (p<0.05). Furthermore, membranes from implants with roentgenographic evidence of osleolysis released significantly higher levels of IL-1 compared to those from membranes without osteolysis. Immunohistochemical analyses showed that many macrophages phagocytized polyethylene and metal debris were present in the membranes from implants with a polyethylene articulation. IL-1 v~s stained on macrophages, fibroblasts, and endothelial cells. In vitro experiment showed that only CM cultured with PE particles significantly increased resorbed area on a dentin slice (p<0.05). However, recombinant IL-1 alone did not stimulate osteoclastic bone resorption. This experiment demonstrates that osteoclastic bone resorption is induced by soluble factors from the cells activated by PE debris around implants. Our results also suggest that unknown soluble factors other than IL-1 or combined effects of various cytokines may play an important role in osteoclastic bone resorption around implants.
WS4-K-2-02 MECHANISM OF BONE RESORPTION IN HIP PROSTHESIS H. Hayashi, Y. Kuroki, K. Hirakawa, Y. Imazato, ~ Hirakawm Dept. of Orthopaedic Surgery, Fujigaoka Hospital, Showa University School of Medicine, Kanagawa, Japan (INTRODUCTION) The progressive enlargement of radiolucent areas has often been observed after hip prosthesis replacement The purpose of this study is to elucidate the mechanism of radiolucent area formation. (MATERIAL & METHODS) The interface membranes and pseudo capsules were obtained from patietns at the time of surgery for revision of either cemented THA or cemenfless bipolar endprosthesis replacement. The lateral capsule was used as controL Tissue samples were divided for both histological and biochemical studies. Historogical specimens were stained with H.E., T a r t r a t e - resistant acid phosphate and immunohistochemical reagents; the latter included a n t i - macrophage antibody (CD68), and anti - T - lymphocyte antibody (MT - 1) Biochemically, Interleukin - I /~ (IL - 1 B), IL - 6, IL - 8, and Tumor Necrosis F a c t o r - a were assayed by ELISA in the supernatant of homogenized samples and organ culture media. Prostagiandin E2 was assayed by radioimmunoassay. Futhermore, radiolucent areas were classified to two types (linear type, and w o r m - eaten type), and these two groups were compared as to the biochemical and histological results. (RESULT) The levels of I L - 6 and I I - 8 in both of the supernatants of homogenized sample and organ culture media from the interface membrane of the acetabular and femoral side were higher than those from control group. Histologically, the interference membranes contained many debris (cement, High density polyethylene (HI)P), and metal) with inflammation, fibrosis, and necrosis. Smaller pieces of HDP debris wereingested by macrophages, and large fragments were surrounded by multinucleated foreign body giant cell~ Cement debris were difficult to visualize, and many of them were could be observed as large vacuolea The interface membranes of the w o r m - eaten type lesion contained more debris, macrophages, T - lymphocytes and multinucleated foreign body giant cells than the linear type lesion did. (DISCUSSION) The bone resorption surrounding the implant after hip prosthesis replacement occurs in different pathways. One pathway might be the stimulation of T - lymphocytes and macrophages by various debris and micromovements, foliowing the release of chemical mediators such as cytokine, which, in turn, activate osteoclasts to absorb bone, another possible mechanism would be the biomechanically unstable implant causing the bone necrosis directly. It appears that a single pathway is insufficient for the bone resorption surrounding implant. It is neccessary to improve the quality of the biomaterial, and to construct biomechanically stable prosthesis, at the same time.
282