Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Adenosine A2A Receptor Agonists: Can They Prevent/Treat Joint Prosthesis Loosening?

Mediero1,  Aranzazu, Frenkel2,  Sally R., Wilder1,  Tuere, Immerman3,  Igor, Hadley3,  Scott, Howell3,  R. Damani, Hawly4,  Maya

Department of Medicine, NYU Langone Medical Center, New York, NY
Department of Orthopaedic Surgery, NYU Hospital for Joint Diseases, New York, NY
Department of Orthopaedic Surgery, NYU Hospital for Joint Diseases
Institut Supérieur des BioSciences de Paris, France
New York Univ Med Ctr, New York, NY

Purpose:

Survival of bone implants depends on biological fixation, and prosthesis loosening can be catastrophic leading to replacement of prostheses. Inflammation and osteoclast-mediated bone resorption in response to wear particles near prostheses contribute to loosening. Because we have demonstrated that adenosine A2A receptor activation is anti-inflammatory and prevents osteoclast formation and function we hypothesized that adenosine A2A receptor agonists might prevent osteoclast-mediated bone resorption at the site of prosthesis wear in a calvarial model of wear particle-induced bone resorption.

Methods:

Eighteen C57Bl/6 mice age 6–8 weeks were anesthetized by intraperitoneal injection of ketamine and xylazine and a 1cm midline sagittal incision was made over the calvarium anterior to the line connecting both ears. Six animals received no particles (control), and 12 received 15 ml of polyethylene particle suspension. Of the 12 mice receiving particulate, 6 were injected subcutaneously at the surgical site with 20 ml of 10 mM CGS21680 (A2A receptor agonist), and 6 mice were injected with saline 0.9%, beginning immediately after incision closure and continuing every other day until sacrifice. Animals were sacrificed after 14 days and the calvaria were removed, fixed, and prepared for microCT and histological staining with TRAP.

Results:

Histologic examination of calvaria demonstrated lymphocytic infiltration in both particle-exposed groups. TRAP staining revealed a reduction in osteoclast differentiation after treatment with CGS21680. mCT showed pitting and increased porosity in both particle-exposed groups compared to controls, although in CGS21680-treated mice the reduction in cortical bone was significantly less than in the untreated particle-exposed mice (p<0.01). Control bone volume/trabecular volume was significantly greater (p<0.005) than in either particulate group, however, calvarial bone from CGS21680-treated mice had significantly greater mean bone volume than did the untreated group (p<0.0005). Trabecular thickness was significantly reduced in both CGS21680-treated and untreated particle-exposed groups as compared to control mice (p<0.05). Finally, digital morphometric analysis of microCTs reveals that CGS21680 significantly reduced the area of bone pitting compared to control particle-treated mice (p<0.05).

 Bone Volume/Trabecular VolumeBone Mineral DensityTrabecular Thickness% Area of bone pitting
Control0.7964 ± 0.0002821.11 ± 138.79 mg/cc0.1080 ± 0.00001 mm4.6 ± 0.6%
Particulate0.7436 ± 0.0005810.28 ± 153.07 mg/cc0.1041 ± 0.00003 mm10.2 ± 1.1%
Particulate + CGS216800.7765 ± 0.0003809.14 ± 161.64 mg/cc0.1079 ± 0.00003 mm7.8 ± 1.2%

Conclusions:

Adenosine A2A receptor activation reduces inflammation and bone destruction due to prosthetic wear particles. This observation suggests that delivery of an adenosine A2A agonist in the cement may enhance orthopedic implant survival, delaying or eliminating the need for revision arthroplasty surgery.

To cite this abstract, please use the following information:
Mediero, Aranzazu, Frenkel, Sally R., Wilder, Tuere, Immerman, Igor, Hadley, Scott, Howell, R. Damani, et al; Adenosine A2A Receptor Agonists: Can They Prevent/Treat Joint Prosthesis Loosening? [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1470
DOI: 10.1002/art.29236

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