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Enhancement of Periprosthetic Bone Quality with Topical Hydroxyapatite-Bisphosphonate Composite
Sanjeev J. Suratwala, MD1; Samuel K. Cho, MD1; Jonathan J. van Raalte1; Sang Hyun Park, PhD2; Sung Wook Seo, MD1; Seong-Sil Chang, MD, PhD1; Thomas R. Gardner, MCE1; Francis Young-In Lee, MD, PhD1
1 Center for Orthopaedic Research, BB 1412, Department of Orthopaedic Surgery, Columbia University, 630 West 168th Street, New York, NY 10032
2 Tissue Healing Laboratory, Los Angeles Orthopaedic Hospital, University of California at Los Angeles, 2400 South Flower Street, Los Angeles, CA 90060
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Disclosure: In support of their research for or preparation of this work, one or more of the authors received, in any one year, outside funding or grants in excess of $10,000 from Stryker, the National Institutes of Health (grant 1R01EB006834) and from the Orthopaedic Research and Education Foundation (OREF). Neither they nor a member of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. A commercial entity (Stryker) paid or directed in any one year, or agreed to pay or direct, benefits in excess of $10,000 to a research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which one or more of the authors, or a member of his or her immediate family, is affiliated or associated.
Investigation performed at the Center for Orthopaedic Research, Department of Orthopaedic Surgery, Columbia University, New York, NY

The Journal of Bone and Joint Surgery, Inc.
J Bone Joint Surg Am, 2008 Oct 01;90(10):2189-2196. doi: 10.2106/JBJS.G.00409
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Background: Implant loosening is associated with inflammatory bone loss induced by ultra-high molecular weight polyethylene wear debris. We hypothesized that a hydroxyapatite-bisphosphonate composite improves periprosthetic bone quality and osseous integration of an intramedullary implant even in the presence of ultra-high molecular weight polyethylene particles in an experimental rat femur model.

Methods: A preliminary in vitro study determined the optimal concentration of zoledronate (50 µM) that would maximally decrease osteoclasts without harming osteoblasts. Hydroxyapatite-coated intramedullary nails were implanted bilaterally in the femora of sixteen rats (the control group), and hydroxyapatite-zoledronate-coated nails were implanted bilaterally in the femora of sixteen rats (the experimental group). Ultra-high molecular weight polyethylene particles were introduced into the femoral canal before implantation. Eight rats from each group were killed at six weeks, and the remaining rats were killed at six months. Periprosthetic bone mass was analyzed by dual x-ray absorptiometry and microcomputed tomography. Osseous integration was examined by biomechanical testing of pullout strength.

Results: The mean bone area (and standard deviation) in the periprosthetic bone region was significantly greater (p < 0.0001) in the hydroxyapatite-zoledronate group (2.388 ± 0.960 mm2) than in the control group (0.933 ± 0.571 mm2). This difference was larger in the six-week group than in the six-month group (p = 0.03). The average peak pullout force for the treated femora (241.0 ± 95.1 N) was significantly greater (p < 0.0001) than that for the controls (55.6 ± 49.0 N). This difference was similar in the six-week and six-month groups. The energy required for nail pullout was significantly greater (p < 0.0001) for the treated femora (521.6 ± 293.8 N-mm) than for the controls (142.2 ± 152.1 N-mm). This difference in energy to pullout was similar in the six-week and six-month groups. Regression analysis demonstrated a high correlation between periprosthetic bone mass and peak pullout force for both the six-week (r = 0.766, p = 0.0005) and six-month (r = 0.838, p < 0.0001) groups.

Conclusions: Surface modification of implants with hydroxyapatite-zoledronate improves periprosthetic bone quality and osseous integration.

Clinical Relevance: Hydroxyapatite-based site-specific delivery of bisphosphonates may be one way of reducing ultra-high molecular weight polyethylene wear particle-induced periprosthetic osteolysis and implant loosening.

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    These activities have been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the American Academy of Orthopaedic Surgeons and The Journal of Bone and Joint Surgery, Inc. The American Academy of Orthopaedic Surgeons is accredited by the ACCME to provide continuing medical education for physicians.
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