While orthopedic implant fixation methods have advanced over the last several decades, failure rates of cementless total joint arthroplasties remain higher than cemented total joint arthroplasties, therefore enhancing bone integration of these implants remains a major clinical challenge. Therapies to stimulate bone formation or prevent bone resorption, such as intermittent administration of parathyroid hormone (PTH) or osteoprotegerin (OPG) treatment may benefit osseointegration to improve fixation and long-term surgical outcomes. In addition, patients resume normal activities of daily living post-operatively, so mechanical loading, a proven anabolic treatment, is ongoing and must be considered in conjunction with these pharmacologic interventions. Before these treatments can be implemented clinically, the influence that mechanical loading, PTH and OPG have on osseointegration must be investigated both at the tissue and cellular levels.
The aim of this study is to better understand the role that systemically delivered anabolic or anti-catabolic agents play in the osseointegration of metallic implants in an in vivo mechanically loaded rabbit model. Our hypothesis is that mechanical loading combined with an anabolic (PTH) agent or an anti-catabolic agent (OPG) will enhance peri-implant cancellous bone volume and osseointegration of a porous metallic implant via effects on both osteoblasts and osteoblasts. Osseointegration into a metallic implant and peri-implant cancellous bone will be assessed by examining bone ingrowth and the peri- prosthetic tissue integrity using mechanical testing, backscattered scanning electron microscopy (BSE), microcomputed tomography (microCT), bone histomorphometry, immunohistochemistry and qRT-PCR. With these experiments we hope to a) demonstrate osseointegration of metallic implants can be enhanced by mechanical loading and administration of a systemic anabolic agent, PTH or a systemic anti-catabolic agent, OPG, and b) explore the cellular mechanisms triggered by these stimuli during osseointegration of metallic implants.

Public Health Relevance

Contemporary metallic implants used in orthopaedics rely on bone ingrowth into the implant for both early and long-term fixation and ultimately clinical success. Failure of total joint implant fixation remains a clinical problem that leads to revision, individual patient morbidity and societal costs. Combining mechanical loading, an anabolic agent such as intermittent parathyroid hormone or an anti-catabolic agent such as osteoprotegerin, may enhance the ingrowth of bone into these metallic implants more rapidly and more robustly, allowing patients to return to function earlier and allow implants to last longer without loosening.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR056802-03
Application #
8256559
Study Section
Special Emphasis Panel (ZRG1-MOSS-C (02))
Program Officer
Panagis, James S
Project Start
2010-07-15
Project End
2014-04-30
Budget Start
2012-05-01
Budget End
2013-04-30
Support Year
3
Fiscal Year
2012
Total Cost
$371,250
Indirect Cost
$146,772
Name
Hospital for Special Surgery
Department
Type
DUNS #
622146454
City
New York
State
NY
Country
United States
Zip Code
10021
Yang, Xu; Willie, Bettina M; Beach, Jocelyn M et al. (2013) Trabecular bone adaptation to loading in a rabbit model is not magnitude-dependent. J Orthop Res 31:930-4