Source: UNIVERSITY OF ILLINOIS submitted to
THE IMPACT OF BISPHOSPHONATE ADMINISTRATION ON CORTICAL BONE
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
TERMINATED
Funding Source
Reporting Frequency
Annual
Accession No.
1002736
Grant No.
(N/A)
Project No.
ILLU-888-376
Proposal No.
(N/A)
Multistate No.
(N/A)
Program Code
(N/A)
Project Start Date
Mar 18, 2014
Project End Date
Sep 30, 2015
Grant Year
(N/A)
Project Director
Stewart, M.
Recipient Organization
UNIVERSITY OF ILLINOIS
2001 S. Lincoln Ave.
URBANA,IL 61801
Performing Department
Veterinary Research & Extension
Non Technical Summary
Accepting that several major equine skeletal diseasesdevelop as a consequence of inadequate osteoclastic activity and the lack of effective remodeling, and that the evidence supporting efficacy is very limited, it is likely that Tildren is incorrectly prescribed in many instances. Of greater concern, the consequences of long-term inhibition with osteoclastic activity include compromised bone remodeling and inhibition of both osteoclastic and OPC activities during bone repair. The latterconcern is the focus of this project.
Animal Health Component
100%
Research Effort Categories
Basic
30%
Applied
70%
Developmental
0%
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
31138101030100%
Knowledge Area
311 - Animal Diseases;

Subject Of Investigation
3810 - Horses, ponies, and mules;

Field Of Science
1030 - Cellular biology;
Goals / Objectives
Extending this currently-active project for one year to 09/30/2015.Note: The purpose of this change is to add an IACUC approval to a previously-approved project.In horses, the bisphosphonate, tiludronate (Tildren), is being increasingly used to treat a range of skeletal conditions where bone resorption is present and is a plausible contributor to clinical signs of lameness. Tildren has been recommended for the treatment of over-riding dorsal spinous processes and navicular disease. Accepting that several major equine skeletal diseases (as examples, third carpal bone disease and McIII palmar condylar sclerosis) develop as a consequence of inadequate osteoclastic activity and ineffective remodeling, it is likely that Tildren is incorrectly prescribed in many instances. Of greater concern, bisphosphonates could also compromise osteo-progenitor cell activities during bone repair. The experiments will address the hypothesis that bisphosphonate administration will delay cortical bone defect repair under conditions where osteo-progenitor migration is a requirement for repair.
Project Methods
The study will be conducted using a caprine metacarpal/metatarsal cortical bone defect model. Skeletally-mature goats will receive tiludronate or vehicle prior to the surgical placement of 6-mm cortical bone defects in the lateral cortices of the cannon bones. In one limb, the periosteum will be stripped from around the defects. In the contralateral limb, the periosteum will remain in place. The effects of periosteal stripping and tiludronate administration on cortical defect repair will be assessed non-invasively by CT and, terminally, by histomorphometry.

Progress 03/18/14 to 09/30/15

Outputs
Target Audience:Members of the target audience include veterinary and biomedical orthopaedic researchers and veterinary surgeons. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?Two graduate students(Drs. MartaBianchessi and Kalyn Herzog)and a DVM student (Michelle Picione BS)worked on this project and gained considerable experience with animal model-based research, transcriptional profiling and bone histomorphometry. How have the results been disseminated to communities of interest?The results have been disseminated through presentations at several scientific conferences (Veterinary Orthopaedic Society, American College of Veterinary Pathologists, and the American College of Wound Healing and Regeneration). What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? We determined that prior bisphosphonate threatment does interfere with cortical bone repair, where the adjacent periosteum is removed. This condition simulates a displaced fracture site, where periosteal stripping is commmon. Periosteal and endosteal callus volumes were also reduced by prior bisphosphonate therapy, but these differences did not reach statistical significance.

Publications


    Progress 03/18/14 to 09/30/14

    Outputs
    Target Audience: Orthopaedic researchers and surgeons/clinicians with an interest in bone repair Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? An MS degree student, a visiting Veterinary Profesor from Brazil (sabbatical leave) and two DVM students have been integrally involved in the study. How have the results been disseminated to communities of interest? Results are still pending. What do you plan to do during the next reporting period to accomplish the goals? Complete the histomorphometric analyses, collate the complete data sets and submit a manuscript of the study for publication. It is also likely that the study will be presented at scientific conferences over the next 12-18 months.

    Impacts
    What was accomplished under these goals? We have completed the surgical model phase of the project, the specimen collections, CT image analyses and microCT image analyses. Processing of the specimens for histomorphometric analyses is being completed. The final analytical aspect of the study will involve the measurement of new bone formation and cortical bone repair in the histological sections.

    Publications