Biomarker Identification in Orthopaedic & Oral Maxillofacial Surgery Subjects to Identify Risks of Bisphosphonate Use

Study Overview
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Brief Summary
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Bisphosphonates are drugs that prevent bone loss by blocking the activity of cells that normally resorb bone. The most common examples of these drugs are Boniva and Fosamax. These drugs are available for oral or intravenous dosing and are prescribed at daily, weekly, biweekly, or monthly intervals. Among the many thousands of individuals who currently take these medications, certain individuals experience atypical femur fractures preceded by prodromal pain, changes in cortical thickening of bone, or bisphosphonate related osteonecrosis of the jaws (BRONJ). Osteonecrosis of the jaws is defined as exposed bone of the jaws for 8 weeks or more and requires surgical treatment. This study will attempt to identify genomic and rna biomarkers that may play a role in differential metabolism of bisphosphonates or indicate tendency toward the severe adverse events associated with these drugs.

Detailed Description
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Collected specimens were subjected to Affymetrix DMET™ Plus Solution analysis. Manuscript is in preparation.

Official Title
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Biomarker Identification in Orthopaedic and Oral Maxillofacial Subjects

Conditions
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Osteoporosis, With or Without Treatment, Bisphosphonate Treatment, Atypical Femur Fracture, Bisphosphonate Related Osteonecrosis of the Jaws (BRONJ), Healthy Volunteers

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Any adult (male or female) age 18 or over meeting any of the following criteria: All participants must be able to provide informed consent for themselves. History of BP treatment with or without BRONJ and/or Femur fracture (typical or atypical) No History of BP treatment with or without BRONJ and/or Femur fracture (typical or atypical) Exclusion Criteria: Children age 17 or younger Adults who cannot or do not make medical decisions for themselves Persons known to be under the jurisdiction of the Department of Corrections Individuals who are pregnant.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| CASES<br>Adults with current or past history of bisphosphonate treatment (exposed) with Bisphosphonate related Osteonecrosis of the Jaws (BRONJ), or, Adults with current or past history of bisphosphonate treatment (exposed) with atypical fracture | |
| COUNTER MATCHED CONTROLS<br>Adults with current or past history of bisphosphonate treatment (exposed) without bisphosphonate related osteonecrosis of the jaws (BRONJ, or, Adults with current or past history of bisphosphonate treatment (exposed) with typical fracture or joint replacement or osteoporosis | |
| MATCHED CONTROLS<br>Adults without current bisphosphonate treatment (unexposed) with Typical fracture (healthy fracture patients) Adults without current bisphosphonate treatment (unexposed) without BRONJ (healthy oral surgery subjects or adults with radionecrosis of the jaws) | |
| Healthy Adult Volunteers<br>Healthy volunteers with or without current bisphosphonate treatment without jaw or extremity pathologies or injuries to contribute blood and saliva samples only. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absorption, Distribution, Metabolism, Excretion (ADME) Profiling of DNA from all sample types vs. normative data for the ADME panel and across study groups | DNA analysis of saliva, blood, and tissues to detect differential response to drugs. DNA will be isolated from each sample and ADME profiling will be performed. Each participant subgroup will be compared to each other using ANOVA modeling. Each participant subgroup will be compared to normative data for the distribution of gene profiles in the general population for each probe on the ADME gene array. | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differential expression of miRNA biomarkers across participant groups within the study | The relative abundance of miRNA across each participant subgroup will be compared using ANOVA modeling. Each participant subgroup will be compared to normative data for the distribution of miRNA expression profiles in the general population for each probe when available. | Baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aclasta, Actonel, alendronate, alendronate/cholecalciferol, Aredia, Atelvia, Boniva, Didronel, etidronate, Fosamax, Fosamax Plus D, ibandronate, pamidronate, Reclast, risedronate, Skelid, tiludronate, zoledronic acid, Zometa, Bisphosphonate, Atypical Femur Fracture (AFF), Osteoporosis, Bisphosphonate Related Osteonecrosis of the Jaw (BRONJ)