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

January 11, 2023 updated by: University of Pennsylvania

Biomarker Identification in Orthopaedic and Oral Maxillofacial Subjects

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.

Study Overview

Status

Completed

Conditions

Detailed Description

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

Study Type

Observational

Enrollment (Actual)

314

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania Health System

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Adults who either have ever taken bisphosphonates (see list under Key Words) and/or who have ever had an atypical femur fracture or bisphosphonate related osteonecrosis of the jaws (BRONJ) or both. Also healthy volunteers.

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
CASES
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
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
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
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?

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
Time Frame: Baseline
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
Time Frame: Baseline
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Pennsylvania

Investigators

  • Principal Investigator: Samir Mehta, MD, University of Pennsylvania, Department of Orthopaedic Surgery
  • Study Director: Annamarie D Horan, PhD, University of Pennsylvania

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 13, 2012

Primary Completion (Actual)

October 30, 2022

Study Completion (Actual)

October 30, 2022

Study Registration Dates

First Submitted

June 7, 2013

First Submitted That Met QC Criteria

June 7, 2013

First Posted (Estimate)

June 11, 2013

Study Record Updates

Last Update Posted (Estimate)

January 13, 2023

Last Update Submitted That Met QC Criteria

January 11, 2023

Last Verified

January 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 815570 (Other Identifier: UPenn IRB)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

IPD Plan Description

The results of this study will be shared in the form of a published article if accepted. Currently, the manuscript is in draft form and pending submission.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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