Biomarker Identification in Orthopaedic & Oral Maxillofacial Surgery Subjects to Identify Risks of Bisphosphonate Use - Full Text View

Purpose

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.

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


Study Type:	Observational
Study Design:	Observational Model: Ecologic or Community Time Perspective: Prospective
Official Title:	Biomarker Identification in Orthopaedic and Oral Maxillofacial Subjects

Resource links provided by NLM:

MedlinePlus related topics: Fractures Leg Injuries and Disorders Osteonecrosis Osteoporosis

U.S. FDA Resources

Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:

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 ] [ Designated as safety issue: No ]
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.

Secondary Outcome Measures:

Differential expression of miRNA biomarkers across participant groups within the study [ Time Frame: Baseline ] [ Designated as safety issue: No ]
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.

Other Outcome Measures:

Microbiome (Bacterial and viral composition) of samples within and across participant groups will be assessed and compared to normative data. [ Time Frame: Baseline ] [ Designated as safety issue: No ]
Using microbial genetic methods, we plan to determine the bacterial and viral diversity found in samples to evaluate the possible role of bacteria on the response to drugs. Microbiome metagenomics established within and across each participant subgroup will be correlated with ADME profiling results to assess the potential impact these two phenomena have on each other.

Biospecimen Retention: Samples With DNA

Saliva will be collected from online participants and DNA analysis will be performed.

Blood and tissue samples will be collected from in-person participants. DNA and RNA analysis will be performed.


Estimated Enrollment:	500
Study Start Date:	May 2013
Estimated Study Completion Date:	April 2018
Estimated Primary Completion Date:	April 2018 (Final data collection date for primary outcome measure)

Groups/Cohorts
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.

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes
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.

Criteria

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.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01875458

Contacts


Contact: Patrick Hesketh, BS	781-985-3556	patrick.hesketh@uphs.upenn.edu
Contact: Annamarie D Horan, MPA, PhD	215-349-8856	horana@uphs.upenn.edu

Locations


United States, Pennsylvania
Online participation via https://www.surveymonkey.com/s/bisphos4ctg	Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Patrick Hesketh 781-985-9556 Patrick.Hesketh@uphs.upenn.edu
University of Pennsylvania Health System	Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Patrick Hesketh, BS 781-985-9556 patrick.hesketh@uphs.upenn.edu
Contact: Annamarie D Horan, MPA, PhD 215-349-8856 horana@uphs.upenn.edu
Principal Investigator: Samir Mehta, MD
Principal Investigator: David C Stanton, MD, DMD

Sponsors and Collaborators

University of Pennsylvania

Investigators


Principal Investigator:	Samir Mehta, MD	University of Pennsylvania, Department of Orthopaedic Surgery
Principal Investigator:	David C Stanton, MD, DMD	University of Pennsylvania, Department of Oral Surgery
Study Director:	Annamarie D Horan, PhD	University of Pennsylvania

More Information

Additional Information:

To participate in this study, and be taken to the Survey Monkey survey, click here. This link exits the ClinicalTrials.gov site


Responsible Party:	University of Pennsylvania
ClinicalTrials.gov Identifier:	NCT01875458 History of Changes
Other Study ID Numbers:	815570 815570
Study First Received:	June 7, 2013
Last Updated:	May 3, 2016
Health Authority:	United States: Office for Human Research Protections (OHRP)

Keywords provided by University of Pennsylvania:


Bisphosphonate Related Osteonecrosis of the Jaw (BRONJ) 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

Additional relevant MeSH terms:


Osteonecrosis Bisphosphonate-Associated Osteonecrosis of the Jaw Osteoporosis Femoral Fractures Bone Diseases, Metabolic Bone Diseases Musculoskeletal Diseases Necrosis Pathologic Processes	Fractures, Bone Wounds and Injuries Leg Injuries Jaw Diseases Stomatognathic Diseases Alendronate Diphosphonates Bone Density Conservation Agents Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 30, 2016