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

NCT01875458 | Completed

• 1 other identifier: 815570
• Study Type: observational
• Target: 314
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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

Keywords

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)

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Differential expression of miRNA biomarkers across participant groups within the study

  Baseline

Study Arms (4)

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 Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

University of Pennsylvania Health System

Philadelphia, Pennsylvania, 19104, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

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

MeSH Terms

Conditions

Osteoporosis; Bisphosphonate-Associated Osteonecrosis of the Jaw

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Osteonecrosis; Jaw Diseases; Stomatognathic Diseases; Necrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Samir Mehta, MD

  University of Pennsylvania, Department of Orthopaedic Surgery

  PRINCIPAL INVESTIGATOR

• Annamarie D Horan, PhD

  University of Pennsylvania

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2013
• First Posted: June 11, 2013
• Study Start: April 13, 2012
• Primary Completion: October 30, 2022
• Study Completion: October 30, 2022
• Last Updated: January 13, 2023

Record last verified: 2023-01

Locations

US (1)