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| ID | Type | Description | Link |
|---|---|---|---|
| 815570 | Other Identifier | UPenn IRB |
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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.
Collected specimens were subjected to Affymetrix DMET™ Plus Solution analysis. Manuscript is in preparation.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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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.
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| Name | Affiliation | Role |
|---|---|---|
| Samir Mehta, MD | University of Pennsylvania, Department of Orthopaedic Surgery | Principal Investigator |
| Annamarie D Horan, PhD | University of Pennsylvania | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Pennsylvania Health System | Philadelphia | Pennsylvania | 19104 | United States |
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.
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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.
| ID | Term |
|---|---|
| D010024 | Osteoporosis |
| D059266 | Bisphosphonate-Associated Osteonecrosis of the Jaw |
| ID | Term |
|---|---|
| D001851 | Bone Diseases, Metabolic |
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D010020 | Osteonecrosis |
| D007571 | Jaw Diseases |
| D009057 | Stomatognathic Diseases |
| D009336 | Necrosis |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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