Serum Protein-Based Indices for the Progression of Fracture Healing and Nonunion
Abstract
The alignment of this proposal is with the Surgical Focus Areal Extremity Fractures, and the proposed research will advance optimal treatment and rehabilitation from musculoskeletal injuries to identify patients that can more quickly return to duty/work. Medical Problem to Be Addressed: Fractures to the limbs are one of the most common injuries that Service members will experience, both during training and in combat. X-rays and verbal questions about how the injured bone feels (whether there is pain and whether the person can use the injured limb) are the current approaches used to follow the progress of bone healing. A major deficiency with x-rays and pain assessments is that they do not tell the physician about what is going on biologically over the course of healing. Such knowledge would help the surgeon to better know whether healing is progressing or whether the fracture is failing to heal. X-rays and pain assessments also do not accurately tell the physician when a person can start to walk on the bone. In addition, failed healing, as diagnosed by x-ray and pain, is made many months after the biology of healing has actually failed. This means that, if there was a tool to follow the biology of healing, diagnosis of failed healing could be made at a significantly earlier time point, leading to earlier intervention for failed healing and shortening the periods that patients are subjected to pain and disability. Rationale for Project: A few studies to date have shown that specific proteins associated with the various biological stages of fracture healing are released from the fractured bone into the serum (blood), and assaying for their presence can be used to follow bone healing. Our recent animal study looked at about 1,300 proteins in the serum across the time course of fracture healing and found that over 800 of these proteins had significantly changed levels after fracture. Recent use of advanced computational modeling has enabled scientists, through the assay of the expression of hundreds of genes and proteins, to develop a number of precision-based diagnostics for a broad number of diseases, enabling both earlier diagnosis and development of new therapies. This leads us to believe that we can successfully develop a serum protein-based biological diagnostic to both follow the progression of fracture healing and identify failed healing at much earlier times than x-rays. Objective: The objective of this research proposal is to identify a set of serum proteins that are predictive of progression of the biological processes of human fracture healing and would be diagnostic for failed healing many months earlier than current diagnostic tools. Study Design: A total of 180 patients with an upper arm bone (humerus) fractures, treated with a sling and immobilization, will be asked to participate in this study. We will screen this number since failed healing only happens in about 15% of patients, so we want to have at least 20 non-healers for comparisons to healers. They will all receive the same treatment standard of care as any other patient with these kinds of fractures. At each standard-of-care visit, 3 mL of blood will be drawn. The expression levels of 90 proteins that were selected based on both prior animal and human studies will have their levels measured over 36 weeks of healing. At the same time, we will use standard x-ray and pain assessments to follow healing, as would be done in the normal fashion. The study will take place in two phases. In the first phase, called the “discovery phase,” we will compare the time courses of serum proteins of 10 non-healers to 10 healers. Using computational modeling of the proteins’ expression comparing the two groups to each other, we will first identify (discover) those proteins that both biologically follow the time course of healing and best predict non-healing. In the second phase of the study, the “validation phase,” we will then repeat the stud
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910796
Entities
People
- Louis Gerstenfeld
Organizations
- Boston University Medical Campus
- United States Army