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oref impact on clinical practice

OREF donors do more than fund grants. A gift to OREF makes possible the kind of research that can have a real impact on patients. The studies below are just a few of the hundreds of projects OREF has funded since 1955. Many of those projects led to significant changes in clinical practice, but all of them increased our knowledge and understanding of musculoskeletal disease and healing.

To learn more about OREF's current grant funding, please visit the Grants section of the website.

Research Impact Profiles

Research Impact Profiles

Christopher J. Dy, MD, MPH

Intramedullary Implant for the Attachment of an External Prosthesis
Washington University in St. Louis
2020 OREF Gladden Orthopaedic Health Disparities Research Grant

Abstract: Disparities in utilization of orthopedic care have been noted throughout the literature, with prior work noting substantial race- and insurance-based disparities in both access and quality of care. Beyond pointing out the disparities that are present, there is a gap in our current understanding of how to address these disparities with interventions that will improve access for vulnerable groups. Our long-term goal is the develop an in-depth understanding of the factors contributing to Insurance-based disparities in orthopedic care delivery and to eventually use this understanding to inform strategies that can eliminate disparities in care. In the proposed work, we will use semi-structured interviews and qualitative analysis techniques to gain perspectives from both patients (Aim 1) and surgeons (Aim 2). This multi-level perspective and rich contextual analysis will allow us to better understand why disparities occur in our community and how we can craft interventions to address these disparities.

Impact: The proposed work is designed to gain a detailed, in-depth understanding for the reasons contributing to insurance-based disparities in orthopedic utilization within our community. Having the perspectives from both patients and surgeons will allow us to design strategies that are both patient-centered and pragmatic for surgeons, allowing us to begin the mission towards eliminating disparities in orthopedic care. The current literature is focused on pointing out disparities in care and identifying vulnerable groups. We hope that our work will continue a shift towards solutions for disparities.;

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John O. Esslinger, MD

Intramedullary Implant for the Attachment of an External Prosthesis
William Beaumont Hospital, Royal Oak, MI
1955 OREF Research Grant

Abstract: Study will investigate the feasibility of a bone implant that would protrude through the skin, to be utilized with an amputation. A tri-prong intramedullary implant of stainless steel.S.M.O. has been made to which two disks of tantalum wire mesh has been attached by means of a plastic material. This is to be inserted into the intramedullary canal of the tibia, muscles and tendons, and to be sutured to the more proximal disk of tantalum mesh. The leg is to be immobilized in a Thomas splint for a varying period post operatively. An external prosthesis will be attached to the implant, and x-ray and clinical follow-up studies carried out.

Impact: “If this were successful, it might readily be utilized in a forearm or arm amputation, as a means by which to more readily attach an external prosthesis, which could be motivated by a cineplasty motor, and eliminate the conventional bulky prosthesis that are now worn.”

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Leesa M. Galatz, MD

The Effects of Nicotine on Tendon to Bone Healing in a Rat Rotator Cuff Injury and Repair
Washington University in St. Louis (at time of grant)
2002 Zimmer/OREF Career Development Grant

Abstract: Many studies have shown that nicotine negatively impacts fracture healing and bone fusion processes. However, very little is known about its effect on tendon and ligament healing. The goal of the present study was to evaluate the effect of nicotine on tendon-to-bone healing.

Impact: Following completion of this study, Dr. Galatz and colleagues published their findings in the Journal of Bone and Joint Surgery. The following is quoted from the Discussion portion of the article.

"Failure of rotator cuff repair is a major clinical problem. Treatment may require additional procedures, and there are often no reliable or predictable surgical options. On the basis of the findings of the present study, we conclude that nicotine causes a delay in tendon-to-bone healing and also causes a delay in scar degradation and remodeling. Therefore, it is advisable that patients cease smoking or using tobacco products before undergoing a rotator cuff repair. Our results also may affect the advisability of using nicotine patches during the perioperative period. Additional studies are necessary in order to elucidate the changes in geometry and biomechanics reported here and to provide potential targets for therapeutic intervention."

Galatz, L. M.; Silva, M. J.; Rothermich, S. Y.; Zaegel, M. A.; Havlioglu, N.; and Thomopoulos, S., ,"Nicotine delays tendon-to-bone healing in a rat shoulder model." The Journal of Bone and Joint Surgery.,. 2027-2034. (2006). https://digitalcommons.wustl.edu/open_access_pubs/1043

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William H. Harris, MD

A Microradiographic, Autoradiographic and Electron Microscopic Study of Bone Resorption
University of Massachusetts Medical School
1960 OREF Research Grant

Abstract: William H. Harris, M.D., director emeritus of the Orthopaedic Biomechanics and Biomaterials Laboratory at Massachusetts General Hospital, received research grants from OREF in 1960 and 1970 for his work involving tetracycline labeling. Tetracyline labeling was developed to help quantify rates of bone formation. According to Dr. Harris, the integrity of the skeleton is based on two processes which occur simultaneously: the formation of bone and the removal (or resorption) of bone. If bone removal exceeds bone formation, the skeleton weakens. Tetracyline labeling helped study these processes by allowing measurement of rates of new bone formation. The tetracycline molecule, an antibiotic, is preferentially incorporated and retained at all sites where new bone is formed. Any new bone formed during the time the tetracycline was in the bloodstream fluoresces under ultraviolet light. To learn whether too little bone formation or too much bone resorption is the culprit in cases of osteoporosis, new bone formation can be measured by administering tetracyline markers at specific time points.

Impact: "The orthopaedic surgeon sees people with metabolic bone diseases in the form of osteoporosis or metabolic bone disease, rarely, but still, in terms of hyperparathyroidism or osteomalasia and the study of the rates of bone formation help understand those diseases.  Surgeons see metastatic cancer all the time.  Somebody comes in with a hole in their bone or a fracture through metastatic cancer and studies of bone formation and bone resorption were crucial to understanding all of these diseases.  What’s actually happened is that medicines have been developed called bisphosphenates, which inhibit or block the resorption of bone.  If your formation continues and you’re not resorbing as much, your bone gets stronger.  So there are millions and millions of people on bisphosphenates to prevent osteoporosis.  And a lot of those basic studies [that resulted in using bisphosphenates to treat osteoporosis] hinged on the ability to measure bone formation. "

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Frederick A. Matsen III, MD

Intracompartmental Pressure Measurement in the Diagnosis of Compartmental Syndrome
University of Washington School of Medicine, Department of Orthopaedics
1976 OREF Research Grant

Abstract: The compartmental syndrome is one of the primary causes of neurmuscular deficit following trauma or surgery of the extremities. In this condition, increased pressure within an osteofascial compartment compromises the circulation to the muscle and nerve within that compartment.This may produce loss of function and eventually death of these tissues. A prompt decompressive fasciotomy will usually prevent permanent functional losses.

In prior studies, a method of monitoring intracompartmental pressure was developed and evaluated. Having demonstrated the accuracy and safety of this technique, we would now like to investigate its usefulness in the evaluation of patients at risk for compartmental syndrome. If the onset of a compartmental syndrome may be reliably detected by objective pressure measurement, the decision to perform a fasciotomy will be greatly facilitated. On the basis of the available data, one would predict that prompt fasciotomy will dramatically reduce the incidence of permanent loss of neuromuscular function in patients with compartmental syndromes.

Impact: “A compartmental syndrome is defined as a condition in which the circulation and function of the contents of a space are compromised by increased pressure within that space. It is now apparent that proper treatment requires prompt diagnosis and decompression. Early diagnosis may be aided by objective monitors of the status of structures at risk.”

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Javad Parvizi, MD

Serum Molecular Markers: A Potential Guide for Re-implantation After Resection Arthroplasty for Periprosthetic Joint Infections
The Rothman Institute, Thomas Jefferson University
2013 OREF Prospective Clinical Research Grant

Abstract: Periprosthetic joint infection (PJI) currently constitutes the most challenging complication after total joint arthroplasty. The gold standard treatment for PJI in North America is two-stage exchange arthroplasty, the success of which averages around 80%. The currently available literature offers no reliable tests to confirm the eradication of infection after resection arthroplasty and thus help guide the surgeon in deciding on the appropriate time for reimplantation. Serum markers such as erythrocyte sedimentation rate (ESR) and C-reactive protein have been shown to have low utility in this situation and are not a good predictor of persistence of infection. Several molecular biomarkers have proven to be very promising in the diagnosis of PJI. The main objective of this study is to identify serum biomarkers that could confirm the eradication of infection or its persistence, in order to guide the surgeon in timing reimplantation surgery, with the goal of improving success rates. This will be a prospective study enrolling 108 patients diagnosed with PJI and referred for 2-stage exchange arthroplasty.

Impact: “The goal of our proposal has been to search for a biomarker that is serum or blood based. During the study, we evaluated the role of D-dimer in diagnosis of PJI and in particular the timing of reimplantation. The use of D-Dimer in diagnosing and treating infection could be a predictable and useful blood test for surgeons when treating their patients for infection. This grant has brought us one step closer to a potential, definitive method for helping to treat patients who get an infection after they have a hip or knee replacement. ”

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Scott Rodeo, MD

PRP Treatment of the ACL-Injured Knee to Decrease the Risk of PTOA
The Hospital for Special Surgery
2021 OREF/AAOS Injectable Orthobiologics of Knee Osteoarthritis Grant

Abstract: The inflammatory joint environment resulting from knee injury and anterior cruciate ligament reconstruction (ACLR) surgery plays a role in the initiation of post-traumatic osteoarthritis (PTOA). Thus, preventative therapies that dampen inflammation early after injury and before surgery may represent an effective therapeutic strategy to prevent PTOA. This blinded randomized controlled study will evaluate the efficacy of platelet-rich plasma (PRP) injection on the resolution of post-injury inflammation and improvement in joint function in patients undergoing ACLR surgery, who are at risk of developing PTOA. Our hypothesis is that PRP-injected knees will demonstrate greater reduction in biomarkers of inflammation, cartilage catabolism, and matrix degrading proteases compared to placebo-injected controls, with associated improvement in knee range of motion, pain, and quadriceps function at 6 months following ACLR surgery. Patients will be randomized to injection 2 weeks before ACLR and a second injection at the time of surgery of either placebo or PRP. We will collect biospecimens and clinical outcomes at different time points, and we will evaluate the ability of PRP of improving outcomes and reducing synovial fluid inflammation. We will use multiomics analyses to identify the composition and bioactivity of PRP associated with improved outcomes.

Impact: “After ACLR surgery patients are at higher risk of developing PTOA. This is primarily because we currently diagnose OA when the damage is irreversible, and because efficacious non-surgical therapies that can stop the disease progression are not yet available. Non-surgical approaches like PRP have shown promising but variable results, in part because of our lack of understanding of the relevant PRP components that impact clinical outcomes. Furthermore, the limited data available related to PRP and knee OA addresses treatment of established OA, but there is no information available about the potential of PRP for prevention of the pathological cascade leading to PTOA. This study will evaluate the efficacy of PRP on the resolution of the inflammatory cascade that may lead to PTOA following ACLR. We will evaluate functional outcomes following PRP injection, and we will use comprehensive cellular and molecular analyses to evaluate how PRP modulates immune responses in the joint. We will also assess the relevant components of PRP with functional impact. These results have the potential to change current clinical practice, allowing us to standardize the characterization and use of regenerative medicine products and ultimately enabling us to apply precision medicine approaches to treat numerous orthopedic conditions.”

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Randy N. Rosier, MD, PhD

Investigation of the Role of Mitochondria in Endochondral Calcification
University of Rochester, Rochester, NY
1984 OREF Career Development Grant

Abstract: The research program will be focused on cellular aspects of endochondral calcification. Calcium and phosphate transport in isolated growth plate chondrocytes will be studied to provide further information on the potential role of cellular sequestration of these ions prior to mineralization. The process of chondrocyte vesiculation and its controlling factors will be investigated. Furthermore techniques of isolation and culture of chondrocytes will provide a basis for potential future studies of normal and abnormal articular chondrocytes and tumor chondrocytes.

Impact: “Presently I feel the chondrocyte isolation and culture system is well-defined and consistent, providing a base for further investigations of the cellular properties of growth plate chondrocytes. Preliminary experiments examining the effects of hormone effectors on vesiculation, cell proliferation, and collagen and proteoglycan synthesis have been initiated recently. Additional techniques for measurement of phosphate transport and intracellular phosphate determination are underway, and should provide a basis for investigation of the effects of phosphate on vesicle release. Two additional secondary projects have been initiated by these ongoing investigations. The first involves the application of the relatively new technique of cell elutriation to separation of chondrocytes from different areas of the growth plate. The second involves parallel vesiculation experiments in well-defined cultures of osteoblasts, to determine whether osteoblasts have the capability to release matrix vesicles under in vitro culture conditions.”

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Carol A. Wise, PhD

Translating Genomics into Early Onset Scoliosis Clinical Care
Texas Scottish Rite Hospital for Children
2020 OREF/SRS/POSNA Transform Practice - Spinal Growth Research Grant

Abstract: Idiopathic scoliosis affects 1% to 2% of the population. Even moderate forms of the disease such as adolescent idiopathic scoliosis can negatively impact a patient’s quality of life due to progressive deformity, disability, and pain. However, the most worrisome form of idiopathic scoliosis occurs early in very young children. If left untreated, early onset scoliosis can lead to severe disability and cardiopulmonary failure.

Although treatment strategies for early onset scoliosis (EOS) continue to improve, there is little understanding of the pathophysiology or genetic etiology of the disease. Carol Wise, PhD, along with her clinical co-investigator Brandon Ramo, MD, intends to change that with her study funded by an OREF/SRS/POSNA grant. Using microarray genotyping and whole exome sequencing (WES)—a modern genetic sequencing technique—she aims to identify disease mutations by sequencing and analyzing at least 100 patients diagnosed with idiopathic early onset scoliosis (iEOS) and their parents. She also plans to identify new genes that are candidates for causing iEOS.

Impact: “Defining the underlying genetic causes of iEOS will open the door to better mechanistic and physiologic understanding of disease, and to novel medical treatments. We also anticipate that by using modern genetic sequencing, a clinically meaningful percentage of these ‘idiopathic’ patients will be revealed to have known genetic diagnoses, information that may inform their care. Our ultimate goal is to improve understanding of iEOS and to translate this knowledge into better treatment and prevention.”

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