Research

Since its creation in 1986, The Limb Preservation Foundation has provided funding for clinical and laboratory research regarding limb preservation including the treatment of osteosarcoma (bone cancer) and non-healing fractures, chemotherapy, and disease transmission during bone and tissue transplants. Foundation funding supported research has led to the development of osteosarcoma treatment protocols that have dramatically increased the survival rate of pediatric bone cancer patients. Our research involving pediatric and extremity bone cancer continues at Colorado State University Animal Cancer Center.

Our Patient Assistance Program is sponsored by Allosource

LIMB PRESERVATION FOUNDATION AND CSU FLINT ANIMAL CANCER CENTER

Research

THE LIMB PRESERVATION FOUNDATION CONTINUES TO FUND CUTTING-EDGE RESEARCH PROGRAMS WITH THE GOAL OF FINDING THE CURE FOR BONE CANCER AND OTHER EXTREMITY DISEASES.

The Limb Preservation Foundation and Colorado State University Flint Animal Cancer Center are at the forefront in advancing research and accelerating improvements for individuals facing life- and limb-threatening conditions through the work provided by the Ross M. Wilkins, M.D. Limb Preservation University Chair in Musculoskeletal Biology and Oncology.

Did you know. . . that some of the leading research in the prevention of limb loss due to cancer, trauma, or infection happens in pet dogs?

Did you know . . . that dogs get bone cancer?

Did you know . . . that discoveries being made in animals are benefiting humans and the discoveries benefiting humans with limbs at risk of amputation are benefiting pets?

Did you know  . . . the best reported long-term survival for bone cancer, the intraarterial chemotherapy protocol developed in cooperation with Colorado State University’s Flint Animal Cancer is utilized at The Denver Clinic for Extremities at Risk for treatment of osteosarcoma and malignant fibroushistiosarcoma of the extremity in children and adults.

 

THIS TWO-WAY EXCHANGE IS CALLED TRANSLATIONAL MEDICINE AND IS A POWERFUL MEANS BY WHICH WE CAN OBTAIN RESULTS OF INVESTIGATIONAL TREATMENT FASTER.

 


Research Partners for More Than 27 Years!

The partnership with The Limb Preservation Foundation and Colorado State University Flint Animal Cancer Center has been going strong for years. It is a unique link focused on how we can partner in the discovery of new cures for cancer, especially when it affects the limbs of patients, both humans, and dogs.

 

BY THIS PARTNERSHIP WE HAVE BEEN ABLE TO MAKE GREAT STRIDES IN LIMB-SAVING TREATMENTS THAT ULTIMATELY ENHANCE AND SAVE LIVES IN BOTH WORLDS, THE HUMAN AND ANIMAL WORLD.

 

Several types of cancer behave almost identical in dogs as they do in people. These include osteosarcoma, the most common primary bone tumor in people and dogs. As naturally occurring cancer progresses more rapidly in dogs, we can obtain results of investigational treatment faster, and if successful, translate those findings to children and adults. The discoveries made in clinical animal patients are translated into human patients and visa versa.

This has been possible through the funding of research and the vision to develop the Ross M. Wilkins, M.D. Limb Preservation University Chair in Musculoskeletal Biology and Oncology at CSU Flint Animal Cancer Center that funds a permanent researcher at Colorado State University and scientist around the globe to reach for new multidisciplinary approaches to the most challenging issue surrounding limb preservation today.

SIGNS AND SYMPTOMS OF OSTEOMYELITIS

People with active osteomyelitis infection describe feeling nauseated and having fever-like symptoms. There is usually tenderness, redness, and warmth in the area of the infection and as well as swelling of the area.  If the osteomyelitis is near a joint there may be a loss of motion at that joint. In addition, pain associated with the infection may lead to reluctance to use the extremity.

When the infection is active there may be drainage from an open area or sinus tract leading to the infected area.  This is less common with chronic or long-term osteomyelitis.

DIAGNOSIS OF OSTEOMYELITIS
Blood tests like erythrocyte sedimentation rate (Sed rate) or C-reactive protein (CRP) are used to determine if there is an active response by the body to some type of infective process. These tests are not specific to osteomyelitis and, if the osteomyelitis is chronic, these tests may be normal.
An MRI or CT scan may be ordered to see if there is a process occurring in the bone but these are also not specific to osteomyelitis. A CT is preferred for infections within the bone while MRI is more sensitive for joint or soft tissue involvement.
Cultures of fluid and tissue from a draining sinus or from an open wound can help in determining the organism causing the infection.
A bone biopsy with cultures is necessary to confirm a diagnosis of osteomyelitis. This is usually done as an open procedure or with CT (CAT) scan guidance.
A PET/CT may be ordered to determine if there is an infective process, especially if other tests do not confirm a diagnosis. Studies are showing the PET/CT is effective in detecting chronic osteomyelitis.1
TREATMENT

Osteomyelitis is a serious infection and if not treated aggressively, or if the infection doesn’t respond to treatment it can result in amputation. A combination of surgery and antibiotic therapy is necessary to adequately treat osteomyelitis.

The goal of surgery is to get rid of any infected bone and tissue, as well as remove any foreign material (orthopedic implants or sutures) that might be present from previous surgery. Once the area has been thoroughly debrided and washout out, the gap created in the bone is filled with some type of antibiotic spacer. Antibiotic impregnated cement beads or pellets are often used as well.

During the debridement, the infected tissue is collected and analyzed so that the organism causing the infection can be identified.  It can take several days for the results to be known but once the type of bacteria is identified an infectious disease specialist can determine the best antibiotic to use to treat the osteomyelitis.

The antibiotics are most often given intravenously (through an IV) and the full course is at least 6 weeks.   During this time, a patient is followed closely by an infectious disease specialist in order to monitor the response to the antibiotic treatment.  Once the infectious disease specialist and the orthopedic surgeon feel the infection has been managed the reconstructive surgery can take place.

There are a number of options for reconstructive surgery following debridement and antibiotic therapy.

These include:

  • the use of allograft (bone bank) tissue,
  • bone and soft tissue transfer (moving bone and muscle from one part of the body to the area),
  • bone transport (use of external fixators to regrow bone in the area),
  • use of orthopedic implants

Each patient’s situation is very different so the orthopedic surgeon will discuss the best options with the patient, educating them on recovery time, anticipated function, and potential for recurrence of the infection.


References
1. Pineda C, Vargas A, Rodríguez AV. Imaging of osteomyelitis: current concepts. Infect. Dis. Clin. North Am. 2006;20 (4): 789-825

Major Research Milestone Achieved

In 2014, The Foundation achieved a major milestone by completing the funding for the Ross M. Wilkins, M.D. Limb Preservation University Chair in Musculoskeletal Biology and Oncology.  This achievement is a commitment, in perpetuity, to advancing research and accelerating improvements for individuals facing life- and limb-threatening conditions.

AlloSource, one of the nation’s largest providers of skin, bone and soft tissue allografts for use in surgical procedures, and the world’s largest processor of cellular bone allografts pledged the lead gift to the University Chair.  The McDonnell Family Foundation and the Ferguson Family joined the campaign as major sponsors, along with many generous supporters of The Limb Preservation Foundation. Colorado State University matched each dollar raised to fund the University Chair.

“Much of my career has been devoted to healing patients affected by disease or trauma threatening the loss of an arm or leg,” said Dr. Ross Wilkins, Founder, and President of The Limb Preservation Foundation. “While we have made many strides over the past 30 years, I envision a day when doctors can tell a bone cancer patient with complete assurance that they will be cured. Clinical and laboratory research will get us there and the generous financial support of the University Chair from our major contributors as well as countless others, takes us one step closer to this vision becoming a reality.”

The Ross M. Wilkins, M.D. Limb Preservation University Chair in Musculoskeletal Biology and Oncology will be lead by a permanent full-time scientific researcher with Ph.D./VMD in Musculoskeletal Biology and Oncology at CSU Flint Animal Cancer Center. The program will ensure on-going advancements in this understudied field of limb loss prevention, coordinating research efforts in tissue engineering, molecular therapeutics, gene therapy, biomechanics, computer modeling, polymer chemistry, bench research, translational medicine and clinical studies efforts with one overarching goal: the health, wholeness, and well-being of patients whose limbs and lives are at risk due to cancer, infection or trauma. Staff will work with researchers at Colorado State University and scientists and medical professionals from around the globe to advance research on current and challenging issues surrounding limb preservation.

Chairs occupy an important place in academia. They are both physical and symbolic. When Dr. Nicole Ehrhart assumes the Wilkins University Chair today, she will receive an actual chair, engraved with her name and the name of the endowment that will fund her cancer research.

Known officially as the Ross M. Wilkins, M.D. Limb Preservation University Chair in Musculoskeletal Biology and Oncology, the maple chair, trimmed in black and gold, is important for what it represents: a $3 million endowment ensuring the research continues in perpetuity, and the fact that Ehrhart is the first woman at Colorado State University appointed to an endowed University Chair.

 

“IT’S THE REMOVAL OF ANOTHER GLASS CEILING,” SAID EHRHART, A VETERINARIAN, BOARD-CERTIFIED SURGICAL ONCOLOGIST AND CSU PROFESSOR OF SURGICAL ONCOLOGY. “I’M VERY HONORED. IT’S AN OPPORTUNITY TO REPRESENT THE FUTURE ON SO MANY LEVELS.”

 

At Colorado State’s Flint Animal Cancer Center, she teaches and treats animal patients. She also studies ways to prevent limb loss and to regenerate bones and muscle in people and animals whose extremities are threatened by cancer, infection, or trauma. Ehrhart employs surgical and bone-grafting techniques, as well as biologics and stem-cell therapies.

Among Colorado State’s highest honors, University Chairs are funding mechanisms used to support outstanding scholars in their quests for new knowledge in critical fields. Ehrhart is one of 14 CSU faculty members holding academic chairs endowed at $3 million.

“This is a tremendous tribute to Dr. Ehrhart’s outstanding leadership as a scientist and scholar,” CSU President Tony Frank said. “That she is the first woman to occupy an endowed University Chair is significant — if long overdue — a milestone for our institution. CSU has been home to exceptional, accomplished women faculty since its founding in 1870, and Dr. Ehrhart carries on that tradition with her groundbreaking work in human and animal health. We are grateful for this chance to celebrate and support her work at the highest levels.”

Ehrhart’s appointment to the University Chair is symbolic for another reason: The chair is named for Dr. Ross Wilkins, a Denver cancer doctor who has collaborated closely with Dr. Stephen Withrow, a veterinarian, University Distinguished Professor and founder of the Flint Animal Cancer Center. The two surgical oncologists together developed limb-sparing techniques that have become a standard of care for pets and people, especially children, with bone cancer.
The doctor and the veterinarian — seeing firsthand the value of their collaboration — spearheaded fund-raising for the chair endowment to ensure that future medical professionals will continue cooperative discoveries to save limbs.

“It’s a great honor to hand it off to you,” Withrow told Ehrhart when they recently conferred in her lab. “I hope I’m alive long enough to see who you hand it off to.”
Ehrhart’s Laboratory of Comparative Musculoskeletal Oncology and Traumatology epitomizes “translational medicine,” in which findings from research into animal disease are applied to human medicine. She has been actively involved in limb preservation research, regenerative medicine, tissue engineering, and sarcoma research for the last 18 years.

Dr. Rod Page, director of the Flint Animal Cancer Center and holder of the Stephen J. Withrow Presidential Chair in Oncology, affirms the endowment’s role in securing the future of limb-sparing research.  “I often say, ‘Cancer is cancer – it doesn’t care what species you are.’ This chair will allow Dr. Ehrhart, and others who come after her in perpetuity, to pursue research that will help save human and animal lives,” he said.

Ehrhart described her appointment to the chair as the pinnacle of her career.  “I’m a veterinarian and I love animals, but I have a great sense of excitement about helping people, too. The greatest thing for me is the opportunity to do both,” she said. “The greatest reward of this chair is that I have the opportunity to make an impact in both worlds.”

Studying disease in dogs provides a fast-track option that saves money and time in moving research discoveries to patients, whether they are four-legged or two-legged. That’s because dogs age faster than humans, meaning they develop the disease and response to treatment in less time.

“To get any new treatment on the market, from laboratory to the patient, it takes 15 to 20 years and somewhere around $12 billion,” Ehrhart said. “The truth is that people who have these types of threatening diseases don’t have that time. They needed our help yesterday. They can’t sit around and wait for this to happen.”

RESEARCHER, TEACHER, DOCTOR

Ehrhart certainly isn’t sitting around waiting.
On a typical day, she checks on mouse cells in her lab on the second floor of the Flint Animal Cancer Center, then heads downstairs to the Veterinary Teaching Hospital for case discussions, or rounds, with 15 oncology residents, students, and other veterinarians.

One recent day, the discussion centered on the difficult questions that arise when a pet is diagnosed with cancer. Ehrhart helped gently lead the reluctant students into a mental health discussion. “I’ve had clients share suicidal thoughts. That’s a scary thing,” she told the room. “I say, ‘Thank you for telling me,’ and I offer them resources. As medical professionals, we have an obligation to help.”

After morning rounds, Ehrhart and a student met with a client whose Basset hound was headed home after successful surgery. After making sure the dog had the right-sized protective collar, she crossed the hospital to the diagnostic imaging center to see another surgical patient’s chest radiographs and was cheered to see the lungs were clear.

Next came surgery. Dressed in blue scrubs and a purple cap, Ehrhart might be hard to pick out in the surgical suite. But two features, in addition to her expert calm, make her stand out: She’s 5 feet 1 inch tall, and a bedazzled gold lanyard peeked out from her V-neck surgical top.

By the end of the day, she was ready to check in with her two teenaged daughters and perhaps enjoy a glass of wine with her husband and friends. In her time off, she is often in the mountains, backpacking, or skiing.

Dr. Nicole Ehrhart and investigators at the Flint Animal Cancer Center are finding new ways to save limbs and improve lives with the help of funding from the 2015 Doug and Sally McCain Pilot Research Grant. Their study entitled  “ Reanimation of Decellularized Skeletal Muscle Scaffold Following Critical Muscle Tissue Loss”  is focused on finding ways to “reanimate” muscle scaffolds in order to provide a custom,  living, functioning muscle unit to replace lost tissue after infection, trauma or cancer.

“Trauma, infection and tumor surgery often results in loss of large portions of muscle tissue.  While surgeons can partially reconstruct these defects by transfer of muscle from other areas of the body, the functional and cosmetic outcomes using such techniques are less than ideal. There are a high number of complications, and function at the site of reconstruction is commonly poor. We need solutions to regenerate muscle tissue in the site of muscle loss without ‘stealing’ large portions of muscle from elsewhere in the body which creates other problems. Tissue engineering and regenerative medicine present a promising potential solution.” says Dr. Ehrhart

Sally and Doug McCain

Sally and Doug McCain

Thanks to the Doug and Sally McCain 2015 Pilot Research Grant they now have the seed money to develop that promise.  The investigative team is currently engaged in an 18 month study to evaluate a method that turns decellularized scaffolds into living muscle, effectively “re-animating” the tissue matrix. Results from the pilot study will allow the team to obtain the initial data required to move into larger studies, eventually involving clinical trials in patients.

Dr. Ehrhart is a Full Professor in the Department of Clinical Sciences at Colorado State University’s Flint Animal Caner Center and holds the Ross M Wilkins MD Limb Preservation University Chair in Musculoskeletal Biology and Oncology

The Limb Preservation Foundation research grants are made possible by individual donors and the fundraising efforts of The Foundation.  The purpose of The Limb Preservation Program is to support exceptional research projects that will help lead to better treatment protocols to save limbs in jeopardy.

Applications are reviewed by the Scientific  Advisory Committee and the Medical Advisory Committee of The Foundation.

Laboratory or clinical research will be considered for funding.  Particular emphasis will be placed on the support of independent junior investigators, postdoctoral, and research fellows (M.D., DVM, or Ph.D. certified).

Pilot studies that will become eligible for further funding through conventional support mechanisms will receive priority.

ELIGIBILITY

Scientists and clinicians of nonprofit research, medical service, and educational institutions are eligible to apply for grants.  Educational institution applicants must have faculty status or a mentor with faculty status.

Pilot Research Grant Recipients

DR. VALERAE LEWIS, OF THE MD ANDERSON CENTER AT THE UNIVERSITY OF TEXAS

PROJECT: Assessing the Efficacy of IL-11 Targeted Treatment for the Treatment of Osteosarcoma

Dr. Lewis graduated from Harvard Medical School in 1993.  She completed her general surgery residency at Beth Israel Medical Center in Boston, Massachusetts in 1994.  From 1994-98 she conducted her Orthopaedic Surgery residency at Harvard Combined Orthopedic Residency Program in Boston.  Dr. Lewis also completed a fellowship in Musculoskeletal Oncology at The University of Chicago.  Currently she is the Associate Professor of Surgery, Ad-Interim Chief of the Department of Orthopaedic Oncology at the University of Texas,  MD Anderson Cancer Center.

Dr. Lewis investigates the linking of chemotherapeutic agents to molecules that hone to the tumor, and the tumor alone, which has the potential to deliver therapy without the systemic side effects now seen with chemotherapy.  Targeted therapy has the potential to not only increase the therapeutic options but make those options more tolerable.

DR. BRUNO FUCHS, OF THE UNIVERSITY OF ZURICH

PROJECT: Assessment of Intraarterial Chemotherapy in an Osteosarcoma Mouse Model of Spontaneous Metastasis

Dr. Fuchs graduated from the University of Zurich, Switzerland Medical School in 1992.  He completed his medical residency in Orthopaedic Surgery at the Universities of Zurich, Bern, and Lausanne.  From 1998-00 he completed an Orthopedic Oncology Fellowship at the Mayo Clinic in Rochester, MN.  He also attended Mayo Graduate School in 2004 and received a Ph.D. in Tumor Biology.  Since 2004, Dr. Fuchs has been the Director of Orthopedic Research at the University of Zurich.

Dr. Fuchs researches a method of intraarterial (IA) infusion using microcatheterisation of the epigastric artery of mice which is developed in their lab.  This method allows assessing the advantages of IA over intravenous chemotherapy in an established mouse model of osteosarcoma provoked by intratibial inoculation of low and high metastatic osteosarcoma cell lines.  The local response to IA Cisplatin as well as its effect on lung metastases will be investigated.

DR. NICOLE EHRHART, VMD OF CSU FLINT ANIMAL CANCER CENTER

Project: Isolated Limb Perfusion Using Samarium for Canine Osteosarcoma: Proof of Concept

Dr. Nicole Ehrhart graduated from the University of Pennsylvania College of Veterinary Medicine in 1990. She completed an internship in general medicine and surgery at the Animal Medical Center in New York City and was accepted into a surgery residency at Colorado State University in 1991. She completed her surgical residency and Master’s degree in Clinical Sciences in 1994 and became Board Certified in Surgery in 1995 during the first year of a 2 year postdoctoral fellowship in Surgical Oncology and Orthopedic Research. Following the completion of her Fellowship she was recruited in 1996 to the University of Illinois College of Biomedical Sciences as an Assistant Professor in Surgical Oncology where she remained for 6 years. In 2002, concurrent with the opening of the new Flint Animal Cancer Center at Colorado State University College of Veterinary Medicine and Biomedical Sciences, she returned to Colorado to join the faculty as a Professor of Surgical Oncology. She holds joint faculty appointments in the School of Biomedical Engineering and the Cell and Molecular Biology Programs is a member of the Gates Regenerative Medicine Center at the University of Colorado and is a University of Colorado Cancer Center member.

Her project focus is on the isolated limb perfusion using Samarium for Canine Osteosarcoma.

DR. FRANCIS ESHUN, M.D. OF CINCINNATI CHILDREN’S HOSPITAL MEDICAL CENTER

PROJECT: Biologic Local Control in Xenograft Models of Pediatric Bone Tumors Using Oncolytic Herpes and anti-VEGF Antibodies

Dr. Eshun graduated from the Univerisity of Ghana medical school in 1996.  He spent one year as an intern at the Korle-bu teaching hospital in Ghana in pediatrics and surgery departments.  He worked at the ER department of the same hospital for a year as a senior house officer and then went to the United Kingdom where he worked for 4 years in pediatrics.  He came to the U.S., and finished residency training in pediatrics at Lincoln Hospital which he completed in 2005.  He joined Cincinnati Children’s Hospital Medical Center in July 2005 as a subspecialty postdoctoral fellow in pediatric hematology/oncology.

Dr. Eshun’s project investigates biologic local control in xenograft models of pediatric bone tumors using the Oncolytic Herpes Virus and anti-VEGF Antibodies.

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