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Clinical Science

CAMPBELL researchers test effectiveness, safety of treatments in clinical trials

A research team working in a high-tech laboratory learns that a certain treatment helps bones heal in mice or tissue grow in pigs. But will it work in humans? And, is it safe? Those are two major questions that clinical trials can help answer.

Interviews and Articles

Dr. Crockarell

ampbell Research Helps Surgeons Know Which New Products Deliver on Promises

"In this field, clinical data seriously lags behind product introduction," said Dr. John Crockarell, a Campbell Clinic surgeon and researcher whose clinical studies help orthopaedic surgeons make informed judgments about what new products will produce the best outcomes over time.

In the last year, Dr. Crockarell analyzed information from Campbell Clinic patients to produce two studies that have been accepted for publication. Using radiographic analysis, Dr. Crockarell learned that Reflection® cementless acetabular components did not wear as well and had higher revision rates that newer polyethylene products. His findings will be published in the Journal of Arthroplasty.

Dr. Crockarell's view of the Contour® reconstruction ring confirmed some of the limitations of this type of device. The American Journal of Orthopaedics will publish his findings in this study.

Change Begs for Research

Dr. Crockarell has seen major changes in total joint replacement since he began practicing at Campbell Clinic in this specialty in 1997. In addition to improvements in the design and materials of implant devices, the decade has brought a greater emphasis on minimally-invasive surgery and better pain management, Dr. Crockarell said.

"Orthopaedic surgeons are always seeking better products and techniques if they mean better outcomes for patients," Dr. Crockarell said. "Clinical research helps us see how a product actually performs once the implant is done. This kind of information is always valuable to the surgeon and of great benefit to the patient."

From the Campbell Foundation Momentum.

In the rapidly-evolving orthopaedic specialty of total joint replacement, clinical data is the tortoise and new products are the hare.

Dr. Murphy

GEM OS1, Bone Graft Treatment

A Less-Painful Alternative

Dr. Drew Murphy, A Campbell Clinic surgeon who is a foot and ankle specialist, is currently overseeing Campbell's participation in a clinical trial involving the use of the GEM OD™1 bone graft treatment in patients who have had foot and ankle fusion surgery.

"Many elective surgeries for correction of deformity of the ankle and foot involve fusion of one or more joints for stability and improved function," Dr. Murphy said. "Most fusion require some type of supplementary graft to improve the success of the fusion."

Traditional graft techniques involve harvesting bone from other sites on a patient's body, which may result in more pain and potential complications. GEM OS1, a synthetic bone graft material developed by BioMinetic Therapeudics, can replace autogenous (from the patient) bone graft in foot and ankle fusion applications. The GEM OS1 material is placed directly into an open surgical site to stimulate bone regenerations.

Dr. Murphy has performed a number of fusion surgeries using the GEM OS1 graft. "Most situations that require bone graft are amenable to using this type of product," he said.

Comparing Results

Campbell Clinic's large patient base makes it a good site for recruiting participants in clinical trials. The GEM OS1 research was a nationwide study, involving numerous centers.

In the clinical trial supervised by Dr. Murphy, researchers compared two groups of patients who had undergone fusion surgery: those who had autogenous bone grafts, and surgeries in which the GEM OS1 material was used. Working with Dr. Murphy in the trial were Campbell Clinic surgeons Dr. Greer Richardson, Dr. Susan Ishikawa, and Dr. David Richardson.

The GEM OS1 study was a non-inferiority trial. Researchers were looking in whether bone regeneration following use of the GEM OS1 material was at least comparable to regeneration following autograft bone graft, without the pain and other negatives associated with the harvesting of the autograft. Assessment of bone regeneration was based on CT scans performed six months after surgery.

Mr. Murphy and his fellow researchers completed their report on the Campbell Clinic-based trial in December 2008. “The final outcome of the multi-center clinical trials in not known yet, but the initial results look promising for the ability to substitute this product for autograft,” Dr. Murphy said.

"Cartilage repair offers hope for the future, especially in dealing with osteoarthritis," Dr. Hasty said. "Osteoarthritis often means the cartilage is gone, and there's only bone on bone."

From the Campbell Foundation Momentum.

With a clinical trial, you take a well-thought-out theory, subject it to rigorous scientific and ethical standards, and find out if it really leads to advances in medicine. Our goal is to identity those advances that ultimately benefit the patient, our number one priority.

Clinical trails are research studies that involve people. Because clinical trails are vital to the development of new and better musculoskeletal procedures, treatments, and devices to benefit patients, Campbell Clinic doctors and researcher participate in a variety of these important research projects.

Subjecting Theory to Reality

"Clinical trials are the best way for doctors to learn what is safe and effective in new devices, procedures, and treatments," said Dr. Terry Canale, President of The Campbell Foundation and Chairman of the Foundation’s Research Committee. "We can observe and assess whether a product or treatment produces the desired result, and how well it works, using very specific and consistent guidelines set forth in the trial. Thousands of people are helped each year as a result of clinical trials, and we participate because we want to help our patients and improve the practice of medicine."

The Campbell Foundation Research Committee received and approves applications for research projects from Campbell Clinic staff physicians and assisting residents, both for basic science and clinical trial projects. The Committee discusses the objective of the study, research method, possible outcome, benefits and funding needs. The Committee also reviews the status of current projects and the publication of completed research papers in national orthopaedic and medical journals.

Clinical Research

Osteoporosis - or porous bone - is the most prevalent bone disease in the nation today. It can lead to fractures of the hip, spine, wrist, and other areas. Osteoporosis is often called the "silent disease" because bone loss occurs without symptoms. More than 10 million Americans have osteoporosis.

Because osteoporosis threatens the quality of life of present and future generations in the Mid-South and around the world, The Campbell Foundation is promoting major research and treatment initiatives that seek to identify the causes of osteoporosis, arrest its progress, improve bone quality so osteoporosis will victimize fewer women and men, and educate people diagnosed with or at risk for osteoporosis about the disease.

Dr. Weikuan Gu, Assistant Professor in the University of Tennessee-Campbell Clinic Department of Orthopaedic Surgery, is leading a team of researchers investigating the functional genonics of bone and osteoporosis to identify genes causing poor bone quality. Dr. Santos F. Martinez and Alice Ruch, RN, oversee Campbell Clinic's Osteoporosis Resource Center that focuses on evaluating and managing the disease. More than 300 patients are treated for osteoporosis at Campbell Clinic each year.

Facts on Osteoporosis

  • In the United States today, 10 million individuals are estimated to already have osteoporosis and another 34 million to have low bone mass, placing them at increased risk for osteoporosis.
  • 80 percent of those affected by osteoporosis are women.
  • One in two women and one in four men over age 50 will have an osteoporosis related fracture in their lifetime.
  • Osteoporosis is responsible for more than 1.5 million fractures annually, including 300,000 hip fractures. Nearly one-fourth of hip fracture patients aged 50 and over die within a year of their fracture.
  • The estimated national expenditures for osteoporotic and associated fractures is $17 billion annually - or $47 million each day.

Osteoporosis is a disease process that can be managed if identified early. Drug therapy and lifestyle changes can make a big difference.

The Research Approach

As with many diseases, a major breakthrough in understanding and controlling osteoporosis is likely to begin in the laboratory. At UT-Campbell Clinic, Dr. Weikuan Gu and other researchers are involved in a study to identify the chromosomal regions responsible for bone quality. In another study, Gu is using mouse models and seeking to identify the gene that has naturally mutated in the mice under study. The genome of mice is very close to that of humans, Gu said.

Advances in genetic research have helped speed up the laborious process of mapping genes. "It used to take several years to find one gene. Now several genes are found in a year," Gu said.

Dr. Gu's lab is equipped with a SpectraMedix machine that not only identifies and sequences genes but also unveils the molecular pathway of disease development, paving the way for drugs to be developed to prevent the disease before it starts.

Other new machines Gu and his team are using for bone studies are a CT scan for small animals (Micro Cat) and a PIXImus, an x-ray machine capable of providing a picture of the skeletal structure of the whole body. This state-of-the-art equipment was purchased with National Institutes of Health (NIH) funding awarded to the Department.

At present, physicians are treating the disease of osteoporosis rather than the individual patient, Gu said. Current and future genetic research will endeavor to uncover ways to treat people individually, based on their genetic makeup.

Treating Osteoporosis

Osteoporosis is a disease that has been readily identified for decades. "There was no treatment for it, and you couldn't quantify it," Dr. Santos Martinez said. "If you were treating it, it was hard to identify progress."

Advances in diagnostic technology, new medications, increased knowledge about diet and exercise, and greater public awareness of the disease, risk factors, and symptoms have influenced progress in the detection and management of osteoporosis in recent decades.

One new educational opportunity available for osteoporosis patients at Campbell Clinic is participation in "Choices for Better Bone Health," a program sponsored by pharmaceutical companies Proctor and Gamble and Merck that provides resources to help participants improve their bone health through self-management.

Patients take part in a seminar series that includes five weeks of instruction on the basics of osteoporosis, drug treatments for the disease, handling back pain and limited mobility, physical therapy or rehab, home safety, injury prevention strategies, nutrition, and other topics.

"There are 10 to 15 patients in each class, and the participants become a support group for each other," said Osteoporosis Program Coordinator Alice Ruch, RN. "To our knowledge, nothing else like this exists in the Memphis area." The program is free and is available to diagnosed and "at risk" patients within Campbell Clinic.

"Osteoporosis is a disease that can be managed if identified early," said Dr. Martinez. "We can try to control it pharmacologically and preventatively. In identifying what can be done, treatments and modalities have been found to make a difference in a year or a short time. Drug therapy and lifestyle changes can make a big difference."

Educational Grant from Smith & Nephew

Educational grant from Smith & Nephew supports residency joint rotation program.

Smith & Nephew Advanced Surgical Devices has demonstrated its commitment to advancing medical research, innovation, and education with an educational grant to The Campbell Foundation in support of education and research in adult reconstruction.

Smith & Nephew's grant to the Foundation will help sponsor the Total Joint Rotation of the Campbell Clinic-University of Tennessee Orthopaedic Residency Program. The grant will help underwrite the cost of educating 24 Campbell Clinic residents in the subspecialty area of joint replacement.

Dr. Terry Canale, President of The Campbell Foundation, said, "This grant demonstrates that Smith & Nephew recognizes the vital role highly-trained physicians play in the healthcare continuum. We look forward to working with Smith & Nephew to take orthopaedic education to new levels of excellence while offering our patients hope for better, more active lives."

The Campbell Clinic-University of Tennessee Orthopaedic Residency Program enables aspiring orthopaedic surgeons to develop and refine their clinical, surgical, and research skills. The accredited, five-year program has a total of 40 full-time residents and ranks in the top eight percent of orthopaedic residency programs in the nation. Nearly 500 medical school graduates vie for the eight positions open each year.

Residents in the program participate in the total joint rotation in their second, fourth, and fifth years. During each rotation, residents spend approximately 50 percent of their time in clinical activities and 50 percent in surgical duties, a practice that allows them to experience continuity of patient care from initial exam and evaluation, through surgical or non-surgical treatment and post-operative rehabilitation.

During the total joint rotation, residents are instructed and mentored by faculty members from the Campbell Clinic staff who have interest and training in the subspecialty of total joint replacement. Physicians who serve on the total joint rotation faculty include Dr. Andrew Crenshaw, Dr. John Crockarell, Dr. James Guyton, Dr. James Harkess, Dr. Robert Heck, Dr. David LaVelle, Dr. Anthony Mascioli, and Dr. Patrick Toy.

The residency program benefits significantly from monthly Journal Club meetings during which the teaching staff and residents review and discuss articles from the Journal of Bone and Joint Surgery and subspecialty journals. Dr. John Crockarell plans to start a Total Joint Journal Club using articles from the Journal of Arthroplasty for discussion. The educational grant helps provide each resident with an individual subscription to the Journal of Arthroplasty. A number of major books and electronic resources will also be added to the Total Joint Library, including the Orthopaedic Knowledge Update series from the American Association of Orthopaedic Surgeons.


Computer Knee Simulator to Improve Total Knee Replacement Outcomes

Modern medicine, for all its miracles, is still an inexact science in many areas. Efforts to make it less so, generally taken place in research labs and facilities across the world, where doctors, engineers, and highly specialized experts work together conducting trials and studies while recording and measuring outcomes. Ongoing research is what advances medical knowledge and skill, and it gives mankind the miracles that increase functionality and save lives.

Dr. William M. Mihalko, Associate Professor, and Dr. John Leicester Williams, Affiliated Professor of Biomedical Engineering at UTHSC from the University of Memphis, are two such researches working to develop a virtual knee simulator that will allow surgeons to perform total knee replacement surgeries, known as a total knee arthroplasty (TKA), on an individualized, patient-by-patient basis.

Dr. Mihalko (left) and Dr. Williams (right) is developing the computer model with the ultimate goal of enabling surgeons to align the knee implant more accurately in accordance with the patient's specific anatomical characteristics for the best results and longest implant wear. Dr. Mihalko is holding a computer-navigated pointer, which allows surgeons to record specific anatomical landmarks during surgery. In his life hand, he holds the upper portion of a total knee implant. By allowing the computer to track the implant and a patient's own anatomy, a customized approach to the surgery is being developed.

"Developing a computer-based model is important because right now we fit every patient into just one set of parameters in the operating room," said Dr. Mihalko, a Campbell Clinic total joint surgeon. "In other words, we align and insert our implants the same way, regardless of the patient's sex, size, age health, or other individual characteristics."

That means that a football linebacker's artificial knee is implanted and positioned the exact same way as a 98-pound ballerina's. It is Mihalko's and Williams's theory that if total knee replacements are inserted in a custom manner to fit the patient's individual characteristics, the percentage of TKAs that meet patient satisfaction will go up.

"We're trying to come up with a tool for the surgeon that helps him predict on an individual basis how a knee implant will function given anatomical variations in soft tissue, muscle forces, support, center of rotation, and those types of things," said Mihalko. "Currently, when we put an implant into a patient, we often have to just visualize some of those things- just take our best guess."

"And a patient won't know if his implant is suitable until he's healed-three months later!" added Dr. Williams. "It's like trying to fit an unconscious person with a pair of shoes. You know how to place the shoe and lace it up, but you really won't know how those shoes will fit-and whether the patient will be comfortable in them-until the person is well enough to walk in them himself."

The two researchers' collective goal is to develop a tool to use in the operating room, where the surgeon will enter the patient's specific anatomical parameters, and a computer model will instantly digitize where that particular patient's ligaments are attached, where his muscles insert around the knee, how his particular body makeup may affect the knee's performance, and other factors critical to a successful patient outcome. And developing such a tool is not easy.

"Our biggest problem is that the knee is such a complex and variable system," said Dr. Mihalko. "Coming up with a computer model that takes into account all of the thousands of variables and all of the ways you can move your knee is challenging to say the least."

Dr. Williams has worked for several years developing simulation software for a computer model that helps the researchers determine how a knee will react when they change implant positions, tighten ligaments, exert muscle forces, and subject the knee to various motions. Those computer predictions are then compared to an actual implanted knee.

"We use a mechanical simulator in the lab to test specimens to determine if the computer's predictions are accurate," said Dr. Mihalko. "In other words, do the two match up? Is what we're predicting in the computer model actually taking place with the real knee implant? If not, we adjust the computer model accordingly and repeat the process."

The mechanical simulator moves knee specimens into squats, lunges, flexes, and extensions. The researchers analyze how the implant reacts while it's still inside the knee, and then they physically remove the implant for further analysis.

"By conducting research this way, we can try to determine what was happening inside the knee while the implant is still in place," says Mihalko. "What factors affected the implant that could make it fail? This implant retrieval method helps us tweak the program and make it more accurate and helpful."

The biggest challenge facing the two researchers is funding. "I spend one0third of my time just writing grants," said Dr. Mihalko. "And this is important research. This type of analysis will introduce a personalized-medicine approach to total knee arthroplasty and allow the best change for the patient to have the longest-functioning, most successful implant during his lifetime. That's also important to those who receive the 600,000 total knee replacements every year."

Source: The Campbell Foundation Momentum

Total Knee Replacement Q & A

with Dr. William M. Mihalko

What is a total knee arthroplasty?
It's where damaged cartilage and bone are surgically removed from the surface of the knee joint and replaced with a man made implant made of metal and plastic.

What causes a person to need a total knee replacement?
The No. 1 cause is osteoarthritis. Various types of injuries can also lead to the need for a knee replacement.

Of the things we can control, what causes the most damage to our knees?
In overweight people, every extra pound of weight places four to five pounds more force on the knee. It's a magnified force. So if a person loses 20 pounds, the knees see 100 pounds less force and they'll last longer. Playing contact sports can also shorten the life of the knee.

How long do knee replacement last?
The average for knee replacement recipients is 65 years old, and the implant should last long as that patient is alive.

What happens when a replacement fails?
The patient feels pain, or the joint is unstable, meaning the patient has to again use a can or a walker. Ten to fifteen percent of knee replacements do not meet patient satisfaction. That is a statistic that our research aims to improve.

Research, New Therapies Offer Hope Amid Rising Tide of Sports-Related Injuries.

The term boomeritis was coined by a Philadelphia orthopaedic surgeon to describe increasingly common sports injuries among people roughly between the ages of 40 and 60. "Booneritis includes ligament and tendon ruptures but also injuries as varied as muscle soreness, sprains and strains, tendonitis and bursitis, arthritis, and fractures caused by trauma and overuse," and Dr. Frederick Azar, a Campbell Clinic sports medicine specialist.

In addition to the growing number of injuries among adult athletes, Dr. Azar said there has also been a sharp rise in sports-related injuries among young people.

"We are seeing a lot more injuries in adolescents that can be attributed to overuse," he said. "More young people are playing sports year-round, and repetitive use can lead to stress fractures and other injuries."

Facts About Sports Medicine Injuries

  • Sports injuries can result form accidents, from poor training practices, from lack of conditioning, and from insufficient warm-up and stretching before beginning exercise.
  • The most common types of sports injuries are muscle sprains and strains, tears of the ligaments that hold joints together, tears of the tendons that support joints and allow them to move, dislocated joints, and fractured bones, including vertebrae.
  • Adults age 25 and over sustained an estimated 2.3 million sports and recreational injuries annually from 1997 through 1999. Recreational sports (including tennis, golf, bowling, and hiking) account for 370,000 injuries.
  • The knee is the most commonly injured joint. Each year, more that 5.5 million people visit orthopaedic surgeons for knee problems.

A brighter outlook for athletes.

The outlook for injured athletes is more optimistic than in the past as a result of new surgical techniques, more aggressive rehabilitation protocols, development in tissue engineering, and promising research.

Finding hope in cartilage transplant.

Campbell Clinic surgeons specializing in sports medicine perform several types of cartilage restoration procedures, according to Dr. Azar. Dr. Azar and other Campbell Foundation researchers are currently engaged in studies using porcine cartilage constructs as they search for new ways to develop health human cartilage tissue for implantation.

"The cells attach themselves to the bone, multiply, and mature to form a cartilage repair," Dr. Azar said. "The procedure is relatively new, and the longevity is unknown at this point. But the success rate is reported to be between 70% and 80%.

Tips for Preventing Sports Injuries

More adults than ever are participating in sports, with a concurrent rise in injuries. Adults may not be as agile and resilient as they were when younger. Some injuries occur when a person tires to move from inactive to a more active lifestyle too quickly. Here are some tips to help prevent sports injuries among adults.

  • Don't be a "weekend warrior,"packing a week's worth of activity into a day or two. Try to maintain a moderate level of activity throughout the week.
  • Gradually increase your exercise level.
  • Accept your body's limits. You may not be able to perform at the same level you did 10-20 years ago. Modify activities as necessary
  • Learn to do your sport right. Using proper form can reduce your risk of overuse injuries such as tendonitis and stress fractures.
  • Use safety gear. Depending on the sport, this may mean a helmet, knee pads, or wrist pads.
  • Strive for a total body workout that includes cardiovascular activity, strength training, and flexibility exercises. Cross-training reduces injury while promoting total fitness.

Corporate Partners Support Training via the Sports Fellowship

Two corporate partners, Arthrex and Smith & Nephew Advanced Surgical Devices have provided support to The Campbell Foundation to sponsor the Sports Medicine Fellowship at UT-Campbell Clinic.

Applications for this Fellowship are selected on competitive basis and must have completed an ACGME accredited residency program in orthopaedic surgery, or an AOA accredited residency in osteopathic surgery. The Fellowship will usually be filled through a national matching program.

Dr. Frederick Azar, Sports Medicine Fellowship Director for The Campbell Foundation, said, "We are grateful to both companies and to our donors for helping us sustain this fellowship. We know that the fellowship benefits our patients by enhancing our sports medicine research, and it complements our residency training program."


Seeking to Speed Recovery, Restore Function

Campbell Clinic physicians are engaged in several clinical studies that seek to improve healing and restore function for patients with orthopaedic injuries due to trauma. Research currently underway includes the following studies:

  • Evaluation of a New Medication to Accelerate Bone Growth/Bone Healing

    Campbell is participating in a multi-center, prospective study to evaluate whether the median healing time in a closed fracture of the tibial shaft can be reduced by 25%.

  • Gait Analysis

    Campbell researchers are gathering information regarding patient gait as healing progresses after surgical intervention following a traumatic injury to an extremity.

  • Study of the Treatment Outcomes of Intra-Articular Gunshot Injuries

    Gunshots are the second most common cause of injury-related death in the U.S. A high number of gunshot injuries are linked with fractures or joint penetration.

    Guidelines for the treatment of civilian low velocity intra-articular gunshot wounds have not been standardized, and the options for treatment are not always well defined. Campbell physicians are conducting an observational study at The MED, evaluating the optimal care of gunshot injuries in order to establish more reliably uniform treatment standards.

Synthes Trauma Fellowship Supports

Surgeon Training

Synthes, the leading skeletal fixation company in North America, has demonstrated its commitment to the education and training of orthopaedic surgeons with a generous grant to The Campbell Foundation to establish the Synthes Trauma Fellowship.

The grant provides funding over a three-year period and enables a trauma fellow to receive 12 months of surgical and clinical training in associate with Campbell Clinic in trauma-related problems.

The first Synthes Trauma Fellow is Dr. Rakesh Mashru, who completed his fellowship in June 2006. Dr. Mashru is a graduate of UMDNJ-New Jersey Medical School and completed his orthopaedic residency at Drexel University.

The Synthes fellow will spend time with the Campbell Clinic trauma faculty and will be exposed to multi-trauma surgical problems, acute and reconstructive surgery, and clinical non-surgical trauma situations. Dr. George W. Wood, II, a trauma specialist who has been on staff at Campbell Clinic since 1980, is chairman of the fellowship.

The Campbell Clinic trauma fellow spends one day each week at the Regional Medical Center in Memphis (The MED), one of the nation's busiest Level I trauma centers. The fellowship also requires that the recipient conduct trauma research, with the expectation that the research will result in a presentation, publication, or both.

Tim Akers, Synthes Regional Manager, said, "Synthes and the Campbell Clinic share a common goal and emphasis on education and research at all levels. This commitment will help lead to solutions that offer improved patient outcomes."

Formed in 1974, Synthes provided instruments and implants to many U.S. hospital, including almost all of the nation's medical school residency training facilities.

Synthes has committed significant resources to assist medical schools in conducting comprehensive post-graduate training programs for orthopaedic surgeons. These courses emphasize practical work in a laboratory setting and enable surgeons to learn how to use Synthes instruments and implants, as well as related surgical techniques.

Taken from the Campbell Foundation Momentum

May 26, 2022