OREF-funded study examines the disease-modifying effect of pelvic osteotomy
Hip dysplasia is a common cause of osteoarthritis of the hip. Although pelvic osteotomy can improve the mechanics of the joint, the effect that the procedure has on the progression of arthritis is unclear. Can cartilage repair itself after joint mechanics improve? If so, what is the relationship between cartilage repair and clinical measures of pain and function after surgery?
Orthopaedic surgeon Young-Jo Kim, MD, PhD, is addressing these questions in a study funded by the Orthopaedic Research and Education Foundation (OREF).
Dr. Kim hopes to find answers by using an experimental imaging technique called delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC).
Recipient of a 2007 OREF Career Development Award, Dr. Kim began his academic career at Massachusetts Institute of Technology, where he studied how the mechanics of joints affects cartilage and the development of osteoarthritis. His interest in orthopaedic surgery eventually led to his studies at Harvard Medical School, where he is an assistant professor.
His work enables him to pursue his passion for both clinical practice and research. “Obviously I enjoy making patients well, but from an intellectual point of view, I think it’s very satisfying to understand and answer some basic questions about how what I do helps patients,” he explained.
A good fit for good function
Optimal function of the hip joint depends on a good fit between the head of the femur and the acetabulum. A good fit results in low pressure within the joint. The decreased depth of the acetabulum associated with hip dysplasia results in less surface area and increases stress in the joint. The misalignment concentrates the pressure toward the outer rim of the socket. The increased mechanical load at the point of contact contributes to cartilage deterioration.
Pelvic osteotomy should—in theory—have a disease-modifying effect on osteoarthritis of the hip, if the disease is not too far advanced. Improving joint mechanics should result in less stress on the cartilage and may allow for cartilage repair. Based on his own and other preliminary studies, “It looks like the joint does have some capacity to recover,” said Dr. Kim. “If you catch the arthritis at an early enough stage, if you correct the abnormal mechanics, then the joint potentially can recover.”
Current measures of success for a pelvic osteotomy include improvements in symptoms and hip function. Some studies have provided indirect—albeit inconsistent—evidence of disease modification; radiographs have seemed to show increased joint space and decreased bone changes associated with osteoarthritis, such as subchondral sclerosis and cysts.
Dr. Kim plans to demonstrate the utility of the dGEMRIC technique, a type of contrast MRI, to measure more directly the condition of cartilage before and after surgery, to confirm the disease-modifying effect of the procedure. “We’re using MRI as a metric to look at how much arthritis patients have before surgery and then to see if the arthritis progresses or if the joint heals itself after surgery,” he explained.
Better diagnosis through technology
In previous studies, Dr. Kim has examined the effect of mechanical overloading on articular cartilage. That work demonstrated how increases in stress result in decreased biosynthesis of glycosaminoglycan (GAG), a component of cartilage. A measure of GAG concentrations should indicate the condition of the cartilage and the severity of arthritis.
Dr. Kim and his colleagues have also demonstrated the potential of a contrast-enhanced MRI technique to measure GAG concentrations in cartilage, using a gadolinium contrast agent approved by the U.S. Food and Drug Administration. The gadolinium complex dissociates into a negatively charged molecule called gadopentetate2-, which is the key to the contrast agent’s capacity for imaging cartilage.
GAGs are also negatively charged. In healthy cartilage, levels of GAGs are high; in degraded cartilage, levels are low. If the contrast agent is given enough time, gadopentetate2- will penetrate into the cartilage in an inversely proportional manner to the GAG levels. Low concentrations of gadopentetate2- indicate healthy cartilage, and high concentrations indicate degraded cartilage. Therefore, the degree of MRI-detected gadopentetate2- functions as a measure of disease severity.
In his OREF-funded study, Dr. Kim and his research team are recruiting 50 participants at least 18 years of age who have osteoarthritis of the hip and are undergoing pelvic osteotomy for developmental hip dysplasia.
Initial assessments will include physical exams to determine functional status and degree of disability. Participants will also complete a self-administered questionnaire used to assess degree of pain, disability, and joint stiffness. Another self-assessment tool—osteoarthritis computer-adaptive testing (OA-CAT), which mimics the flexibility of a clinical assessment by tailoring questions based on previous responses—will also be used.
In addition to contrast MRI, standard radiographs will be used to grade joint congruency, measure the minimum joint space, and identify secondary bone changes associated with osteoarthritis.
A complete round of imaging, clinical exams, and patient self-assessments will occur 6 months, 1 year, and 2 years after surgery. Dr. Kim hypothesizes that changes in the dGEMRIC results will indicate that the cartilage is recovering. His group will also correlate dGEMRIC-detected changes in cartilage with clinical outcomes. He anticipates finding a strong correlation between cartilage recovery and improved symptoms and function.
The investigation may also have practical applications for clinical practice by defining a threshold for recovery and enabling orthopaedists to predict improvement or decline after surgery based on preoperative cartilage degradation.
If this study does demonstrate the potential of cartilage to recover in arthritic joints, dGEMRIC may serve as a valuable research tool for assessing the disease-modifying effects of other experimental surgical treatments or drugs in clinical trials.
Dr. Kim also noted the value of this research to patients. “Their pressing concerns are, ‘Am I going to feel better? How long is my joint going to last?’” His work may provide orthopaedic surgeons with tools to help answer those questions.
Jay Lenn is a contributing writer for OREF and can be contacted at email@example.com