Keeping you up to date on recent headlines in orthopedics.

Cationic CT contrast agents improve visualization of joint cartilage ... In its quest to find new strategies to treat osteoarthritis and other diseases, a Boston University-led research team has reported finding a new computer tomography contrast agent for visualizing the special distributions of glycosaminoglycans (GAGs) - the anionic sugars that account for the strength of joint cartilage. Assessing the local variations in GAGs are of significant interest for the study of cartilage biology and for the diagnosis of cartilage disease like osteoarthritis, which afflicts more than 27 million in people in the U.S. In their research paper, "Effect of Contrast Agent Change on Visualization of Articular Cartilage Using Computer Tomography: Exploiting Electrostatic Interactions for Improved Sensitivity," just published on line in the Journal of the American Chemical Society, they describe new contrast agents that selectively bind to the GAGs in articular cartilage. Articular or joint cartilage is the smooth hydrated tissue in the ends of bones in load-bearing joints, such as knees, hips and shoulders. The loss of GAGs from these joints is the hallmark of osteoarthritis, a degenerative joint disease in which wear or trauma results in damage to the cartilage surface. To better see the differentiation between healthy and unhealthy cartilage, contrast agents provide the visual tool to assess GAG content. However, the current contrast agents used with CT or MRI rely on limited diffusion of the anionic or negative ion-charged contrast agents into the target tissue, the study noted. So researchers hypothesized that cationic contrast agents would be electrostatically attracted to anionic GAGs to provide a more sensitive technique for imaging cartilage. And they focused on using the more widely accessible CT equipment because it can image cartilage and bone simultaneously, enable rapid three-dimensional reconstruction of the tissue and achieve higher spatial resolution over shorter acquisition times compared to MRI systems. The team synthesized three cationic or positive ion-charged iodine-based X-ray contrast agents. Using the femur of a rabbit, they reported gaining better and more specific images for the cartilage tissue than with current negative ion-charged contrast agents. "Compared to commercially available contrast agents under the same experimental conditions, these new cationic agents are three times more sensitive for imaging cartilage," said Mark Grinstaff, Boston University Professor of Chemistry and Biomedical Engineering who co-led the team. The researchers noted that the ability to acquire information about localized GAG content, morphology and cartilage thickness on tissue samples will, in the future, aid in the diagnosis and treatment of osteoarthritis. And while the data presented a compelling case for continued development of cationic CT contrast agents, the research team cautioned that the suitability for in vivo applications remains to be determined, adding that toxicity levels and radiation dosage will be the focus of future studies. "However, the ability to characterize ex vivo cartilage samples is clearly evident," the study concludes.

Bacteria for building better bone replacements ... Bacteria that manufacture hydroxyapatite (HA) could be used to make stronger, more durable bone implants. Professor Lynne Macaskie from the University of Birmingham (Birmingham, UK) recently presented work to the Society for General Microbiology's meeting at Heriot-Watt University (Edinburgh, Scotland). Using Serratia bacteria, the research showed that the bacterial cells stuck tightly to surfaces such as titanium alloy, polypropylene, porous glass and polyurethane foam by forming a biofilm layer containing biopolymers that acted as a strong adhesive. The HA coating then builds up over the surface. For practical use, the HA layer must stick tightly, then the material is dried and heated to destroy the bacteria. A micro-manipulation technique used to measure the force needed to overcome the bioglue adhesion showed that dried biofilm stuck 20-times more tightly than fresh biofilm. When coated with HA the adhesion was several times more again. Slightly roughening the surface made the bioglue much more effective. Currently, bone implant materials are made by spraying-on hydroxyapatite. This does not have good mechanical strength and the spraying only reaches visible areas. This biocoating method reaches all the hidden surfaces as the bacteria can "swim" into hidden nooks and crannies. Bacterial HA also has better properties than HA made chemically as the nanocrystals of HA produced by the bacteria are much smaller than HA crystals produced chemically, giving them a high mechanical strength.

New treatment for hand disorder show promise ... Researchers in the Department of Orthopedics at Stony Brook University Medical Center (Stony Brook, New York) have developed an injectable form of the enzyme, collagenase, that significantly improves outcomes of Dupuytren's contracture, a debilitating disorder caused by progressive accumulation of collagen that deforms fingers and limits motion. Reported in the Sept. 3, 2009, issue of The New England Journal of Medicine, the study involved treatment of 308 patients with Duputren's disease in 16 sites nationwide. The results indicate that the injections are safe and effective. Collagenase injections may offer another treatment option to hand surgery, the standard treatment. Dupuytren's disease is a progressive genetic fibroproliferative disorder in which normal collagen production and deposition in the hand fascia is disrupted and abnormal amounts of collagen production build nodules in the palm of the hand. Eventually collagen build-up produces cords in the hands of patients causing the fingers to be "bent" and unable to extend. This reduces finger dexterity to a high degree, to a point where common activities such as typing, cooking and even shaking hands become difficult and severely compromised. Millions worldwide are affected by Duputren's contracture, with the highest incidence (3%-6%) being in the Caucasian population of Northern European ancestry. The condition is more common in men than women and increases in incidence with advancing age, diabetes, epilepsy, smoking, and excess use of alcohol. Co-Principal Investigators Lawrence Hurst, MD, Professor and Chair of the SBUMC Department of Orthopedics, and Marie Badalamente, PhD, Professor of Orthopedics, began working with collagenase more than 15 years ago in their laboratory when they first realized the enzyme had potential to treat Dupuytren's disease. With FDA permission, clinical research Phase 2 trials were conducted in more than 200 patients using injections of collagenase as an experimental treatment for Dupuytren's disease. By 2007, Hurst and Badalamente began enrolling patients in a FDA-regulated multicenter Auxilium Pharmaceuticals (Malvern, Pennsylvania) Phase 3 clinical trial that involved collagenase injections to treat the condition. "Our study revealed that injections of the collagenase into the cords causing the finger contractures weaken the cords significantly," says Hurst. "The next day we found that we could manipulate the patient's fingers and break the cords causing the contracture. The result is frequently a normally functioning hand." Among all the cords causing joint contracture that were injected with collagenase, 84.7% showed improvement, compared with placebo (11.8%). In addition, collagenase-injected joint contractures showed a much greater percent reduction in the contracture from baseline to 30 days after the final injection 79.3% compared to 11.4%, respectively.

Resident duty-hour reform associated with increased complication rate ... A new study finds a 2003 reform of the length of resident on-duty hours has led to an increase in the rate of perioperative complications for patients treated for hip fractures. Among other restrictions, this reform limited the resident workweek to 80 hours. The resulting complications vary significantly, with an increasing rate of worse outcomes seen in teaching hospitals, according to a study published in the September 2009 issue of The Journal of Bone and Joint Surgery. "The data suggests a statistically significant increase in selected complications after implementation of the duty-hour reforms in teaching hospitals, where residents help deliver care, compared to non-teaching hospitals. This may go against common assumptions regarding outcomes as they relate to the length of resident hours," said study lead author James Browne, MD, an orthopedic surgeon currently completing a fellowship in Rochester, Minnesota. The study was performed at Duke University Medical Center (Durham, North Carolina). On July 1, 2003, The Accreditation Council for Graduate Medical Education implemented a resident duty-hour reform for all medical and surgical residents, including orthoaedic resident surgeons, in the U.S. Browne and his co-authors at Duke reviewed data from teaching and nonteaching hospitals for 48,430 patients treated for hip fractures in a nationwide inpatient sample database, reviewing two groups: the first from 2001 and 2002 before resident duty-hour reform; and the second in 2004 and 2005 after reform. This study sought to measure changes in the rate of patient death or resulting in-hospital complications since this reform. No increase in death rates was found, but an increase in resulting negative outcomes was found in teaching hospitals compared to nonteaching hospitals. The undesired results included increases in the rate of pneumonia, hematoma, transfusion, renal complications, and nonroutine discharge. In addition to an increase in the rate of medical complications, the study also notes an increase in length and cost of stay in teaching hospitals.

— Compiled by Holland Johnson, MDD
holland.johnson@ahcmedia.com