If you don't ask questions, it's hard to find answers. It may be a simple premise, but it's one that is an underlying force for the Orthopaedic Research Society. An arm of the American Academy of Orthopaedic Surgeons, the ORS numbers around 2,100 members, as compared to 27,000 members in the AAOS. Still, the small sub-group hopes to find novel therapies and solutions so that the much larger group of surgeons can add new tools to their specialized skill sets to positively impact patient outcomes. "What will the cures be 10 … 15 … 20 years from now? … that's what the Othopaedic Research Society is about," says Edward Schwarz, PhD, spokesperson for the ORS and a professor of orthopaedics at the University of Rochester in New York. "There are several, so to speak, 'Holy Grails' in orthopaedics," he continues. "The biggest is articular cartilage damage." Numerous studies have underscored the relationship between bone changes and articular cartilage damage as seen in osteoarthritis, but finding the right connections to slow or reverse that damage have not been nearly as easy. The avascular nature of articular cartilage leaves it with very limited capacity to heal or repair. "It's estimated that 60 million Americans have osteoarthritis," says Schwarz, "and we essentially have very little other than painkillers to treat it. … How do we stimulate a repair or regenerative response in cartilage? … That is a fundamental question that is being asked." Another focus topic for the ORS is trying to get a handle on low back pain. "The number one reason most people go to the doctor is low back pain," he notes. Still, researchers don't really understand the root causes. While an imaging study on someone with severe low back pain might well show a collapsed disc, a similar picture might be seen in another patient over 50 years of age who has no back pain. Why does one patient hurt to a point of not being able to carry out normal activities while another functions without any real pain response? One theory, says Schwartz, is that degeneration may cause inflammation, which in turn actually causes changes in the bone … it may be these bone changes, rather than the collapse of the disc or nerve compression, that causes the pain. "The approach that would be taken by the scientist in the Orthopaedic Research Society is to genetically engineer mice to either be missing a gene or to have an additional gene," Schwarz says of using mouse models to measure changes in the bone or disc microenvironment. Researchers study both the knockout mouse (missing gene) and the transgenic mouse (added gene) to see if the changes impact the response to injury. "What genes are up-regulated? What genes are down-regulated in response to injury?" he says of questions researchers hope to answer. Schwarz notes that if a healing response is observed, then ultimately physicians might be able to introduce a gene that would be activated whenever a disc was injured. A third area of avid research is repair of the rotator cuff. "The rotator cuff is actually a tendon that inserts into bone on one end of the shoulder and muscle on the other. It's very common for adults to get tears in their tendons over time," Schwarz says. However, he adds, "It's very, very difficult to repair these … for many, when they tear, they can't really be repaired." In severe cases, surgeons typically suture the tendon from a cadaver (or artificial tendon material) to the muscle on one end and screw it into the bone on the other. "But those are not biologic attachments and so they tend to fail," says Schwarz, adding that the graph is viewed as a foreign material so scar tissue often forms around it, stopping blood flow and preventing a biological integration by the host. "Our goal is to use stem cells, gene therapies and biological factors like proteins to stimulate a biological integration into muscle and into bone. If it can integrate, the body would see it as self and would repair it as normal tissue," he continues. Realizing medical breakthroughs is not just a possibility; researchers believe it is a probability. Schwarz points to the development of inhibitors of tumor necrosis factor (also known as anti-TNF therapy) to effectively treat rheumatoid arthritis as one example of bench science making its way to the commercial marketplace and improving patient outcomes. While much of the focus is clearly on the future, Schwarz says that as a society, ORS has also been called upon to answer an immediate need. "Due to our continuing conflicts in the Middle East, our members have been more and more getting involved with the special interests of the Department of Defense," he notes. He adds that in modern war, it has become apparent that body armor is quite protective. Because the torso is now typically well shielded, soldiers tend to either take a hit to the head and die or get hit lower and suffer very serious injuries to the limbs but survive. "There is a real need for us to come up with alternative treatments to deal with these horrific war issues … that's another area that's been an emerging focus for our members." For more information on the Orthopaedic Research Society, go online to www.ors.org. The annual meeting, which highlights the latest in research, is scheduled for Feb. 11-14, 2007 in San Diego.