Whether a joint degenerates and develops arthrosis or recovers is a question of stress and load distribution. This is the root idea behind the German Federal Ministry of Education and Research (BMBF) funded research association OVERLOAD-PrevOp, a Germany-wide cooperation dedicated to gonarthrosis – or osteoarthritis of the knee. Experts from the fields of medicine, pain research, and psychology are working hand-in-hand with bio-chemists, sports scientists, and mathematicians as part of this undertaking. In Berlin, four institutions at once are involved: Charité – Universitätsmedizin Berlin, Freie Universität, Humboldt-Universität, and the Konrad-Zuse-Zentrum.

Concentrated interdisciplinary know-how is urgently needed. Based on estimates from the German Society for Rheumatology (DGRh), five million people suffer from osteoarthritis in Germany, usually affecting the knees or hips. This disease thus is a major burden for the healthcare system and the national economy. “The economic factor is huge,” according to Professor Wolfgang Ertel, an orthopedic consultant and trauma surgeon. “Approximately three billion euros are spent annually for treatment, and the costs due to sick leave are equally high.”

Targeted Training to Avoid Surgical Procedures and Pain

Malalignment or overloading plays a role in the degeneration of joint cartilage and one section of this research alliance – OVERLOAD – is exploring precisely this. PrevOp, on the other hand, is examining how pain and operations can be prevented by targeted training. “The main idea that drives our project is stopping the development of osteoarthritis at an early stage in test persons – or at least slowing the rate of progression,” says Ertel, who also heads the Klinik für Unfall- und Wiederherstellungschirurgie (Clinic for Trauma and Reconstructive Surgery) at Charité. The right form of movement is crucial here. At his clinic, affected individuals undergo muscle-building training using a vibration device. The vibration ensures that the load placed on the joint isn’t static –it is evenly distributed. The hypothesis that guides the research is that an evenly distributed load on the joint promotes the regeneration of cartilage.

This idea is not born out of thin air. The research group led by Petra Knaus, a bio-chemist, has observed the effect of homogenous force distribution on a molecular level. Within small bio-reactors, they embedded cartilage cells in a 3D matrix to subject them to mechanical stress that simulates a training load. The biochemists were able to observe that special signaling pathways, which play a key role in regeneration processes, were activated in the cartilage cells under these conditions. Knaus and her team now want to examine cell material from their patients at various phases of the disease and compare it to the cell models in order to develop new therapeutic approaches. “Our collaboration with clinics gives us the big advantage of direct access to cell material from patients.”

Making It Possible to Predict the Course of the Disease

Sports scientists at Humboldt-Universität also subject their study participants to a training program. They, however, are interested only in individuals who don’t yet suffer from osteoarthritis, but who belong to a risk group because they suffered an injury to their anterior cruciate ligament. The resulting instability of the joint leads to excessive strain and possibly to osteoarthritis. Professor Adamantios Arampatzis, head of the Department for Training and Movement Sciences at Humboldt-Universität’s Institute for Sports Sciences, explains that “following an injury, communication between the nerve and the muscle must be relearned and coordinated to again allow for articulated movement. Specialized neuromuscular training can support this process. As part of a low-resistance but sustained training program, various types of unstable padding are used to cause unexpected disruptions to the motion sequence. According to Arampatzis, these disruptions “force the muscles and nerves to once again coordinate their actions. This reestablishes sensorimotor control, and the knee becomes more stable.”

All the data collected from the clinical studies, the molecular-biological investigations, and the cell models are subsequently passed on to mathematicians who develop mathematical models using the data. In the future this information shall be used to make predictions for the course of the disease.

Researching osteoarthritis, a very widespread condition, is a major undertaking for which scientists also depend on those who are affected. At the Charité Clinic for Trauma Surgery, for example, doctors are on the lookout for additional test persons with early-stage gonarthrosis. The problem is that many affected individuals delay consulting a doctor, says Wolfgang Ertel: “Many prefer to take pain killers and we don’t see them until their knee no longer works.” Many factors play a role in this disease, which makes it all the more important to take a broad approach in the search for therapies. “With its unique composition of experts from so many fields, the research alliance OVERLOAD-PrevOp offers an outstanding basis for this research effort.”