The Continually Evolving Challenges of Osteoarthritis Research
I am pleased to share this summary of Dr. Tom Andriacchi’ s career. It is interesting to see how his perception of OA evolved over more than 40 years of research. Recognizing that OA involves multiple organ systems at scales from the whole body to the molecule has sent him on a continually evolving journey to incorporate and learn new disciplines. While incorporating new disciplines was challenging it had a major impact on his research career. The following illustrates several examples of challenges he encountered over the span of his research career. Tom hopes these examples will help young investigators to recognize that evolving research views to address unexpected results can be challenging but often leads to new opportunities to study the complexity of OA.
Tom’s first challenge occurred (≈1974) as a post-doctoral fellow while he was studying total joint replacement. At that time there were frequent mechanical failures of hip and knee replacement. This problem seemed well suited for a mechanical engineer since it involved engineering materials (metal and plastic). However, he found it was wrong to assume this was purely an engineering problem. He recognized the need to understand how joint design influenced patient function and conversely how patient function influenced the mechanical demands on the joint. Tom realized he needed to change his approach and study the gait of patients with joint replacement. While this change required him to develop and learn new methods for gait analysis, the insight from these gait studies produced information that helped to improve design criteria and outcomes of total joint replacement.
The next impactful challenge he faced was trying to interpret the unexpected finding that ambulatory mechanics could influence the clinical pathogenesis and progression of knee OA. This started with a study of the high tibial osteotomy (HTO) for medial knee OA. That study showed it was clinically beneficial for patients with knee OA to have lower dynamic load at the knee (knee adduction moment or KAM) during gait. This finding had a substantial impact that led to numerous gait studies of OA as well as interventions to modify gait to lower the KAM. One intervention from Tom’s lab included a low-cost shoe that was shown to reduce the KAM and knee pain in a clinical trial.
The HTO study led to one of the most pivotal and challenging findings in his career. Specifically, his lab found that gait mechanics could be associated with prospective changes in cartilage morphology and influenced changes in serum biomarkers. The challenge here was that these studies required integrating diverse disciplines into his research protocols. A key outcome from these studies was that biomarker sensitivity to OA could be increased using walking as a mechanical stimulus. This outcome led to developing an “OA stress test” that involved testing for changes in OA biomarkers that resulted from walking on treadmill. The OA stress test produced evidence that mechanically stimulated biomarker changes could be associated with prospective cartilage changes.
The current challenge (still evolving) is to gain a better understanding of the interaction among the multiple signaling pathways from the scale of the whole-body mechanics to the molecule that influence OA. While his perspective has continued to evolve to include biological and morphological elements associated with OA, he remains a mechanical engineer. As such, it has become clear to him that the impact of mechanics has not been well integrated with biological and structural elements. To this end he introduced a new term “mechanokines” as mechanical signals to be considered with cytokines in a manner that integrates mechanics into the biological and morphological studies of OA. Finally, after looking back over 40 years of studying OA, he acknowledges his career reflects the meaning of a quote from Albert Einstein “It is not that I'm so smart. But I stay with the questions much longer.”
It is our great honor to have awarded Dr. Tom Andriacchi the 2020 Lifetime Achievement Award.