Introduction

Reliable joint preservation still eludes us. The biomechanical environment, the intra-articular milieu, the cells in the form of chondrocytes, mesenchymal stem cells and immune cells, and the regeneration of a durable cartilage matrix presents us with a formidable list of challenges.

Content

Results of techniques such as osteotomy and joint distraction aiming to decrease the dynamic load on a failing joint surface suggest that the biomechanical environment of the joint is critical. Outcomes of observational studies and clinical trials using these methods suggest that they may provide both symptomatic improvement and signs of joint cartilage regeneration. However, large, randomized, pivotal trials with low risk of bias and long follow-up are still lacking.

Chondrocyte implantation, using a variety of methods, has been practiced for many years. While there are success stories, there are also stories of failure, and we remain unable to a priori reliably predict responders and non-responders. Pivotal trials showing efficacy and cost-effectiveness are absent. The unregulated use of intra-articular injections of stem cells, platelets and other blood products continues to expand in the absence of clear evidence of benefit and lack of harm.

In spite of numerous drug candidates having been tested in phase III clinical trials, there is no drug approved by the regulatory authorities that has shown disease modification in osteoarthritis, i.e. an improvement in symptoms accompanied by preservation or improvement of joint structure. The FDA has recently recognized osteoarthritis as a serious disease, opening for novel trial designs and an accelerated approval path. Together with recognition of early stages of osteoarthritis, this may facilitate development of novel treatments for joint preservation.