Non-surgical treatments are usually the first choice for the management of knee degeneration, especially in the early osteoarthritis (OA) phase when no clear lesions or combined abnormalities need to be addressed surgically. Early OA may be addressed by a wide range of non-surgical approaches, from non-pharmacological modalities to dietary supplements and pharmacological therapies, as well as physical therapies and novel biological minimally invasive procedures involving injections of various substances to obtain a clinical improvement and possibly a disease-modifying effect. Numerous pharmaceutical agents are able to provide clinical benefit, but no one has shown all the characteristic of an ideal treatment, and side effects have been reported at both systemic and local level. Patients and physicians should have realistic outcome goals in pharmacological treatment, which should be considered together with other conservative measures. Among these, exercise is an effective conservative approach, while physical therapies lack literature support. Even though a combination of these therapeutic options might be the most suitable strategy, there is a paucity of studies focusing on combining treatments, which is the most common clinical scenario. Further studies are needed to increase the limited evidence on non-surgical treatments and their combination, to optimize indications, application modalities, and results with particular focus on early OA. In fact, most of the available evidence regards established OA. Increased knowledge about degeneration mechanisms will help to better target the available treatments and develop new biological options, where preliminary results are promising, especially concerning early disease phases. Specific treatments aimed at improving joint homoeostasis, or even counteracting tissue damage by inducing regenerative processes, might be successful in early OA, where tissue loss and anatomical changes are still at very initial stages.
Keywords: Cartilage degeneration; Conservative treatment; Early osteoarthritis; Knee; Non-surgical treatment.