Low-dose radiotherapy of osteoarthritis: from biological findings to clinical effects—challenges for future studies

Abstract

Osteoarthritis (OA) is one of the most common and socioeconomically relevant diseases, with rising incidence and prevalence especially with regard to an ageing population in the Western world. Over the decades, the scientific perception of OA has shifted from a simple degeneration of cartilage and bone to a multifactorial disease involving various cell types and immunomodulatory factors. Despite a wide range of conventional treatment modalities available, a significant proportion of patients remain treatment refractory. Low-dose radiotherapy (LDRT) has been used for decades in the treatment of patients with inflammatory and/or degenerative diseases and has proven a viable option even in cohorts of patients with a rather poor prognosis. While its justification mainly derives from a vast body of empirical evidence, prospective randomized trials have until now failed to prove the effectiveness of LDRT. Nevertheless, over the decades, adaptions of LDRT treatment modalities have evolved using lower dosages with establishment of different treatment schedules for which definitive clinical proof is still pending. Preclinical research has revealed that the immune system is modulated by LDRT and very recently osteoimmunological mechanisms have been described. Future studies and investigations further elucidating the underlying mechanisms are an essential key to clarify the optimal patient stratification and treatment procedure, considering the patients’ inflammatory status, age, and sex. The present review aims not only to present clinical and preclinical knowledge about the mechanistic and beneficial effects of LDRT, but also to emphasize topics that will need to be addressed in future studies. Further, a concise overview of the current status of the underlying radiobiological knowledge of LDRT for clinicians is given, while seeking to stimulate further translational research.

Low-dose radiotherapy for greater trochanteric pain syndrome—a single-centre analysis

“…Both LDRT and SIs act primarily as anti-inflammatory agents, although these two therapeutic modalities enact this role differently at cellular and molecular levels [ 26 ]. LDRT affects, among others, endothelial cells, thus decreasing adhesion of leukocytes and monocytes as well as inducing production of anti-inflammatory cytokines (e.g., interleukin 10) [ 27 ]. Of particular interest, in our cohort, the application of two LDRT series with a 2-month interval seems to offer a significantly greater chance of achieving GR in comparison to one series only.…”

ArthroRad trial: randomized multicenter single-blinded trial on the effect of low-dose radiotherapy for painful osteoarthritis—final results after 12-month follow-up

“…The optimal dose remains a point of debate. In the radiobiological literature, the highest effect was recorded after a dose of 0.5 Gy, whereas an effect on macrophages was found after 0.1 Gy [ 13 ]. Unfortunately, we could not find preclinical data for doses as low as 0.05 Gy in the literature.…”

“…The most recent overview of biological findings and their consequences for the clinical radiotherapy application has been given by Weissmann et al. [ 13 ].…”

Sprifermin for Treatment of Osteoarthritis: Recombinant Fibroblast Growth Factor 18 as a Possible Disease-Modifying Knee Osteoarthritis Drug

“…Following the guidelines of the German Society for Orthopedics and Orthopedic Surgery and the German Professional Association of Orthopedists and Trauma Surgeons, the goals of treatment are to mitigate the symptoms, i.e., pain relief, to improve QoL and mobility, and to slow the progression of the disease [6]. Conservative treatment comprises physical and physiotherapeutic measures including spa and low-dose radiotherapy therapy [45,46], orthopedic aids and orthoses, weight loss if indicated and pharmacotherapy. However, conservative measures are often of limited efficacy due to their onset in already advanced stages of the disease when structural deterioration is often advanced.…”