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Osteoarthritis (OA) is a painful, degenerative disease that affects the tissues of the joint spaces, such as the shoulder. Conventional medical treatment options, such as corticosteroid injections and anti-inflammatory medications, are not always sufficient to alleviate the symptoms from this disease. Low dose radiotherapy is a newer treatment option for patients with shoulder osteoarthritis and has shown positive outcomes. However, the problem is that there is a paucity of literature about treatment planning considerations for this new treatment option. The purpose of this case study was to provide an example of treatment planning techniques and considerations for shoulder osteoarthritis. Treatment techniques for shoulder LDRT, such as treatment field borders, prescribed dose, beam arrangements, appropriate beam energy, and special considerations are discussed., (Copyright © 2024 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

Objective: Updated report about the randomized comparison of the effect of radiotherapy on painful osteoarthritis (OA) applying a standard dose vs. a very low dose regime after a follow-up of 1 year., Patients and Methods: Patients presenting with OA of the hand/finger and knee joints were included. After randomization (every joint region was randomized separately) the following protocols were applied: (a) standard arm: total dose 3.0 Gy, single fractions of 0.5 Gy twice a week; (b) experimental arm: total dose 0.3 Gy, single fractions of 0.05 Gy twice a week. The dosage was blinded for the patients. For evaluation the scores after 1‑year visual analog scale (VAS), Knee Injury and Osteoarthritis Outcome Score-Short Form (KOOS-PS), Short Form Score for the Assessment and Quantification of Chronic Rheumatic Affections of the Hands (SF-SACRAH) and 12-item Short-Form Health Survey (SF-12) were used (for further details: see [1])., Results: The standard dose was applied to 77 hands and 33 knees, the experimental dose was given to 81 hands and 30 knees. After 12 months, the data of 128 hands and 45 knees were available for evaluation. Even after this long time, we observed a favorable response of pain to radiotherapy in both trial arms; however, there were no reasonable statistically significant differences between both arms concerning pain, functional, and quality of life scores. Side effects did not occur. The only prognostic factor was the pain level before radiotherapy., Conclusions: We found a favorable pain relief and a limited response in the functional and quality of life scores in both treatment arms. The possible effect of low doses such as 0.3 Gy on pain is widely unknown., (© 2023. The Author(s).)

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., (© 2023. The Author(s).)

Rheumatoid arthritis (RA) and osteoarthritis (OA) have a significant impact on the quality of life of patients around the world, causing significant pain and disability. Furthermore, the drugs used to treat these conditions frequently have side effects that add to the patient's burden. Photobiomodulation (PBM) has emerged as a promising treatment approach in recent years. PBM effectively reduces inflammation by utilizing near-infrared light emitted by lasers or LEDs. In contrast to photothermal effects, PBM causes a photobiological response in cells, which regulates their functional response to light and reduces inflammation. PBM's anti-inflammatory properties and beneficial effects in arthritis treatment have been reported in numerous studies, including animal experiments and clinical trials. PBM's effectiveness in arthritis treatment has been extensively researched in arthritis-specific cells. Despite the positive results of PBM treatment, questions about specific parameters such as wavelength, dose, power density, irradiation time, and treatment site remain. The goal of this comprehensive review is to systematically summarize the mechanisms of PBM in arthritis treatment, the development of animal arthritis models, and the anti-inflammatory and joint function recovery effects seen in these models. The review also goes over the evaluation methods used in clinical trials. Overall, this review provides valuable insights for researchers investigating PBM treatment for arthritis, providing important references for parameters, model techniques, and evaluation methods in future studies.

Purpose: This retrospective study analyzed the long-term effects of radiosynoviorthesis (RSO) with special emphasis to local joint pain in patients from 4 different RSO centers in Germany and Austria., Methods: A total of 168 finger joints in 147 patients with digital joint OA were investigated. The indication for RSO was based on both clinical complaints and a proven synovitis, despite anti-inflammatory pharmacotherapy and previous intra-articular corticosteroid injections. Radiosynoviorthesis was performed according to international guidelines. A numeric visual analog scale (VAS) before and after treatment was used to measure the outcome. Follow-up was done for at least 2 years after treatment, in some patients even over 10 years., Results: Radiosynoviorthesis resulted in a significant reduction of VAS values in most of the patients, lasting for the whole period of follow-up. Two-thirds of the treated joints showed clinically relevant improvement, if a reduction of 30% in VAS values was defined as a reasonable cutoff. The best results were achieved in thumb base joints., Conclusions: This article confirms that RSO is a suitable treatment option for digital joint OA with a proven synovitis. The analgesic effect is long-lasting and comparable to the success of RSO in patients with rheumatoid arthritis., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Despite its clinical use and investigation in other countries, low dose radiation therapy (LDRT) in the treatment of osteoarthritis (OA) is minimally used in the United States (US). Numerous recent studies published outside the US have shown moderate to long-term pain relief and improvement of mobility after treatment with LDRT for joints affected by OA. Here, we review the most recent literature published on the use of LDRT in OA. We provide a brief outline on the epidemiology, pathophysiology, current treatments, and health care burden of OA within the US. We provide a brief history of the historic use of LDRT in the US as well as a history of LDRT within the modern era of radiation oncology, discuss criticisms of LDRT including recently published randomized trials questioning its benefit as well as the risk of secondary malignancy from LDRT, and provide an outline of treatment planning considerations and recommendations regarding dose and fractionation, energy, beam arrangements, and immobilization techniques. LDRT has been shown to be a cost-effective, noninvasive treatment with minimal side effects. Further investigation into the potential role in the treatment of OA with modern LDRT is recommended., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Abstract: A novel device in the veterinary market uses a colloid containing radioactive 117m Sn to treat osteoarthritis in the synovial joints of canines. The technique of injecting a radioisotope to restore synovia is referred to as radiosynoviorthesis. The outpatient canine procedure uses a maximum administration of 222 MBq of 117m Sn injected into one or more joints. Due to the 13.91 d half-life and 158.6 keV gamma output of 117m Sn, abiding by the annual public dose limit of 1 mSv is of primary regulatory concern. The therapy protocol starts with a pre-screening questionnaire to establish owner and animal behavior patterns. The questionnaire is used to determine the duration of written time and distance limitations post therapy. In this study, external radiation doses to owners were measured by providing optically stimulated luminescent dosimeters (OSLD) for up to 30 d post-treatment of the pet. Twelve owners were measured over various time frames at two licensed locations independent of each other. In one location, the average (OSLD) measured 0.029 mSv over a 14-d wear period. In the second location, the average (OSLD) measured 0.057 mSv over a 30-d wear period; both values were well below the recommended annual public dose. The overall average extrapolated external radiation dose was estimated at 0.092 mSv, while the maximum dose estimate was 0.25 mSv. The (OSLD) results and extrapolated owner doses provide reasonable assurance that the public dose limits will be met., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Health Physics Society.)

Purpose: Randomized comparison of the effect of radiotherapy on painful osteoarthritis (OA) applying a standard-dose vs. a very-low-dose regime PATIENTS AND METHODS: Patients with OA of the hand and knee joints were included. Further inclusion criteria: symptoms for more than 3 months, favorable general health status, age above 40 years. Patients with prior local radiotherapy, trauma, rheumatoid arthritis, or vascular diseases were excluded. After randomization (every joint was randomized separately), the following protocols were applied: standard arm: total dose 3.0 Gy, single fractions of 0.5 Gy twice weekly; experimental arm: total dose 0.3 Gy, single fractions of 0.05 Gy twice weekly. The dosage was not known to the patients. The patients were examined 3 and 12 months after radiotherapy. Scores like VAS (visual analogue scale), KOOS-SF (the knee injugy and osteoarthritis outcome score), SF-SACRAH (short form score for the assessment and quantification of chronic rheumatic affections of the hands), and SF-12 (short form 12) were used., Results: A total of 64 knees and 172 hands were randomized. 3.0 Gy was applied to 87 hands and 34 knees, 0.3 Gy was given to 85 hands and 30 knees. After 3 months, we observed good pain relief after 3 Gy and after 0.3 Gy, there was no statistically significant difference. Side effects were not recorded. The trial was closed prematurely due to slow recruitment., Conclusion: We found favorable pain relief and a limited response in the functional and quality of life scores in both arms. The effect of low doses such as 0.3 Gy on pain is widely unknown. Further trials are necessary to compare a conventional dose to placebo and to further explore the effect of low doses on inflammatory disorders., (© 2021. The Author(s).)

Pain is the most common symptom of osteoarthritis, and spinal glia is known to contribute to this symptom. Therapeutic ultrasound and laser therapy have been used to effectively treat osteoarthritis, with few adverse effects. Thus, this study aimed to investigate the effects of ultrasound and photobiomodulation on the symptoms and evaluate the participation of spinal glia in osteoarthritis-induced nociception in mice. Male Swiss mice were subjected to osteoarthritis induction with a 0.1-mg intra-articular injection of monosodium iodoacetate. Additionally, the mice received chronic ultrasound or photobiomodulation treatment for 21 days or a single treatment at day 14. Nociception was evaluated using von Frey filaments, and osteoarthritis symptoms were assessed by analysis of gait, joint temperature, and knee joint diameter. The role of spinal microglia and astrocytes on nociception was evaluated via an intrathecal injection of minocycline or fluorocitrate, and the spinal release of IL-1β and TNF-α was assessed by ELISA after chronic treatment with ultrasound or photobiomodulation. Our data showed that both single and chronic treatment with ultrasound or photobiomodulation attenuated the osteoarthritis-induced nociception. No differences in gait, knee joint temperature, or knee joint diameter were found. The intrathecal injection of minocycline and fluorocitrate decreased the osteoarthritis-induced nociception. There was an increase in the spinal levels of TNF-α, which was reverted by chronic ultrasound and laser treatments. These results suggest that osteoarthritis induces nociception and glial activation via spinal release of TNF-α and that the chronic treatment with ultrasound or photobiomodulation decreased nociception and TNF-α release., (© 2021. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

The purpose of this study is to evaluate the effects of photobiomodulation (PBM) therapy in chondrocyte response by in vitro experiments and cartilage repair using an experimental model of osteoarthritis (OA) in the knee of rats. The in vitro experiment was performed with chondrocyte cells, and they were divided into two groups: non-irradiated and irradiated with PBM (808 nm; 0.8 J or 1.4 J). Then, cell proliferation was evaluated after 1, 3, and 5 days. The experimental model of osteoarthritis (OA) was performed in the knee of 64 Wistar rats, and they were assorted into control group (CG), PBM (808 nm; 1.4 J). The results of in vitro showed that PBM 1.4 J increased cell proliferation, on days 1 and 5. However, after 3 days was demonstrated a significant increase in cell proliferation in PBM 0.8 J. The in vivo experiment results demonstrated, on histological analysis, that PBM presented less intense signs of tissue degradation with an initial surface discontinuity at the superficial zone and disorganization of the chondrocytes in the cartilage region when compared to CG, after 4 and 8 weeks. These findings were confirmed by immunohistochemistry and qRT-PCR analysis which showed that PBM increased IL-4, IL-10, COL-2, Aggrecan, and TGF-β which are anabolic factors and acts on extracellular matrix. Also, PBM reduces the IL1-β, an inflammatory marker that operates as a catabolic factor on articular cartilage. In conclusion, these results suggest that PBM may have led to a return to tissue homeostasis, promoting chondroprotective effects and stimulating the components of the articular tissue., (© 2021. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Background: Hand osteoarthritis (HOA) is one of the most common causes of pain and functional disability in western countries and there is still no definitive cure. Low-dose radiation therapy (LDRT) has anti-inflammatory properties that have shown to be effective in the symptomatic relief of various degenerative musculoskeletal disorders. We designed a clinical protocol using LDRT for symptomatic HOA and present results and tolerance in the first 100 patients included., Materials and Methods: Between April 2015 and March 2021, 100 patients with a median age of 60 were treated. Fifty-seven patients suffering from proximal/distal interphalangeal joint pain, 40 patients with thumb arthritis, 2 patients with radiocarpal joint affection and 1 patient with metacarpophalangeal joint pain were enrolled. LDRT comprised of 6 fractions of 0.5-1 Gy on every other day up to a total dose of 3-6 Gy. Clinical response was evaluated according to the visual analog scale (VAS) for pain level and the von Pannewitz score (VPS) for joint functionality. Any patients not achieving subjective adequate pain relief after 8 weeks of treatment were offered a second identical LDRT course., Results: With a median follow-up of 10.5 months (range 7.55-12.45), 94% reported an improvement in the pain, with a significant reduction in the VAS level after 3, 6 and 12 months (p < 0.001). Sixty-three patients needed a second course of treatment at a median time interval of 12 weeks (range 9-14). The mean VAS score before treatment was 8 (range 3-10). After treatment, it was 5 (range 1-10). After 3, 6 and 12 months, the mean VAS scores were 4 (range 0-9), 3 (range 0-9) and 3.5 (range 0-9), respectively. Seventy patients reported functionality improvements after LDRT according to the von Pannewitz score. No acute or late complications were observed., Conclusion: LDRT appears to be safe and useful for HOA and is associated with good rates of pain relief and functionality improvements. However, further studies are necessary to confirm these promising results., (© 2021. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Osteoarthritis (OA) is the leading degenerative joint disease in the western world and leads, if left untreated, to a progressive deterioration of joint functionality, ultimately reducing quality of life. Recent data has shown, that especially OA of the ankle and foot are among the most frequently affected regions. Current research in OA points towards a complex involvement of various cell and tissue types, often accompanied by inflammation. Low-dose radiotherapy (LDRT) is widely used for the treatment of degenerative and inflammatory diseases. While the reported analgesic effects are well known, the underlying molecular mechanisms are only poorly understood. We therefore correlated a clinical approach, looking at pain reduction in 196 patients treated with LDRT with a pre-clinical approach, utilizing the K/BxN serum transfer mouse model using flow cytometry and multiplex ELISA for analysis. While an improvement of symptoms in the majority of patients was found, patients suffering from symptoms within the tarsi transversa show a significantly lower level of improvement. Further, a significant impact of therapy success was detected depending on whether only one or both feet were affected. Further, patients of younger age showed a significantly better outcome than older ones while needing fewer treatment series. When looking on a cellular level within the mouse model, a systemic alteration of immune cells namely a shift from CD8+ to CD4+ T cells and reduced numbers of DCs was observed. A general reduction of inflammatory cytokines was detected, with significant alterations in IL-4 and IL-17 levels, all of which could potentially be responsible for the highly effective clinical improvement in patients. Taken together our data indicate that LDRT can be regarded as a highly effective treatment option for patients suffering from OA of the foot and ankle, in terms of analgesic effects, especially in younger patients. Furthermore, the observed effects are mediated by an interplay of cellular and soluble immune factors, as observed in the K/BxN serum transfer model. With this interdisciplinary approach we aim to encourage the usage of LDRT as an additive treatment strategy not only as a last resort, but also earlier in the course of disease., Competing Interests: MH conflict of interest with Merck Serono (advisory role, speakers’ bureau, honoraria, travel expenses, research funding); MSD (advisory role, speakers’ bureau, honoraria, travel expenses, research funding); AstraZeneca (research funding); Novartis (research funding); BMS (advisory role, honoraria, speakers’ bureau); Teva (travel expenses). RF conflict of interest Astra-Zeneca and MSD as well as honoraria from Merck Serono, Astra-Zeneca, MSD, Novocure and research funding from Fresenius Nutrition, Merck Oncology, MSD, Astra-Zeneca, Novocure and Siemens AG. FP reports grants and speaker fees from Siemens Healthcare GmbH not related to the present work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Weissmann, Rückert, Zhou, Seeling, Lettmaier, Donaubauer, Nimmerjahn, Ott, Hecht, Putz, Fietkau, Frey, Gaipl and Deloch.)

Objective: Chronic pain associated with osteoarthritis (OA) often leads to reduced function and engagement in activities of daily living. Current pharmacological treatments remain relatively ineffective. This study investigated the efficacy of photobiomodulation therapy (PBMT) on cartilage integrity and central pain biomarkers in adult male Wistar rats., Design: We evaluated the cartilage degradation and spinal cord sensitization using the monoiodoacetate (MIA) model of OA following 2 weeks of delayed PBMT treatment (i.e., 15 days post-MIA). Multiple behavioral tests and knee joint histology were used to assess deficits related to OA. Immunohistochemistry was performed to assess chronic pain sensitization in spinal cord dorsal horn regions. Furthermore, we analyzed the principal components related to pain-like behavior and cartilage integrity., Results: MIA induced chronic pain-like behavior with respective cartilage degradation. PBMT had no effects on overall locomotor activity, but positive effects on weight support ( P = 0.001; effect size [ES] = 1.01) and mechanical allodynia ( P = 0.032; ES = 0.51). Greater optical densitometry of PBMT-treated cartilage was evident in superficial layers ( P = 0.020; ES = 1.34), likely reflecting the increase of proteoglycan and chondrocyte contents. In addition, PBMT effects were associated to decreased contribution of spinal glial cells to pain-like behavior ( P = 0.001; ES = 0.38)., Conclusion: PBMT during the chronic phase of MIA-induced OA promoted cartilage recovery and reduced the progression or maintenance of spinal cord sensitization. Our data suggest a potential role of PBMT in reducing cartilage degradation and long-term central sensitization associated with chronic OA.

Objective: Radiosynovectomy (RSO) describes the internal low-dose radiotherapy of the synovia via intra-articular administration of small radioactive particles. Since the introduction of biologics, the main aetiology of arthritic joints for RSO changed to mostly osteoarthritis with concordant change in typically affected joints. Thus, the effect of RSO in thumb basal joint arthritis (BJTh) with focus on osteoarthritis needs to be explored., Design: From 2017 to 2020, 219 BJTh were treated in 125 patients, 17 patients with rheumatoid arthritis (RA) and 108 patients with osteoarthritis (OA). The therapeutic effect was assessed using a four-step subjective scoring., Results: 20% of the treated joints were symptom free, 48% had a very good response, 16% slight and 16% no response. RSO was performed in 71 patients singularly and in 54 patients repetitively. The mean response duration was 6.8 months with a maximum of 48 months. 35% of patients had post-therapeutic pain relief followed by relapse after 3 months. Response duration showed no significant difference the between first and repetitive therapy, primary responder and primary non-responder and RA and OA., Conclusion: In thumb basal joint arthritis, RSO leads to response rates from 66 to 79%, mean response duration from 6 to 12 months and individual response duration 48 months. The present results are in line with previously published response rates in smaller joints. In respect to 35% of patients with relapse within 3 months post-therapy, we recommend a primary follow-up after 3-4 months., (© 2021. The Japanese Society of Nuclear Medicine.)

Background: Retrospective studies have described the effectiveness of low-dose radiotherapy (LD-EBRT) in painful arthrosis of small finger joints, but two recent prospective studies have yielded ambiguous results. To generate accurate data for the planning of a trial, we conducted a prospective, monocentric, observational study to describe the effects of LD-EBRT as precisely as possible. Methods : Twenty-five consecutive patients with symptomatic trapeziometacarpal (TMC) arthrosis were irradiated with 6 × 0.5 Gy. Before, 3, and 12 months after LD-EBRT, we assessed subjective endpoints (modified "von-Pannewitz score", 10-point visual analogue scale (VAS), "patient-rated wrist evaluation" (PRWE)), and objective measurements ("active range of motion" (AROM), Kapandji index, grip strength, pinch grip). Results : At 3/12 months, 80%/57% reported partial and 4%/18% complete remission according to the "von-Pannewitz" score. VAS "overall pain" significantly decreased from a median of seven (IQR 4) at baseline to three (IQR 6; p = 0.046) and to two (IQR 2; p = 0.013). Similar results were obtained for VAS "pain during exercise", VAS "pain during daytime", and VAS "function". "PRWE overall score" was reduced from 0.5 at baseline (SD 0.19) to 0.36 (SD 0.24, p = 0.05) and to 0.27 (SD 0.18, p = 0.0009). We found no improvements of the objective endpoints (AROM, Kapandji, grip strength) except for flexion, which increased from 64° (SD 12°) at baseline to 73° (SD 9.7°, p = 0.046) at 12 months. Conclusions: We recommend the PRWE score as a useful endpoint for further studies for this indication. To prove a 15% superiority over sham irradiation, we calculated that 750 patients need to be prospectively randomized.

The treatment of chronic inflammatory and degenerative diseases by low dose radiation therapy (LDRT) is promising especially for patients who were refractory for classical therapies. LDRT aims to reduce pain of patients and to increase their mobility. Although LDRT has been applied since the late 19th century, the immunological mechanisms remain elusive. Within the prospective IMMO-LDRT01 trial (NCT02653079) the effects of LDRT on the peripheral blood immune status, as well as on pain and life quality of patients have been analyzed. Blood is taken before and after every serial irradiation with a single dose per fraction of 0.5Gy, as well as during follow-up appointments in order to determine a detailed longitudinal immune status by multicolor flow cytometry. Here, we report the results of an interim analysis of 125 patients, representing half the number of patients to be recruited. LDRT significantly improved patients' pain levels and induced distinct systemic immune modulations. While the total number of leukocytes remained unchanged in the peripheral blood, LDRT induced a slight reduction of eosinophils, basophils and plasmacytoid dendritic cells and an increase of B cells. Furthermore, activated immune cells were decreased following LDRT. Especially cells of the monocytic lineage correlated to LDRT-induced improvements of clinical symptoms, qualifying these immune cells as predictive biomarkers for the therapeutic success. We conclude that LDRT improves pain of the patients by inducing systemic immune modulations and that immune biomarkers could be defined for prediction by improved patient stratification in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer KL declared a past co-authorship with authors UG and BF to the handling editor., (Copyright © 2021 Donaubauer, Becker, Weissmann, Fröhlich, Muñoz, Gryc, Denzler, Ott, Fietkau, Gaipl and Frey.)

Purpose: Painful osteoarthritis is common in elderly patients, and low-dose radiotherapy has been demonstrated to provide effective symptomatic treatment. We examined the analgesic effects of low-dose radiotherapy for osteoarthritis in the elderly aiming to reveal potential differences in the response rates relating to increasing age., Methods: A retrospective analysis was performed at two university hospitals including elderly patients (≥ 65 years) undergoing radiotherapy for osteoarthritis between 2008 and 2020. Pain intensity and response were quantified using the numerical rating scale (NRS) and the Pannewitz score. Age groups were defined for young old (65-74 years), older old (75-84 years), and oldest old patients (≥ 85 years)., Results: In all, 970 patients with 1185 treated sites and a median age of 76 years were analyzed. Mean NRS was 66 at baseline (t0), 53 after radiotherapy (t1), and 44 at first follow-up (t2) (p < 0.001 for t0-t1, t1-t2, and t0-t2). At t1, 1.5% exhibited a Pannewitz score of 0 (no pain), 58.5% of 1-2 (less pain), 36.1% of 3 (equal pain), and 3.9% of 4 (worse pain), while at t2, pain response shifted towards 6.9% (0), 58.6% (1-2), 28.1% (3), and 6.3% (4). Pain response did not differ between age groups at t1 (p = 0.172) or t2 (p = 0.684). In addition, pain response after re-irradiation (n = 384 sites) was 61.0% and was comparable between age groups (p = 0.535)., Conclusion: Low-dose radiotherapy results in pain reduction in about two-thirds of treated sites with no difference relating to increasing age, showing that radiotherapy is an effective analgesic treatment for osteoarthritis even at advanced ages., (© 2021. The Author(s).)

Abstract: Tin-117m (117mSn) is used to treated dogs with osteoarthritic joints by radiosynoviorthesis. The internal conversion and Auger electrons emitted by the 117mSn provide the therapeutic effect. Sn-117m also emits gamma rays, of which the most significant is 158.6 keV. The external radiation field around a treated dog is of interest to limit the dose to the owners/caretakers of the dog. The dog's torso attenuates the radiation being emitted toward the opposite side of the dog's body. This leads to a radiation field that is significantly non-isotropic. This study characterizes the anisotropy of this field to permit maximum dose rate measurements to be used to calculate the dose to individuals in the vicinity of the dog. Measurements were made in nine directions and at two distances, 0.3 and 1.0 m, to characterize common distances and spatial orientations for human-dog interactions. From these measurements, the percent reduction in the average dose rate compared to the maximum dose rate was determined. From a radiation safety perspective, the important factor is the minimum amount of shielding effectiveness or percent reduction that can be expected. A reasonable measure for this value is the fifth percentile of the shielding effectiveness distribution. The fifth percentile shielding effectiveness measures are 27% and 21% at 0.3 and 1.0 m, respectively., Competing Interests: This work was funded by Exubrion Therapeutics®, Buford, GA. The authors declare no other potential conflicts of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Health Physics Society.)

This retrospective study examined whether arthrocentesis combined with 10 sessions of low-level laser therapy (LLLT) improved the clinical outcomes of patients with temporomandibular joint osteoarthritis (TMJ-OA) compared with arthrocentesis alone. Data from two groups of patients (total: n=36) with unilateral TMJ-OA were evaluated. The groups were established according to their treatment regimens: Group 1 (arthrocentesis alone; n=19) and Group 2 (arthrocentesis plus LLLT; n=17). All patients had been diagnosed in accordance with the Research Diagnostic Criteria for Temporomandibular Joint Disorders (RDC/TMD) (Axis I Group IIIb) protocol. They all underwent the same arthrocentesis protocol, but those in Group 2 also received 10 sessions of LLLT immediately afterwards. The outcome variables were the visual analogue scale scores (VAS 1, VAS 2) for various treatment outcomes and millimetric measurements of mandibular movements over both the short and long term. Intra-group comparisons showed significant short and long-term improvements for both groups, but outcomes were better over the long term than the short term in both. In addition, greater improvements in muscle palpation scores and mandibular movements were achieved in Group 2 than in Group 1. In conclusion, although both techniques improved joint pain and function, a combination with LLLT seemed to have an additional benefit for myofascial components., (Copyright © 2020 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Osteoarthritis (OA) is a chronic degenerative joint disease and is considered as the most common cause of pain and disability. To the best of our knowledge, it is generally observed that there is a lack of evidence on the effects of low-level laser therapy (LLLT) on inflammatory cytokines in OA. The present review aims to appraise the current evidence of efffects of LLLT on inflammatory cytokines in OA of the knee. Medical databases such as Medline, PubMed, EMBASE, PEDro CINAHL, Web of Science, Cochrane register, and Google reference were searched from its inception to June 2019. Articles that meet the inclusion criteria: subjects (animals-Wistar rats) induced with OA; rats with age group of 50-90 days; weight of 150-300 g; finding the effects of LLLT; reporting inflammatory cytokines; and articles written in English were included. The reviewers assessed the methodological quality of the primary studies. Data of inflammatory cytokines IL-1β, IL-6, TNF-α, and MMP-13 were extracted for analysis. The Q (x 2 ) test and I 2 statistics analysis were performed to find the heterogeneity evaluation. Standard mean difference (SMD) and its 95% confidence interval (CI) were used to synthesize the data. Two hundred eleven potential articles were identified and 186 articles were excluded based on the selection criteria. The rest of the 25 articles were read and 8 articles were selected for further study. From the study, it is observed that the laser therapy group had mild to moderate improvement than control group in IL-1β, TNF-α, and MMP-13 (IL-1β; SMD 1.21 [95% CI - 0.278, 2.704], TNF-α; SMD 5.19 [95% CI 2.413, 7.961], and MMP-13 SMD - 1.45 [95% CI - 5.121, 2.211]), while IL-6 [SMD 3.11 (95% CI 0.662, 5.549] did not show any considerable improvement after laser therapy. The present review provides the evidence of LLLT-dependent reduction of IL-1β, TNF-α, and MMP-13, and its ability to modulate proliferation of inflammatory cells, which makes LLLT a suitable treatment for OA. Though the included studies showed a high heterogeneity in treatment parameter, the beneficial effect of LLLT on changes in inflammatory cytokines, such as IL-6, seems to be unaffected.

Background: Osteoarthritis (OA), the most common degenerative joint disease, is associated with severe functional limitation and impairment of quality of life. Numerous reports have documented the clinical efficacy of low-dose radiotherapy (LD-RT) in the management of various inflammatory disorders, including OA. In this paper, we assessed the clinical literature involving the use of LD-RT in the treatment of OA, its dose-response features, possible underlying mechanistic features, and optimal therapeutic dose range., Methods: We carried out a systematic review based on the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statements and evaluated articles meeting the inclusion criteria for this review., Results: A total of 361 articles were identified from databases, such as Scopus, PubMed, Embase, and Science Direct out of which 224 articles were duplicates and were discarded. Of the remaining 137 articles, 74 articles were un-related, 27 articles were review articles, eight were conference abstracts, three were letters, two were editorials, two were notes, and one was a book chapter. Finally, 20 articles met all the inclusion criteria and were included in this systematic review., Discussion: Several single-arm retrospective/prospective studies showed advantages for LD-RT in the management of OA in terms of pain relief, improvement of mobility and function, and showed minimal side effects. Mechanistic considerations involve positive subcellular effects mediated by the activation of a nuclear factor erythroid 2-related transcription factor (Nrf2) mediated antioxidant response. Further research on both the short- and long-term effects of LD-RT on OA and other inflammatory disorders is recommended.

Transforming growth factor β1(TGF-β1)/Smad3 pathway promotes the pathological progression of subchondral bone in osteoarthritis. The aim of this study is to determine the effect of low-intensity pulsed ultrasound (LIPUS) on the pathological progression and TGF-β1/Smad3 pathway of subchondral bone in temporomandibular joint osteoarthritis (TMJOA). Rabbit TMJOA model was established by type II collagenase induction. The left joint in this model was continuously stimulated with LIPUS for 3 and 6 weeks (1 MHz; 30 mW/cm 2 ) for 20 min/day. The morphological and histological features of subchondral bone were respectively examined by microcomputed tomography and Safranin-O staining. The number of osteoclasts was quantitatively assessed by tartrate-resistant acid phosphatase staining. Immunohistochemistry and Western blot analysis were conducted to evaluate the protein expression of Cathepsin K and TGF-β1/Smad3 pathway. The results indicated that LIPUS could improve the trabecular microstructure and histological characteristics of subchondral bone in rabbit TMJOA. It also suppressed abnormal subchondral bone resorption and activation of TGF-β1/Smad3 pathway, characterized by the number of osteoclasts, protein expression levels of Cathepsin K, TGF-β1, type II TGFβ receptor, and phosphorylated Smad3 (pSmad3) were decreased. In conclusion, LIPUS promoted the quality of subchondral bone by suppressing osteoclast activity and TGF-β1/Smad3 pathway in rabbit TMJOA., (© 2020 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Purpose: Osteoarthritis is a common disease, with a prevalence of symptomatic disease of 8.9%. One treatment option is radiotherapy. Most published samples were treated with an orthovoltage technique or with a telecobalt device. A lot of radiotherapy institutions are nowadays using linear accelerators for treatment of osteoarthritis. There is a discussion on whether the treatment results achieved with a linear accelerator are comparable to those with the orthovoltage technique. The aim of this study is to analyze the results of radiotherapy for osteoarthritis with a linear accelerator and compare the results with reference to different joints., Materials and Methods: The analysis was performed in patients of two German radiotherapy institutions and included 295 irradiated joints. Pain was documented with the numeric rating scale (NRS). Evaluation of the NRS was done before and directly after each radiation therapy course as well as for the follow-up of 24 months. The median age of the patients was 65 years, with 39.0% male and 61.0% female patients. Most frequently, osteoarthritis of the knee (34.6%) or the finger (15.9%) was treated., Results: We could find a significant response to radiotherapy. Median pain for the whole sample was 7 on the NRS before radiotherapy, 4 after 6 weeks, and 3 after 12 and 24 months. The percentage of patients with 0 or 1 on the NRS was 33.8% 12 months after radiotherapy. All investigated subgroups had a significant reduction of pain., Conclusion: Radiotherapy of osteoarthritis with a linear accelerator is an effective treatment which is very well tolerated. All analyzed subgroups show a good response to radiotherapy for at least 24 months. Orthovoltage therapy seems to be superior to treatment with a linear accelerator in a case-related analysis of the published samples. Further investigations should be performed for a definitive answer to this question.

Objective:  The study objective was to evaluate the long-term effect of radiosynoviorthesis (RSO) on the progression of radiological and nuclear-medical osteoarthritic features of hip and ankle joint in patients with osteoarthritis and rheumatoid arthritis., Patients and Methods:  The study included 89 hip joints of 81 patients, of which 48 had osteoarthritis (OA) and 33 had rheumatoid arthritis (RA). In terms of ankle joints, 64 patients were included of which 43 suffered from OA and 21 from RA. The mean follow-up time was 9.2 years for OA and 8.9 years for RA patients. Patients with RA were the active control group. Structural alterations of the hip joints were evaluated following Kellgren-Lawrence score and of ankle joint following Takakura score for both disease entities. For the evaluation of synovitis 2-phase bone scintigraphy was performed., Results:  RSO could prevent radiologic status deterioration among 70.6 % of hip osteoarthritic patients and 73.7 % among the hip RA patients. No structural progression was observed in 79.1 % of the treated ankle joints in patients with OA and in 85.7 % of the ankle joints in patients with RA.The scintigraphic response rate for the hip joints of OA patients was 68.6 %, 76.3 % for hip joints of RA patients, 83.1 %, ankle joints of OA patients, and 90.4 % ankle joints of RA patients.The radiographic and scintigraphic RSO response rates were not significantly higher for both joints in RA than OA patients., Conclusion:  RSO can be a good alternative in the treatment of synovitis and prevention of deterioration of inflammatory and radiographic features even in patients suffering from osteoarthritis and rheumatoid arthritis. RSO may have also a long-term effect to stop or delay progression of both diseases., Competing Interests: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: Osteoarthritis of the ankle and tarsal joints is less common than osteoarthritis of the knee or hip, but the associated disability is at least as severe as that of the other major joints of the lower limb. The results for total arthroplasty are still not satisfactory. For this reason, arthrodesis is still the gold standard of non-joint-conserving surgery. For the reason of functionality, joint-conserving therapies play a major role in treatment of ankle and tarsal osteoarthritis. Low-dose radiotherapy has a long history of treatment of osteoarthritis. The aim of this survey was to examine the results of low-dose radiotherapy for osteoarthritis of the ankle and tarsal joints., Materials and Methods: The analysis was performed on patients of three German radiotherapy institutions and included 66 irradiated joints. Pain was documented with the numeric rating scale (NRS). Evaluation of the NRS was done before and directly after each radiation therapy course as well as for the follow-up of 24 months. The median age of the patients was 68 years, with 24.5% male and 75.5% female patients. The upper ankle was treated in 37.9%, the lower ankle in 27.3% and the tarsal joints in 34.8%., Results: We could find a significant response to radiotherapy. For the whole sample, the median pain was 7 on the NRS before radiotherapy, 5 after 6 and 12 weeks, and 4 after 12 months. The percentage of patients with 0 or 1 on the NRS was 19.6% 12 months after radiotherapy. An improvement of joint mobility could be detected in 56.7% of the cases. All investigated subgroups had a significant reduction in pain., Conclusion: Radiotherapy of ankle and tarsal osteoarthritis is an effective treatment without showing side effects. All analysed subgroups show a good response to radiotherapy for at least 24 months.

Background: Osteoarthritis (OA) is common in dogs and causes chronic pain that affects the quality of life and may not respond to analgesics., Objective: The objective of this study was to determine whether low-level laser therapy (LLLT) would improve the quality of life and help reducing systemic analgesics, in dogs with OA., Methods: Seventeen client-owned dogs diagnosed with OA and associated pain were included. The diagnosis of OA was confirmed by orthopedic and radiographic examination. Pain was evaluated in each dog with the canine brief pain inventory (CBPI), compiled by the dog owners, as well as with a visual analog scale (VAS) and the colorado state canine chronic pain scale, used by the clinician. The LLLT was performed weekly in each study dog, for a total period of 6 weeks. The CBPI was then repeated at 2, 4, 6, and 8 weeks after the first laser session, whereas the VAS was reassessed at weeks 2 and 6. The dogs were observed for the occurrence of laser-related side effects., Results: Both CBPI and VAS were significantly reduced after the first laser session (9.2 ± 3.8 and 5.2 ± 1.1, respectively) compared to pretreatment values (11.8 ± 3.6 and 7.6 ± 0.9, respectively; and p = 0.018 and p < 0.001, respectively) and continued to decrease over time until the end of the therapy. Based on these results and improved function, as assessed by the orthopedic surgeon, the pharmacological analgesic therapy was reduced by the clinician at week 2 in 13 of 17 dogs. Laser-related side effects were not observed., Conclusion: This retrospective report provides a basis for future investigations, needed to clarify whether laser therapy may be beneficial to treat canine OA-associated pain. The preliminary findings are promising and suggest that LLLT may help reducing the analgesic administration and improving client satisfaction and the quality of life of dogs with OA., Competing Interests: The authors declare that there is no conflict of interest. This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Background: Osteoarthritis is the most common musculoskeletal disease. Extracorporeal shockwave therapy had shown an effect on osteoarthritis in both some animal experiments and clinical studies, but there was no systematic review to confirm the value of shockwave therapy in the treatment of all types of osteoarthritis and compare it with other traditional therapies (especially traditional Chinese medicine)., Method: PubMed, Medline, the Cochrane Central Register of Controlled Trials, Web of Science, Chinese National Knowledge Infrastructure, WANFANG database, and VIP database were searched up to December 10, 2019, to identify randomized controlled trials comparing shockwave therapy and other treatments for osteoarthritis. Visual analogue scale and the Western Ontario and McMaster Universities Osteoarthritis Index were extracted and analyzed by RevMan and STATA software as outcomes of pain reduction and functional improvement. Adverse reactions were recorded to evaluate the safety of shockwave therapy., Results: Shockwave therapy had significant improvement in both pain reduction and functional improvement compared with placebo, corticosteroid, hyaluronic acid, medication, and ultrasound ( P < 0.05). In functional improvement, shockwave therapy showed statistical improvement compared with kinesiotherapy and moxibustion ( P < 0.05) but not with acupotomy surgery ( P = 0.24). A significant difference between shockwave therapy and platelet-rich plasma was observed in pain reduction ( P < 0.05) but not in functional improvement ( P = 0.89). Meanwhile, a statistical difference was found between shockwave therapy and fumigation in functional improvement ( P < 0.05) but not in pain reduction ( P = 0.26). Additionally, there was no statistically significant difference between shockwave therapy and manipulation in both pain reduction ( P = 0.21) and functional improvement ( P = 0.45). No serious adverse reaction occurred in all of studies., Conclusions: Extracorporeal shockwave therapy could be recommended in the treatment of osteoarthritis as a noninvasive therapy with safety and effectiveness, but the grade of recommendations needs to be discussed in a further study., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2020 Lu Chen et al.)

Currently, there is no imaging procedure for radionuclide therapy utilizing Erbium-169 (Er-169). We have recently published the first post-radiosynovectomy imaging of Er-169 citrate in a case report (Farahati et al., 2017). In this study, we performed in-vitro and in-vivo studies to evaluate the feasibility to assess the distribution of Er-169 citrate after radiosynovectomy in fourteen patients with seventeen affected joints treated for refractory chronic synovitis. Post-radiosynovectomy imaging revealed the feasibility of post-radiosynovectomy detection and distribution utilizing Er-169 citrate in all cases. However, additional in-vitro studies including in-vitro imaging, gamma spectrometry and analysis of half-life indicated that emitted gamma-rays of the Ytterbium-169 in the radiopharmaceutical together with bremsstrahlung induced by Er-169 are the imaging source of emitted counts. Post-radiosynovectomy imaging utilizing Er-169 citrate is feasible and should be implemented in the guidelines for theranostics for quality control, patient safety and therapy monitoring., (Copyright © 2019. Published by Elsevier Ltd.)

Purpose: Osteoarthritis is a common disease with a prevalence of approximately 8.9% among the average population. One treatment option is low-dose radiotherapy. Some authors mention that they apply a second or third course of radiation for recurrent pain or partial or no response to the initial course. As the results of re-irradiation have not been analysed systematically, the aim of this study was to document the results of repeated radiation treatment and to identify those patients who will benefit., Methods and Materials: The analysis was performed on patients of three German radiotherapy institutions and included 217 re-irradiated joints. Pain was documented with the numeric rating scale (NRS). Evaluation of the NRS was done before and directly after each radiation therapy as well as at the follow-up of 24 months. The median age of the patients was 67 years, with 40% male and 60% female patients. Re-irradiation was indicated because the initial radiotherapy resulted in no response in 21.2%, in partial response in 41.5%, and in recurrent pain in 37.3%., Results: We found a significant response to re-irradiation. For the whole sample, the median pain was 6 before re-irradiation, 4 after 6 weeks, and 3 after 12 weeks, 6 months, 12 months, and 24 months. The percentage of patients being free of pain or with very little pain was approximately 25% 12 months after re-irradiation. All subgroups, notably those with no response to the first course versus partial response to the first course versus recurrent pain, had significant reduction of pain., Conclusion: Re-irradiation of osteoarthritis is an effective and safe treatment. All subgroups showed a good response to re-irradiation for at least 24 months.

Purpose: The aim of this retrospective clinical quality assessment was to evaluate the efficacy of low-dose radiotherapy (RT) for painful benign skeletal disorders., Methods: Patients with different painful benign skeletal disorders (arthrosis and enthesopathies) were recruited for this retrospective clinical quality assessment between January 2014 and December 2015. RT was applied with a linear accelerator. Single doses of 0.5 Gy (total dose 3.0-5.0 Gy) were used. Pain was measured before and immediately after RT (early response) by a 10-point visual analogue scale (VAS). We defined a VAS score of 0-2 as a good response. Pain relief was measured during follow-up., Results: A total of 598 evaluable patients (394 females, 204 males) with a mean age of 61.4 years (range 33-81 years) were recruited. The median VAS score was 7.0 (interquartile range [IQR] 2) before treatment and 5.0 (IQR 4) upon completion of RT (p < 0.001). A good response was achieved upon completion of RT in 83 patients (13.9%), with a median follow-up of 38 months (range 29-47 months) in 373 patients (62.4%; p < 0.001). In general, RT had a better effect on enthesopathies than on arthrosis., Conclusion: Low-dose RT is a very effective treatment for the management of painful benign skeletal disorders. Due to the delayed onset of analgesic effects, low-dose RT results in significantly improved long-term efficacy compared to the results immediately after RT. These findings confirm the results of other retrospective, prospective, and randomized trials.

Background: Musculoskeletal disorders caused by osteoarthritis (MSDs/OA) are a growing problem in the modern industrialized society in Canada. Overall aging of the general population and a progressive lack of exercise contribute to this alarming increase. Moreover, a range of chronic conditions including cardiovascular and mental diseases show significantly higher comorbidity with MSDs/OA. Conventional medical treatment for MSDs/OA includes nonsteroidal anti-inflammatory drugs and opiate pain killers. These drugs have major drawbacks such as a relative lack of efficacy, potential for addiction, and even death (Vioxx scandal). Photobiomodulation (PBM) was discovered over 50 years ago but has still not attained widespread acceptance by the medical community. This is partly due to uncertainty about the precise molecular mechanisms of action and a bewildering array of different wavelengths and dosimetric parameters employed in reported studies. Objective: The goal of this review was to survey literature reports of PBM, also known as low-level laser therapy used for treatment of MSDs/OA, concentrating on the growth over time, different wavelengths employed, and application to different joints. Methods: We searched the PubMed database for publication of study on PBM to treat the most common joints. Results: We show that the field of PBM to treat MSDs/OA is expanding exponentially over the past 20 years. A trend has emerged over time for more power to achieve better effective treatments, and the understanding of the physiological effect of safe parameters has improved. There is, however, no consensus on the best set of parameters to treat a specific patient indication. Conclusions: Finally, we highlight gaps in our knowledge and the barriers to further clinical trials. We suggest that the growing body of evidence indicating efficacy, and the almost total lack of side effects, should encourage continued clinical research to support clinical applications where better rehabilitation treatments are much needed.

The aim of this study was to compare the effects of photobiomodulation (PBM) associated with an aerobic and an aquatic exercise training on the degenerative process related to osteoarthritis (OA) in the articular cartilage in rats. Fifty male Wistar rats were randomly divided into 5 groups: OA control group (CG), OA plus aerobic training group (AET), OA plus aquatic training group (AQT), OA plus aerobic training associated with PBM group (AETL), OA plus aquatic training associated with PBM group (AQTL). The aerobic training (treadmill; 16 m/min; 50 min/day) and the aquatic training (water jumping; 50-80% of their body mass) started 4 weeks after the surgery and they were performed 3 days/week for 8 weeks. Moreover, PBM was performed after the physical exercise trainings on the left joint. Morphological characteristics and immunoexpression of IL-10, TGF-β, and collagen type I (Col I) and II (Col II) of the articular cartilage were evaluated. The results showed that all the treated groups (exercise and PBM) presented less intense signs of degradation (measured by histopathological analysis and OARSI grade system). Additionally, aerobic and aquatic exercise training rats (associated or not with PBM) showed increased IL-10 (AET p = 0.0452; AETL p = 0.03; AQTL p = 0.0193) and Col II (AET p = 0.012; AQT p = 0.0437; AETL p = 0.0001; AQTL p = 0.0001) protein expression compared to CG. Furthermore, a statistically higher TGF-β expression was observed in AET (p = 0.0084) and AETL (p = 0.0076) compared to CG. These results suggest that PBM associated with aerobic and aquatic exercise training were effective in mediating chondroprotective effects and maintaining the integrity of the articular tissue in the knees of OA rats.

Objectives: Low-dose radiation therapy (LDRT) is widely used as treatment for osteoarthritis (OA) in some countries, while relatively unknown in others. Systematic literature review displayed a lack of high-level evidence for beneficial effects in clinical practice. The aim was to assess the efficacy of LDRT on symptoms and inflammation in hand OA patients in a randomised, blinded, sham-controlled trial, using validated outcome measures., Design: Hand OA patients, ≥50 years, with pain ≥5 (scale 0-10) and non-responding to conservative therapy were included and randomised 1:1 to receive LDRT (6 × 1 Gy in 2 weeks) or sham (6 × 0 Gy in 2 weeks). Primary outcome was the proportion of OMERACT-OARSI responders, 3 months post-intervention. Secondary outcomes were pain and functioning (Australian/Canadian Hand Osteoarthritis Index; AUSCAN), quality of life (Short Form Health Survey; SF36) and inflammatory outcomes: erythrocyte sedimentation rate and C-reactive protein serum levels, effusion, synovial thickening and power Doppler signal on ultrasound (range 0-3)., Results: Fifty-six patients were included. After 3 months, no significant difference in responders was observed between groups (LDRT: 8 (29%); sham: 10 (36%); difference -7% (95%CI -31-17%)). Also, differences in clinical and inflammatory outcomes between groups were small and not significant., Conclusions: We were unable to demonstrate a substantial beneficial effect of LDRT on symptoms and inflammation in patients with hand OA, compared to sham treatment. Although a small effect can not be excluded, a treatment effect exceeding 20% is very unlikely, given the confidence interval. Therefore, in the absence of other high-level evidence, we advise against the use LDRT as treatment for patients with hand OA., Clinical Trial Registration Number: NTR4574 (Dutch Trial Register)., (Copyright © 2018 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Background: Osteoarthritis (OA) is a serious degenerative joint disease. It is one of the main causes of disability in the world. Current treatment modalities have numerous side effects. Subsequently, health experts are looking for alternative therapies., Objectives: The aim of the study was to evaluate the early effects of low-level laser therapy (LLLT) vs intraarticular (IA) corticosteroids (CS) on acute temporomandibular joint osteoarthritis (TMJOA)., Material and Methods: Sixty rats were divided into 3 groups: group 1- untreated OA; group 2 - OA treated with CS; and group 3 - OA treated with LLL. Half of the animals in each group were sacrificed at 1 and 4 weeks post treatment. The temporomandibular joint was dissected and evaluated histochemically, using quantitative real-time polymerase chain reaction (qRT-PCR), and radiographically., Results: Histochemically, Safranin-O staining revealed an obvious reduction in proteoglycans in the untreated osteoarthritic group. However, both of the treated groups showed a moderate increase in glycosaminoglycan (GAG) staining. As for the qRT-PCR results, caspase-3 showed the highest mean value in the untreated OA group, followed by the CS group, while the lowest mean value was recorded in the LLL group. Radiographically, the condyle showed erosion, flattening, osteophyte formation, and sclerosis in the untreated group, but there was great improvement in both of the treated groups., Conclusions: Both laser and cortisone showed reparative and formative effects, as evidenced by the increases in the proteoglycan content. However, LLL was superior in its anti-apoptotic effects. Cone beam computed tomography (CBCT) is a valuable tool in assessing osseous abnormalities.

Purpose: To explore the potential molecular mechanism of low-intensity pulsed ultrasound (LIPUS) in the treatment of temporomandibular joint osteoarthritis (TMJ-OA), and identify the target genes for therapy of TMJ-OA., Methods: Rat TMJ-OA was induced by unilateral occlusal trauma (UOT). At 8 weeks, the experimental group rats were treated by LIPUS for 4 weeks (5 days every week). The cartilage was examined by histological techniques. Gene expression profile in control, placebo and LIPUS-treated group were measured by RNA sequencing (RNA-Seq). Gene oncology (GO) and kyoto encyclopedia of genes and genomes (KEGG) annotated were performed and ten differentially expressed genes (DEGs) were further validated in another individual by quantitative real-time polymerase chain reaction (qRT-PCR). Per-2, a circadian rhythm gene, was further confirmed by western blot., Results: TMJ-OA model was successfully established in rats through UOT. LIPUS played a positive role in attenuating the retrogression of cartilage. The cartilage lesion was determined by HE and Safranin-O staining. A significant and bran-new gene profile of 58 mRNAs was obtained from the RNA-Seq (LIPUS-treated/placebo) and generated approximately 30GB data. Annotation, functional classification and pathway of the data were analyzed based on GO and KEGG database and ten candidate DEGs were identified. Some of these genes were proved to be related to OA, such as matrix-degrading enzyme (ADAMTS-8), complement (C1qa, C3, C5aR1). Some were reported for the first time in TMJ-OA, such as circadian gene (Per-2, Dbp, Npas2 and Arntl). According to the results of qRT-PCR validation, the sequencing data was with a high degree of credibility. The circadian gene Per-2 was up-regulated by LIPUS in TMJ-OA on the mRNA and protein level., Conclusion: This study reveals the potential therapeutic genes related to TMJ-OA. Especially the circadian Per-2 gene was detected up-regulated by the treatment of LIPUS. It provides us a precious, new target OA-related gene and further investigation of gene-function will provide us new insights in understanding the potential mechanical underling TMJ-OA., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: Low-level laser therapy (LLLT) is a form of light therapy that triggers biochemical changes within cells. Photons are absorbed by cellular photoreceptors, triggering chemical alterations and potential biochemical benefits to the human body. LLLT has been used in pain management for years and is also known as cold laser therapy, which uses low-frequency continuous laser of typically 600 to 1000 nm wavelength for pain reduction and healing stimulation. Many studies have demonstrated analgesic and anti-inflammatory effects provided by photobiomodulation in both experimental and clinical trials., Objective: The purpose of this research article was to present a summary of the possible pain management benefits of LLLT., Results: In cold laser therapy, coherent light of wavelength 600 to 1000 nm is applied to an area of concern with hope for photo-stimulating the tissues in a way that promotes and accelerates healing. This is evidenced by the similarity in absorption spectra between oxidized cytochrome c oxidase and action spectra from biological responses to light. LLLT, using the properties of coherent light, has been seen to produce pain relief and fibroblastic regeneration in clinical trials and laboratory experiments. LLLT has also been seen to significantly reduce pain in the acute setting; it is proposed that LLLT is able to reduce pain by lowering the level of biochemical markers and oxidative stress, and the formation of edema and hemorrhage. Many studies have demonstrated analgesic and anti-inflammatory effects provided by photobiomodulation in both experimental and clinical trials., Conclusion: Based on current research, the utilization of LLLT for pain management and osteoarthritic conditions may be a complementary strategy used in clinical practice to provide symptom management for patients suffering from osteoarthritis and chronic pain.

The aim of this study was to evaluate the biostimulation (BS) effect of the gallium-aluminum-arsenide (GaAlAs) diode laser by histopathology with an experimental osteoarthritis (OA) model in the temporomandibular joints (TMJ) of rabbits, in the early period. GaAlAs diode laser is used for pain reduction in TMJ disorders. Twenty-four adult male New Zealand white rabbits were randomly divided into three equal groups: Control Group (CG), Study Group 1 (SG-1), and Study Group 2 (SG-2). Mono-iodoacetate (MIA) was administered to the right TMJs of all rabbits. The rabbits did not undergo any treatment for four weeks to allow the development of osteoarthritis. In SG-1, laser BS was applied to the rabbits at 940 nm, 5 W, and 15 J/cm2 in continuous wave mode at 48-hour intervals for 14 sessions; and in SG-2, laser BS was applied with the same parameters at 24-hour intervals for 28 sessions. Laser BS was not applied to the rabbits in CG. All rabbits were sacrificed simultaneously. The TMJ cartilage, osteochondral junction, chondrocyte appearance, and subchondral ossification were evaluated histopathologically. There was no statistically significant difference between the groups in terms of cartilage, osteochondral junction, chondrocyte appearance, and subchondral ossification values (p > 0.05). The laser BS protocol used in the study had no positive histopathological effects on TMJ OA in the early period.

This study aimed to determine whether photobiomodulation therapy (PBMT) could improve the bioavailability and chondroprotective benefits of mesenchymal stem cells injected into the knees of rats used as an experimental model of osteoarthritis (OA) as well as reduce the expression of matrix metalloproteinases (MMPs) and degradation of type II collagen (COL2-1) in the cartilage. Adipose-derived stem/stromal cells (ADSCs) were collected from three male Fischer 344 rats and characterized by flow cytometry. Fifty female Fischer 344 rats were distributed into five groups of 10 animals each. These groups were as follows: control, OA, OA PBMT, OA ADSC, and OA ADSC PBMT. OA was induced in the animals using a 4% papain solution. Animals from the OA ADSC and OA ADSC PBMT groups received an intra-articular injection of 10 × 10 6 ADSCs and were treated with PBMT by irradiation (wavelength: 808 nm, power: 50 mW, energy: 42 J, energy density: 71.2 J/cm 2 , spot size: 0.028). Euthanasia was performed 7 days after the first treatment. The use of PBMT alone and the injection of ADSCs resulted in downregulation of pro-inflammatory cytokines and MPs in cartilage compared to the OA group. PBMT and ADSCs caused upregulation of tissue inhibitors of MPs 1 and 2 and mRNA and protein expression of COL2-1 in cartilage compared to the OA group. The intra-articular injection of ADSCs and PBMT prevented joint degeneration resulting from COL2-1 degradation and modulated inflammation by downregulating cytokines and MMPs in the OA group.

The aim of this study was to compare the effects of combined treatment with chondroitin sulfate and glucosamine sulfate (CS/Gl) and photobiomodulation (PBM) on the degenerative process related to osteoarthritis (OA) in the articular cartilage in rats. Forty male Wistar rats were randomly divided into four groups: OA control group (CG); OA animals submitted to PBM treatment (PBM); OA animals submitted to CS/Gl treatment (CS/Gl); OA submitted to CS/GS associated with PBM treatments (GS/Gl + PBM). The CS/Gl started 48 h after the surgery, and they were performed for 29 consecutive days. Moreover, PBM was performed after the CS/Gl administration on the left joint. Morphological characteristics and immunoexpression of interleukin 10 (IL-10) and 1 beta (IL-1β) and collagen type II (Col II) of the articular cartilage were evaluated. The results showed that all treated groups (CS/Gl and PBM) presented attenuation signs of degenerative process (measured by histopathological analysis) and lower density chondrocytes [PBM (p = 0.0017); CS/Gl (p = 0.0153) and CS/Gl + PBM (p = 0.002)]. Additionally, CS/Gl [associated (p = 0.0089) or not with PBM (p = 0.0059)] showed significative lower values for OARSI grade evaluation. Furthermore, CS/GS + PBM decreased IL-1β protein expression (p = 0.0359) and increased IL-10 (p = 0.028) and Col II imunoexpression (p = 0.0204) compared to CG. This study showed that CS/Gl associated with PBM was effective in modulating inflammatory process and preventing the articular tissue degradation in the knees OA rats.

Background: In low level laser therapy (LLLT) low wattage lasers are used to irradiate the affected skin areas, joints, nerves, muscles and tendons without any sensation or thermal damage. Although the exact mechanism of its effect is still unknown, it seems beyond dispute that LLLT induces a variety of stimulating processes at the cellular level affecting cell repair mechanisms, the vascular system and lymphatic system. LLLT has been popular among orthopaedic practitioners for many years, whereas university medicine has remained rather sceptical about it., Objectives: Overview of studies on the efficacy of LLLT in the treatment of rheumatic orthopaedic conditions, i. e. muscle, tendon lesions and arthropathies., Materials and Methods: Narrative literature review (PubMed, Web of Science)., Results: While earlier studies often failed to demonstrate the efficacy of LLLT, several recent studies of increasing quality proved the efficacy of LLLT in the treatment of multiple musculoskeletal pain syndromes like neck or lower back pain, tendinopathies (especially of the Achilles tendon) and epicondylolpathies, chronic inflammatory joint disorders like rheumatoid arthritis or chronic degenerative osteoarthritis of the large and small joints. In addition, there is recent evidence that LLLT can have a preventive capacity and can enhance muscle strength and accelerate muscle regeneration., Conclusion: LLLT shows potential as an effective, noninvasive, safe and cost-efficient means to treat and prevent a variety of acute and chronic musculoskeletal conditions. Further randomized controlled studies, however, are required to confirm this positive assessment.

Development of persistent deep cutaneous ulceration is a rare and serious complication of radiosynovectomy, an extended procedure used in the treatment of chronic synovitis. Cutaneous radiation necrosis is a rare complication of synovectomy, probably as a result of radiocolloid para-articular injection. This rare phenomenon should be suspected when an ulcer adjacent to an articulation appears several days or even months after a radiation synovectomy. It can turn into a challenging diagnosis for rheumatologists, orthopaedists and dermatologists, especially in those cases with a late development of the skin lesions. Recognition of this potential side effect is important in order to establish a proper therapeutic strategy and avoid unnecessary treatments. Surgical excision appears to be the treatment of choice. We report two patients with knee osteoarthritis treated with intra-articular injection of Yttrium-90 who developed persistent cutaneous ulcers secondary to radiation necrosis., (© 2016 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

The objective of this study was to evaluate the effects of photobiomodulation therapy (PBMT) on inflammatory indicators, i.e., inflammatory mediators (TNF-α and CINC-1), and pain characterized by hyperalgesia and B1 and B2 receptor activation at 6, 24, and 48 h after papain-induced osteoarthritis (OA) in rats. Fifty-four rats were subjected to hyperalgesia evaluations and then divided randomly into three groups-a control group and two groups OA and OA PBMT group by using laser parameters at wavelength (808 nm), output power (50 mW), energy per point (4 Joules), power density (1.78 W/cm 2 ), laser beam (0.028 cm 2 ), and energy density (144 J/cm 2 )-the induction of osteoarthritis was then performed with 20-μl injections of a 4 % papain solution dissolved in 10 μl of saline solution, to which 10 μl of cysteine solution (0.03 M). The statistical analysis was performed using two-way ANOVA with Bonferroni's post hoc test for comparisons between the 6, 24, and 48 h and team points within each group, and between the control, injury, and PBMT groups, and p < 0.05 was considered to indicate a significant difference. The hyperalgesia was evaluated at 6, 24, and 48 h after the injury. PBMT at a wavelength of 808 nm and doses of 4 J, administered afterward, promotes increase at the threshold of pressure stimulus at 6, 24, and 48 h after application and promote cytokine attenuation levels (TNF and CINC-1) and bradykinin receptor (B1 and B2) along the experimental period. We conclude that photobiomodulation therapy was able to promote the reduction of proinflammatory cytokines such as TNF-α and CINC-1, to reduce the gene and protein expression of the bradykinin receptor (B1 and B2), as well as increasing the stimulus response threshold of pressure in an experimental model of acute osteoarthritis.

Objective: The aim of this study was to evaluate the effects of an aquatic exercise program and low-level laser therapy (LLLT) (associated or not) on degenerative modifications and inflammatory mediators on the articular cartilage using an experimental model of knee OA., Method: Forty male Wistar rats were divided into 4 groups: knee OA - without treatment (OA); OA plus exercise program group (OAE); OA plus LLLT (OAL); OA plus exercise program associated with LLLT (OAEL). Trained rats performed a water-jumping program carrying a load equivalent to 50-80 % of their body mass strapped to their chest. The laser irradiation was used either as the only method or after the exercise training had been performed, at 2 points contact mode (medial and lateral side of the left joint). The treatments started 4 weeks after the surgery, 3 days/week for 8 weeks., Results: The results revealed that all treated groups (irradiated or not) exhibited a better pattern of tissue organization, with less fibrillation and irregularities along the articular surface and improved chondrocytes organization. Also, a lower cellular density and structural damage (OARSI score) and higher thickness values were observed in all treated groups. Additionally, OAE and OAEL showed a reduced expression in IL-1β and caspase-3 as compared with OA. Furthermore, a statistically lower MMP-13 expression was only observed in OAEL as compared with OA., Conclusion: These results suggest that aquatic exercise program and LLLT were effective in preventing cartilage degeneration. Also, physical exercise program presented anti-inflammatory effects in the knees in OA rats.

Aim: The precise localisation of osteoarthritic and inflammatory changes is crucial for selective treatment planning of radiosynovectomy (RSV). The present study evaluated the diagnostic accuracy of planar bone imaging and SPECT for the detection of pathological bone metabolism and inflammation in joints of the foot and ankle, compared with SPECT/CT., Patients, Methods: 39 patients (mean age 65.6 ± 11.1 years) with suspected inflammatory osteoarthritis underwent SPECT/CT of the feet. After injection of approximately 500 MBq 99mTc DPD, all patients had three-phase planar bone imaging and late-phase hybrid SPECT/CT. late-phase SPECT, and CT of the foot. Increased bone metabolism and blood-pool was assigned to the respective joint of the fore-, mid-, and hindfoot, using SPECT/CT as the reference standard., Results: Overall, SPECT had a higher sensitivity than planar imaging (0.80 vs 0.68, n.s.). The advantage of SPECT was most obvious in the anatomically complex midfoot area (0.63 vs 0.26, p < 0.05) and less obvious in the forefoot (0.85 vs 0.79, n.s.) and hindfoot (0.89 vs 0.89, n.s.). The overall concordance (Cohen`s Kappa) between SPECT/CT and planar (late-phase) imaging and SPECT was high for the forefoot and the hindfoot (planar: 0.78/0.81; SPECT 0.86/0.88) and comparatively low for the midfoot (planar: 0.27; SPECT 0.61)., Conclusion: SPECT was significantly superior to planar bone imaging for the detection of joint lesions in the midfoot. The differences between SPECT and planar imaging in the fore- and hindfoot were not significant, most likely due to the inherently less complex anatomy. Compared with SPECT alone, a benefit from the use of SPECT/CT can be observed in the midfoot region where it facilitates the identification of the correct joint for RSV.

The purpose of this work was to evaluate the efficacy of low-dose radiotherapy (RT) for thumb carpometacarpal osteoarthritis (rhizarthrosis). The responses of 84 patients (n = 101 joints) were analyzed 3 months after therapy (n = 65) and at 12 months (n = 27). Patients were treated with 6 fractions of 1 Gy, two times a week, with a linear accelerator. At the end of therapy, about 70 % of patients reported a response (partial remission or complete remission), 3 months later about 60 %, and 1 year after treatment 70 %. In univariate regression analysis, higher patient age and field size greater than 6 × 4 cm were associated with response to treatment, while initial increase of pain under treatment was predictive for treatment failure. Duration of RT series (more than 18 days), gender, time of symptoms before RT, stress pain or rest pain, or prior ortheses use, injections, or surgery of the joint were not associated with treatment efficacy. In multivariate regression analysis, only field size and initial pain increase were highly correlated with treatment outcome. In conclusion, RT represents a useful treatment option for patients suffering from carpometacarpal osteoarthritis. In contrast to other benign indications, a larger field size (>6 × 4 cm) seems to be more effective than smaller fields and should be evaluated in further prospective studies.

Objectives: To determine if a single low dose of radiation therapy in dogs with osteoarthritis of the elbow joint was associated with a detectable improvement in their lameness and pain as documented by force platform gait analysis., Methods: In this cohort longitudinal observational study, five Labrador Retrievers with lameness due to elbow osteoarthritis that was unresponsive to medical treatment were removed from all non-steroidal anti-inflammatory and analgesic medications. A single treatment of radiation therapy delivering 10 Gray was performed on the affected elbow joint(s). Force platform gait analysis was used to assess the ground reaction forces of a limb affected with elbow osteoarthritis both before and after radiation therapy., Results: Significant differences occurred in the weight-bearing on an affected limb with elbow osteoarthritis after radiation therapy at weeks six and 14. Change due to treatment was particularly apparent in dogs with unilateral elbow osteoarthritis., Clinical Significance: Administering a single low dose of radiation therapy may have a short-term benefit in dogs with elbow osteoarthritis, which is similar to the evidence supporting the use of radiation therapy in horses with orthopaedic disease.

Background and Objective: Osteoarthritis (OA) is a common chronic disorder. While research usually focuses on OA of the large joints, OA of the hand receives relatively little attention resulting in a lack of a therapeutic gold standard. Low level laser therapy (LLLT)/photobiomodulation therapy has been successfully used to treat a variety of medical conditions. Nevertheless, its merits in the treatment of (hand) OA remain controversial. The aim of the present study was to examine the longitudinal effect of LLLT on the three major hand OA symptoms-pain, swelling, reduced joint mobility-in patients suffering from Bouchard's and Heberden's OA., Study Design/materials and Methods: Thirty-four patients (32 females) aged 61.21 ± 2.13 years were administered 5-10 LLLT sessions to 85 joints (47 proximal and 38 distal interphalangeal joints). Therapy took place twice a week. Pain (Visual Analogue Scale), ring size (perimeter in mm), and range of motion (extension/flexion) were measured at baseline and after five treatments for all patients, and additionally after seven sessions and 8 weeks after treatment ended for patients who received more than five and seven treatments, respectively. Eighteen patients (37 joints) received only five treatments, 10 patients (29 joints) were administered seven treatments, and six patients (19 joints) were administered 10 LLLT sessions., Results: LLLT significantly reduced pain and ring size and increased range of motion after five and seven treatments (all P's < 0.001). The effects were very large (all η(2) 's > 0.14). No further significant change occurred between 7 and 10 treatments. The effects achieved after seven sessions persisted for 8 weeks., Conclusions: LLLT is a safe, non-invasive, efficient and efficacious means to reduce pain and swelling and to increase joint mobility in patients suffering from Heberden's and Bourchard's OA. Further randomized controlled studies are needed to examine medium- to long-term effects as well as the ideal LLLT parameters. Lasers Surg. Med. 48:498-504, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Low-dose radiotherapy (LD-RT) has been widely used for treatment of non-malignant disorders since its introduction and animal studies show anti-inflammatory effects in osteoarthritis (OA). However, the evidence for its effect in clinical practice remains unclear. Therefore, the aim of this study is to systematically summarise the literature on effectiveness of LD-RT on pain and functioning in patients with OA and its safety. Broad search terms were used to search PubMed, EMBASE and Web of Science. Primary inclusion criteria were osteoarthritis as indication, radiotherapy as intervention, written in English, German or Dutch and published since 1980. Study quality was assessed using the EPHPP Quality Assessment Tool for Quantitative Studies (scale: strong, moderate, weak). Seven studies were suitable for inclusion, all with retrospective uncontrolled observational design. Methodological quality of all studies was judged as weak. Most studies used 2-3 RT sessions per week for 2 weeks, some with booster session after 6 weeks. Generally, non-validated single-item measurement instruments were used to evaluate the effect of LD-RT on pain and function. Across the studies, in 25-90 and 29-71 % of the patients pain and functioning improved, respectively. Side effects were described in one study, none were reported. Our results show that there is insufficient evidence for efficacy or to confirm the safety of LD-RT in treatment of OA, due to absence of high-quality studies. Therefore, a well-designed, sham-controlled and blinded randomised trial, using validated outcome measures is warranted to demonstrate the value of LD-RT for OA in clinical practice.