Considered the most common musculoskeletal disease in the aging population, osteoarthritis (OA) is highly prevalent among adults and it results in substantial personal and societal costs.1 OA is a chronic disease affecting joints and periarticular tissues and is characterized by progressive degeneration of articular cartilage and by changes in the subchondral bone.2 Knee OA is clinically characterized by joint pain, morning stiffness, and decreased mobility, which may reduce the quality of life (QoL) of adults.3 Thus investigating evidence-based non-pharmacological management is of pivotal importance.

International clinical guidelines strongly recommend physical exercise as a non-pharmacological treatment for OA.4–6 The benefits of exercises for improving pain and function in people with knee OA were well established in a systematic review.7 In adequate doses, a strengthening program for lower limbs improves muscle weakness by increasing muscle recruitment and/or mass, which may decrease internal knee forces, reducing pain intensity and dysfunction.7 Therefore, muscle strengthening is recognized as core treatment for knee OA8,9 and should be individually prescribed through progressive exercise programs.10

Laser therapy or photobiomodulation (PBM), another non-pharmacological approach, may induce analgesic and anti-inflammatory effects.11 However, the body of evidence and recommendations on the use of PBM for knee OA are inconclusive.4 The American Academy of Orthopaedic Surgeons is unable to recommend for or against the use of PBM in patients with symptomatic knee OA12 and the Osteoarthritis Research Society International (OARSI) guidelines conditionally recommend the use of laser therapy for this condition.4

While some randomized controlled trials (RCTs) have investigated the isolated effect of PBM on knee OA,13–16 there is incipient research on the combination of PBM with therapeutic exercise programs.17–22 Moreover, these studies present some limitations, such as having a small sample size,18,19,21,22 lacking a control group,18,21,22 failing to simultaneously perform the PBM and the exercise program interventions,19,22 being unable to conduct a long-term follow-up,18–21 limiting participation to only female21 or male18 participants, and performing only a few treatment sessions.19

Considering that exercises should be prescribed for OA symptoms management,7 this study aimed to evaluate whether PBM provides incremental therapeutic benefits for pain, physical function (e.g. standing and sitting in a chair, walking, ascending and descending stair), and QoL in patients with knee OA.

This study adhered to the Standard Protocol Items: Recommendations for Interventional Trials,23 the OARSI Clinical Trials Recommendations,24 and the Template for Intervention Description and Replication checklist guidelines.25 The results are reported according to the Consolidated Standards of Reporting Trials statement for RCTs of non-pharmacologic treatments.26 Due to delay in processing, the trial was registered on the Brazilian Clinical Trials Registration Platform (RBR-8f4s9d) within 3 months of the start of the study, which is before completion of data collection for any participants. The protocol was approved by the Institutional Human Ethics Committee of the Universidade Federal de São Carlos, São Paulo, Brazil (No. 65685517.9.0000.5504). Enrollment of participants began in March 2018 and data collection ceased in June 2020.

A total of 794 participants were assessed for eligibility, and 127 were randomized as follows: 41 were assigned to the Exercise group, 44 to the Exercise plus Active PBM group, and 42 to the Exercise plus Placebo PBM group. Dropout rates of 18% and 45% occurred at the post-intervention and at the 6-month follow-up assessments, respectively. A detailed flow diagram of the participants’ progress through the trial is shown in Fig. 1.

Fig. 1.

Flow diagram of participants through the trial. BMI, body mass index; ITT, intention-to-treat.

(0.49MB).

Participants attended 17 (of planned 24) treatment sessions on average. Anthropometric and clinical characteristics at baseline are presented in Table 1. Values are expressed as means (standard deviation) for continuous variables and N (%) for frequency variables.

Table 2 summarizes the primary and secondary outcome scores. Self-reported measures and physical performance were similar between groups at baseline. Although all groups presented significant clinically relevant improvement (p<0.05) in all outcome measures and assessments, there were no significant differences between the groups in all outcomes immediately after treatment, and at three or at six months (Table 3).

This study aimed to evaluate whether PBM provides incremental therapeutic benefits for pain, physical function, and QoL in patients with knee OA. The findings indicate that the addition of on average 17 PBM sessions to an exercise program did not result in incremental benefits for pain, physical function, or QoL in this population.

The 2019 OARSI guidelines strongly recommended land-based exercise as a core treatment for individuals with knee OA.4 Also, there is a large body of high-quality evidence for the effectiveness of therapeutic exercises for people with knee OA.7,32,33 According to this literature, a progressive exercise program can improve muscle weakness, limited range of motion, deficient proprioception, impaired balance, and poor cardiovascular fitness in people with knee OA. An appropriate strengthening program for lower limbs enhances muscle strength, which may decrease internal knee forces, reducing pain and dysfunction.7 Other advantages of exercise prescription for this population include weight loss, emotional well-being, and improvement in overall health.8 It is noteworthy that exercise has similar effect sizes for pain intensity as pharmacologic interventions, such as nonsteroidal anti-inflammatory drugs.34 This is consistent with our findings, which show significant improvements—greater than the MCID—in pain within groups over time, which further supports the benefits of a regular exercise program.

PBM is suggested to provide an anti-inflammatory effect, decreasing the inflammatory infiltrate and the release of pro-inflammatory cytokines.35 Specifically, for chronic joint diseases, PBM is performed to reduce pain intensity and modulate inflammatory processes.36,37 But, based on inconsistent conclusions from systematic reviews38–40 and conditional recommendations from practice guidelines the clinical effectiveness of PBM for knee OA is still unclear.4

The authors of a systematic reviews with meta-analysis (9 RCTs, n = 518) found no significant differences in improvements in pain and WOMAC scores between active and placebo PBM for knee OA.38 The findings of this review (e.g. the lack of effectiveness of PBM treatment) were attributed to the heterogeneity of the methodological designs of the RCTs analyzed. In contrast, the meta-analysis by Rayegani et al.39 (14 RCTs, n = 678) indicated a significant reduction in pain at rest and upon activity and in WOMAC scores for patients who received active PBM compared to placebo PBM, however there was no significant difference in the WOMAC pain subscale between groups. Finally, Stausholm and colleagues40 meta-analyzed 22 trials (n = 1063 patients) and also reported significant improvements in pain and disability with PBM. They concluded that PBM therapy is effective in knee OA both with and without exercise therapy as cointervention. Nevertheless, the authors stated that “strength training was seemingly only used as an adjunct to PBM in two of the included trials, and thus more trials with this combination of treatments are needed.” The lack of consistency in results may be due to differences in study design and treatment parameters.

Alfredo and colleagues17 investigated PBM combined with exercises for knee OA. The participants were randomly assigned to active or placebo laser groups. PBM was performed with an energy of 3 J/point to nine points for 9 sessions, prior to the strengthening program phase, which was performed three times a week for eight weeks. The authors observed significant improvement in pain and function for both groups with no differences between groups. Also, there were no significant differences between the active and placebo PBM groups in all outcomes at the three- and six-month follow-ups.22 The limitations of the study were the small sample size (n = 20), the lack of a control group, and not having performed the PBM simultaneously with the exercise phase.17 While these limitations were addressed in the current RCT, our results also indicated no additional benefits of PBM.

Another RCT studied the effects of PBM concurrently with exercises in patients with knee OA.18 Fifty-three men were randomly allocated into one of three groups: high-intensity laser therapy and exercise; low-intensity laser therapy and exercise; and placebo low-intensity laser therapy and exercise. The PBM was applied twice a week for six weeks while the participants performed the exercise program at home three times a week for eight weeks. Pain (VAS) and knee function (WOMAC) were assessed before and immediately after treatment. In contrast to our study, active PBM in combination with exercise resulted in additional improvements in pain and function when compared with exercise alone. Limitations of this study were the absence of follow-up beyond the end of the intervention and the inclusion of males only. de Paula Gomes and colleagues19 combined PBM therapy, delivered by a cluster device of laser and light-emitting diodes, with an exercise program for knee OA. Comparing the three groups (exercise, exercise plus active PBM, and exercise plus placebo PBM) immediately after treatment, active PBM (23.55 J per session) combined with the exercise program was significantly more effective at reducing pain compared with exercise alone or exercise plus placebo PBM. However, the combination was not more efficacious in terms of WOMAC physical function, which is similar to our findings. Limitations included a small sample size (n = 20), a short-period intervention (10 sessions), and recruiting people from only one physical therapy center, which were addressed in our study.

An RCT20 investigated the efficacy of an exercise program and PBM, simultaneously and separately, for knee OA. Thus, participants were allocated into control group, laser group, exercise group, or laser plus exercise group (n = 28 per group). WOMAC questionnaire and gait measures were assessed at baseline and immediately after treatment. Only those in the exercise group had a significant improvement in WOMAC scores immediately after treatment. As an important limitation, the study presented a total dropout rate of 46.4%.

Finally, our findings are consistent with the outcomes of an RCT21 that investigated the use of PBM combined with strengthening exercises. Other than the light source, the PBM parameters in that study were very similar to our protocol, with an output power of 100 mW on continuous near-infrared wavelength and a total energy of 56 J applied per knee. Both the active PBM plus exercise and placebo PBM plus exercise groups presented an improvement in WOMAC scores at the end of treatment; however, there were no significant differences between groups – as we have observed in our groups. As mentioned by the authors,21 this observation reaffirms “the positive effects of the exercise and the lack of an extra effect of PBM” on this condition.

Major strengths of this study were the inclusion of a sham treatment to minimize bias in the PBM groups; and to the best of our knowledge, we have performed the longest therapeutic sessions period and the largest sample size of any studies conducted on this topic to date. Because the per protocol analysis states the effect of treatment assignment under adherence to the treatment protocol, and the ITT analysis provides a consistent effect estimate according to the treatment assignment, both analyses were performed.41 We only reported the most conservative approach, e.g. the ITT analysis, because results were similar.

The main limitation of this study was the high dropout rate. Most participants abandoned the trial during the interventional period because they were not treated with PBM in our study. Although in this period the dropout rate was below 20%, the 3- and 6-month follow-up assessments surpassed this rate, showing dropout rates of 30% and 45% respectively. It is worth noting that the COVID-19 pandemic contributed in 2020 to an important sample loss, as social distancing and restrictions occurred. Also, it was not possible to blind participants from the exercise group to the exercise plus active or placebo PBM groups.

In conclusion, PBM did not provide incremental therapeutic benefits over a strengthening exercise program for pain, physical function, or quality of life for our patients with knee OA.