Med Lasers 2024; 13(2): 82-89  https://doi.org/10.25289/ML.24.011
Phototherapy for osteoarthritis management: a narrative review
Andrew Padalhin1, Phil-Sang Chung2,3, Seung Hoon Woo2,3
1Beckman Laser Institute, Cheonan, Republic of Korea
2Medical Laser Research Center, Dankook University, Cheonan, Republic of Korea
3Department of Otorhinolaryngology-Head and Neck Surgery, Dankook University College of Medicine, Cheonan, Republic of Korea
Correspondence to: Andrew Padalhin
E-mail: doy_padalhin@yahoo.com
ORCID: https://orcid.org/0000-0002-3869-5720
Received: May 17, 2024; Accepted: June 17, 2024; Published online: June 21, 2024.
© Korean Society for Laser Medicine and Surgery. All rights reserved.

This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Osteoarthritis (OA) is characterized by chronic joint degeneration, particularly prevalent in the aging population. Current therapeutic options to address the symptoms of pain and reduced mobility provide limited relief and carry a significant risk of adverse effects. Thus, there is a need to explore non-invasive alternative therapies to manage OA symptoms while preventing disease progression and promoting joint tissue regeneration. This review examined studies conducted in the last 10 years to determine the potential of light-based therapy, particularly focusing on three key aspects: pain management and improvement of articular function; use of complementary light therapy; and stimulation of articular cartilage repair. Various studies have investigated the efficacy of phototherapy, particularly low-level laser therapy, in alleviating pain, improving functionality, and enhancing articular cartilage repair in OA patients. Efforts have also been made to investigate the regenerative potential of phototherapy in stimulating articular cartilage repair. Despite promising findings, several challenges remain, including the lack of standardized testing methods for evaluating the efficacy of laser therapy on OA joints and the need for further research to bridge the gap between early-stage OA in humans and the advanced stages of the disease. Nonetheless, laser therapy presents a non-invasive, well-tolerated treatment option with potential benefits for individuals with OA. Further research is warranted to optimize treatment protocols and explore potential synergistic effects with other interventions.
Keywords: Knee osteoarthritis; Laser therapy; Photobiomodulation; Pain management; Low-level light therapyKnee osteoarthritis; Laser therapy; Photobiomodulation; Pain management; Low-level light therapy
INTRODUCTION

Osteoarthritis (OA) affects the entire synovial joint, involving cartilage, synovium, and bone, leading to cartilage degeneration. The process involves two phases: a biosynthetic phase where chondrocytes attempt repair, followed by a degradative phase where enzyme activity accelerates cartilage erosion [1-4]. Biochemical studies have revealed increased synthesis of extracellular matrix (ECM) components in osteoarthritic cartilage, with chondrocytes attempting to repair damage through heightened anabolic activity. This heightened activity in OA chondrocytes may be due to improved access to proliferative factors or damage to the collagen matrix. Molecular biology techniques reveal active synthesis of cartilage proteins by OA chondrocytes, but at some point, anabolic activity can’t match catabolic activity, leading to tissue degeneration [1,2]. In OA, the balance between matrix synthesis and degradation is disrupted, with inflammatory cytokines and growth factors playing crucial roles. Chondrocytes produce and retain active and inactive forms of bone morphogenetic proteins, influencing ECM synthesis. Additionally, fragments of fibronectin and link protein stimulate matrix degradation and repair attempts [3,5].

While cell death is considered a key feature in OA cartilage degeneration, reports on the extent of apoptosis vary widely. However, recent studies suggest that apoptosis occurs at a low rate in OA cartilage, with minimal impact on the disease progression [1,2,6]. Increased chondrocyte proliferation likely leads to chondrocyte clustering, a characteristic of OA cartilage. Empty lacunae indicative of cell death are primarily found in the calcified cartilage layer, which may become detrimental in advanced OA stages. Nitric oxide (NO) has been implicated as a mediator in OA, inhibiting proteoglycan synthesis and chondrocyte response to growth factors [2,5]. Additionally, NO may contribute to apoptosis in chondrocytes and synovial cells. OA is distinguished by the development of osteophytes, which are prominent osteochondral nodules [3,7]. Mechanical and humoral factors likely contribute to their formation, arising from tissue near the chondro-synovial junction or perichondrium. Osteophytes represent new cartilage and bone development in OA joints, potentially aiding joint stabilization.

OA is a chronic and prevalent musculoskeletal disorder that significantly affects quality of life and economic encumbrance. OA could be associated with considerable physical disability, regardless of the type of the affected joints. Knee osteoarthritis (KOA), the most common type of OA, is the chronic degeneration of the articular cartilage [8]. OA is becoming more problematic as the population ages. OA is one of the most common joint disorders in the elderly and is currently getting more prevalent in certain populations with increasing age demographics [2,4,6]. Even though several conservative therapies have been developed for the management of articular joint OA, only modest treatment effects were reported for most individual interventions. Treatment is with analgesics, nonsteroidal anti-inflammatory drugs (ibuprofen and diclofenac), and COX2 inhibitors. Still, these therapies have significant risks of adverse effects, such as gastrointestinal bleeding with non-steroidal anti-inflammatory drugs and myocardial infarction with COX2 inhibitors [9]. Thus there is a need for further development of alternative non-invasive therapeutics for managing osteoarthritic symptoms which would also ideally prevent progression of joint degeneration and promote joint tissue regeneration. This paper will look into previous studies that investigated the potential of using light-based therapy for OA. Primarily focusing on three aspects to which phototherapy has been widely applied: pain management and improvement of articular function; complementary light therapy for oa; and stimulation of articular cartilage repair.

METHOD OF COLLECTION AND REVIEW OF STUDIES

For this review, studies involving photo therapy were searched through PubMed using the following keywords: osteoarthritis; laser therapy, low-level light therapy, and photobiomodulation. The search for published articles was limited to experimental, pre-clinical, and clinical research papers particularly involving KOA excluding existing review papers. Studies conducted before 2014 were no longer considered to emphasize developments and findings within the past decade. Table 1 shows the articles included in this literature review chronologically listed.

Table 1 . List of studies from the past 10 years regarding the use of phototherapy for treatment of KOA

YearType of laser therapyFinding and result
2014Gal-Al-As diode laserLLLT effectively reduced pain in KOA [10]
810/890 nm
2014Gal-Al-As diode laserResults indicate short-term application of LLLT at particular acupuncture points effectively reduced pain and improved patients’ quality of life [11]
Endolaser 476, 830 nm
applied on acupuncture points with straight leg exercise
2014Nine diode cluster laserEstablished protocol for evidenced-based practice of incorporating phototherapy with the recommended exercise program [12]
PainAwayTM, 905/875/670 nm
combined with exercise program
2022Low power laserLLLT can be effective for treating elderly osteoarthritic patients ineligible for surgery or prolotherapy [13]
Weberneedle®, 658/810 nm
knee irradiation applied through intra-articular optic fiber insert
2023PEMFT and LLLT deviceBoth PEMFT and LLLT had positive effects, with PEMFT being more effective in improving pain and mobility scores [14]
PhysioGoTM 500I, 660/808 nm
2023Laser pulse deviceIncorporating ICT, SDT, or PHOTO into a workout regimen for people with KOA doesn’t enhance the clinical advantages compared to solely engaging in exercise [15]
Ibramed, 904 nm compared to Interferential current therapy and short-wave therapy combined with an Exercise program
2023LLLT- BTL-5825SL, 830 nmAdding HILT to knee rehabilitation resulted in greater enhancements in pain relief, physical functionality, and knee-related disability compared to LLLT [16]
HILT- BTL 6000 HIL, 1,064 nm combined with knee rehabilitation exercises
2018Nine diode cluster laserExercise with phototherapy proves to be effective in alleviating pain for patients with KOA [17]
PainAway/PainCureTM,
905/875/640 nm
Combined with exercise program
20217 LED cluster, 808 nmPhysical exercise with PHOTO improved IL-10 levels and functional capacity in KOA patients [18]
Combined with exercise with inflammatory protein monitoring
2018Laser treatment, 904 nm combined with interferential current therapyProposed clinical study investigating the effect of laser therapy and interferential current therapy [19]
2018Infrared laser, 808 nm combined with ultrasoundCombination of LLLT and ultrasound therapy effectively diminishes pain and enhanced functional performance in women diagnosed with KOA [20]
2020Gal-Al-As laserEstablishing protocol study for application of laser acupuncture and electroacupuncture for KOA treatment [21]
LaserPen, 810 nm combined with electroacupuncture
2020Injectable PRP-ChitosanIn vivo andn in vitro teste proved efficacy of the thermoresponsive hydrogel containing black phosphorus for phototherapy of arthritis [22]
Thermoresponsive hydrogel with black phosphorus activated using NIR laser, 808 nm
2024Laser diode, 808/205 nmIntra-articular injection of stem cells and LLLT was effective in improving knee osteoarthritis in animal models [23]
Combined with intra-articular injection of mesenchymal stem cell
2023Knee arthroplasty postoperative treatment with Gal-Al-As laser, LASERPEN, 804 nm or Bioptron Light, 480-3,400 nmUtilizing LLLT and Bioptron light therapy may prove beneficial in managing immediate and acute knee discomfort and inflammation during initial phases of recuperation following total knee arthroplasty [24]
2014Magnetic infrared laserMIL treatment hinders cartilage degradation and promotes the proliferation of chondrocytes in rat KOA [25]
MILTA-F-8-01, 850 nm
2019Gal-Al-As LaserLaser acupuncture mitigates cartilage degradation by suppressing TNF-α and elevating extracellular matrix macromolecules in adjuvant-induced arthritis in rats [26]
Aculas-AM, 780 nm
2022Laser acupuncture, 670 nmLaser acupuncture therapy has the potential to alleviate cartilage degradation and facilitate tissue repair in postmenopausal osteoarthritic rats [27]
2019As-Ga laserLLLT maintained the glycosaminoglycan content, minimized cellular alterations, and decreased the inflammatory response [28]
BiosetTM, 830 nm
2021LED lamp array, 635 nmCombining preventative LED irradiation with antioxidants offers a novel therapeutic approach for treating early-stage OA [29]
2021NIR laser (808 nm) activated release of rapamycin and bilirubin from MOF-decorated mesoporous polydopamine (MPDA) based dual-drug delivery systemThe light activated dual-drug delivery nanoplatform was demonstrated to be anti-inflammatory and anti-apoptotic effects and is capable of restoring energy metabolism of chondrocytes preventing cartilage degeneration in animal models [30]
2023NIR laser (808 nm) triggered photocatalytic and photothermal bifunctional MOF nanozymeAdaptable multifunctional nanozymes efficiently mend damaged cartilage mitochondria and stimulate cartilage regeneration [31]

KOA, knee osteoarthritis; PEMFT, pulsed electromagnetic field therapy; LLLT, low-level laser therapy; LED, light-emitting diode; NIR, near-infrared light; MOF, metal-organic framework; ICT, interferential current therapy; SDT, shortwave diathermy therapy; PHOTO, photobiomodulation; HILT, high-intensity laser therapy; IL, interleukin; MIL, magnetic infrared laser; TNF, transforming growth factor.


PAIN MANAGEMENT AND IMPROVED ARTICULAR FUNCTION

As most cases of OA are diagnosed based on the symptomatic presentation of pain and decreased functionality, this condition is primarily addressed through management. Thus, the direct application of light-based therapy has been examined in the clinical setting. These studies include dosing experiments, alternative spots for laser application, and a comparison of phototherapy against other conventional treatments (isolated exercise, electromagnetic field, interferential current, and shortwave diathermy). Several studies have investigated the efficacy of phototherapy, particularly low-level laser therapy (LLLT), in the management of KOA. Most of these studies have noted the application of alleviating pain in injured tissues. Earlier studies [10-12] primarily focused on the effect of different wavelength and location of irradiation. One study evaluated the effectiveness of LLLT in reducing pain and improving knee function in elderly patients with KOA [10]. This study made use of a Gal-Al-As diode laser device at 810 and 890 nm wavelengths with irradiation performed on the frontal side or the backside of the knee joint respectively, 3 times for 4 weeks with a total of 46 J/cm2 total energy [10]. Another randomized controlled trial compared active LLLT applied to acupuncture points with placebo LLLT in combination with exercise demonstrating significant improvements in pain and knee function in the active LLLT group [11]. Moreover, a study conducted on elderly patients with KOA and suprapatellar bursitis found that LLLT led to a significant increase in knee joint functional status and a decrease in inflammation-related synovial fluid proteins [13]. Furthermore, a randomized controlled trial compared the effects of pulsed electromagnetic field therapy (PEMFT) and LLLT on pain and physical function in KOA patients. Although both interventions resulted in significant improvements, PEMFT was considered more effective in terms of improving both pain and physical function [14]. Additionally, a prospective randomized controlled trial comparing the inclusion of interferential current therapy, shortwave diathermy therapy, and photobiomodulation (PBM) into an exercise program for KOA indicated improvement in various outcome measures. However, there were no clinically relevant differences among these groups, suggesting similar efficacy among the treatment modalities [15]. Another approach for pain management for arthritis is cold therapy. This approach aids in reducing inflammation, swelling, and provides a numbing effect on the affected area. Currently, there are no existing studies comparing or combining light therapy with cold therapy, thus this can be an interesting subject matter for future studies. Overall, these studies suggest moderate success in the utilization of phototherapy, particularly LLLT, as a non-invasive treatment option for KOA, offering significant pain relief and functional improvement. Although the main aim of the current approach for OA focuses on pain management and increasing functionality, these have demonstrated that phototherapy can be an alternative or can be effectively combined with other treatment modalities to improve pain and functionality in osteoarthritic knee joints.

COMPLEMENTARY LIGHT THERAPY

Phototherapy can be used as a complementary treatment alongside other modalities such as physical therapy, exercise, and medication. It can enhance the overall effectiveness of treatment and provide additional benefits to patients with OA. Several studies have investigated the potential benefits of combining phototherapy with other therapies for KOA management. Based on the criteria established for the collection of relevant studies involving phototherapy and KOA, two independent studies were found to have similar results when comparing LLLT and high-intensity laser therapy (HILT) in conjunction with exercise in KOA patients. Both laser therapies were found to be effective in reducing pain and improving knee function, with HILT showing greater effectiveness. More so, both laser therapies combined with exercise were more effective than exercise alone in treating KOA [8,16]. Another study examined the clinical effects of combining either pulsed laser therapy or light-emitting diode (LED) irradiation with exercise in KOA patients, showing reductions in pain intensity and increased functionality with the active treatments [17]. Furthermore, combining PBM therapy with physical exercise was found to improve functional capacity and increase interleukin-10 levels in KOA patients [18]. Additionally, a separate study evaluated the effects of LLLT and interferential current on pain and function in mid and old-aged KOA patients, aiming to provide insights into their combined efficacy [19]. Furthermore, research on women with KOA investigated co-treatments with ultrasound and LLLT with or without therapeutic exercises resulting in similar positive results [20]. The effect of combined electroacupuncture and laser acupuncture (LA) in KOA management was also investigated resulting in relatively successful pain management leading to improved mobility [21]. Aside from combining phototherapy with recommended exercise or other energy-based treatments, it has also been applied together with biologics, biomaterial, and cell-based treatment for KOA. A novel therapeutic approach combining black phosphorus nanosheets with platelet-rich plasma and a chitosan thermoresponsive hydrogel showed promising results for rheumatic arthritis management in animal models [22]. Likewise, a study combining mesenchymal stem cell injection and LLLT in animal models of OA showed superior improvements in OA indicators compared to each therapy alone, suggesting potential for further investigation [23]. Lastly, a clinical study has also indicated that light therapy can also be used for pain and rehabilitation after joint replacement surgery. LLLT and Bioptron hyperlight therapy after knee arthroplasty showed benefits in pain reduction, range of motion improvement, and opioid reduction [24]. These studies collectively highlight the potential of combining phototherapy with other therapies for improving pain relief, function, and overall management of OA.

STIMULATION OF ARTICULAR CARTILAGE REPAIR

Although phototherapy has seen success in managing pain, relieving inflammation, and increasing the functionality of articulated joints, there have also been efforts made to employ this approach for the regeneration of articular cartilage. Several studies have explored the potential of phototherapy in protecting and stimulating the growth of cartilage tissue in OA, employing various techniques and approaches. Firstly, magnetic infrared laser (MIL) therapy showed promising results in improving knee joint function and reducing edema in OA rats. MIL treatment not only increased the presence of cartilage components but also inhibited cartilage degradation, indicating anti-inflammatory and cartilage-protective effects. Additionally, MIL therapy promoted cartilage formation and chondrocyte proliferation without adverse effects, suggesting its potential as a therapeutic option for OA [25]. Similarly, two studies explored the potential of LA [26,27]. LA demonstrated chondroprotective effects in rats with adjuvant-induced arthritis, a model for rheumatoid arthritis and early-stage postmenopausal OA. LA reduced ankle edema and inflammation-induced hyperalgesia, while also decreasing levels of proinflammatory cytokines and increasing ECM macromolecules, indicating attenuation of cartilage degradation in rheumatoid arthritis and suggesting LA as a potential therapeutic option [26]. Additionally, LA treatment increased proteoglycan content and reduced cartilage degradation, suggesting its potential as a non-pharmacological intervention for postmenopausal OA [27]. LLLT using a gallium arsenide laser at 830 nm also showed promising results in preservation of glycosaminoglycan content, reducing cellular changes, and attenuating inflammation in an experimental model of microcrystalline arthritis in rats. Laser therapy increases levels of cartilage-regenerating factors while decreasing levels of inflammatory markers, suggesting its potential to preserve cartilage integrity and reduce inflammation [28]. Aside from laser-based treatments, PBM with red LED therapy also demonstrated significant reductions in inflammation and improvements in matrix gene expression in OA-like chondrocytes under oxidative stress. Correspondingly, the combined application of LED irradiation and antioxidants presented synergistic indicating a novel therapeutic approach for early OA treatment [29]. Similar observations were also concluded from recent studies involving nanoparticles and enzymes activated with near-infrared light (NIR) lasers. A novel dual-drug delivery system incorporating a metal-organic framework-decorated mesoporous polydopamine nanoparticle loaded with rapamycin and bilirubin showed promising results in delaying cartilage degeneration in an anterior cruciate ligament transection-induced OA animal model. Upon irradiation of the injection site, the nanoparticles release rapamycin and bilirubin leading to the preservation glycosaminoglycan content, reduction of apoptosis, enhanced autophagy, and improved mitochondrial energy metabolism in chondrocytes, making it suitable for articular OA therapy [30]. Similarly, NIR sensitive nanozymes showed promising results in repairing mitochondrial function, reducing oxidative stress which in turn promoted cartilage regeneration. This approach effectively reduced OA severity and improved intracellular mitochondrial morphology in rats [31]. The aforementioned studies collectively suggest that various forms of phototherapy hold promise as a non-invasive treatment for protecting cartilage tissue, reducing inflammation, and promoting cartilage regeneration in osteoarthritic joint tissue.

SUMMARY

The majority of the studies reviewed here utilize NIR wavelengths, which are particularly effective for penetrating deep tissues. Fig. 1 summarizes the general modes of application of light therapy for pain management and treatment of KOA. Based on the articles surveyed, light therapy can be used as a treatment for OA symptoms. It generally works by boosting cellular repair through increased adenosine triphosphate production and improved mitochondrial function, while also reducing inflammation through cytokine modulation. While research is ongoing to determine optimal treatment parameters and confirm overall effectiveness, light therapy has the potential to improve pain, joint function, and mobility for people with OA. Though valuable insights have been gained from research involving joint replacements and animal models, these studies typically focus on the early and late stages of OA. Notably, there is currently no standardized method for assessing how laser therapy impacts osteoarthritic joints. There is a critical need for research that fills the gaps between these stages, including investigations into high-risk populations, early-stage OA in humans, and the progression of animal models to advanced OA. Initial studies show promise, suggesting that data from both animal models and advanced human OA are pertinent. Laser therapy, being non-invasive and well-tolerated, presents an alternative to medication or surgery, thus reducing the risk of side effects and complications. However, its efficacy may vary depending on factors such as disease severity, affected joints, and individual response. Further research is necessary to establish optimal treatment approaches and explore potential synergies with other interventions.

Figure 1. Current modes of application of light therapy for pain management and treatment of osteoarthritis. Light gets absorbed by special molecules inside the cell’s energy factories (mitochondria). When these powerhouses are activated, they make more energy for the cell, which leads to increase in reactive oxygen species and nitric oxide especially in stem cells. These cells increase their activity that which help heal damaged tissues. They also release helpful chemical messengers that talk to nearby cells and promote healing. ATP, adenosine triphosphate; ROS, reactive oxygen species; NO, nitric oxide.
CONCLUSION

In summary, the reviewed studies underscore the potential of phototherapy as a non-invasive, well-tolerated alternative for managing OA, particularly KOA. Phototherapy, especially LLLT, has shown promise in alleviating pain, improving functionality, and promoting articular cartilage repair. Furthermore, the combination of phototherapy with other treatment modalities, such as physical therapy, exercise, and biologic therapies, suggests enhanced therapeutic outcomes. Despite these promising findings, there remain challenges, including the lack of standardized assessment methods and the need for further research to optimize treatment protocols and explore synergistic effects. As the population ages and the prevalence of OA increases, further investigations into the efficacy and optimization of phototherapy could significantly impact the management of this chronic and debilitating condition.

SUPPLEMENTARY MATERIALS

None.

ACKNOWLEDGMENTS

None.

AUTHOR CONTRIBUTIONS

Conceptualization: AP. Data curation: AP. Formal analysis: AP. Funding acquisition: SHW, PSC. Investigation: all authors. Methodology: AP, SHW. Project administration: SHW, PSC. Validation: all authors. Visualization: AP. Writing–original draft: all authors. Writing–review & editing: all authors.

CONFLICT OF INTEREST

Andrew Padalhin and Phil-Sang Chung are editorial board members of the journal but was not involved in the review process of this manuscript. Otherwise, there is no conflict of interest to declare.

FUNDING

This work was supported by the Dankook Institute of Medicine & Optics in 2023. Funding was supported by the following grants: Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education (RS-2023-00247651 and NRF-2020R1A6A1A 03043283); Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health & Welfare (HI20C2088); Leading Foreign Research Institute Recruitment Program through NRF funded by the Ministry of Science and ICT (NRF-2023K1A4A3A02057280); and Korea Medical Device Development Fund grant funded by the Ministry of Science and ICT, the Ministry of Trade, Industry and Energy, the Ministry of Health & Welfare, the Ministry of Food and Drug Safety (KMDF_PR_20200901_0027-03), Republic of Korea.

DATA AVAILABILITY

None.

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Funding Information
  • Dankook Institute of Medicine & Optics
     
     
  • National Research Foundation of Korea
      10.13039/501100003725
      RS-2023-00247651, NRF-2020R1A6A1A 03043283, NRF-2023K1A4A3A02057280
  • Ministry of Education
      10.13039/501100002701
      RS-2023-00247651, NRF-2020R1A6A1A 03043283
  • Korea Health Industry Development Institute
      10.13039/501100003710
      HI20C2088
  • Ministry of Health and Welfare
      10.13039/501100003625
      HI20C2088, KMDF_PR_20200901_0027-03
  • Ministry of Science and ICT, South Korea
      10.13039/501100014188
      NRF-2023K1A4A3A02057280, KMDF_PR_20200901_0027-03
  • Ministry of Trade, Industry and Energy
      10.13039/501100003052
      KMDF_PR_20200901_0027-03
  • Ministry of Food and Drug Safety
      10.13039/501100003569
      KMDF_PR_20200901_0027-03

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