Guest Editorial
Photomedicine and Laser Surgery Volume 33, Number 3, 2015 ª Mary Ann Liebert, Inc. Pp. 121–122 DOI: 10.1089/pho.2015.9850
Can We Treat Knee Osteoarthritis with Photomedicine? O. Sahap Atik, MD
K
nee osteoarthritis is a common joint disease affecting middle-aged and elderly people. It results from a complex system of interacting mechanical, biological, and biochemical factors.1 There is strong evidence that bone marrow lesions, including dense bone islands, may cause decrease in the elasticity in subchondral bone.1,2 Leukotrienes and prostaglandins in synovial fluid play a role in the pathogenesis of osteoarthritis.3 Eventually, these previously mentioned factors may result in the initiation and progression of cartilage erosion, leading to osteoarthritis. Treatment modalities for osteoarthritis aim to decrease pain and increase range of motion, improving functional independence and quality of life. Photomedicine [earlier terms: low-level laser therapy (LLLT), laser biostimulation, photobiomodulation] is one of the nonpharmacological treatment modalities for the conservative management of osteoarthritis. It was introduced as an alternative treatment for osteoarthritis decades ago, but its beneficial effects are still controversial. Photomedicine might induce anti-inflammation, inhibiting production of inflammatory mediators. Alves et al. reported that photomedicine (LLLT) was efficient in modulating inflammatory mediators [interleukin (IL)-1b, IL-6] and inflammatory cells (macrophages and neutrophils), which correlated with the histology that showed a reduction in the inflammatory process.4 Baraba´s et al. demonstrated that a single diode laser irradiation of the synovial samples of patients with osteoarthritis can statistically significantly alter the expression of some proteins in vitro.5 Comparative analysis, conducted by dos Santos et al., of two low-level laser doses (doses of 2 and 4 J) on the expression of inflammatory mediators and on neutrophils and macrophages in acute joint inflammation showed that both laser modalities were efficient in reducing cellular inflammation and decreasing the expression of IL-1b and IL-6.6 There was more reduction in tumor necrosis factor (TNF)-a with a dose of 2 J than with a dose of 4 J. A single application with 2 J was more efficient in modulating inflammatory mediators and inflammatory cells. In a progressive osteoarthritis rabbit model, Wang et al. demonstrated that photomedicine (LLLT) plays a protective role against cartilage degradation and synovitis.7 In another study, in a osteoarthritis rat model, Moon et al. used magnetic infrared laser irradiation. They suggested that LLLT
with a static magnetic field inhibits cartilage degradation and enhances chondrocyte proliferation.8 A systematic review and meta-analysis of randomized placebo-controlled trials revealed that LLLT administered with optimal doses in an intensive 2- to 4-week treatment regimen, seemed to offer clinically relevant short-term pain relief in osteoarthritis of the knee.9 In another systematic review, the clinical effectiveness of LLLT on joint pain was investigated. The review showed that laser therapy on the joint reduced pain in patients.10 There are recent studies reporting the effects of LLLT on knee osteoarthritis. Hegedus et al. designed a study to examine the pain-relieving effect of LLLT and possible microcirculatory changes measured by thermography in patients with knee osteoarthritis. They showed that LLLT reduced pain in knee osteoarthritis and improved microcirculation in the irradiated area.11 The effect of LLLT on pain relief and functional performance in patients with chronic knee osteoarthritis was investigated by Alghadir et al.12 LLLT seemed to be an effective modality for short-term pain relief and functional improvement in patients with chronic knee osteoarthritis. Soleimanpour et al. searched the effect of LLLT on knee osteoarthritis in a prospective study.13 They concluded that LLLT was effective in reducing pain in knee osteoarthritis. A randomized double-blind placebo-controlled trial was conducted by Alfredo et al. to estimate the effects of LLLT, in combination with exercises, on pain, function, range of motion, muscular strength, and quality of life in patients with osteoarthritis of the knee.14 They suggested that LLLT, when associated with exercises, was effective in decreasing pain and improving function in patients with osteoarthritis of the knees. Keshie et al. compared the effects of LLLT and highintensity laser therapy (HILT) combined with exercise on pain relief and functional improvement in patients with knee osteoarthritis.15 They concluded that laser (either LLLT or HILT) combined with exercise was more effective than placebo laser with exercise, whereas the effect of HILT and exercise in combination was much more effective in decreasing pain and increasing functional capacity. Although many studies using laser therapy have been conducted to decrease pain and improve function, the beneficial effects of photomedicine are still controversial. This
Department of Orthopedic Surgery, Faculty of Medicine, Gazi University, Ankara, Turkey.
121
122
is probably because of lacking or heterogeneous data on laser type (HeNe, GaAs, GaAsAl), wavelength (632, 785, 810, 830, 850, 890, 904 nm), laser mode (continuous, pulsed), distance of probe from skin, irradiation points (2–8 points), duration of treatment (20 sec to 7 min), mean power out (30–800 mW), energy density (0.218–48 J cm2), irradiation energy per point (0.13–6 J), spot size (0.028– 0.0451 cm2), number of sessions, and site of application of photobiomodulation. On the other hand, until the last decade, the target tissue for the treatment of knee osteoarthritis was cartilage. Recently, this has been changed, because of new data demonstrating that the pathogenesis involves not only cartilage but also subchondral bone and other soft tissues, including synovial tissue in the joints.16,17 Do we know the answer to the question of whether photobiomodulation should be used as a drug equivalent?18 I would say, ‘‘not yet.’’ However, we already know that when laser is used in optimal dosage with optimal technique, and overtreatment is avoided, laser does not cause any damage to the treated and adjacent tissues.19 As mentioned by Lanzafame, overselling the attributes and benefits of photobiomodulation must be avoided; our path forward is best paved with careful research and methodical testing of parameters and treatment paradigms, coupled with honest evaluation of the results, both positive and negative.20
ATIK
8. 9.
10. 11.
12.
13.
14.
15.
References
1. Martel-Pelletier J, Pelletier JP. Is osteoarthritis a disease involving only cartilage or other articular tissues? Eklem Hastalik Cerrahisi 2010;21:2–14. 2. Atik OS, Tokgo¨z N. Do periarticular dense bone islands cause cartilage destruction? Eklem Hastalik Cerrahisi 2013;24:39–40. 3. Sahap Atik O. Leukotriene B4 and prostaglandin E2-like activity in synovial fluid in osteoarthritis. Prostaglandins Leukot Essent Fatty Acids 1990;39:253–254. 4. Alves AC, Vieira R, Leal-Junior E, et al. Effect of lowlevel laser therapy on the expression of inflammatory mediators and on neutrophils and macrophages in acute joint inflammation. Arthritis Res Ther 2013;15:R116. 5. Baraba´s K, Bakos J, Zeitler Z, et al. Effects of laser treatment on the expression of cytosolic proteins in the synovium of patients with osteoarthritis. Lasers Surg Med 2014;46:644–649. 6. dos Santos SA, Alves AC, Leal-Junior EC, et al. Comparative analysis of two low-level laser doses on the expression of inflammatory mediators and on neutrophils and macrophages in acute joint inflammation. Lasers Med Sci 2014;29:1051–1058. 7. Wang P, Liu C, Yang X, et al. Effects of low-level laser therapy on joint pain, synovitis, anabolic, and catabolic
16. 17. 18. 19. 20.
factors in a progressive osteoarthritis rabbit model. Lasers Med Sci 2014;29:1875–1885. Moon CH, Kwon O, Woo CH, et al. Therapeutic effect of irradiation of magnetic infrared laser on osteoarthritis rat model. Photochem Photobiol 2014;90:1150–1159. Bjordal JM, Johnson MI, Lopes-Martins RAB, Bogen B, Chow R, Ljunggren AE. Short-term efficacy of physical interventions in osteoarthritic knee pain. A systematic review and meta-analysis of randomised placebo-controlled trials. BMC Musculoskelet Disord 2007;8:51. Jang H, Lee H. Meta-analysis of pain relief effects by laser irradiation on joint areas. Photomed Laser Surg 2012;30: 405–417. Hegedus B, Viharos L, Gervain M, Galfi M. The effect of low-level laser in knee osteoarthritis: A double-blind, randomized, placebo-controlled trial. Photomed Laser Surg 2009;27:577–584. Alghadir A, Omar MTA, Al-Askar AB, Al-Muteri NK. Effect of low-level laser therapy in patients with chronic knee osteoarthritis: a single-blinded randomized clinical study. Lasers Med Sci 2014;29:749–755. Soleimanpour H, Gahramani K, Taheri R, et al., The effect of low-level laser therapy on knee osteoarthritis: prospective, descriptive study. Lasers Med Sci 2014;29:1695– 1700. Alfredo PP, Bjordal JM, Dreyer SH, et al. Efficacy of low level laser therapy associated with exercises in knee osteoarthritis: a randomized double-blind study. Clin Rehabil 2012;26:523–533. Keshie AR, Alayat MSM, Ali MME. High-intensity versus low-level laser therapy in the treatment of patients with knee osteoarthritis: a randomized controlled trial. Lasers Med Sci 2014;29:1371–1376. Castan˜eda S, Roman-Blas JA, Largo R, Herrero-Beaumont G. Subchondral bone as a key target for osteoarthritis treatment. Biochem Pharmacol 2012;83:315–323. Atik OS. Is subchondral bone the crucial point for the pathogenesis and the treatment of osteoarthritis? Eklem Hastalik Cerrahisi 2014;25:1. Karu T. Is it time to consider photobiomodulation as a drug equivalent? Photomed Laser Surg 2013;31:189–191. Atik OS. Laser does not cause osteonecrosis when properly used. Photomed Laser Surg 2013;31:45–46. Lanzafame RJ. Photobiomodulation: an enlightened path emerges. Photomed Laser Surg 2013;31:299–300.
Address correspondence to: O. Sahap Atik, MD Bugday Sokak 6/27 Kavaklidere Ankara 06700 Turkey E-mail: [email protected]
Photomedicine and Laser Surgery Volume 33, Number 3, 2015 ª Mary Ann Liebert, Inc. Pp. 121–122 DOI: 10.1089/pho.2015.9850
Can We Treat Knee Osteoarthritis with Photomedicine? O. Sahap Atik, MD
K
nee osteoarthritis is a common joint disease affecting middle-aged and elderly people. It results from a complex system of interacting mechanical, biological, and biochemical factors.1 There is strong evidence that bone marrow lesions, including dense bone islands, may cause decrease in the elasticity in subchondral bone.1,2 Leukotrienes and prostaglandins in synovial fluid play a role in the pathogenesis of osteoarthritis.3 Eventually, these previously mentioned factors may result in the initiation and progression of cartilage erosion, leading to osteoarthritis. Treatment modalities for osteoarthritis aim to decrease pain and increase range of motion, improving functional independence and quality of life. Photomedicine [earlier terms: low-level laser therapy (LLLT), laser biostimulation, photobiomodulation] is one of the nonpharmacological treatment modalities for the conservative management of osteoarthritis. It was introduced as an alternative treatment for osteoarthritis decades ago, but its beneficial effects are still controversial. Photomedicine might induce anti-inflammation, inhibiting production of inflammatory mediators. Alves et al. reported that photomedicine (LLLT) was efficient in modulating inflammatory mediators [interleukin (IL)-1b, IL-6] and inflammatory cells (macrophages and neutrophils), which correlated with the histology that showed a reduction in the inflammatory process.4 Baraba´s et al. demonstrated that a single diode laser irradiation of the synovial samples of patients with osteoarthritis can statistically significantly alter the expression of some proteins in vitro.5 Comparative analysis, conducted by dos Santos et al., of two low-level laser doses (doses of 2 and 4 J) on the expression of inflammatory mediators and on neutrophils and macrophages in acute joint inflammation showed that both laser modalities were efficient in reducing cellular inflammation and decreasing the expression of IL-1b and IL-6.6 There was more reduction in tumor necrosis factor (TNF)-a with a dose of 2 J than with a dose of 4 J. A single application with 2 J was more efficient in modulating inflammatory mediators and inflammatory cells. In a progressive osteoarthritis rabbit model, Wang et al. demonstrated that photomedicine (LLLT) plays a protective role against cartilage degradation and synovitis.7 In another study, in a osteoarthritis rat model, Moon et al. used magnetic infrared laser irradiation. They suggested that LLLT
with a static magnetic field inhibits cartilage degradation and enhances chondrocyte proliferation.8 A systematic review and meta-analysis of randomized placebo-controlled trials revealed that LLLT administered with optimal doses in an intensive 2- to 4-week treatment regimen, seemed to offer clinically relevant short-term pain relief in osteoarthritis of the knee.9 In another systematic review, the clinical effectiveness of LLLT on joint pain was investigated. The review showed that laser therapy on the joint reduced pain in patients.10 There are recent studies reporting the effects of LLLT on knee osteoarthritis. Hegedus et al. designed a study to examine the pain-relieving effect of LLLT and possible microcirculatory changes measured by thermography in patients with knee osteoarthritis. They showed that LLLT reduced pain in knee osteoarthritis and improved microcirculation in the irradiated area.11 The effect of LLLT on pain relief and functional performance in patients with chronic knee osteoarthritis was investigated by Alghadir et al.12 LLLT seemed to be an effective modality for short-term pain relief and functional improvement in patients with chronic knee osteoarthritis. Soleimanpour et al. searched the effect of LLLT on knee osteoarthritis in a prospective study.13 They concluded that LLLT was effective in reducing pain in knee osteoarthritis. A randomized double-blind placebo-controlled trial was conducted by Alfredo et al. to estimate the effects of LLLT, in combination with exercises, on pain, function, range of motion, muscular strength, and quality of life in patients with osteoarthritis of the knee.14 They suggested that LLLT, when associated with exercises, was effective in decreasing pain and improving function in patients with osteoarthritis of the knees. Keshie et al. compared the effects of LLLT and highintensity laser therapy (HILT) combined with exercise on pain relief and functional improvement in patients with knee osteoarthritis.15 They concluded that laser (either LLLT or HILT) combined with exercise was more effective than placebo laser with exercise, whereas the effect of HILT and exercise in combination was much more effective in decreasing pain and increasing functional capacity. Although many studies using laser therapy have been conducted to decrease pain and improve function, the beneficial effects of photomedicine are still controversial. This
Department of Orthopedic Surgery, Faculty of Medicine, Gazi University, Ankara, Turkey.
121
122
is probably because of lacking or heterogeneous data on laser type (HeNe, GaAs, GaAsAl), wavelength (632, 785, 810, 830, 850, 890, 904 nm), laser mode (continuous, pulsed), distance of probe from skin, irradiation points (2–8 points), duration of treatment (20 sec to 7 min), mean power out (30–800 mW), energy density (0.218–48 J cm2), irradiation energy per point (0.13–6 J), spot size (0.028– 0.0451 cm2), number of sessions, and site of application of photobiomodulation. On the other hand, until the last decade, the target tissue for the treatment of knee osteoarthritis was cartilage. Recently, this has been changed, because of new data demonstrating that the pathogenesis involves not only cartilage but also subchondral bone and other soft tissues, including synovial tissue in the joints.16,17 Do we know the answer to the question of whether photobiomodulation should be used as a drug equivalent?18 I would say, ‘‘not yet.’’ However, we already know that when laser is used in optimal dosage with optimal technique, and overtreatment is avoided, laser does not cause any damage to the treated and adjacent tissues.19 As mentioned by Lanzafame, overselling the attributes and benefits of photobiomodulation must be avoided; our path forward is best paved with careful research and methodical testing of parameters and treatment paradigms, coupled with honest evaluation of the results, both positive and negative.20
ATIK
8. 9.
10. 11.
12.
13.
14.
15.
References
1. Martel-Pelletier J, Pelletier JP. Is osteoarthritis a disease involving only cartilage or other articular tissues? Eklem Hastalik Cerrahisi 2010;21:2–14. 2. Atik OS, Tokgo¨z N. Do periarticular dense bone islands cause cartilage destruction? Eklem Hastalik Cerrahisi 2013;24:39–40. 3. Sahap Atik O. Leukotriene B4 and prostaglandin E2-like activity in synovial fluid in osteoarthritis. Prostaglandins Leukot Essent Fatty Acids 1990;39:253–254. 4. Alves AC, Vieira R, Leal-Junior E, et al. Effect of lowlevel laser therapy on the expression of inflammatory mediators and on neutrophils and macrophages in acute joint inflammation. Arthritis Res Ther 2013;15:R116. 5. Baraba´s K, Bakos J, Zeitler Z, et al. Effects of laser treatment on the expression of cytosolic proteins in the synovium of patients with osteoarthritis. Lasers Surg Med 2014;46:644–649. 6. dos Santos SA, Alves AC, Leal-Junior EC, et al. Comparative analysis of two low-level laser doses on the expression of inflammatory mediators and on neutrophils and macrophages in acute joint inflammation. Lasers Med Sci 2014;29:1051–1058. 7. Wang P, Liu C, Yang X, et al. Effects of low-level laser therapy on joint pain, synovitis, anabolic, and catabolic
16. 17. 18. 19. 20.
factors in a progressive osteoarthritis rabbit model. Lasers Med Sci 2014;29:1875–1885. Moon CH, Kwon O, Woo CH, et al. Therapeutic effect of irradiation of magnetic infrared laser on osteoarthritis rat model. Photochem Photobiol 2014;90:1150–1159. Bjordal JM, Johnson MI, Lopes-Martins RAB, Bogen B, Chow R, Ljunggren AE. Short-term efficacy of physical interventions in osteoarthritic knee pain. A systematic review and meta-analysis of randomised placebo-controlled trials. BMC Musculoskelet Disord 2007;8:51. Jang H, Lee H. Meta-analysis of pain relief effects by laser irradiation on joint areas. Photomed Laser Surg 2012;30: 405–417. Hegedus B, Viharos L, Gervain M, Galfi M. The effect of low-level laser in knee osteoarthritis: A double-blind, randomized, placebo-controlled trial. Photomed Laser Surg 2009;27:577–584. Alghadir A, Omar MTA, Al-Askar AB, Al-Muteri NK. Effect of low-level laser therapy in patients with chronic knee osteoarthritis: a single-blinded randomized clinical study. Lasers Med Sci 2014;29:749–755. Soleimanpour H, Gahramani K, Taheri R, et al., The effect of low-level laser therapy on knee osteoarthritis: prospective, descriptive study. Lasers Med Sci 2014;29:1695– 1700. Alfredo PP, Bjordal JM, Dreyer SH, et al. Efficacy of low level laser therapy associated with exercises in knee osteoarthritis: a randomized double-blind study. Clin Rehabil 2012;26:523–533. Keshie AR, Alayat MSM, Ali MME. High-intensity versus low-level laser therapy in the treatment of patients with knee osteoarthritis: a randomized controlled trial. Lasers Med Sci 2014;29:1371–1376. Castan˜eda S, Roman-Blas JA, Largo R, Herrero-Beaumont G. Subchondral bone as a key target for osteoarthritis treatment. Biochem Pharmacol 2012;83:315–323. Atik OS. Is subchondral bone the crucial point for the pathogenesis and the treatment of osteoarthritis? Eklem Hastalik Cerrahisi 2014;25:1. Karu T. Is it time to consider photobiomodulation as a drug equivalent? Photomed Laser Surg 2013;31:189–191. Atik OS. Laser does not cause osteonecrosis when properly used. Photomed Laser Surg 2013;31:45–46. Lanzafame RJ. Photobiomodulation: an enlightened path emerges. Photomed Laser Surg 2013;31:299–300.
Address correspondence to: O. Sahap Atik, MD Bugday Sokak 6/27 Kavaklidere Ankara 06700 Turkey E-mail: [email protected]
