Topical non-steroidal anti-inflammatory drugs (NSAIDs) are one of the commonly used drugs in the treatment of sports injury, but their standardized and rational use lacks evidence-based medical guidance. This guideline working group selected clinically important issues, fully collected the opinions of patients and clinical staff, and discussed them with the expert group. Based on the existing literature evidence, the "clinical practice guidelines for topical NSAIDs in the treatment of sports injury" was formulated following the methods and principles of international guidelines. In this guideline, 7 clinical concerns were finally selected, and a total of 22 recommendations were formed. Including the status, indications, contraindications, efficacy, combined application, use in special populations, adverse reactions, and countermeasures of topical NSAIDs in the treatment of sports injury. The purpose of this guideline is to provide evidence for orthopedics, sports medicine, rehabilitation medicine, sports science, and other practitioners in the treatment of sports injury, to promote the more standardized and rational use of topical NSAIDs.
Citation: Chinese Society of Sports Medicine, Chinese Orthopaedic Association, Chinese Society of Physical Medicine and Rehabilitation, China Sport Science Society of Sports Medicine, China Medicine Education Association, Beijing Research Association for Chronic Diseases Control and Health Education. Clinical practice guidelines for topical NSAIDs in the treatment of sports injury (2024 edition). Chinese Journal of Evidence-Based Medicine, 2024, 24(5): 497-509. doi: 10.7507/1672-2531.202402074 Copy
1. | 于永慧. “全民健身”与“健康中国”的理论阐释和政策思考. 北京体育大学学报, 2019, 42(2): 25-35. |
2. | 朱文辉, 陈世益. 外用非甾体抗炎药(NSAIDs)治疗肌肉骨骼系统疼痛的研究进展. 中国运动医学杂志, 2016, 35(5): 506-508. |
3. | Paoloni JA, Milne C, Orchard J, et al. Non-steroidal anti-inflammatory drugs in sports medicine: guidelines for practical but sensible use. Br J Sports Med, 2009, 43(11): 863-865. |
4. | 中华医学会运动医疗分会, 外用NSAIDs疼痛治疗中国专家委员会. 外用非甾体抗炎药治疗肌肉骨骼系统疼痛的中国专家共识. 中国医学前沿杂志(电子版), 2016, 8(7): 24-27. |
5. | 曲绵域, 于长隆. 实用运动医学. 北京: 北京大学医学出版社, 2003. |
6. | Rae K, Orchard J. The orchard sports injury classification system (OSICS) version 10. Clin J Sport Med, 2007, 17(3): 201-204. |
7. | 陈世益, 冯华. 现代骨科运动医学. 上海: 复旦大学出版社, 2020. |
8. | Timpka T, Jacobsson J, Bickenbach J, et al. What is a sports injury. Sports Med, 2014, 44(4): 423-428. |
9. | Mueller-Wohlfahrt HW, Haensel L, Mithoefer K, et al. Terminology and classification of muscle injuries in sport: the Munich consensus statement. Br J Sports Med, 2013, 47(6): 342-350. |
10. | Ross AG, Donaldson A, Poulos RG. Nationwide sports injury prevention strategies: a scoping review. Scand J Med Sci Sports, 2021, 31(2): 246-264. |
11. | van Mechelen W, Hlobil H, Kemper HC. Incidence, severity, aetiology and prevention of sports injuries: a review of concepts. Sports Med, 1992, 14(2): 82-99. |
12. | 周谋望. 我国运动创伤康复的历史与展望. 中国康复医学杂志, 2019, 34(8): 885-887. |
13. | von Rosen P, Heijne A, Frohm A, et al. High injury burden in elite adolescent athletes: a 52-week prospective study. J Athl Train, 2018, 53(3): 262-270. |
14. | Moseid CH, Myklebust G, Fagerland MW, et al. The prevalence and severity of health problems in youth elite sports: a 6-month prospective cohort study of 320 athletes. Scand J Med Sci Sports, 2018, 28(4): 1412-1423. |
15. | Flood A, Waddington G, Thompson K, et al. Increased conditioned pain modulation in athletes. J Sports Sci, 2017, 35(11): 1066-1072. |
16. | 李志刚, 万滋衡, 梁莹. 社区人群业余体育活动中运动损伤的调查与分析. 中国医药导刊, 2010, 12(6): 1097-1098. |
17. | Christopher S, Tadlock BA, Veroneau BJ, et al. Epidemiological profile of pain and non-steroid anti-inflammatory drug use in collegiate athletes in the United States. BMC Musculoskelet Disord, 2020, 21(1): 561. |
18. | Hunter DJ, Bierma-Zeinstra S. Osteoarthritis. Lancet, 2019, 393(10182): 1745-1759. |
19. | 中华医学会骨科学分会关节外科学组, 中国医师协会骨科医师分会骨关节炎学组, 国家老年疾病临床医学研究中心(湘雅医院), 等. 中国骨关节炎诊疗指南(2021年版). 中华骨科杂志, 2021, 41(18): 1291-1314. |
20. | Cui A, Li H, Wang D, et al. Global, regional prevalence, incidence and risk factors of knee osteoarthritis in population-based studies. EClinicalMedicine, 2020, 26: 29-30. |
21. | Feucht CL, Patel DR. Analgesics and anti-inflammatory medications in sports: use and abuse. Pediatr Clin North Am, 2010, 57(3): 751-774. |
22. | Shah AK, Wei G, Lanman RC, et al. Percutaneous absorption of ketoprofen from different anatomical sites in man. Pharm Res, 1996, 13(1): 168-172. |
23. | Weiler JM. Medical modifiers of sports injury. The use of nonsteroidal anti-inflammatory drugs (NSAIDs) in sports soft-tissue injury. Clin Sports Med, 1992, 11(3): 625-644. |
24. | Derry S, Wiffen PJ, Kalso EA, et al. Topical analgesics for acute and chronic pain in adults - an overview of Cochrane Reviews. Cochrane Database Syst Rev, 2017, (5): CD008609. |
25. | Warner DC, Schnepf G, Barrett MS, et al. Prevalence, attitudes, and behaviors related to the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in student athletes. J Adolesc Health, 2002, 30(3): 150-153. |
26. | Holmes N, Cronholm PF, Duffy AJ, et al. Nonsteroidal anti-inflammatory drug use in collegiate football players. Clin J Sport Med, 2013, 23(4): 283-286. |
27. | McPherson ML, Cimino NM. Topical NSAID formulations. Pain Med, 2013, (14 Suppl 1): S35-S39. |
28. | Galer BS. All topical NSAIDs not created equal--understanding topical analgesic drug formulations. Pain, 2008, 139(1): 237-238. |
29. | Gorski T, Cadore EL, Pinto SS, et al. Use of NSAIDs in triathletes: prevalence, level of awareness and reasons for use. Br J Sports Med, 2011, 45(2): 85-90. |
30. | Choi E, Nahm FS, Han WK, et al. Topical agents: a thoughtful choice for multimodal analgesia. Korean J Anesthesiol, 2020, 73(5): 384-393. |
31. | Zeng C, Doherty M, Persson MSM, et al. Comparative efficacy and safety of acetaminophen, topical and oral non-steroidal anti-inflammatory drugs for knee osteoarthritis: evidence from a network meta-analysis of randomized controlled trials and real-world data. Osteoarthritis Cartilage, 2021, 29(9): 1242-1251. |
32. | Roberts MS, Cheruvu HS, Mangion SE, et al. Topical drug delivery: history, percutaneous absorption, and product development. Adv Drug Deliv Rev, 2021, 177: 113929. |
33. | Beetge E, du Plessis J, Müller DG, et al. The influence of the physicochemical characteristics and pharmacokinetic properties of selected NSAID's on their transdermal absorption. Int J Pharm, 2000, 193(2): 261-264. |
34. | Leppert W, Malec-Milewska M, Zajaczkowska R, et al. Transdermal and topical drug administration in the treatment of pain. Molecules, 2018, 23(3): 681. |
35. | Kienzler JL, Gold M, Nollevaux F. Systemic bioavailability of topical diclofenac sodium gel 1% versus oral diclofenac sodium in healthy volunteers. J Clin Pharmacol, 2010, 50(1): 50-61. |
36. | Hagen M, Baker M. Skin penetration and tissue permeation after topical administration of diclofenac. Curr Med Res Opin, 2017, 33(9): 1623-1634. |
37. | Figueras A, Capellà D, Castel JM, et al. Spontaneous reporting of adverse drug reactions to non-steroidal anti-inflammatory drugs. A report from the Spanish System of Pharmacovigilance, including an early analysis of topical and enteric-coated formulations. Eur J Clin Pharmacol, 1994, 47(4): 297-303. |
38. | Rannou F, Pelletier JP, Martel-Pelletier J. Efficacy and safety of topical NSAIDs in the management of osteoarthritis: evidence from real-life setting trials and surveys. Semin Arthritis Rheum, 2016, 45(4 Suppl): S18-S21. |
39. | Barkin RL. Topical nonsteroidal anti-inflammatory drugs: the importance of drug, delivery, and therapeutic outcome. Am J Ther, 2015, 22(5): 388-407. |
40. | Diaz RL, Gardeazabal J, Manrique P, et al. Greater allergenicity of topical ketoprofen in contact dermatitis confirmed by use. Contact Dermatitis, 2006, 54(5): 239-243. |
41. | Plaza-Serón Mdel C, Ayuso P, Pérez-Sánchez N, et al. Copy number variation in ALOX5 and PTGER1 is associated with NSAIDs-induced urticaria and/or angioedema. Pharmacogenet Genomics, 2016, 26(6): 280-287. |
42. | Laidlaw TM, Cahill KN. Current knowledge and management of hypersensitivity to aspirin and NSAIDs. J Allergy Clin Immunol Pract, 2017, 5(3): 537-545. |
43. | Sitenga GL, Ing EB, Van Dellen RG, et al. Asthma caused by topical application of ketorolac. Ophthalmology, 1996, 103(6): 890-892. |
44. | 陈耀龙, 杨克虎, 王小钦, 等. 中国制订/修订临床诊疗指南的指导原则(2022版). 中华医学杂志, 2022, 102(10): 697-703. |
45. | Guyatt G, Oxman AD, Akl EA, et al. GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol, 2011, 64(4): 383-394. |
46. | Chen Y, Yang K, Marušic A, et al. A reporting tool for practice guidelines in health care: the RIGHT statement. Ann Intern Med, 2017, 166(2): 128-132. |
47. | Huang X, Lin J, Demner-Fushman D. Evaluation of PICO as a knowledge representation for clinical questions. AMIA Annu Symp Proc, 2006, 2006: 359-363. |
48. | Diamond IR, Grant RC, Feldman BM, et al. Defining consensus: a systematic review recommends methodologic criteria for reporting of Delphi studies. J Clin Epidemiol, 2014, 67(4): 401-409. |
49. | Derry S, Moore RA, Gaskell H, et al. Topical NSAIDs for acute musculoskeletal pain in adults. Cochrane Database Syst Rev, 2015, (6): CD007402. |
50. | Derry S, Conaghan P, Da Silva JA, et al. Topical NSAIDs for chronic musculoskeletal pain in adults. Cochrane Database Syst Rev, 2016, (4): CD007400. |
51. | Deng ZH, Zeng C, Yang Y, et al. Topical diclofenac therapy for osteoarthritis: a meta-analysis of randomized controlled trials. Clin Rheumatol, 2016, 35(5): 1253-1261. |
52. | Zeng C, Wei J, Persson MSM, et al. Relative efficacy and safety of topical non-steroidal anti-inflammatory drugs for osteoarthritis: a systematic review and network meta-analysis of randomised controlled trials and observational studies. Br J Sports Med, 2018, 52(10): 642-650. |
53. | Mu R, Bao CD, Chen ZW, et al. Efficacy and safety of loxoprofen hydrogel patch versus loxoprofen tablet in patients with knee osteoarthritis: a randomized controlled non-inferiority trial. Clin Rheumatol, 2016, 35(1): 165-173. |
54. | Altman RD, Dreiser RL, Fisher CL, et al. Diclofenac sodium gel in patients with primary hand osteoarthritis: a randomized, double-blind, placebo-controlled trial. J Rheumatol, 2009, 36(9): 1991-1999. |
55. | Bannuru RR, Osani MC, Vaysbrot EE, et al. OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthritis Cartilage, 2019, 27(11): 1578-1589. |
56. | Abdulla A, Adams N, Bone M, et al. Guidance on the management of pain in older people. Age Ageing, 2013, (42 Suppl 1): i1-i57. |
57. | Kolasinski SL, Neogi T, Hochberg MC, et al. 2019 American College of Rheumatology/Arthritis Foundation guideline for the management of osteoarthritis of the hand, hip, and knee. Arthritis Care Res (Hoboken), 2020, 72(2): 149-162. |
58. | Bruyère O, Honvo G, Veronese N, et al. An updated algorithm recommendation for the management of knee osteoarthritis from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO). Semin Arthritis Rheum, 2019, 49(3): 337-350. |
59. | Arden NK, Perry TA, Bannuru RR, et al. Non-surgical management of knee osteoarthritis: comparison of ESCEO and OARSI 2019 guidelines. Nat Rev Rheumatol, 2021, 17(1): 59-66. |
60. | Rafanan BS, Valdecañas BF, Lim BP, et al. Consensus recommendations for managing osteoarthritic pain with topical NSAIDs in Asia-Pacific. Pain Manag, 2018, 8(2): 115-128. |
61. | Wiffen PJ, Xia J. Systematic review of topical diclofenac for the treatment of acute and chronic musculoskeletal pain. Curr Med Res Opin, 2020, 36(4): 637-650. |
62. | Serinken M, Eken C, Tunay K, et al. Ketoprofen gel improves low back pain in addition to IV dexketoprofen: a randomized placebo-controlled trial. Am J Emerg Med, 2016, 34(8): 1458-1461. |
63. | Predel HG, Giannetti B, Pabst H, et al. Efficacy and safety of diclofenac diethylamine 1.16% gel in acute neck pain: a randomized, double-blind, placebo-controlled study. BMC Musculoskelet Disord, 2013, 14: 250. |
64. | van den Bekerom MPJ, Sjer A, Somford MP, et al. Non-steroidal anti-inflammatory drugs (NSAIDs) for treating acute ankle sprains in adults: benefits outweigh adverse events. Knee Surg Sports Traumatol Arthrosc, 2015, 23(8): 2390-2399. |
65. | Serinken M, Eken C, Elicabuk H. Topical ketoprofen versus placebo in treatment of acute ankle sprain in the emergency department. Foot Ankle Int, 2016, 37(9): 989-993. |
66. | Vuurberg G, Hoorntje A, Wink LM, et al. Diagnosis, treatment and prevention of ankle sprains: update of an evidence-based clinical guideline. Br J Sports Med, 2018, 52(15): 956. |
67. | Spacca G, Cacchio A, Forgács A, et al. Analgesic efficacy of a lecithin-vehiculated diclofenac epolamine gel in shoulder periarthritis and lateral epicondylitis: a placebo-controlled, multicenter, randomized, double-blind clinical trial. Drugs Exp Clin Res, 2005, 31(4): 147-154. |
68. | Pattanittum P, Turner T, Green S, et al. Non-steroidal anti-inflammatory drugs (NSAIDs) for treating lateral elbow pain in adults. Cochrane Database Syst Rev, 2013, (5): CD003686. |
69. | Burnham R, Gregg R, Healy P, et al. The effectiveness of topical diclofenac for lateral epicondylitis. Clin J Sport Med, 1998, 8(2): 78-81. |
70. | May JJ, Lovell G, Hopkins WG. Effectiveness of 1% diclofenac gel in the treatment of wrist extensor tenosynovitis in long distance kayakers. J Sci Med Sport, 2007, 10(1): 59-65. |
71. | Mazières B, Rouanet S, Guillon Y, et al. Topical ketoprofen patch in the treatment of tendinitis: a randomized, double blind, placebo controlled study. J Rheumatol, 2005, 32(8): 1563-1570. |
72. | Ginsberg F, Famaey JP. Double-blind, randomized crossover study of the percutaneous efficacy and tolerability of a topical indomethacin spray versus placebo in the treatment of tendinitis. J Int Med Res, 1991, 19(2): 131-136. |
73. | Bussin E, Cairns B, Gerschman T, et al. Topical diclofenac vs placebo for the treatment of chronic Achilles tendinopathy: a randomized controlled clinical trial. PLoS One, 2021, 16(3): e0247663. |
74. | Jurca T, Józsa L, Suciu R, et al. Formulation of topical dosage forms containing synthetic and natural anti-inflammatory agents for the treatment of rheumatoid arthritis. Molecules, 2020, 26(1): 24. |
75. | Nagai N, Yoshioka C, Ito Y. Topical therapies for rheumatoid arthritis by gel ointments containing indomethacin nanoparticles in adjuvant-induced arthritis rat. J Oleo Sci, 2015, 64(3): 337-346. |
76. | Rolf C, Engström B, Beauchard C, et al. Intra-articular absorption and distribution of ketoprofen after topical plaster application and oral intake in 100 patients undergoing knee arthroscopy. Rheumatology (Oxford), 1999, 38(6): 564-567. |
77. | Bukhari KA, Khan IA, Ishaq S, et al. Formulation and evaluation of diclofenac potassium gel in sports injuries with and without phonophoresis. Gels, 2022, 8(10): 612. |
78. | Cagnie B, Vinck E, Rimbaut S, et al. Phonophoresis versus topical application of ketoprofen: comparison between tissue and plasma levels. Phys Ther, 2003, 83(8): 707-712. |
79. | Wetzel D, Menke W, Dieter R, et al. Escin/diethylammonium salicylate/heparin combination gels for the topical treatment of acute impact injuries: a randomised, double blind, placebo controlled, multicentre study. Br J Sports Med, 2002, 36(3): 183-188. |
80. | Sethi V, Van der Laan L, Gupta S, et al. Perspectives of healthcare professionals towards combination use of oral paracetamol and topical non-steroidal inflammatory drugs in managing mild-to-moderate pain for osteoarthritis in a clinical setting: an exploratory study. J Pain Res, 2022, 15: 2263-2272. |
81. | Sethi V, Qin L, Cox E, et al. Model-based meta-analysis supporting the combination of acetaminophen and topical diclofenac in acute pain: a therapy for mild-to-moderate osteoarthritis pain. Pain Ther, 2024, 13(1): 145-159. |
82. | Serinken M, Eken C, Tünay K, et al. Topical ketoprofen versus placebo in children presenting with ankle sprain to the emergency department: a randomized controlled study. Pediatr Emerg Care, 2020, 36(8): e447-e450. |
83. | Underwood M, Ashby D, Carnes D, et al. Topical or oral ibuprofen for chronic knee pain in older people. The TOIB study. Health Technol Assess, 2008, 12(22): iii-iv, ix-155. |
84. | Underwood M, Ashby D, Cross P, et al. Advice to use topical or oral ibuprofen for chronic knee pain in older people: randomised controlled trial and patient preference study. BMJ, 2008, 336(7636): 138-142. |
85. | Makris UE, Kohler MJ, Fraenkel L. Adverse effects of topical nonsteroidal antiinflammatory drugs in older adults with osteoarthritis: a systematic literature review. J Rheumatol, 2010, 37(6): 1236-1243. |
86. | Carnes D, Anwer Y, Underwood M, et al. Influences on older people's decision making regarding choice of topical or oral NSAIDs for knee pain: qualitative study. BMJ, 2008, 336(7636): 142-145. |
87. | Klinger G, Stahl B, Fusar-Poli P, et al. Antipsychotic drugs and breastfeeding. Pediatr Endocrinol Rev, 2013, 10(3): 308-317. |
88. | Bloor M, Paech M. Nonsteroidal anti-inflammatory drugs during pregnancy and the initiation of lactation. Anesth Analg, 2013, 116(5): 1063-1075. |
89. | Evans JM, McMahon AD, McGilchrist MM, et al. Topical non-steroidal anti-inflammatory drugs and admission to hospital for upper gastrointestinal bleeding and perforation: a record linkage case-control study. BMJ, 1995, 311(6996): 22-26. |
90. | Schjerning AM, McGettigan P, Gislason G. Cardiovascular effects and safety of (non-aspirin) NSAIDs. Nat Rev Cardiol, 2020, 17(9): 574-584. |
91. | Lin TC, Solomon DH, Tedeschi SK, et al. Comparative risk of cardiovascular outcomes between topical and oral nonselective nsaids in Taiwanese patients with rheumatoid arthritis. J Am Heart Assoc, 2017, 6(11): e006874. |
92. | Delungahawatta T, Pokharel A, Paz R, et al. Topical diclofenac-induced hepatotoxicity. J Community Hosp Intern Med Perspect, 2023, 13(3): 108-112. |
93. | de Abajo FJ, Montero D, Madurga M, et al. Acute and clinically relevant drug-induced liver injury: a population based case-control study. Br J Clin Pharmacol, 2004, 58(1): 71-80. |
94. | Katsuno T, Togo K, Ebata N, et al. Burden of renal events associated with nonsteroidal anti-inflammatory drugs in patients with osteoarthritis and chronic low back pain: a retrospective database study. Pain Ther, 2021, 10(1): 443-455. |
95. | Andrews PA, Sampson SA. Topical non-steroidal drugs are systemically absorbed and may cause renal disease. Nephrol Dial Transplant, 1999, 14(1): 187-189. |
- 1. 于永慧. “全民健身”与“健康中国”的理论阐释和政策思考. 北京体育大学学报, 2019, 42(2): 25-35.
- 2. 朱文辉, 陈世益. 外用非甾体抗炎药(NSAIDs)治疗肌肉骨骼系统疼痛的研究进展. 中国运动医学杂志, 2016, 35(5): 506-508.
- 3. Paoloni JA, Milne C, Orchard J, et al. Non-steroidal anti-inflammatory drugs in sports medicine: guidelines for practical but sensible use. Br J Sports Med, 2009, 43(11): 863-865.
- 4. 中华医学会运动医疗分会, 外用NSAIDs疼痛治疗中国专家委员会. 外用非甾体抗炎药治疗肌肉骨骼系统疼痛的中国专家共识. 中国医学前沿杂志(电子版), 2016, 8(7): 24-27.
- 5. 曲绵域, 于长隆. 实用运动医学. 北京: 北京大学医学出版社, 2003.
- 6. Rae K, Orchard J. The orchard sports injury classification system (OSICS) version 10. Clin J Sport Med, 2007, 17(3): 201-204.
- 7. 陈世益, 冯华. 现代骨科运动医学. 上海: 复旦大学出版社, 2020.
- 8. Timpka T, Jacobsson J, Bickenbach J, et al. What is a sports injury. Sports Med, 2014, 44(4): 423-428.
- 9. Mueller-Wohlfahrt HW, Haensel L, Mithoefer K, et al. Terminology and classification of muscle injuries in sport: the Munich consensus statement. Br J Sports Med, 2013, 47(6): 342-350.
- 10. Ross AG, Donaldson A, Poulos RG. Nationwide sports injury prevention strategies: a scoping review. Scand J Med Sci Sports, 2021, 31(2): 246-264.
- 11. van Mechelen W, Hlobil H, Kemper HC. Incidence, severity, aetiology and prevention of sports injuries: a review of concepts. Sports Med, 1992, 14(2): 82-99.
- 12. 周谋望. 我国运动创伤康复的历史与展望. 中国康复医学杂志, 2019, 34(8): 885-887.
- 13. von Rosen P, Heijne A, Frohm A, et al. High injury burden in elite adolescent athletes: a 52-week prospective study. J Athl Train, 2018, 53(3): 262-270.
- 14. Moseid CH, Myklebust G, Fagerland MW, et al. The prevalence and severity of health problems in youth elite sports: a 6-month prospective cohort study of 320 athletes. Scand J Med Sci Sports, 2018, 28(4): 1412-1423.
- 15. Flood A, Waddington G, Thompson K, et al. Increased conditioned pain modulation in athletes. J Sports Sci, 2017, 35(11): 1066-1072.
- 16. 李志刚, 万滋衡, 梁莹. 社区人群业余体育活动中运动损伤的调查与分析. 中国医药导刊, 2010, 12(6): 1097-1098.
- 17. Christopher S, Tadlock BA, Veroneau BJ, et al. Epidemiological profile of pain and non-steroid anti-inflammatory drug use in collegiate athletes in the United States. BMC Musculoskelet Disord, 2020, 21(1): 561.
- 18. Hunter DJ, Bierma-Zeinstra S. Osteoarthritis. Lancet, 2019, 393(10182): 1745-1759.
- 19. 中华医学会骨科学分会关节外科学组, 中国医师协会骨科医师分会骨关节炎学组, 国家老年疾病临床医学研究中心(湘雅医院), 等. 中国骨关节炎诊疗指南(2021年版). 中华骨科杂志, 2021, 41(18): 1291-1314.
- 20. Cui A, Li H, Wang D, et al. Global, regional prevalence, incidence and risk factors of knee osteoarthritis in population-based studies. EClinicalMedicine, 2020, 26: 29-30.
- 21. Feucht CL, Patel DR. Analgesics and anti-inflammatory medications in sports: use and abuse. Pediatr Clin North Am, 2010, 57(3): 751-774.
- 22. Shah AK, Wei G, Lanman RC, et al. Percutaneous absorption of ketoprofen from different anatomical sites in man. Pharm Res, 1996, 13(1): 168-172.
- 23. Weiler JM. Medical modifiers of sports injury. The use of nonsteroidal anti-inflammatory drugs (NSAIDs) in sports soft-tissue injury. Clin Sports Med, 1992, 11(3): 625-644.
- 24. Derry S, Wiffen PJ, Kalso EA, et al. Topical analgesics for acute and chronic pain in adults - an overview of Cochrane Reviews. Cochrane Database Syst Rev, 2017, (5): CD008609.
- 25. Warner DC, Schnepf G, Barrett MS, et al. Prevalence, attitudes, and behaviors related to the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in student athletes. J Adolesc Health, 2002, 30(3): 150-153.
- 26. Holmes N, Cronholm PF, Duffy AJ, et al. Nonsteroidal anti-inflammatory drug use in collegiate football players. Clin J Sport Med, 2013, 23(4): 283-286.
- 27. McPherson ML, Cimino NM. Topical NSAID formulations. Pain Med, 2013, (14 Suppl 1): S35-S39.
- 28. Galer BS. All topical NSAIDs not created equal--understanding topical analgesic drug formulations. Pain, 2008, 139(1): 237-238.
- 29. Gorski T, Cadore EL, Pinto SS, et al. Use of NSAIDs in triathletes: prevalence, level of awareness and reasons for use. Br J Sports Med, 2011, 45(2): 85-90.
- 30. Choi E, Nahm FS, Han WK, et al. Topical agents: a thoughtful choice for multimodal analgesia. Korean J Anesthesiol, 2020, 73(5): 384-393.
- 31. Zeng C, Doherty M, Persson MSM, et al. Comparative efficacy and safety of acetaminophen, topical and oral non-steroidal anti-inflammatory drugs for knee osteoarthritis: evidence from a network meta-analysis of randomized controlled trials and real-world data. Osteoarthritis Cartilage, 2021, 29(9): 1242-1251.
- 32. Roberts MS, Cheruvu HS, Mangion SE, et al. Topical drug delivery: history, percutaneous absorption, and product development. Adv Drug Deliv Rev, 2021, 177: 113929.
- 33. Beetge E, du Plessis J, Müller DG, et al. The influence of the physicochemical characteristics and pharmacokinetic properties of selected NSAID's on their transdermal absorption. Int J Pharm, 2000, 193(2): 261-264.
- 34. Leppert W, Malec-Milewska M, Zajaczkowska R, et al. Transdermal and topical drug administration in the treatment of pain. Molecules, 2018, 23(3): 681.
- 35. Kienzler JL, Gold M, Nollevaux F. Systemic bioavailability of topical diclofenac sodium gel 1% versus oral diclofenac sodium in healthy volunteers. J Clin Pharmacol, 2010, 50(1): 50-61.
- 36. Hagen M, Baker M. Skin penetration and tissue permeation after topical administration of diclofenac. Curr Med Res Opin, 2017, 33(9): 1623-1634.
- 37. Figueras A, Capellà D, Castel JM, et al. Spontaneous reporting of adverse drug reactions to non-steroidal anti-inflammatory drugs. A report from the Spanish System of Pharmacovigilance, including an early analysis of topical and enteric-coated formulations. Eur J Clin Pharmacol, 1994, 47(4): 297-303.
- 38. Rannou F, Pelletier JP, Martel-Pelletier J. Efficacy and safety of topical NSAIDs in the management of osteoarthritis: evidence from real-life setting trials and surveys. Semin Arthritis Rheum, 2016, 45(4 Suppl): S18-S21.
- 39. Barkin RL. Topical nonsteroidal anti-inflammatory drugs: the importance of drug, delivery, and therapeutic outcome. Am J Ther, 2015, 22(5): 388-407.
- 40. Diaz RL, Gardeazabal J, Manrique P, et al. Greater allergenicity of topical ketoprofen in contact dermatitis confirmed by use. Contact Dermatitis, 2006, 54(5): 239-243.
- 41. Plaza-Serón Mdel C, Ayuso P, Pérez-Sánchez N, et al. Copy number variation in ALOX5 and PTGER1 is associated with NSAIDs-induced urticaria and/or angioedema. Pharmacogenet Genomics, 2016, 26(6): 280-287.
- 42. Laidlaw TM, Cahill KN. Current knowledge and management of hypersensitivity to aspirin and NSAIDs. J Allergy Clin Immunol Pract, 2017, 5(3): 537-545.
- 43. Sitenga GL, Ing EB, Van Dellen RG, et al. Asthma caused by topical application of ketorolac. Ophthalmology, 1996, 103(6): 890-892.
- 44. 陈耀龙, 杨克虎, 王小钦, 等. 中国制订/修订临床诊疗指南的指导原则(2022版). 中华医学杂志, 2022, 102(10): 697-703.
- 45. Guyatt G, Oxman AD, Akl EA, et al. GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol, 2011, 64(4): 383-394.
- 46. Chen Y, Yang K, Marušic A, et al. A reporting tool for practice guidelines in health care: the RIGHT statement. Ann Intern Med, 2017, 166(2): 128-132.
- 47. Huang X, Lin J, Demner-Fushman D. Evaluation of PICO as a knowledge representation for clinical questions. AMIA Annu Symp Proc, 2006, 2006: 359-363.
- 48. Diamond IR, Grant RC, Feldman BM, et al. Defining consensus: a systematic review recommends methodologic criteria for reporting of Delphi studies. J Clin Epidemiol, 2014, 67(4): 401-409.
- 49. Derry S, Moore RA, Gaskell H, et al. Topical NSAIDs for acute musculoskeletal pain in adults. Cochrane Database Syst Rev, 2015, (6): CD007402.
- 50. Derry S, Conaghan P, Da Silva JA, et al. Topical NSAIDs for chronic musculoskeletal pain in adults. Cochrane Database Syst Rev, 2016, (4): CD007400.
- 51. Deng ZH, Zeng C, Yang Y, et al. Topical diclofenac therapy for osteoarthritis: a meta-analysis of randomized controlled trials. Clin Rheumatol, 2016, 35(5): 1253-1261.
- 52. Zeng C, Wei J, Persson MSM, et al. Relative efficacy and safety of topical non-steroidal anti-inflammatory drugs for osteoarthritis: a systematic review and network meta-analysis of randomised controlled trials and observational studies. Br J Sports Med, 2018, 52(10): 642-650.
- 53. Mu R, Bao CD, Chen ZW, et al. Efficacy and safety of loxoprofen hydrogel patch versus loxoprofen tablet in patients with knee osteoarthritis: a randomized controlled non-inferiority trial. Clin Rheumatol, 2016, 35(1): 165-173.
- 54. Altman RD, Dreiser RL, Fisher CL, et al. Diclofenac sodium gel in patients with primary hand osteoarthritis: a randomized, double-blind, placebo-controlled trial. J Rheumatol, 2009, 36(9): 1991-1999.
- 55. Bannuru RR, Osani MC, Vaysbrot EE, et al. OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthritis Cartilage, 2019, 27(11): 1578-1589.
- 56. Abdulla A, Adams N, Bone M, et al. Guidance on the management of pain in older people. Age Ageing, 2013, (42 Suppl 1): i1-i57.
- 57. Kolasinski SL, Neogi T, Hochberg MC, et al. 2019 American College of Rheumatology/Arthritis Foundation guideline for the management of osteoarthritis of the hand, hip, and knee. Arthritis Care Res (Hoboken), 2020, 72(2): 149-162.
- 58. Bruyère O, Honvo G, Veronese N, et al. An updated algorithm recommendation for the management of knee osteoarthritis from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO). Semin Arthritis Rheum, 2019, 49(3): 337-350.
- 59. Arden NK, Perry TA, Bannuru RR, et al. Non-surgical management of knee osteoarthritis: comparison of ESCEO and OARSI 2019 guidelines. Nat Rev Rheumatol, 2021, 17(1): 59-66.
- 60. Rafanan BS, Valdecañas BF, Lim BP, et al. Consensus recommendations for managing osteoarthritic pain with topical NSAIDs in Asia-Pacific. Pain Manag, 2018, 8(2): 115-128.
- 61. Wiffen PJ, Xia J. Systematic review of topical diclofenac for the treatment of acute and chronic musculoskeletal pain. Curr Med Res Opin, 2020, 36(4): 637-650.
- 62. Serinken M, Eken C, Tunay K, et al. Ketoprofen gel improves low back pain in addition to IV dexketoprofen: a randomized placebo-controlled trial. Am J Emerg Med, 2016, 34(8): 1458-1461.
- 63. Predel HG, Giannetti B, Pabst H, et al. Efficacy and safety of diclofenac diethylamine 1.16% gel in acute neck pain: a randomized, double-blind, placebo-controlled study. BMC Musculoskelet Disord, 2013, 14: 250.
- 64. van den Bekerom MPJ, Sjer A, Somford MP, et al. Non-steroidal anti-inflammatory drugs (NSAIDs) for treating acute ankle sprains in adults: benefits outweigh adverse events. Knee Surg Sports Traumatol Arthrosc, 2015, 23(8): 2390-2399.
- 65. Serinken M, Eken C, Elicabuk H. Topical ketoprofen versus placebo in treatment of acute ankle sprain in the emergency department. Foot Ankle Int, 2016, 37(9): 989-993.
- 66. Vuurberg G, Hoorntje A, Wink LM, et al. Diagnosis, treatment and prevention of ankle sprains: update of an evidence-based clinical guideline. Br J Sports Med, 2018, 52(15): 956.
- 67. Spacca G, Cacchio A, Forgács A, et al. Analgesic efficacy of a lecithin-vehiculated diclofenac epolamine gel in shoulder periarthritis and lateral epicondylitis: a placebo-controlled, multicenter, randomized, double-blind clinical trial. Drugs Exp Clin Res, 2005, 31(4): 147-154.
- 68. Pattanittum P, Turner T, Green S, et al. Non-steroidal anti-inflammatory drugs (NSAIDs) for treating lateral elbow pain in adults. Cochrane Database Syst Rev, 2013, (5): CD003686.
- 69. Burnham R, Gregg R, Healy P, et al. The effectiveness of topical diclofenac for lateral epicondylitis. Clin J Sport Med, 1998, 8(2): 78-81.
- 70. May JJ, Lovell G, Hopkins WG. Effectiveness of 1% diclofenac gel in the treatment of wrist extensor tenosynovitis in long distance kayakers. J Sci Med Sport, 2007, 10(1): 59-65.
- 71. Mazières B, Rouanet S, Guillon Y, et al. Topical ketoprofen patch in the treatment of tendinitis: a randomized, double blind, placebo controlled study. J Rheumatol, 2005, 32(8): 1563-1570.
- 72. Ginsberg F, Famaey JP. Double-blind, randomized crossover study of the percutaneous efficacy and tolerability of a topical indomethacin spray versus placebo in the treatment of tendinitis. J Int Med Res, 1991, 19(2): 131-136.
- 73. Bussin E, Cairns B, Gerschman T, et al. Topical diclofenac vs placebo for the treatment of chronic Achilles tendinopathy: a randomized controlled clinical trial. PLoS One, 2021, 16(3): e0247663.
- 74. Jurca T, Józsa L, Suciu R, et al. Formulation of topical dosage forms containing synthetic and natural anti-inflammatory agents for the treatment of rheumatoid arthritis. Molecules, 2020, 26(1): 24.
- 75. Nagai N, Yoshioka C, Ito Y. Topical therapies for rheumatoid arthritis by gel ointments containing indomethacin nanoparticles in adjuvant-induced arthritis rat. J Oleo Sci, 2015, 64(3): 337-346.
- 76. Rolf C, Engström B, Beauchard C, et al. Intra-articular absorption and distribution of ketoprofen after topical plaster application and oral intake in 100 patients undergoing knee arthroscopy. Rheumatology (Oxford), 1999, 38(6): 564-567.
- 77. Bukhari KA, Khan IA, Ishaq S, et al. Formulation and evaluation of diclofenac potassium gel in sports injuries with and without phonophoresis. Gels, 2022, 8(10): 612.
- 78. Cagnie B, Vinck E, Rimbaut S, et al. Phonophoresis versus topical application of ketoprofen: comparison between tissue and plasma levels. Phys Ther, 2003, 83(8): 707-712.
- 79. Wetzel D, Menke W, Dieter R, et al. Escin/diethylammonium salicylate/heparin combination gels for the topical treatment of acute impact injuries: a randomised, double blind, placebo controlled, multicentre study. Br J Sports Med, 2002, 36(3): 183-188.
- 80. Sethi V, Van der Laan L, Gupta S, et al. Perspectives of healthcare professionals towards combination use of oral paracetamol and topical non-steroidal inflammatory drugs in managing mild-to-moderate pain for osteoarthritis in a clinical setting: an exploratory study. J Pain Res, 2022, 15: 2263-2272.
- 81. Sethi V, Qin L, Cox E, et al. Model-based meta-analysis supporting the combination of acetaminophen and topical diclofenac in acute pain: a therapy for mild-to-moderate osteoarthritis pain. Pain Ther, 2024, 13(1): 145-159.
- 82. Serinken M, Eken C, Tünay K, et al. Topical ketoprofen versus placebo in children presenting with ankle sprain to the emergency department: a randomized controlled study. Pediatr Emerg Care, 2020, 36(8): e447-e450.
- 83. Underwood M, Ashby D, Carnes D, et al. Topical or oral ibuprofen for chronic knee pain in older people. The TOIB study. Health Technol Assess, 2008, 12(22): iii-iv, ix-155.
- 84. Underwood M, Ashby D, Cross P, et al. Advice to use topical or oral ibuprofen for chronic knee pain in older people: randomised controlled trial and patient preference study. BMJ, 2008, 336(7636): 138-142.
- 85. Makris UE, Kohler MJ, Fraenkel L. Adverse effects of topical nonsteroidal antiinflammatory drugs in older adults with osteoarthritis: a systematic literature review. J Rheumatol, 2010, 37(6): 1236-1243.
- 86. Carnes D, Anwer Y, Underwood M, et al. Influences on older people's decision making regarding choice of topical or oral NSAIDs for knee pain: qualitative study. BMJ, 2008, 336(7636): 142-145.
- 87. Klinger G, Stahl B, Fusar-Poli P, et al. Antipsychotic drugs and breastfeeding. Pediatr Endocrinol Rev, 2013, 10(3): 308-317.
- 88. Bloor M, Paech M. Nonsteroidal anti-inflammatory drugs during pregnancy and the initiation of lactation. Anesth Analg, 2013, 116(5): 1063-1075.
- 89. Evans JM, McMahon AD, McGilchrist MM, et al. Topical non-steroidal anti-inflammatory drugs and admission to hospital for upper gastrointestinal bleeding and perforation: a record linkage case-control study. BMJ, 1995, 311(6996): 22-26.
- 90. Schjerning AM, McGettigan P, Gislason G. Cardiovascular effects and safety of (non-aspirin) NSAIDs. Nat Rev Cardiol, 2020, 17(9): 574-584.
- 91. Lin TC, Solomon DH, Tedeschi SK, et al. Comparative risk of cardiovascular outcomes between topical and oral nonselective nsaids in Taiwanese patients with rheumatoid arthritis. J Am Heart Assoc, 2017, 6(11): e006874.
- 92. Delungahawatta T, Pokharel A, Paz R, et al. Topical diclofenac-induced hepatotoxicity. J Community Hosp Intern Med Perspect, 2023, 13(3): 108-112.
- 93. de Abajo FJ, Montero D, Madurga M, et al. Acute and clinically relevant drug-induced liver injury: a population based case-control study. Br J Clin Pharmacol, 2004, 58(1): 71-80.
- 94. Katsuno T, Togo K, Ebata N, et al. Burden of renal events associated with nonsteroidal anti-inflammatory drugs in patients with osteoarthritis and chronic low back pain: a retrospective database study. Pain Ther, 2021, 10(1): 443-455.
- 95. Andrews PA, Sampson SA. Topical non-steroidal drugs are systemically absorbed and may cause renal disease. Nephrol Dial Transplant, 1999, 14(1): 187-189.