The evidence of low-intensity pulsed ultrasound for in vitro, animal and human fracture healing

British Medical Bulletin

Volumn 100, Issue 1, 2011, Pages 39-57

  De Albornoz, Pilar Martinez ^a   Khanna, Anil ^b   Longo, Umile Giuseppe ^c   Forriol, Francisco ^d   Maffulli, Nicola ^e  

^a Hospital FREMAP   (Spain)

^b KEELE UNIVERSITY SCHOOL OF MEDICINE   (United Kingdom)

^c UNIVERSITY CAMPUS BIO MEDICO   (Italy)

^d UNIVERSIDAD SAN PABLO CEU   (Spain)

^e QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

Author keywords

fracture healing; low intensity pulsed ultrasound; physical stimulation therapy

Indexed keywords

ARTICLE; BONE DEFECT; FRACTURE HEALING; FRACTURE NONUNION; HUMAN; IN VITRO STUDY; LEG LENGTHENING; LOW INTENSITY PULSED ULTRASOUND; LOW LEVEL LASER THERAPY; NONHUMAN; PRIORITY JOURNAL; STIMULATION; TREATMENT RESPONSE;

ANIMALS; DISEASE MODELS, ANIMAL; EVIDENCE-BASED MEDICINE; FRACTURE HEALING; FRACTURES, BONE; HUMANS; TREATMENT OUTCOME; ULTRASONIC THERAPY;

EID: 83255189668     PISSN: 00071420     EISSN: 14718391     Source Type: Journal    
DOI: 10.1093/bmb/ldr006     Document Type: Article

References (85)

1. Praemer A, Furner S, Rice DP. Musculoskeletal Conditions in the United States. Park Ridge, IL: The American Academy of Orthopaedic Surgeons, 1992,85-124.
2. Einhorn TA. Enhancement of fracture-healing. J Bone Joint Surg Am 1995;77-A:940-56.
3. Rubin C, Bolander M, Ryaby JP et al. The use of low-intensity ultrasound to accelerate the healing of fractures. J Bone Joint Surg Am 2001;83:259-270. (Pubitemid 32163721)
4. Mayr E, Rudzki MM, Rudzki M et al. Does low intensity, pulsed ultrasound speed healing of scaphoid fractures? Handchir Mikrochir Plast Chir 2000;32:115-22. (Pubitemid 30337181)
5. Pigozzi F, Moneta MR, Giombini A et al. Low-intensity pulsed ultrasound in the conservative treatment of pseudoarthrosis. J Sports Med Phys Fitness 2004;44:173-8. (Pubitemid 38931603)
6. Lu H, Qin L, Cheung W et al. Low-intensity pulsed ultrasound accelerated bone-tendon junction healing through regulation of vascular endothelial growth factor expression and cartilage formation. Ultrasound Med Biol 2008;34:1248-60. (Pubitemid 352010463)
7. Lu H, Qin L, Fok P et al. Low-intensity pulsed ultrasound accelerates bone-tendon junction healing: a partial patellectomy model in rabbits. Am J Sports Med 2006;34:1287-96. (Pubitemid 44050215)
8. Lirani-Galvão AP, Jorgetti V, da Silva OL. Comparative study of how low-level laser therapy and low-intensity pulsed ultrasound affect bone repair in rats. Photomed Laser Surg 2006;24:735-40. (Pubitemid 46106712)
9. Spadaro JA, Albanese SA. Application of low-intensity ultrasound to growing bone in rats. Ultrasound Med Biol 1998;24:567-73. (Pubitemid 28252451)
10. Malizos KN, Papachristos AA, Protopappas VC et al. Transosseous application of lowintensity ultrasound for the enhancement and monitoring of fracture healing process in a sheep osteotomy model. Bone 2006;38:530-9.
11. Speed CA. Therapeutic ultrasound in soft tissue lesions. Rheumatology (Oxford) 2001;40:1331-6.
12. Baker KG, Robertson VJ, Duck FA. A review of therapeutic ultrasound: bio-physical effects. Phys Ther 2001;81:1351-8.
13. Wolff J. Das Gaesetz der Transformation der Knochen. Berlin: A. Hirchwald, 1892.
14. Dyson M. Therapeutic applications of ultrasound. In: Nyhorg WL, Ziskin MC. (ed). Biological Effects of Ultrasound. New York: Churchill Livingstone, 1985, 121-133.
15. Duarte LR. The stimulation of bone growth by ultrasound. Arch Orthop Trauma Surg 1983;101:153-159. (Pubitemid 13092928)
16. Xavier CAM, Duarte LR. Treatment of nonunions by ultrasound stimulation: first clinical applications. Read at the Annual Meeting of the American Academy of Orthopaedic Surgeons, San Francisco, California, 25 January, 1987.
17. Pilla AA, Mont MA, Nasser PR et al. Non-invasive low-intensity pulsed ultrasound accelerates bone healing in the rabbit. J Orthop Trauma 1990;4:246-253.
18. Wang SJ, Lewallen DG, Bolander ME et al. Low intensity ultrasound treatment increases strength in a rat femoral fracture model. J Orthop Res 1994;12:40-7. (Pubitemid 24070787)
19. Azuma Y, Ito M, Harada Y et al. Low-intensity pulsed ultrasound accelerates rat femoral fracture healing by acting on the various cellular reactions in the fracture callus. J Bone Miner Res 2001;16:671-80. (Pubitemid 32230595)
20. Hantes ME, Mavrodontidis AN, Zalavras CG et al. Low intensity transosseous ultrasound accelerates osteotomy healing in a sheep fracture model. J Bone Joint Surg Am 2004;86-A:2275-82. (Pubitemid 39349964)
21. Shakouri K, Eftekharsadat B, Oskuie MR et al. Effect of low-intensity pulsed ultrasound on fracture callus mineral density and flexural strength in rabbit tibial fresh fracture. J Orthop Sci 2010;15:240-4.
22. Takikawa S, Matsui N, Kokubu T et al. Low-intensity pulsed ultrasound initiates bone healing in rat nonunion fracture model. J Ultrasound Med 2001;20:197-205. (Pubitemid 32185196)
23. Lu CC, Liu YC, Cheng YM et al. Augmentation of tendon-bone interface healing with lowintensity pulsed ultrasound. Orthopedics 2009;32:173.
24. McClure SR, Miles K, Vansickle D et al. The effect of variable waveform low-intensity pulsed ultrasound in a fourth metacarpal osteotomy gap model in horses. Ultrasound Med Biol 2010;36:1298-305.
25. Yang KH, Park SJ. Stimulation of fracture healing in a canine ulna full-defect model by lowintensity pulsed ultrasound. Yonsei Med J 2001;42:503-8.
26. Chan CW, Qin L, Lee KM et al. Dose-dependent effect of low-intensity pulsed ultrasound on callus formation during rapid distraction osteogenesis. J Orthop Res 2006;24:2072-9. (Pubitemid 44717969)
27. Uglow MG, Peat RA, Hile MS et al. Low-intensity ultrasound stimulation in distraction osteogenesis in rabbits. Clin Orthop Relat Res 2003;417:303-12. (Pubitemid 37499537)
28. Coords M, Breitbart E, Paglia D et al. The effects of low-intensity pulsed ultrasound upon diabetic fracture healing. J Orthop Res. 2011;29:181-8.
29. Gebauer GP, Lin SS, Beam HA et al. Low-intensity pulsed ultrasound increases the fracture callus strength in diabetic BB Wistar rats but does not affect cellular proliferation. J Orthop Res 2002;20:587-92. (Pubitemid 34461019)
30. Li J, Waugh LJ, Hui SL et al. Low-intensity pulsed ultrasound and nonsteroidal antiinflammatory drugs have opposing effects during stress fracture repair. J Orthop Res 2007;25:1559-67. (Pubitemid 350293803)
31. Perry MJ, Parry LK, Burton VJ et al. Ultrasound mimics the effect of mechanical loading on bone formation in vivo on rat ulnae. Med Eng Phys 2009;31:42-7.
32. Ryaby JT. Clinical effects of electromagnetic and electric fields on fracture healing. Clin Orthop Relat Res 1998;355:S205-15.
33. Parvizi J, Wu CC, Lewallen DG et al. Low-intensity ultrasound stimulates proteoglycan synthesis in rat chondrocytes by increasing aggrecan gene expression. J Orthop Res 1999;17:488-94. (Pubitemid 29383607)
34. Li JK, Lin JC, Liu HC et al. Comparison of ultrasound and electromagnetic field effects on osteoblast growth. Ultrasound Med Biol 2006;32:769-75.
35. Wu CC, Lewallen DG, Bolander ME et al. Exposure to low intensity ultrasound stimulates aggrecan gene expression by cultured chondrocytes. Trans Orthop Res Soc 1996;21:622.
36. Reher P, Harris M, Whiteman M et al. Ultrasound stimulates nitric oxide and prostaglandin E2 production by human osteoblasts. Bone 2002;31:236-41. (Pubitemid 34754453)
37. Ryaby JT, Mathew J, Duarte-Alves P. Low intensity pulsed ultrasound affects adenylate cyclase and TGF-ß synthesis in osteoblastic cells. Trans Orthop Res Soc 1992;17:590.
38. Takayama T, Suzuki N, Ikeda K et al. Low-intensity pulsed ultrasound stimulates osteogenic differentiation in ROS 17/2.8 cells. Life Sci 2007;80:965-71. (Pubitemid 46186424)
39. Leskinen JJ, Karjalainen HM, Olkku A et al. Genome-wide microarray analysis of MG-63 osteoblastic cells exposed to ultrasound. Bone 2008;43:348-54.
40. Watanuki M, Kishimoto KN, Kotajima S et al. Effect of low-intensity pulsed ultrasound on scaffold-free ectopic bone formation in skeletal muscle. Ups J Med Sci 2009;114:242-8.
41. Naruse K, Mikuni-Takagaki Y, Urabe K et al. Therapeutic ultrasound induces periosteal ossification without apparent changes in cartilage. Connect Tissue Res 2009;50:55-63.
42. Sant'Anna EF, Leven RM, Virdi AS et al. Effect of low intensity pulsed ultrasound and BMP-2 on rat bone marrow stromal cell gene expression. J Orthop Res 2005;23:646-52. (Pubitemid 40631338)
43. Leung KS, Lee WS, Tsui HF et al. Complex tibial fracture outcomes following treatment with low-intensity pulsed ultrasound. Ultrasound Med Biol 2004;30:389-95.
44. Choffie M, Duarte LR. Low-intensity pulsed ultrasound and effects on ununited fractures. Read at the Orthopaedic Health Conference, University Hospital, University of Sao Paulo, Brazil, June 15, 1994.
45. Knoch GH, Klug W. Stimulation of Fracture Healing with Ultrasound. Translated by Telger TC. New York: Springer, 1991.
46. Dijkman BG, Sprague S, Bhandari M. Low-intensity pulsed ultrasound: nonunions. Indian J Orthop 2009;43:141-8.
47. Griffin XL, Costello I, Costa ML. The role of low intensity pulsed ultrasound therapy in the management of acute fractures: a systematic review. J Trauma 2008;65:1446-52.
48. Walker NA, Denegar CR, Preische J. Low-intensity pulsed ultrasound and pulsed electromagnetic field in the treatment of tibial fractures: a systematic review. J Athl Train 2007;42:530-5. (Pubitemid 351377902)
49. Heckman JD, Ryaby JP, McCabe J et al. Acceleration of tibial fracture-healing by noninvasive, low-intensity pulsed ultrasound. J Bone Joint Surg Am 1994;76-A:26-34. (Pubitemid 24081801)
50. Kristiansen TK, Ryaby JP, McCabe J et al. Accelerated healing of distal radial fractures with the use of specific, low-intensity ultrasound. A multicenter, prospective, randomized, doubleblind, placebo-controlled study. J Bone Joint Surg Am 1997;79-A:961-73. (Pubitemid 27310566)
51. Heckman JD, Sarasohn-Kahn J. The economics of treating tibia fractures. The cost of delayed unions. Bull Hosp Joint Dis 1997;56:63-72.
52. Food and Drug Administration. TaIk Paper. Rockville, MD: Food and Drug Administration, United States Department of Health and Human Services, 12 October 1994.
53. Busse JW, Bhandari M, Kulkarni AV et al. The effect of low-intensity pulsed ultrasound therapy on time to fracture healing: a meta-analysis. Can Med Assoc J 2002;166:437-41. (Pubitemid 34164092)
54. Busse JW, Kaur J, Mollon B et al. Low intensity pulsed ultrasonography for fractures: systematic review of randomised controlled trials. BMJ 2009;338:b351.
55. Watanabe Y, Matsushita T, Bhandari M et al. Ultrasound for fracture healing: current evidence. J Orthop Trauma 2010;24(Suppl. 1):S56-61.
56. Mundi R, Petis S, Kaloty R et al. Low-intensity pulsed ultrasound: Fracture healing. Indian J Orthop 2009;43:132-40.
57. Lubbert PH, van der Rijt RH, Hoorntje LE et al. Low-intensity pulsed ultrasound (LIPUS) in fresh clavicle fractures: a multi-centre double blind randomised controlled trial. Injury 2008;39:1444-52.
58. Rue JP, Armstrong DW III, Frassica FJ et al. The effect of pulsed ultrasound in the treatment of tibial stress fractures. Orthopedics 2004;27:1192-5. (Pubitemid 39549595)
59. Emami A, Petrén-Mallmin M, Larsson S. No effect of low-intensity ultrasound on healing time of intramedullary fixed tibial fractures. J Orthop Trauma 1999;13:252-7.
60. Handolin L, Kiljunen V, Arnala I et al. The effect of low intensity ultrasound and bioabsorbable self-reinforced poly-L-lactide screw fixation on bone in lateral malleolar fractures. Arch Orthop Trauma Surg 2005;125:317-21. (Pubitemid 40895352)
61. Gebauer D, Mayr E, Orthner E et al. Low-intensity pulsed ultrasound: effects on nonunions. Ultrasound Med Biol 2005;31:1391-402. (Pubitemid 41434056)
62. Lerner A, Stein H, Soudry M. Compound high-energy limb fractures with delayed union: our experience with adjuvant ultrasound stimulation (Exogen). Ultrasonics 2004;42:915-7.
63. Nolte PA, van der Krans A, Patka P et al. Low-intensity pulsed ultrasound in the treatment of nonunions. J Trauma 2001;51:693-702. (Pubitemid 33029286)
64. Mayr E, Frankel V, Ruter A. Ultrasound-an alternative healing method for nonunions? Arch Orthop Trauma Surg 2000;120:1-8. (Pubitemid 30009177)
65. Rutten S, Nolte PA, Korstjens CM et al. Low-intensity pulsed ultrasound increases bone volume, osteoid thickness and mineral apposition rate in the area of fracture healing in patients with a delayed union of the osteotomized fibula. Bone 2008;43:348-54.
66. Gebauer D, Correll J. Pulsed low-intensity ultrasound: a new salvage procedure for delayed unions and nonunions after leg lengthening in children. J Pediatr Orthop 2005;25:750-4. (Pubitemid 41546410)
67. El-Mowafi H, Mohsen M. The effect of low-intensity pulsed ultrasound on callus maturation in tibial distraction osteogenesis. Int Orthop 2005;29:121-4. (Pubitemid 40558562)
68. Tsumaki N, Kakiuchi M, Sasaki J et al. Low-intensity pulsed ultrasound accelerates maturation of callus in patients treated with opening-wedge high tibial osteotomy by hemicallotasis. J Bone Joint Surg Am 2004;86-A:2399-405. (Pubitemid 39473078)
69. Gold SM, Wasserman R. Preliminary results of tibial bone transports with pulsed low intensity ultrasound. J Orthop Trauma 2005;19:10-6. (Pubitemid 40309432)
70. Silverstein P. Smoking and wound healing. Am J Med 1992;93:225-245.
71. Cook SD, Ryaby JP, McCabe J et al. Acceleration of tibia and distal radius fracture healing in patients who smoke. Clin Orthop Relat Res 1997;337:198-207. (Pubitemid 27172065)
72. Binderman I, Zor U, Kaye AM et al. The transduction of mechanical force into biochemical events in bone cells may involve activation of phospholipase A2. Calcif Tissue Internat 1988;42:261-66.
73. Rubin C, Gross T, Qin YX et al. Differentiation of the bone-tissue remodeling response to axial and torsional loading in the turkey ulna. J Bone Joint Surg 1996;78-A:1523-33. (Pubitemid 26357524)
74. Wang FS, Kuo YR, Wang CJ et al. Nitric oxide mediates ultrasound-induced hypoxia-inducible factor-1a activation and vascular endothelial growth factor-A expression in human osteoblasts. Bone 2004;35:114-23.
75. Rawool NM, Goldberg BB, Forsberg F et al. Power Doppler assessment of vascular changes during fracture treatment with low-intensity ultrasound. J Ultrasound Med 2003;22:145-53. (Pubitemid 36143088)
76. Yang KH, Parvizi J, Wang SJ et al. Exposure to low intensity ultrasound increases aggrecan gene expression in a rat femur fracture model. J Orthop Res 1996;14:802-9. (Pubitemid 26376526)
77. Parvizi J, Parpura V, Greenleaf JF et al. Calcium signaling is required for ultrasoundstimulated aggrecan synthesis by rat chondrocytes. J Orthop Res 2002;20:51-7. (Pubitemid 34071421)
78. Yang KH, Wang SJ, Lewallen DG et al. Low intensity ultrasound stimulates fracture healing in rat model: biomechanical and gene expression analysis. Trans Orthop Res Soc 1994;19:519.
79. Barker KG, Robertson VJ, Duck FA. A review of therapeutic ultrasound: bio-physical effects. Phy Ther 2001;81:1351-8. (Pubitemid 32619718)
80. Jansen JH, Jahr H, Verhaar JA et al. Stretch-induced modulation of matrix metalloproteinases in mineralizing osteoblasts via extracellular signal-regulated kinase-1/2. J Orthop Res 2006;24:1480-8. (Pubitemid 44083264)
81. Warden SJ, Fuchs RK, Kessler CK et al. Ultrasound produced by a conventional therapeutic ultrasound unit accelerates fracture repair. Phys Ther 2006;86:1118-27. (Pubitemid 44148063)
82. Yang RS, Lin WL, Chen YZ et al. Regulation by ultrasound treatment on the integrin expression and differentiation of osteoblasts. Bone 2005;36:276-83.
83. Tang CH, Yang RS, Huang TH et al. Ultrasound stimulates cyclooxygenase-2 expression and increases bone formation through integrin, focal adhesion kinase, phosphatidylinositol 3-kinase, and Akt pathway in osteoblasts. Mol Pharmacol 2006;69:2047-57.
84. Bandow K, Nishikawa Y, Ohnishi T et al. Low-intensity pulsed ultrasound (LIPUS) induces RANKL, MCP-1, and MIP-1beta expression in osteoblasts through the angiotensin II type 1 receptor. J Cell Physiol 2007;211:392-8. (Pubitemid 46580093)
85. Mukai S, Ito H, Nakagawa Y et al. Transforming growth factor-beta1 mediates the effects of low-intensity pulsed ultrasound in chondrocytes. Ultrasound Med Biol 2005;31:1713-21. (Pubitemid 41774690)