References

    1. Heckman JD, Ryaby JP, McCabe J, Frey J, Kilcoyne RF. Acceleration of tibial fracture-healing by non-invasive, low-intensity pulsed ultrasound. J Bone Joint Surg Am. 1994;76(1):26-34.
    2. Kristiansen TK, Ryaby JP, McCabe J, Frey JJ, Roe LR. Accelerated healing of distal radial fractures with the use of specific, low-intensity ultrasound. A multicenter, prospective, randomized, double-blind, placebo-controlled study. J Bone Joint Surg Am. 1997;79(7):961-73.
    3. Nolte PA, van der Krans A, Patka P, Janssen IM, Ryaby JP, Albers GH. Low-intensity pulsed ultrasound in the treatment of nonunions. J Trauma. 2001;51(4):693-703.
    4. Bioventus LLC. Data on File, RPT-001321.
    5. Schofer MD, Block JE, Aigner J, Schmelz A. Improved healing response in delayed unions of the tibia with low-intensity pulsed ultrasound: results of a randomized sham-controlled trial. BMC Musculoskelet Disord. 2010;11(1):229. doi:10.1186/1471-2474-11-229.
    6. Zura R, Xiong Z, Einhorn T, Watson JT, Ostrum RF, Prayson MJ, Della Rocca GJ, Mehta S, McKinley T, Wang Z, Steen RG. Epidemiology of Fracture Nonunion in 18 Human Bones. JAMA Surg. 2016 Nov 16;151
    7. Lerner A, Stein H, Soudry M. Compound high-energy limb fractures with delayed union: our experience with adjuvant ultrasound stimulation (exogen). Ultrasonics. 2004;42(1-9):915-7.
    8. Hernandez RK, Do TP, Critchlow CW, Dent RE, Jick SS. Patient-related risk factors for fracture-healing complications in the United Kingdom General Practice Research Database. Acta Orthop. 2012;83(6):653-60.
    9. Cook SD, Ryaby JP, McCabe J, Frey JJ, Heckman JD, Kristiansen TK. Acceleration of tibia and distal radius fracture healing in patients who smoke. Clin Orthop Relat Res. 1997;(337):198-207.
    10. Scolaro JA, Schenker ML, Yannascoli S, Baldwin K, Mehta S, Ahn J. Cigarette smoking increases complications following fracture: a systematic review. J Bone Joint Surg Am. 2014;96(8):674-81
    11. iData Research. U.S. Market Report Suite for Orthopedic Trauma Devices: 2019. https://idataresearch.com/product/trauma-devices-market-united-states/. Last accessed July 29, 2021.
    12. Bioventus LLC. Data on file, RPT-000965.
    1. Zura R, Mehta S, Della Rocca GJ, Jones J, Steen RG. A cohort study of 4,190 patients treated with low-intensity pulsed ultrasound (LIPUS): findings in the elderly versus all patients. BMC Musculoskelet Disord. 2015;16:45. doi:10.1186/s12891-015-0498-1.
    2. Salem KH, Schemlz A. Low-intensity pulsed ultrasound shortens the treatment time in tibial distraction osteogenesis. Int Orthop. 2014;38(7):1477-82.
    3. Roussignol X, Currey C, Duparc F, Dujardin F. Indications and results for the Exogen™ ultrasound system in the management of non-union: a 59-case pilot study. Orthop Traumatol Surg Res. 2012;98(2):206-13.
    4. Dudda M, Hauser J, Muhr G, Esenwein SA. Low-intensity pulsed ultrasound as a useful adjuvant during distraction osteogenesis: a prospective, randomized controlled trial. J Trauma. 2011;71(5):1376-80.
    5. El-Mowafi H, Mohsen M. The effect of low-intensity pulsed ultrasound on callus maturation in tibial distraction osteogenesis. Int Orthop. 2005;29(2):121-4.
    6. Gold SM, Wasserman R. Preliminary results of tibial bone transports with pulsed low intensity ultrasound (EXOGEN). J Orthop Trauma. 2005;19:10-16.
    7. Mayr E. Rudzki MM, Rudzki M, Borchardt B, Häusser H, Rüter A. Does low intensity, pulsed ultrasound speed healing of scaphoid fractures? Handchir Mikrochir Plast Chir. 2000;32(2):115-22.
    8. Nolte P, Anderson R, Strauss E, et al. Heal rate of metatarsal fractures: A propensity matching study of patients treated with low-intensity pulsed ultrasound (LIPUS) vs. surgical and other treatments. Injury. 2016;47(11):2584-2590.
    9. Leung KS, Lee WS, Tsui HF, Liu PP, Cheung WH. Complex tibial fracture outcomes following treatment with low-intensity pulsed ultrasound. Ultrasound Med Biol. 2004 Mar;30(3):389-95.
    10. Tsumaki N, Kakiuchi M, Sasaki J, Ochi T, Yoshikawa H. 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(11):2399-405.
    11. Song MH, Kim T-J, Kang SH, Song H-R. Low-intensity pulsed ultrasound enhances callus consolidation in distraction osteogenesis of the tibia by the technique of lengthening over the nail procedure. BMC Musculoskeletal Disorders. 2019;20(1):108.
    12. Coughlin MJ, Smith BW, Traughber P. The evaluation of the healing rate of subtalar arthrodeses, part 2: the effect of low-intensity ultrasound stimulation. Foot Ankle Int. 2008;29(10):970-7.
    13. Gebauer D, Mayr E, Orthner E, Ryaby JP. Low-intensity pulsed ultrasound: effects on nonunions. Ultrasound Med Biol. 2005;31(10):1391-402.
    14. Kinami Y, Noda T, Ozaki T. Efficacy of low-intensity pulsed ultrasound treatment for surgically managed fresh diaphyseal fractures of the lower extremity: multi-center retrospective cohort study. J Orthop Sci. 2013;18(3):410-8.
    15. Jingushi S, Mizuno K, Matsushita T, Itoman M. Low-intensity pulsed ultrasound treatment for postoperative delayed union or nonunion of long bone fractures. J Orthop Sci. 2007;12(1):35-41.
    16. 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(2):173-8.
    17. Rutten S, Nolte PA, Guit GL, Bouman DE, Albers GH. Use of low-intensity pulsed ultrasound for posttraumatic nonunions of the tibia: a review of patients treated in the Netherlands. J Trauma. 2007;62(4):902-8.
    18. Watanabe Y, Arai Y, Takenaka N, Kobayashi M, Matsushita T. Three key factors affecting treatment results of low-intensity pulsed ultrasound for delayed unions and nonunions: instability, gap size, and atrophic nonunion. J Orthop Sci. 2013;18(5):803-10.
    19. Zura R, Della Rocca GJ, Mehta S, et al. Treatment of chronic (>1 year) fracture nonunion: heal rate in a cohort of 767 patients treated with low-intensity pulsed ultrasound (LIPUS). Injury. 2015;46(10):2036-41.
    20. Greenleaf JF, Kinnick RR, Bronk JT, Bolander ME, Ultrasound induced tissue motion during fracture treatment? Ultrasound Med Biol. 2003;26(5):S157-8.
    21. Tang CH, Yang RS, Huang TH, Lu DY, Chuang WJ, Huang TF, Fu WM. Ultrasound stimulates cyclooxygenase-2 expression and increases bone formation through integrin, focal adhesion kinase, phosphatidylinositol 3-kinase, and Akt pathway in osteoblasts, Pharmacol. 2006;69(6):2047-57. doi:10.1124/mol.105.022160.
    22. Naruse K, Sekiya H, Harada Y, et al. Prolonged endochondral bone healing in senescence is shortened by low-intensity pulsed ultrasound in a manner dependent on COX-2. Ultrasound Med Biol. 2010;36(7):1098-108. doi:10.1016/j.ultrasmedbio.2010.04.011.
    23. Azuma Y, Ito M, Harada Y, Takagi H, Ohta T, Jingushi S. 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(4):671-80.
    24. Morrison W. What to know about bone fracture repair. Last updated July 11, 2018. https://www.medicalnewstoday.com/articles/322419
    25. Romanò C, Messina J, Meani E. Low-intensity ultrasound for the treatment of infected nonunions. Quaderni di Infezioni Osteoarticolari. 1999; 83-93.
    26. Wedro B. Broken fracture (broken bone). Last updated February 2, 2020. https://www.emedicinehealth.com/bone_fracture_broken_bone/article_em.htm.
    27. General information about pain after a fracture. Accessed July 30, 2021. https://osteoporosis.ca/after-the-fracture/table-of-contents/general-information-about-pain-after-a-fracture/
    28. Brazier Y. Fractures: types, causes, symptoms, and treatment. Last updated December 14, 2017. https://www.medicalnewstoday.com/articles/319174.
    29. NYU Langone Health. Diagnosing nonhealing fractures. Accessed July 30, 2021.https://nyulangone.org/conditions/nonhealing-fractures-in-adults/diagnosis.
    30. Access Ortho. How long do fractures take to heal? How long will I be in a cast/brace? Last updated March 19, 2020. https://www.accessortho.com.au/2020/03/how-long-do-fractures-take-to-heal-how-long-will-i-be-in-a-cast-brace/.
    31. Silva JC. Bone fracture repair: procedures, risks, and healing time. Last updated July 11, 2018. https://www.medicalnewstoday.com/articles/322419.
    32. Cluett J. How bone growth stimulators work. Last updated March 29, 2020. verywellhealth.com/bone-growth-stimulator-4587797.
    33. Cook JJ, Summers NJ, Cook EA. Healing in the new millennium: bone stimulators: an overview of where we’ve been and where we may be heading. Clin Podiatr Med Surg. 2015;32(1)45-59. doi:10.1016/j.cpm.2014.09.003.
    34. Lai CH, Chen SC, Chiu LH, et al. Effects of low-intensity pulsed ultrasound, dexamethasone/TGF-ß1 and/or BMP-2 on the transcriptional expression of genes in human mesenchymal stem cells: chondrogenic vs. osteogenic differentiation. Ultrasound Med Biol. 2010;36(6):1022-33. doi:10.1016/j.ultrasmedbio.2010.03.014.
    35. Sant’Anna EF, Leven RM, Virdi AS, Sumner DR. Effect of low intensity pulsed ultrasound and BMP-2 on rat bone marrow stromal cell gene expression. J Orthop Res. 2005;23(3):646-52. doi:10.1016/j.orthres.2004.09.007.
    36. Heckman and Sarasohn-Kahn. Bulletin Hospital Joint Diseases. 1997:56(1):63-72
    37. Leighton R, Watson JT, Giannoudis P, Papakostidis C, Harrison A, Steen RG. Healing of fracture nonunions treated with low-intensity pulsed ultrasound (LIPUS): A systematic review and meta-analysis. Injury. 2017 Jul;48(7):1339-1347. 50 should start the Bioventus report section with: Bioventus LLC. Humerus nonunion claims based on EXOGEN Registry. Data on file, RPT-000396.
    38. Bioventus LLC. Humerus nonunion claims based on EXOGEN Registry. Data on file, RPT-000396.
    39. Bioventus LLC. Clavicle nonunion claims based on EXOGEN Registry. Data on file, RPT-000409.
    40. Bioventus LLC. Scaphoid nonunion claims based on EXOGEN Registry. Data on file, RPT-000398.
    41. Bioventus LLC. Radius/ulna nonunion claims based on EXOGEN Registry. Data on file, RPT-000410.
    42. Bioventus LLC. Femur nonunion claims based on EXOGEN Registry. Data on file, RPT-000395.
    43. Bioventus LLC. Hand/wrist nonunion claims based on EXOGEN Registry. Data on file, RPT-000411.
    44. Bioventus LLC. Ankle nonunion claims based on EXOGEN Registry. Data on file, RPT-000408.
    45. Bioventus LLC. Tibia nonunion claims based on EXOGEN Registry. Data on file, RPT-000391.
    46. Bioventus LLC. Metatarsal nonunion claims based on EXOGEN Registry. Data on file, RPT-000389.
    47. Bioventus LLC. Foot nonunion claims based on EXOGEN Registry. Data on file, RPT-000412.
    48. Leung KS, Cheung WH, Zhang C, Lee KM, Lo HK. Low intensity pulsed ultrasound stimulates osteogenic activity of human periosteal cells. Clin Orthop Relat Res. 2004;(418):253-9. doi:10.1097/00003086-200401000-00044.
    49. Bioventus LLC. Data on file, RPT-000368.
    50. Harrison, A. and Alt, V., 2021. Low-intensity pulsed ultrasound (LIPUS) for stimulation of bone healing – A narrative review. Injury, 52, pp.S91-S96. doi:10.1016/j.injury.2021.05.002
    51. Coords M, Breitbart E, Paglia D, et al. The effects of low-intensity pulsed ultrasound upon diabetic fracture healing. J Orthop Res. 2011;29(2):181-8.

Summary of Indications for Use
EXOGEN is indicated for the non-invasive treatment of osseous defects (excluding vertebra and skull) that includes the treatment of delayed unions, nonunions,* stress fractures and joint fusion. EXOGEN is also indicated for the acceleration of fresh fracture heal time, repair following osteotomy, repair in bone transport procedures and repair in distraction osteogenesis procedures.

There are no known contraindications for the EXOGEN device. Safety and effectiveness have not been established for individuals lacking skeletal maturity, pregnant or nursing women, patients with cardiac pacemakers, on fractures due to bone cancer, or on patients with poor blood circulation or clotting problems. Some patients may be sensitive to the ultrasound gel.

Full prescribing information can be found in product labeling, at EXOGEN.com, or by calling Bioventus Customer Service.

*A nonunion is considered to be established when the fracture site shows no visibly progressive signs of healing.