Journal of Korean Dental Science

Korean Academy of Dental Science (대한치의학회)
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Polydeoxyribonucleotide, as a Novel Approach for the Management of Medication-Related Osteonecrosis of the Jaw: A Preliminary Observational Study

  • Jung, Junho (Department of Oral and Maxillofacial Surgery, School of Dentistry, Kyung Hee University) ;
  • Lim, Hae Soo (E-TOP Dental Clinic) ;
  • Lee, Deok-Won (Department of Oral and Maxillofacial Surgery, School of Dentistry, Kyung Hee University)
  • Received : 2018.11.19
  • Accepted : 2018.12.28
  • Published : 2018.12.30
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Abstract

Purpose: Polydeoxyribonucleotide (PDRN), consisting of a mixture of deoxyribonucleotide polymers, has been suggested to have anti-inflammatory effects and enhance angiogenesis as an adenosine $A_{2A}$ receptor agonist. The aim of this study was to report the effectiveness of PDRN as an adjuvant therapy after surgical debridement in MRONJ (medication-related osteonecrosis of the jaw) patients. Materials and Methods: Five patients (1 male, 4 females, age 65~79 years) who were diagnosed with MRONJ stage 2 or 3 underwent surgical debridement and PDRN mucosal injection. After surgical debridement, patients were subject to daily injection with 1 ml of PDRN around the surgical wound for 14 days. Result: The patients' symptoms gradually disappeared. The surgical wound uneventfully healed, and no recurrence was observed during the follow-up period. Conclusion: Although further studies are required, the present study first describes the possibility of PDRN as a useful option for MRONJ treatment.

Keywords

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Fig. 1. Clinical photographs showing surgical wounds. (A) Preoperative photograph. (B) Immediate postoperative. (C) Ten days postoperative. (D) One-month postoperative. (E) Six months postoperative.

Table 1. Demographic data of the patients and their follow­up result

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References

  1. Ruggiero SL, Dodson TB, Fantasia J, Goodday R, Aghaloo T, Mehrotra B, O'Ryan F; American Association of Oral and Maxillofacial Surgeons. American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw--2014 update. J Oral Maxillofac Surg. 2014; 72: 1938-56. https://doi.org/10.1016/j.joms.2014.04.031
  2. Bodem JP, Schaal C, Kargus S, Saure D, Mertens C, Engel M, Hoffmann J, Freudlsperger C. Surgical management of bisphosphonate-related osteonecrosis of the jaw stages II and III. Oral Surg Oral Med Oral Pathol Oral Radiol. 2016; 121: 367-72. https://doi.org/10.1016/j.oooo.2015.10.033
  3. Khan AA, Morrison A, Hanley DA, Felsenberg D, McCauley LK, O'Ryan F, Reid IR, Ruggiero SL, Taguchi A, Tetradis S, Watts NB, Brandi ML, Peters E, Guise T, Eastell R, Cheung AM, Morin SN, Masri B, Cooper C, Morgan SL, Obermayer-Pietsch B, Langdahl BL, Al Dabagh R, Davison KS, Kendler DL, Sandor GK, Josse RG, Bhandari M, El Rabbany M, Pierroz DD, Sulimani R, Saunders DP, Brown JP, Compston J; International Task Force on Osteonecrosis of the Jaw. Diagnosis and management of osteonecrosis of the jaw: a systematic review and international consensus. J Bone Miner Res. 2015; 30: 3-23. https://doi.org/10.1002/jbmr.2405
  4. Nisi M, La Ferla F, Karapetsa D, Gennai S, Ramaglia L, Graziani F, Gabriele M. Conservative surgical management of patients with bisphosphonaterelated osteonecrosis of the jaws: a series of 120 patients. Br J Oral Maxillofac Surg. 2016; 54: 930-5. https://doi.org/10.1016/j.bjoms.2016.06.015
  5. Weber JB, Camilotti RS, Ponte ME. Efficacy of laser therapy in the management of bisphosphonaterelated osteonecrosis of the jaw (BRONJ): a systematic review. Lasers Med Sci. 2016; 31: 1261-72. https://doi.org/10.1007/s10103-016-1929-4
  6. Freiberger JJ, Padilla-Burgos R, McGraw T, Suliman HB, Kraft KH, Stolp BW, Moon RE, Piantadosi CA. What is the role of hyperbaric oxygen in the management of bisphosphonate-related osteonecrosis of the jaw: a randomized controlled trial of hyperbaric oxygen as an adjunct to surgery and antibiotics. J Oral Maxillofac Surg. 2012; 70: 1573-83. https://doi.org/10.1016/j.joms.2012.04.001
  7. Owosho AA, Estilo CL, Huryn JM, Yom SK. Pentoxifylline and tocopherol in the management of cancer patients with medication-related osteonecrosis of the jaw: an observational retrospective study of initial case series. Oral Surg Oral Med Oral Pathol Oral Radiol. 2016; 122: 455-9. https://doi.org/10.1016/j.oooo.2016.06.019
  8. Jung J, Yoo HY, Kim GT, Lee JW, Lee YA, Kim DY, Kwon YD. Short-term teriparatide and recombinant human bone morphogenetic protein-2 for regenerative approach to medication-related osteonecrosis of the jaw: a preliminary study. J Bone Miner Res. 2017; 32: 2445-52. https://doi.org/10.1002/jbmr.3237
  9. Norholt SE, Hartlev J. Surgical treatment of osteonecrosis of the jaw with the use of platelet-rich fibrin: a prospective study of 15 patients. Int J Oral Maxillofac Surg. 2016; 45: 1256-60. https://doi.org/10.1016/j.ijom.2016.04.010
  10. Han JH, Jung J, Hwang L, Ko IG, Nam OH, Kim MS, Lee JW, Choi BJ, Lee DW. Anti-inflammatory effect of polydeoxyribonucleotide on zoledronic acid-pretreated and lipopolysaccharide-stimulated RAW 264.7 cells. Exp Ther Med. 2018; 16: 400-5.
  11. Galeano M, Bitto A, Altavilla D, Minutoli L, Polito F, Calo M, Lo Cascio P, Stagno d'Alcontres F, Squadrito F. Polydeoxyribonucleotide stimulates angiogenesis and wound healing in the genetically diabetic mouse. Wound Repair Regen. 2008; 16: 208-17. https://doi.org/10.1111/j.1524-475X.2008.00361.x
  12. Bitto A, Polito F, Irrera N, D'Ascola A, Avenoso A, Nastasi G, Campo GM, Micali A, Bagnato G, Minutoli L, Marini H, Rinaldi M, Squadrito F, Altavilla D. Polydeoxyribonucleotide reduces cytokine production and the severity of collageninduced arthritis by stimulation of adenosine A(2A) receptor. Arthritis Rheum. 2011; 63: 3364-71. https://doi.org/10.1002/art.30538
  13. Ramanathan M, Pinhal-Enfield G, Hao I, Leibovich SJ. Synergistic up-regulation of vascular endothelial growth factor (VEGF) expression in macrophages by adenosine A2A receptor agonists and endotoxin involves transcriptional regulation via the hypoxia response element in the VEGF promoter. Mol Biol Cell. 2007; 18: 14-23. https://doi.org/10.1091/mbc.e06-07-0596
  14. Ripamonti CI, Maniezzo M, Campa T, Fagnoni E, Brunelli C, Saibene G, Bareggi C, Ascani L, Cislaghi E. Decreased occurrence of osteonecrosis of the jaw after implementation of dental preventive measures in solid tumour patients with bone metastases treated with bisphosphonates. The experience of the National Cancer Institute of Milan. Ann Oncol. 2009; 20: 137-45. https://doi.org/10.1093/annonc/mdn526
  15. Kang B, Cheong S, Chaichanasakul T, Bezouglaia O, Atti E, Dry SM, Pirih FQ, Aghaloo TL, Tetradis S. Periapical disease and bisphosphonates induce osteonecrosis of the jaws in mice. J Bone Miner Res. 2013; 28: 1631-40. https://doi.org/10.1002/jbmr.1894
  16. Altavilla D, Bitto A, Polito F, Marini H, Minutoli L, Di Stefano V, Irrera N, Cattarini G, Squadrito F. Polydeoxyribonucleotide (PDRN): a safe approach to induce therapeutic angiogenesis in peripheral artery occlusive disease and in diabetic foot ulcers. Cardiovasc Hematol Agents Med Chem. 2009; 7: 313-21. https://doi.org/10.2174/187152509789541909
  17. Jeong EK, Jang HJ, Kim SS, Lee SY, Oh MY, Kim HJ, Eom DW, Ham JY, Han DJ. Protective effect of polydeoxyribonucleotide against renal ischemiareperfusion injury in mice. Transplant Proc. 2016; 48: 1251-7. https://doi.org/10.1016/j.transproceed.2016.01.028
  18. Kang SH, Choi MS, Kim HK, Kim WS, Bae TH, Kim MK, Chang SH. Polydeoxyribonucleotide improves tendon healing following achilles tendon injury in rats. J Orthop Res. 2018; 36: 1767-76. https://doi.org/10.1002/jor.23796
  19. Irrera N, Arcoraci V, Mannino F, Vermiglio G, Pallio G, Minutoli L, Bagnato G, Anastasi GP, Mazzon E, Bramanti P, Squadrito F, Altavilla D, Bitto A. Activation of A2A receptor by PDRN reduces neuronal damage and stimulates $WNT/{\beta}$-CATENIN driven neurogenesis in spinal cord injury. Front Pharmacol. 2018; 9: 506. https://doi.org/10.3389/fphar.2018.00506
  20. Yoon YC, Lee DH, Lee MY, Yoon SH. Polydeoxyribonucleotide injection in the treatment of chronic supraspinatus tendinopathy: a casecontrolled, retrospective, comparative study with 6-month follow-up. Arch Phys Med Rehabil. 2017; 98: 874-80. https://doi.org/10.1016/j.apmr.2016.10.020
  21. Noh TK, Chung BY, Kim SY, Lee MH, Kim MJ, Youn CS, Lee MW, Chang SE. Novel antimelanogenesis properties of polydeoxyribonucleotide, a popular wound healing booster. Int J Mol Sci. 2016; 17: 1448. https://doi.org/10.3390/ijms17091448
  22. Kim S, Kim J, Choi J, Jeong W, Kwon S. Polydeoxyribonucleotide improves peripheral tissue oxygenation and accelerates angiogenesis in diabetic foot ulcers. Arch Plast Surg. 2017; 44: 482-9. https://doi.org/10.5999/aps.2017.00801