Pathogenesis and multidisciplinary management of medication-related osteonecrosis of the jaw

Abstract

Medication-related osteonecrosis of the jaw (MRONJ) is a serious side effect of bone-modifying agents and inhibits angiogenesis agents. Although the pathogenesis of MRONJ is not entirely clear, multiple factors may be involved in specific microenvironments. The TGF-β1 signalling pathway may have a key role in the development of MRONJ. According to the clinical stage, multiple variables should be considered when selecting the most appropriate treatment. Therefore, the prevention and management of treatment of MRONJ should be conducted in patient-centred multidisciplinary team collaborative networks with oncologists, dentists and dental specialists. This would comprise a closed responsibility treatment loop with all benefits directed to the patient. Thus, in the present review, we aimed to summarise the pathogenesis, risk factors, imaging features, clinical staging, therapeutic methods, prevention and treatment strategies associated with MRONJ, which may provide a reference that can inform preventive strategies and improve the quality of life for patients in the future.

References

[1] Marx RE. Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J. Oral. Maxillofac. Surg., 2003, 61: 1115-1117.

[2] Ruggiero SL, . American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw-2014 update. American Association of Oral and Maxillofacial Surgeons. J. Oral. Maxillofac. Surg., 2014, 72: 1938-1956.

[3] Dodson TB. The frequency of medication-related osteonecrosis of the jaw and its associated risk factors. Oral. Maxillofac. Surg. Clin. North Am., 2015, 27: 509-516.

[4] Yarom N, . Medication-related osteonecrosis of the jaw: MASCC/ISOO/ASCO clinical practice guideline. J. Clin. Oncol., 2019, 37: 2270-2290.

[5] Lo JC, . Prevalence of osteonecrosis of the jaw in patients with oral bisphosphonate exposure. J. Oral. Maxillofac. Surg., 2010, 68: 243-253.

[6] Nowicki B, . Medication-related osteonecrosis of the jaw in a minipig model: parameters for developing a macroscopic, radiological, and microscopic grading scheme. J. Craniomaxillofac. Surg., 2019, 47: 1162-1169.

[7] Khan AA, . Diagnosis and management of osteonecrosis of the jaw: a systematic review and international consensus. J. Bone Min. Res., 2015, 30: 3-23.

[8] Matsuura T, . Distinct characteristics of mandibular bone collagen relative to long bone collagen: relevance to clinical dentistry. Biomed. Res. Int., 2014, 2014: 769414.

[9] Saad F, . Incidence, risk factors, and outcomes of osteonecrosis of the jaw: integrated analysis from three blinded active-controlled phase III trials in cancer patients with bone metastases. Ann. Oncol., 2012, 23: 1341-1347.

[10] Yamaza T, . Mouse mandible contains distinctive mesenchymal stem cells. J. Dent. Res., 2011, 90: 317-324.

[11] Abdik H, . The effects of bisphosphonates on osteonecrosis of jaw bone: a stem cell perspective. Mol. Biol. Rep., 2019, 1: 763-776.

[12] Taniguchi, N. et al. BPs induced reactive oxygen species inhibit proliferation and migration of oral fibroblast: a pathogenesis of bisphosphonate-related osteonecrosis of the jaw. J. Periodontol. https://doi.org/10.1002/JPER.19-0385 (2019).

[13] Li M, . Decreased osteogenic ability of periodontal ligament stem cells leading to impaired periodontal tissue repair in BRONJ patients. Stem Cells Dev., 2020, 29: 156-168.

[14] de Souza Faloni AP, . Jaw and long bone marrows have a different osteoclastogenic potential. Calcif. Tissue Int., 2011, 88: 63-74.

[15] Abe T, . Zoledronic acid increases the circulating soluble RANKL level in mice, with a further increase in lymphocyte-derived soluble RANKL in zoledronic acid- and glucocorticoid-treated mice stimulated with bacterial lipopolysaccharide. Cytokine, 2016, 83: 1-7.

[16] Wehrhan F, . Bisphosphonate-associated osteonecrosis of the jaw is linked to suppressed TGFβ1-signaling and increased Galectin-3 expression: a histological study on biopsies. J. Transl. Med., 2011, 9

[17] Manzano-Moreno FJ, . Bisphosphonate modulation of the gene expression of different markers involved in osteoblast physiology: possible implications in bisphosphonate-related osteonecrosis of the jaw. Int. J. Med. Sci., 2018, 15: 359-367.

[18] Yasuda H, . Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro. Endocrinology, 1998, 139: 1329-1337.

[19] Di Nisio C, . RANK/RANKL/OPG signaling pathways in necrotic jaw bone from bisphosphonate-treated subjects. Eur. J. Histochem., 2015, 59: 2455.

[20] Chen L, . Network-based method for identifying co-regeneration genes in bone, dentin, nerve and vessel tissues. Genes, 2017, 10: E252.

[21] Kim HJ, . Zoledronate enhances osteocyte-mediated osteoclast differentiation by IL-6/RANKL axis. Int J. Mol. Sci., 2019, 20: E1467.

[22] Shibahara T. Antiresorptive agent-related osteonecrosis of the jaw (ARONJ): a twist of fate in the bone. Tohoku J. Exp. Med., 2019, 247: 75-86.

[23] Hansen T, Kunkel M, Weber A, James, Kirkpatrick C. Osteonecrosis of the jaws in patients treated with BPs-Histomorphologic analysis in comparison with infected osteoradionecrosis. J. Oral. Pathol. Med., 2006, 35: 155-160.

[24] Di Fede O, . The dental management of patients at risk of medication-related osteonecrosis of the jaw: new paradigm of primary prevention. Biomed. Res. Int., 2018, 2018: 2684924.

[25] Soundia A, . Zoledronate impairs socket healing after extraction of teeth with experimental periodontitis. J. Dent. Res., 2018, 97: 312-320.

[26] Li CL, . Role of periodontal disease in bisphosphonate-related osteonecrosis of the jaws in ovariectomized rats. Clin. Oral. Implants Res., 2016, 27: 1-6.

[27] Otto S, . Bisphosphonate-related osteonecrosis of the jaw: is pH the missing part in the pathogenesis puzzle?. J. Oral. Maxillofac. Surg., 2010, 68: 1158-1161.

[28] Tsao C, . Oral health risk factors for bisphosphonate-associated jaw osteonecrosis. J. Oral. Maxillofac. Surg., 2013, 71: 1360-1366.

[29] Kim S, . IL-36 induces bisphosphonate-related osteonecrosis of the jaw-like lesions in mice by inhibiting TGF-β-mediated collagen expression. J. Bone Min. Res., 2017, 32: 309-318.

[30] Kalyan S, Quabius ES, Wiltfang J, Monig H, Kabelitz D. Can peripheral blood gammadelta T cells predict osteonecrosis of the jaw? An immunological perspective on the adverse drug effects of aminobisphosphonate therapy. J. Bone Min. Res., 2013, 28: 728-735.

[31] Hagelauer N, Pabst AM, Ziebart T, Ulbrich H, Walter C. In vitro effects of bisphosphonates on chemotaxis, phagocytosis, and oxidative burst of neutrophil granulocytes. Clin. Oral. Investig., 2015, 19: 139-148.

[32] Patntirapong S, Poolgesorn M. Alteration of macrophage viability, differentiation, and function by BPs. Oral. Dis., 2018, 24: 1294-1302.

[33] Ferrari-Lacraz S, Ferrari S. Do RANKL inhibitors (denosumab) affect inflammation and immunity?. Osteoporos. Int, 2011, 22: 435-446.

[34] Zhu W, . Zoledronic acid promotes TLR-4-mediated M1 macrophage polarization in bisphosphonate-related osteonecrosis of the jaw. FASEB J., 2019, 33: 5208-5219.

[35] Vincenzi B, . Serum VEGF levels as predictive marker of bisphosphonate-related osteonecrosis of the jaw. J. Hematol. Oncol., 2012, 5: 56.

[36] Fantasia JE. The role of antiangiogenic therapy in the development of osteonecrosis of the jaw. Oral. Maxillofac. Surg. Clin. North Am., 2015, 27: 547-553.

[37] Misso G, . Evaluation of the in vitro and in vivo antiangiogenic effects of denosumab and zoledronic acid. Cancer Biol. Ther., 2012, 13: 1491-1500.

[38] Kuroshima S, Sasaki M, Sawase T. Medication-related osteonecrosis of the jaw: a literature review. J. Oral. Biosci., 2019, 61: 99-104.

[39] Khan AA, . Case-based review of osteonecrosis of the jaw (ONJ) and application of the international recommendations for management from the International Task Force on ONJ. J. Clin. Densitom., 2017, 20: 8-24.

[40] Tokuda H, . Involvement of MAP kinases in TGF‑beta‑stimulated vascular endothelial growth factor synthesis in osteoblasts. Arch. Biochem. Biophys., 2003, 415: 117-125.

[41] Lee KH, . Identifying genetic variants underlying medication-induced osteonecrosis of the jaw in cancer and osteoporosis: a case control study. J. Transl. Med., 2019, 17

[42] Ishtiaq S, . The effect of nitrogen containing bisphosphonates, zoledronate and alendronate, on the production of pro-angiogenic factors by osteoblastic cells. Cytokine, 2015, 71: 154-160.

[43] Reid IR, Bolland MJ, Grey AB. Is bisphosphonate-associated osteonecrosis of the jaw caused by soft tissue toxicity?. Bone, 2007, 41: 318-320.

[44] Simon MJ, Niehoff P, Kimmig B, Wiltfang J, Acil Y. Expression profile and synthesis of different collagen types I, II, III, and V of human gingival fibroblasts, osteoblasts, and SaOS-2 cells after bisphosphonate treatment. Clin. Oral. Investig., 2010, 14: 51-58.

[45] Border WA, . Natural inhibitor of transforming growth factor-beta protects against scarring in experimental kidney disease. Nature, 1992, 360: 361-364.

[46] Lescaille G, . Osteonecrosis of the jaw and nonmalignant disease: is there an association with rheumatoid arthritis?. J. Rheumatol., 2013, 40: 781-786.

[47] de Molon RS, . Rheumatoid arthritis exacerbates the severity of osteonecrosis of the jaws (ONJ) in mice. A randomized, prospective, controlled animal study. J. Bone Min. Res., 2016, 8: 1596-1607.

[48] Peer A, Khamaisi M. Diabetes as a risk factor for medication-related osteonecrosis of the jaw. J. Dent. Res., 2015, 94: 252-260.

[49] Bastida-Lertxundi N, . Pharmacogenomics in medication-related osteonecrosis of the jaw: a systematic literature review. Eur. Rev. Med. Pharm. Sci., 2019, 23: 10184-10194.

[50] Katz J, . Genetic polymorphisms and other risk factors associated with bisphosphonate induced osteonecrosis of the jaw. Int J. Oral. Maxillofac. Surg., 2011, 40: 605-611.

[51] Borromeo GL. A large case-control study reveals a positive association between bisphosphonate use and delayed dental healing and osteonecrosis of the jaw. J. Bone Min. Res., 2014, 29: 1363-1368.

[52] Qi WX, Tang LN, He AN, Yao Y, Shen Z. Risk of osteonecrosis of the jaw in cancer patients receiving denosumab: a meta-analysis of seven randomized controlled trials. Int J. Clin. Oncol., 2014, 19: 403-410.

[53] Fedele S, . Up to a quarter of patients with osteonecrosis of the jaw associated with antiresorptive agents remain undiagnosed. Br. J. Oral. Maxillofac. Surg., 2015, 53: 13-17.

[54] Huber FA, . Medication-related osteonecrosis of the jaw-comparison of bone imaging using ultrashort echo-time magnetic resonance imaging and cone-beam computed tomography. Invest. Radio., 2020, 55: 160-167.

[55] Sánchez-López JD, Cariati P, Cambil-Martin J, Villegas-Calvo M, Moreno-Martin ML. Use of bone scintigraphy in the early diagnosis of bisphosphonate related osteonecrosis of the jaw. Case report and review of the literature. J. Clin. Exp. Dent., 2018, 10: e1235-e1237.

[56] Arce K, Assael LA, Weissman JL, Markiewicz MR. Imaging findings in bisphosphonate-related osteonecrosis of jaws. J. Oral. Maxillofac. Surg., 2009, 67: 75-84.

[57] Sim IeW, Sanders KM, Borromeo GL, Seymour JF, Ebeling PR. Declining incidence of medication-related osteonecrosis of the jaw in patients with cancer. J. Clin. Endocrinol. Metab., 2015, 100: 3887-3893.

[58] Filleul O, Crompot E, Saussez S. Bisphosphonate-induced osteonecrosis of the jaw: a review of 2,400 patient cases. J. Cancer Res Clin. Oncol., 2010, 136: 1117-1124.

[59] Kajizono M, . Incidence and risk factors of osteonecrosis of the jaw in advanced cancer patients after treatment with zoledronic acid or denosumab: a retrospective cohort study. Biol. Pharm. Bull., 2015, 38: 1850-1855.

[60] Hong CHL, . A systematic review of dental disease management in cancer patients. Support Care Cancer, 2018, 26: 155-174.

[61] Vandone AM, . Impact of dental care in the prevention of bisphosphonate-associated osteonecrosis of the jaw: a single-center clinical experience. Ann. Oncol., 2012, 23: 193-200.

[62] Stanton DC, Balasanian E. Outcome of surgical management of bisphosphonate-related osteonecrosis of the jaws: review of 33 surgical cases. J. Oral. Maxillofac. Surg., 2009, 67: 943-950.

[63] Thumbigere-Math V, . Bisphosphonate-related osteonecrosis of the jaw: clinical features, risk factors, management, and treatment outcomes of 26 patients. J. Oral. Maxillofac. Surg., 2009, 67: 1904-1913.

[64] Yarom N, . Rapid onset of osteonecrosis of the jaw in patients switching from bisphosphonates to denosumab. Oral. Surg. Oral. Med Oral. Pathol. Oral. Radio., 2018, 125: 27-30.

[65] Rabelo GD, . Bisphosphonate-related osteonecrosis of the jaws and its array of manifestations. J. Maxillofac. Oral. Surg., 2015, 14: 699-705.

[66] Clarke BM, . Bisphosphonates and jaw osteonecrosis: the UAMS experience. Otolaryngol. Head. Neck Surg., 2007, 136: 396-400.

[67] Wessel JH, Dodson TB, Zavras AI. Zoledronate, smoking, and obesity are strong risk factors for osteonecrosis of the jaw: a case-control study. J. Oral. Maxillofac. Surg., 2008, 66: 625-631.

[68] Carlson ER, Fleisher KE, Ruggiero SL. Metastatic cancer identified in osteonecrosis specimens of the jaws in patients receiving intravenous bisphosphonate medications. J. Oral. Maxillofac. Surg., 2013, 71: 2077-2086.

[69] Basch E. The missing voice of patients in drug-safety reporting. N. Engl. J. Med., 2010, 362: 865-869.

[70] Gilligan T, . Patient-clinician communication: American Society of Clinical Oncology consensus guideline. J. Clin. Oncol., 2017, 35: 3618-3632.

[71] Schiodt M, . A multicenter case registry study on medication-related osteonecrosis of the jaw in patients with advanced cancer. Support Care Cancer, 2018, 26: 1905-1915.

[72] Ferlito S, . Treatment of bisphosphonate-related osteonecrosis of the jaws: presentation of a protocol and an observational longitudinal study of an Italian series of cases. Br. J. Oral. Maxillofac. Surg., 2012, 50: 425-429.

[73] Rodrigues P, Hering F, Imperio M. Safety of I.V. nonnitrogen bisphosphonates on the occurrence of osteonecrosis of the jaw: long-term follow-up on prostate cancer patients. Clin. Genitourin. Cancer, 2015, 13: 199-203.

[74] Lesclous P, . Relevance of surgical management of patients affected by bisphosphonate-associated osteonecrosis of the jaws. A prospective clinical and radiological study. Clin. Oral. Investig., 2014, 18: 391-399.

[75] Ortega C, . Osteonecrosis of the jaw in prostate cancer patients with bone metastases treated with zoledronate: a retrospective analysis. Acta Oncol., 2007, 46: 664-668.

[76] Hellstein JW, . Managing the care of patients receiving antiresorptive therapy for prevention and treatment of osteoporosis: executive summary of recommendations from the American Dental Association Council on Scientific Affairs. J. Am. Dent. Assoc., 2011, 142: 1243-12451.

[77] Moretti F, Pelliccioni GA, Montebugnoli L, Marchetti C. A prospective clinical trial for assessing the efficacy of a minimally invasive protocol in patients with bisphosphonate-associated osteonecrosis of the jaws. Oral. Surg. Oral. Med Oral. Pathol. Oral. Radio. Endod., 2011, 112: 777-782.

[78] Thorn JJ, Sorensen H, Weis-Fogh U, Andersen M. Autologous fibrin glue with growth factors in reconstructive maxillofacial surgery. Int J. Oral. Maxillofac. Surg., 2004, 33: 95-100.

[79] Scoletta M, Arduino PG, Dalmasso P, Broccoletti R, Mozzati M. Treatment outcomes in patients with bisphosphonate-related osteonecrosis of the jaws: a prospective study. Oral. Surg. Oral. Med Oral. Pathol. Oral. Radio. Endod., 2010, 110: 46-53.

[80] Schubert M, . The Saxon bisphosphonate register: therapy and prevention of bisphosphonate-related osteonecrosis of the jaws. Oral. Oncol., 2012, 48: 349-354.

[81] Dayisoylu EH, . The effects of adjunctive parathyroid hormone injection on bisphosphonate-related osteonecrosis of the jaws: an animal study. Int J. Oral. Maxillofac. Surg., 2013, 42: 1475-1480.

[82] Cheung A, Seeman E. Teriparatide therapy for alendronate-associated osteonecrosis of the jaw. N. Engl. J. Med., 2010, 363: 2473-2474.

[83] El-Rabbany M, Sgro A, Lam DK, Shah PS, Azarpazhooh A. Effectiveness of treatments for medication-related osteonecrosis of the jaw: a systematic review and meta-analysis. J. Am. Dent. Assoc., 2017, 148: 584-594.

[84] Jung J, . 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 Min. Res, 2017, 32: 2445-2452.

[85] Yoshiga D, . Weekly teriparatide injections successfully treated advanced bisphosphonate-related osteonecrosis of the jaws. Osteoporos. Int., 2013, 24: 2365-2369.

[86] Liu Y, . Anabolic agents: what is beyond osteoporosis?. Osteoporos. Int., 2018, 29: 1009-1022.

[87] Martos-Fernandez M, . Pentoxifylline, tocopherol, and clodronate for the treatment of mandibular osteoradionecrosis: a systematic review. Oral. Surg. Oral. Med Oral. Pathol. Oral. Radio., 2018, 125: 431-439.

[88] Epstein MS, Wicknick FW, Epstein JB, Berenson JR, Gorsky M. Management of bisphosphonate-associated osteonecrosis: pentoxifylline and tocopherol in addition to antimicrobial therapy. initial case Ser. Oral. Surg. Oral. Med Oral. Pathol. Oral. Radio. Endod., 2010, 110: 593-596.

[89] Magremanne M, Reychler H. Pentoxifylline and tocopherol in the treatment of yearly zoledronic acid-related osteonecrosis of the jaw in a corticosteroid-induced osteoporosis. J. Oral. Maxillofac. Surg., 2014, 72: 334-337.

[90] 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: 455-459.

[91] Yalcin-Ulker GM, Cumbul A, Duygu-Capar G, Uslu U, Sencift K. Preventive effect of phosphodiesterase inhibitor pentoxifylline against medication-related osteonecrosis of the jaw: an animal study. J. Oral. Maxillofac. Surg., 2017, 75: 2354-2368.

[92] Jiang Q. Natural forms of vitamin E: metabolism, antioxidant, and anti-inflammatory activities and their role in disease prevention and therapy. Free Radic. Biol. Med., 2014, 72: 76-90.

[93] Ji X, . Antibiotic effects on bacterial profile in osteonecrosis of the jaw. Oral. Dis., 2012, 18: 85-95.

[94] Advisory Task Force on Bisphosphonate-Related Ostenonecrosis of the Jaws, American Association of Oral and Maxillofacial Surgeons. American association of oral and maxillofacial surgeons position paper on bisphosphonate-related osteonecrosis of the jaws. J. Oral. Maxillofac. Surg., 2007, 65: 369-376.

[95] Ruggiero SL. Bisphosphonate-related osteonecrosis of the jaw: an overview. Ann. N. Y Acad. Sci., 2011, 1218: 38-46.

[96] Bagán J, . Recommendations for the prevention, diagnosis, and treatment of osteonecrosis of the jaw (ONJ) in cancer patients treated with bisphosphonates. Med Oral. Patol. Oral. Cir. Bucal, 2007, 12: E336-E340.

[97] Weitzman R, . Critical review: updated recommendations for the prevention, diagnosis, and treatment of osteonecrosis of the jaw in cancer patients-May 2006. Crit. Rev. Oncol. Hematol., 2007, 62: 148-152.

[98] Lam DK, Sándor GK, Holmes HI, Evans AW, Clokie CM. A review of bisphosphonate-associated osteonecrosis of the jaws and its management. J. Can. Dent. Assoc., 2007, 73: 417-422.

[99] Carter GD, Goss NAN. Bisphosphonates and avascular necrosis of the jaws. Aust. Dent. J., 2003, 48: 268.

[100] Pogrel MA. Bisphosphonates and bone necrosis. J. Oral. Maxillofac. Surg., 2004, 62: 391-392.

[101] Ruggiero SL, Mehrotra B, Rosenberg TJ, Engroff SL. Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases. J. Oral. Maxillofac. Surg., 2004, 62: 527-534.

[102] Ruggiero SL, Fantasia J, Carlson E. Bisphosphonate-related osteonecrosis of the jaw: background and guidelines for diagnosis, staging and management. Oral. Surg. Oral. Med Oral. Pathol. Oral. Radio. Endod., 2006, 102: 433-441.

[103] Wilde F, . The role of surgical therapy in the management of intravenous bisphosphonates-related osteonecrosis of the jaw. Oral. Surg. Oral. Med Oral. Pathol. Oral. Radio. Endod., 2011, 111: 153-163.

[104] de Souza Tolentino E, . Adjuvant therapies in the management of medication-related osteonecrosis of the jaws: systematic review. Head. Neck, 2019, 41: 4209-4228.

[105] McLeod NM, Patel V, Kusanale A, Rogers SN, Brennan PA. Bisphosphonate osteonecrosis of the jaw: a literature review of UK policies versus international policies on the management of bisphosphonate osteonecrosis of the jaw. Br. J. Oral. Maxillofac. Surg., 2011, 49: 335-342.

[106] Seth R, Futran ND, Alam DS, Knott PD. Outcomes of vascularized bone graft reconstruction of the mandible in bisphosphonate-related osteonecrosis of the jaws. Laryngoscope, 2010, 120: 2165-2171.

[107] Pautke C, . Fluorescence-guided bone resection in bisphosphonate-related osteonecrosis of the jaws: first clinical results of a prospective pilot study. J. Oral. Maxillofac. Surg., 2011, 69: 84-91.

[108] Berrone M, Florindi FU, Carbone V, Aldiano C, Pentenero M. Stage 3 medication-related osteonecrosis of the posterior maxilla: surgical treatment using a pedicled buccal fat pad flap: case reports. J. Oral. Maxillofac. Surg., 2015, 73: 2082-2086.

[109] Melville JC, . A technique for the treatment of oral-antral fistulae resulting from medication-related osteonec-rosis of the maxilla: the combined buccal fat pad flap and radical sinusotomy. Oral. Surg. Oral. Med Oral. Pathol. Oral. Radio., 2016, 122: 287-291.

[110] Mirancille A, . Improvement of postnatal neovascularization by human adipose tissue-derived stem cells. Circulation, 2004, 110: 349-355.

[111] Farre-Guasch E, Martí-Pages C, Hernandez-Alfaro F, Klein-Nulend J, Casals N. Buccal fat pad, an oral access source of human adipose stem cells with potential for osteochondral tissue engineering: an in vitro study. Tissue Eng. Part C Methods, 2010, 16: 1083-1094.

[112] Hakobyan K, Poghosyan Y, Kasyan A. The use of buccal fat pad in surgical treatment of ‘Krokodil’ drug-related osteonecrosis of maxilla. J. Craniomaxillofac. Surg., 2018, 46: 831-836.

[113] Lee NK, . A crucial role for reactive oxygen species in RANKL-induced osteoclast differentiation. Blood, 2005, 106: 852-859.

[114] Freiberger JJ. Utility of hyperbaric oxygen in treatment of bisphosphonate-related osteonecrosis of the jaws. J. Oral. Maxillofac. Surg., 2009, 67: 96-106.

[115] Rupel K, . A systematic review of therapeutical approaches in bisphosphonates-related osteonecrosis of the jaw (BRONJ). Oral. Oncol., 2014, 50: 1049-1057.

[116] Freiberger JJ, . Hyperbaric oxygen treatment and bisphosphonate-induced osteonecrosis of the jaw: a case series. J. Oral. Maxillofac. Surg., 2007, 65: 1321-1327.

[117] Freiberger JJ, . 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: 1573-1583.

[118] Rollason V, . Interventions for treating bisphosphonate-related osteonecrosis of the jaw (BRONJ). Cochrane Database Syst. Rev., 2016, 2: CD008455.

[119] Beth-Tasdogan NH, Mayer B, Hussein H, Zolk O. Interventions for managing medication-related osteonecrosis of the jaw. Cochrane Database Syst. Ver., 2017, 10: CD012432.

[120] Favia G, Tempesta A, Limongelli L, Crincoli V, Maiorano E. Medication-related osteonecrosis of the jaw: surgical or non-surgical treatment?. Oral. Dis., 2018, 24: 238-242.

[121] Altay MA, Tasar F, Tosun E, Kan B. Low-level laser therapy supported surgical treatment of bisphosphonate related osteonecrosis of jaws: a retrospective analysis of 11 cases. Photomed. Laser Surg., 2014, 32: 468-475.

[122] Vescovi P, . Nd:YAG laser biostimulation in the treatment of bisphosphonate-associated osteonecrosis of the jaw: clinical experience in 28 cases. Photomed. Laser Surg., 2008, 26: 37-46.

[123] Vescovi P, . Surgical approach and laser applications in BRONJ osteoporotic and cancer patients. J. Osteoporos., 2012, 2012: 585434.

[124] Scoletta M, Arduino PG, Reggio L, Dalmasso P, Mozzati M. Effect of low-level laser irradiation on bisphosphonate-induced osteonecrosis of the jaws: preliminary results of a prospective study. Photomed. Laser Surg., 2010, 28: 179-184.

[125] Vescovi P, . Early surgical laser-assisted management of bisphosphonate-related osteonecrosis of the jaws (BRONJ): a retrospective analysis of 101 treated sites with long-term follow-up. Photomed. Laser Surg., 2012, 30: 5-13.

[126] Wang JV, Schoenberg E, Saedi N, Ibrahim O. Platelet-rich plasma, collagen peptides, and stem cells for cutaneous rejuvenation. J. Clin. Aesthet. Dermatol., 2020, 13: 44-49.

[127] Plachokova AS, Nikolidakis D, Mulder J, Jansen JA, Creugers NH. Effect of plateletrich plasma on bone regeneration in dentistry: a systematic review. Clin. Oral. Implants Res., 2008, 19: 539-545.

[128] Curi MM, . Bisphosphonate-related osteonecrosis of the jaws-an initial case series report of treatment combining partial bone resection and autologous platelet-rich plasma. J. Oral. Maxillofac. Surg., 2011, 69: 2465-2472.

[129] Adornato MC, Morcos I, Rozanski J. The treatment of bisphosphonate-associated osteonecrosis of the jaws with bone resection and autologous platelet-derived growth factors. J. Am. Dent. Assoc., 2007, 138: 971-977.

[130] Lopez-Jornet P, Sanchez Perez A, Amaral Mendes R, Tobias A. Medication-related osteonecrosis of the jaw: is autologous platelet concentrate application effective for prevention and treatment? A systematic review. J. Craniomaxillofac. Surg., 2016, 44: 1067-1072.

[131] Del Fabbro M, Gallesio G, Mozzati M. Autologous platelet concentrates for bisphosphonate-related osteonecrosis of the jaw treatment and prevention. A systematic review of the literature. Eur. J. Cancer, 2015, 51: 62-74.

[132] Bennardo F, . Autologous platelet-rich fibrin injections in the management of facial cutaneous sinus tracts secondary to medication-related osteonecrosis of the jaw. Dermatol. Ther., 2020, 26: e13334.

[133] Myoken Y, Fujita Y, Okamoto T. Modified submental island flap for the surgical treatment of 4 patients with stage 3 medication-related osteonecrosis of the mandible. J. Oral. Maxillofac. Surg., 2020, 78: 29-34.

Funding

National Natural Science Foundation of China (National Science Foundation of China)(81970924)