Open Access
Review
Impaired Osteoclastogenesis in Medication-Related Osteonecrosis and Potential Clinical Management with BMP-2
Author Information
Submitted: 5 Nov 2024 | Revised: 18 Dec 2024 | Accepted: 19 Dec 2024 | Published: 23 Dec 2024
Abstract
Medication-related osteonecrosis of the jaw (MRONJ) is a rare, but severe, complication of applying inhibitors of osteoclasts, specifically bisphosphonates and the monoclonal antibody of receptor activator of nuclear factor kappa-Β ligand (RANKL), inhibitors of angiogenesis, and some chemotherapeutics. MRONJ is painful for the patients, while current treatments are unsatisfactory. Thus, it is imperative to understand the etiology and pathogenesis of MRONJ to improve treatment options and enable prevention. Various hypotheses have been proposed over the years to elucidate the pathogenesis of MRONJ. Noticeably, impaired osteoclastogenesis shines some light on novel preventive and treatment strategies. In this review, we summarized the current understanding of the role of osteoclastogenesis in the development of MRONJ and have put forward a hypothesis concerning the application of BMP2 in the clinical management strategy for MRONJ.
Graphical Abstract
Keywords
References
1.
Ruggiero, S.L.; Mehrotra, B.; Rosenberg, T.J.; et al. Osteonecrosis of the jaws associated with the use of bisphosphonates: A review of 63 cases. J. Oral. Maxillofac. Surg. 2004, 62, 527–534. https://doi.org/10.1016/j.joms.2004.02.004.
2.
Van den Wyngaert, T.; Huizing, M.T.; Vermorken, J.B. Bisphosphonates and osteonecrosis of the jaw: Cause and effect or a post hoc fallacy? Ann. Oncol. 2006, 17, 1197–1204. https://doi.org/10.1093/annonc/mdl294.
3.
Goss, A.N. Medicinal Mishap: Osteonecrosis of the jaw and denosumab. Aust. Prescr. 2022, 45, 208–211. https://doi.org/10.18773/austprescr.2022.066.
4.
Aghaloo, T.L.; Felsenfeld, A.L.; Tetradis, S. Osteonecrosis of the Jaw in a Patient on Denosumab. J. Oral. Maxillofac. Surg. 2010, 68, 959–963. https://doi.org/10.1016/j.joms.2009.10.010.
5.
Greuter, S.; Schmid, F.; Ruhstaller, T.; et al. Bevacizumab-associated osteonecrosis of the jaw. Ann. Oncol. 2008, 19, 209–212. https://doi.org/10.1093/annonc/mdn653.
6.
Maluf, G.; Caldas, R.J.; Fregnani, E.R.; et al. A rare case of bevacizumab-related osteonecrosis of the jaw associated with dental implants. Int. J. Implant. Dent. 2019, 5, 34. https://doi.org/10.1186/s40729-019-0188-0.
7.
Wang, L.; Huang, J.; Tang, Z. Chemotherapeutics-induced osteonecrosis of the jaw in a patient with acute promyelocytic leukemia: A rare case report. Oral. Oncol. 2022, 124, 1056–1059. https://doi.org/10.1016/j.oraloncology.2021.105659.
8.
Henien, M.; Carey, B.; Hullah, E.; et al. Methotrexate-associated osteonecrosis of the jaw: A report of two cases. Oral. Surg. Oral. Med. Oral. Pathol. Oral. Radiol. 2017, 124, e283–e287. https://doi.org/10.1016/j.oooo.2017.09.005.
9.
Hasegawa, T.; Ueda, N.; Yamada, S.I.; et al. Denosumab-related osteonecrosis of the jaw after tooth extraction and the effects of a short drug holiday in cancer patients: A multicenter retrospective study. Osteoporos. Int. 2021, 32, 2323–2333. https://doi.org/10.1007/s00198-021-05995-3.
10.
Barry, E.; Taylor, T.; Patel, J.; et al. The incidence of medication-related osteonecrosis of the jaw following tooth extraction in patients prescribed oral bisphosphonates. Br. Dent. J. 2021, 1–5. https://doi.org/10.1038/s41415-021-3620-9.
11.
Seki, K.; Kaneko, T.; Kamimoto, A.; et al. Medication-related osteonecrosis of the jaw after tooth extraction in patients receiving pharmaceutical treatment for osteoporosis: A retrospective cohort study. J. Dent. Sci. 2022, 17, 1619–1625. https://doi.org/10.1016/j.jds.2022.03.014.
12.
Tam, Y.; Kar, K.; Nowzari, H.; et al. Osteonecrosis of the Jaw after Implant Surgery in Patients Treated with Bisphosphonates–A Presentation of Six Consecutive Cases. Clin. Implant. Dent. Relat. Res. 2014, 16, 751–761. https://doi.org/10.1111/cid.12048.
13.
Kwon, Y.-D.; Jo, H.; Kim, J.-E.; et al. A clinical retrospective study of implant as a risk factor for medication-related osteonecrosis of the jaw: Surgery vs loading? Maxillofac. Plast. Reconstr. Surg. 2023, 45, 31. https://doi.org/10.1186/s40902-023-00398-2.
14.
Davison, M.R.; Lyardet, L.; Preliasco, M.; et al. Aminobisphosphonate-treated ewes as a model of osteonecrosis of the jaw and of dental implant failure. J. Periodontol. 2020, 91, 628–637. https://doi.org/10.1002/JPER.19-0213.
15.
de-Freitas, N.; Lima, L.; de-Moura, M.; et al. Bisphosphonate treatment and dental implants: A systematic review. Med. Oral. Patol. Oral. Cir. Bucal 2016, 21, e644. https://doi.org/10.4317/medoral.20920.
16.
Marx, R.E. Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: A growing epidemic. J. Oral. Maxillofac. Surg. 2003, 61, 1115–1117. https://doi.org/10.1016/s0278-2391(03)00720-1.
17.
Ruggiero, S.L.; Dodson, T.B.; Fantasia, J.; et al. 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, 1938–1956. https://doi.org/10.1016/j.joms.2014.04.031.
18.
Campisi, G.; Mauceri, R.; Bedogni, A.; et al. Re: AAOMS Position Paper on Medication-Related Osteonecrosis of the Jaw-2022 Update. J. Oral. Maxillofac. Surg. 2022, 80, 1723–1724. https://doi.org/10.1016/j.joms.2022.07.149.
19.
Khan, A.A.; Morrison, A.; Hanley, D.A.; et al. 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, 323. https://doi.org/10.1002/jbmr.2405.
20.
Kuroshima, S.; Al-Omari, F.A.; Sasaki, M.; et al. Medication-related osteonecrosis of the jaw: A literature review and update. Genesis 2022, 60, e23500. https://doi.org/10.1002/dvg.23500.
21.
Nassif, A.; Lignon, G.; Asselin, A.; et al. Transcriptional Regulation of Jaw Osteoblasts: Development to Pathology. J. Dent. Res. 2022, 101, 859–869. https://doi.org/10.1177/00220345221074356.
22.
Yoshida, T.; Vivatbutsiri, P.; Morriss-Kay, G.; et al. Cell lineage in mammalian craniofacial mesenchyme. Mech. Dev. 2008, 125, 797–808. https://doi.org/10.1016/j.mod.2008.06.007.
23.
Azari, A.; Schoenmaker, T.; de Souza Faloni, A.P.; et al. Jaw and long bone marrow derived osteoclasts differ in shape and their response to bone and dentin. Biochem. Biophys. Res. Commun. 2011, 409, 205–210. https://doi.org/10.1016/j.bbrc.2011.04.120.
24.
Clark, R.; Park, S.Y.; Bradley, E.W.; et al. Mouse mandibular–derived osteoclast progenitors have differences in intrinsic properties compared with femoral–derived progenitors. JBMR Plus 2024, 8, ziae029. https://doi.org/10.1093/jbmrpl/ziae029.
25.
Inoue, K.; Mikuni-Takagaki, Y.; Oikawa, K.; et al. A Crucial Role for Matrix Metalloproteinase 2 in Osteocytic Canalicular Formation and Bone Metabolism. J. Biol. Chem. 2006, 281, 33814–33824. https://doi.org/10.1074/jbc.M607290200.
26.
Saad, F.; Brown, J.E.; Van Poznak, C.; et al. 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. https://doi.org/10.1093/annonc/mdr435.
27.
Kang, B.; Cheong, S.; Chaichanasakul, T.; et al. Periapical Disease and Bisphosphonates Induce Osteonecrosis of the Jaws in Mice. J. Bone Miner. Res. 2013, 28, 1631–1640. https://doi.org/10.1002/jbmr.1894.
28.
Aghaloo, T.L.; Kang, B.; Sung, E.C.; et al. Periodontal disease and bisphosphonates induce osteonecrosis of the jaws in the rat. J. Bone Miner. Res. 2011, 26, 1871–1882. https://doi.org/10.1002/jbmr.379.
29.
Kawahara, M.; Kuroshima, S.; Sawase, T. Clinical considerations for medication-related osteonecrosis of the jaw: A comprehensive literature review. Int. J. Implant. Dent. 2021, 7, 47. https://doi.org/10.1186/s40729-021-00323-0.
30.
McGowan, K.; McGowan, T. Ivanovski, Risk factors for medication-related osteonecrosis of the jaws: A systematic review. Oral. Dis. 2018, 24, 527–536. https://doi.org/10.1111/odi.12708.
31.
Yamamoto, S.; Maeda, K.; Kouchi, I.; et al. Development of Antiresorptive Agent-Related Osteonecrosis of the Jaw After Dental Implant Removal: A Case Report. J. Oral. Implantol. 2018, 44, 359–364. https://doi.org/10.1563/aaid-joi-D-18-00032.
32.
Park, J.-H.; Lee, J.-R.; Lee, H.; et al. No increased risk of osteonecrosis of the jaw in osteoporotic patients with dental implants: A nationwide cohort study. Clin. Oral. Investig. 2024, 28, 83. https://doi.org/10.1007/s00784-023-05483-4.
33.
Nase, J.B.; Suzuki, J.B. Osteonecrosis of the jaw and oral bisphosphonate treatment. J. Am. Dent. Assoc. 2006, 137, 1115–1119. https://doi.org/10.14219/jada.archive.2006.0350.
34.
Huang, Y.-F.; Lin, K.-C.; Liu, S.-P.; et al. The association between the severity of periodontitis and osteonecrosis of the jaw in patients with different cancer locations: A nationwide population-based study. Clin. Oral. Investig. 2022, 26, 3843–3852. https://doi.org/10.1007/s00784-021-04175-1.
35.
Lorenzo-Pouso, A.I.; Pérez-Sayáns, M.; Chamorro-Petronacci, C.; et al. Association between periodontitis and medication-related osteonecrosis of the jaw: A systematic review and meta-analysis. J. Oral. Pathol. Med. 2020, 49, 190–200. https://doi.org/10.1111/jop.12963.
36.
Katsarelis, H.; Shah, N.P.; Dhariwal, D.K.; et al. Infection and Medication-related Osteonecrosis of the Jaw. J. Dent. Res. 2015, 94, 534–539. https://doi.org/10.1177/0022034515572021.
37.
Hansen, T.; Kunkel, M.; Springer, E.; et al. Actinomycosis of the jaws—Histopathological study of 45 patients shows significant involvement in bisphosphonate-associated osteonecrosis and infected osteoradionecrosis. Virchows Arch. 2007, 451, 1009–1017. https://doi.org/10.1007/s00428-007-0516-2.
38.
Könönen, E.; Wade, W.G. Actinomyces and Related Organisms in Human Infections. Clin. Microbiol. Rev. 2015, 28, 419–442. https://doi.org/10.1128/CMR.00100-14.
39.
Allen, M.R.; Burr, D.B. The Pathogenesis of Bisphosphonate-Related Osteonecrosis of the Jaw: So Many Hypotheses, So Few Data. J. Oral Maxillofac. Surg. 2009, 67, 61–70. https://doi.org/10.1016/j.joms.2009.01.007.
40.
D’Agostino, S.; Valentini, G.; Dolci, M.; et al. Potential Relationship between Poor Oral Hygiene and MRONJ: An Observational Retrospective Study. Int. J. Environ. Res. Public. Health 2023, 20, 5402. https://doi.org/10.3390/ijerph20075402.
41.
Sedghizadeh, P.P.; Kumar, S.K.S.; Gorur, A.; et al. Identification of Microbial Biofilms in Osteonecrosis of the Jaws Secondary to Bisphosphonate Therapy. J. Oral. Maxillofac. Surg. 2008, 66, 767–775. https://doi.org/10.1016/j.joms.2007.11.035.
42.
Kubek, D.J.; Burr, D.B.; Allen, M.R. Ovariectomy stimulates and bisphosphonates inhibit intracortical remodeling in the mouse mandible. Orthod. Craniofac Res. 2010, 13, 214–222. https://doi.org/10.1111/j.1601-6343.2010.01497.x.
43.
Wu, L.; Luo, Z.; Liu, Y.; et al. Aspirin inhibits RANKL-induced osteoclast differentiation in dendritic cells by suppressing NF-κB and NFATc1 activation. Stem Cell Res. Ther. 2019, 10, 375. https://doi.org/10.1186/s13287-019-1500-x.
44.
Huja, S.S.; Fernandez, S.A.; Hill, K.J.; et al. Remodeling dynamics in the alveolar process in skeletally mature dogs. The Anatomical Record Part A: Discoveries in Molecular. Cell. Evol. Biol. 2006, 288A, 1243–1249. https://doi.org/10.1002/ar.a.20396.
45.
Takeshita, S.; Kaji, K.; Kudo, A. Identification and Characterization of the New Osteoclast Progenitor with Macrophage Phenotypes Being Able to Differentiate into Mature Osteoclasts. J. Bone Miner. Res. 2000, 15, 1477–1488. https://doi.org/10.1359/jbmr.2000.15.8.1477.
46.
Chen, X.; Zhi, X.; Wang, J.; et al. RANKL signaling in bone marrow mesenchymal stem cells negatively regulates osteoblastic bone formation. Bone Res. 2018, 6, 34. https://doi.org/10.1038/s41413-018-0035-6.
47.
Neve, A.; Corrado, A.; Cantatore, F.P. Osteoblast physiology in normal and pathological conditions. Cell Tissue Res. 2011, 343, 289–302. https://doi.org/10.1007/s00441-010-1086-1.
48.
Xiong, J.; Onal, M.; Jilka, R.L.; et al. Matrix-embedded cells control osteoclast formation. Nat. Med. 2011, 17, 1235–1241. https://doi.org/10.1038/nm.2448.
49.
Nakashima, T.; Hayashi, M.; Fukunaga, T.; et al. Evidence for osteocyte regulation of bone homeostasis through RANKL expression. Nat. Med. 2011, 17, 1231–1234. https://doi.org/10.1038/nm.2452.
50.
Zerbini, C.A.F.; McClung, M.R. Odanacatib in postmenopausal women with low bone mineral density: A review of current clinical evidence. Ther. Adv. Musculoskelet. Dis. 2013, 5, 199–209. https://doi.org/10.1177/1759720X13490860.
51.
Noble, B. Bone microdamage and cell apoptosis. Eur. Cell Mater. 2003, 6, 46–56. https://doi.org/10.22203/eCM.v006a05.
52.
Cheung, W.Y.; Fritton, J.C.; Morgan, S.A.; et al. Pannexin-1 and P2X7-Receptor Are Required for Apoptotic Osteocytes in Fatigued Bone to Trigger RANKL Production in Neighboring Bystander Osteocytes. J. Bone Miner. Res. 2016, 31, 890–899. https://doi.org/10.1002/jbmr.2740.
53.
Andreev, D.; Liu, M.; Weidner, D.; et al. Osteocyte necrosis triggers osteoclast-mediated bone loss through macrophage-inducible C-type lectin. J. Clin. Investig. 2020, 130, 4811–4830. https://doi.org/10.1172/JCI134214.
54.
Yang, J.; Dong, D.; Luo, X.; et al. Iron Overload-Induced Osteocyte Apoptosis Stimulates Osteoclast Differentiation Through Increasing Osteocytic RANKL Production In Vitro. Calcif. Tissue Int. 2020, 107, 499–509. https://doi.org/10.1007/s00223-020-00735-x.
55.
Karsdal, M.A.; Neutzsky-Wulff, A.V.; Dziegiel, M.H.; et al. Osteoclasts secrete non-bone derived signals that induce bone formation. Biochem. Biophys. Res. Commun. 2008, 366, 483–488. https://doi.org/10.1016/j.bbrc.2007.11.168.
56.
Daponte, V.; Henke, K.; Drissi, H. Current perspectives on the multiple roles of osteoclasts: Mechanisms of osteoclast–osteoblast communication and potential clinical implications. Elife 2024, 13, e95083. https://doi.org/10.7554/eLife.95083.
57.
Shin, B.; Kupferman, J.; Schmidt, E.; et al. Rac1 Inhibition Via Srgap2 Restrains Inflammatory Osteoclastogenesis and Limits the Clastokine, SLIT3. J. Bone Miner. Res. 2020, 35, 789–800. https://doi.org/10.1002/jbmr.3945.
58.
Hsiao, C.-Y.; Chen, T.-H.; Chu, T.-H.; et al. Calcitonin Induces Bone Formation by Increasing Expression of Wnt10b in Osteoclasts in Ovariectomy-Induced Osteoporotic Rats. Front. Endocrinol. 2020, 11, 613. https://doi.org/10.3389/fendo.2020.00613.
59.
Keller, J.; Catala-Lehnen, P.; Huebner, A.K.; et al. Calcitonin controls bone formation by inhibiting the release of sphingosine 1-phosphate from osteoclasts. Nat. Commun. 2014, 5, 5215. https://doi.org/10.1038/ncomms6215.
60.
Park-Wyllie, L.Y. Bisphosphonate Use and the Risk of Subtrochanteric or Femoral Shaft Fractures in Older Women. JAMA 2011, 305, 783. https://doi.org/10.1001/jama.2011.190.
61.
Lenart, B.A.; Neviaser, A.S.; Lyman, S.; et al. Association of low-energy femoral fractures with prolonged bisphosphonate use: A case control study. Osteoporos. Int. 2009, 20, 1353–1362. https://doi.org/10.1007/s00198-008-0805-x.
62.
Wang, M.; Wu, Y.; Girgis, C.M. Bisphosphonate Drug Holidays: Evidence from Clinical Trials and Real-World Studies. JBMR Plus 2022, 6, e10629. https://doi.org/10.1002/jbm4.10629.
63.
Lamy, O.; Stoll, D.; Aubry-Rozier, B.; et al. Stopping Denosumab. Curr. Osteoporos. Rep. 2019, 17, 815. https://doi.org/10.1007/s11914-019-00502-4.
64.
Bone, H.G.; Bolognese, M.A.; Yuen, C.K.; et al. Effects of Denosumab Treatment and Discontinuation on Bone Mineral Density and Bone Turnover Markers in Postmenopausal Women with Low Bone Mass. J. Clin. Endocrinol. Metab. 2011, 96, 972–980. https://doi.org/10.1210/jc.2010-1502.
65.
Kim, A.S.; Girgis, C.M.; McDonald, M.M. Osteoclast Recycling and the Rebound Phenomenon Following Denosumab Discontinuation. Curr. Osteoporos. Rep. 2022, 20, 505–515. https://doi.org/10.1007/s11914-022-00756-5.
66.
Fleisch, H. Bisphosphonates in Bone Disease: From the Laboratory to the Patient, 4th ed.; Academic Press: San Diego, CA, USA, 2000.
67.
Fleisch, H.; Russell, R.G.; Francis, M.D. Diphosphonates inhibit hydroxyapatite dissolution in vitro and bone resorption in tissue culture and in vivo. Science 1969, 165, 1262–1264. https://doi.org/10.1126/science.165.3899.1262.
68.
Rogers, M.J. From Molds and Macrophages to Mevalonate: A Decade of Progress in Understanding the Molecular Mode of Action of Bisphosphonates. Calcif. Tissue Int. 2004, 75, 451–461. https://doi.org/10.1007/s00223-004-0024-1.
69.
Lehenkari, P.P.; Kellinsalmi, M.; Näpänkangas, J.P.; et al. Further Insight into Mechanism of Action of Clodronate: Inhibition of Mitochondrial ADP/ATP Translocase by a Nonhydrolyzable, Adenine-Containing Metabolite. Mol. Pharmacol. 2002, 61, 1255–1262. https://doi.org/10.1124/mol.61.5.1255.
70.
Russell, R.G.; Croucher, P.I.; Rogers, M.J. Bisphosphonates: Pharmacology, mechanisms of action and clinical uses. Osteoporos. Int. 1999, 9, S66–S80. https://doi.org/10.1007/pl00004164.
71.
Varenna, M.; Zucchi, F.; Failoni, S.; et al. Intravenous neridronate in the treatment of acute painful knee osteoarthritis: A randomized controlled study. Rheumatology 2015, 54, 1826–1832. https://doi.org/10.1093/rheumatology/kev123.
72.
Shea, G.K.H.; Zhang, C.; Suen, W.S.; et al. Oral Zoledronic acid bisphosphonate for the treatment of chronic low back pain with associated Modic changes: A pilot randomized controlled trial. J. Orthop. Res. 2022, 40, 2924–2936. https://doi.org/10.1002/jor.25304.
73.
Reid, I.R.; Wen, J.; Mellar, A.; et al. Effect of oral zoledronate administration on bone turnover in older women. Br. J. Clin. Pharmacol. 2023, 89, 1099–1104. https://doi.org/10.1111/bcp.15559.
74.
Attina, G.; Mastrangelo, S.; Ruggiero, A. The Role of Bisphosphonates in Childhood Diseases. Biomed. Pharmacol. J. 2021, 14, 1501–1507. https://doi.org/10.13005/bpj/2251.
75.
Bellido, T.; Plotkin, L.I. Novel actions of bisphosphonates in bone: Preservation of osteoblast and osteocyte viability. Bone 2011, 49, 50–55. https://doi.org/10.1016/j.bone.2010.08.008.
76.
Kim, H.J.; Kim, H.J.; Choi, Y.; et al. Zoledronate Enhances Osteocyte-Mediated Osteoclast Differentiation by IL-6/RANKL Axis. Int. J. Mol. Sci. 2019, 20, 1467. https://doi.org/10.3390/ijms20061467.
77.
Simon, J.A.; Recknor, C.; Moffett, A.H.; et al. Impact of denosumab on the peripheral skeleton of postmenopausal women with osteoporosis. Menopause 2013, 20, 130–137. https://doi.org/10.1097/GME.0b013e318267f909.
78.
Tsourdi, E.; Langdahl, B.; Cohen-Solal, M.; et al. Discontinuation of Denosumab therapy for osteoporosis: A systematic review and position statement by ECTS. Bone 2017, 105, 11–17. https://doi.org/10.1016/j.bone.2017.08.003.
79.
Ikebuchi, Y.; Aoki, S.; Honma, M.; et al. Coupling of bone resorption and formation by RANKL reverse signalling. Nature 2018, 561, 195–200. https://doi.org/10.1038/s41586-018-0482-7.
80.
Baron, R.; Ferrari, S.; Russell, R.G.G. Denosumab and bisphosphonates: Different mechanisms of action and effects. Bone 2011, 48, 677–692. https://doi.org/10.1016/j.bone.2010.11.020.
81.
Kim, T.Y.; Bauer, D.C.; McNabb, B.L.; et al. Comparison of BMD Changes and Bone Formation Marker Levels 3 Years After Bisphosphonate Discontinuation: FLEX and HORIZON-PFT Extension I Trials. J. Bone Miner. Res. 2019, 34, 810–816. https://doi.org/10.1002/jbmr.3654.
82.
Taylor, K.H.; Middlefell, L.S.; Mizen, K.D. Osteonecrosis of the jaws induced by anti-RANK ligand therapy. Br. J. Oral. Maxillofac. Surg. 2010, 48, 221–223. https://doi.org/10.1016/j.bjoms.2009.08.030.
83.
Tofé, V.I.; Bagán, L.; Bagán, J.V. Osteonecrosis of the jaws associated with denosumab: Study of clinical and radiographic characteristics in a series of clinical cases. J. Clin. Exp. Dent. 2020, 12, e676. https://doi.org/10.4317/jced.57019.
84.
Jung, S.; Kim, J.; Park, J.H.; et al. A 5-year retrospective cohort study of denosumab induced medication related osteonecrosis of the jaw in osteoporosis patients. Sci. Rep. 2022, 12, 8641. https://doi.org/10.1038/s41598-022-11615-9.
85.
Boquete-Castro, A.; Gómez-Moreno, G.; Calvo-Guirado, J.L.; et al. Denosumab and osteonecrosis of the jaw. A systematic analysis of events reported in clinical trials. Clin. Oral. Implant. Res. 2016, 27, 367–375. https://doi.org/10.1111/clr.12556.
86.
Hu, K.; Olsen, B.R. The roles of vascular endothelial growth factor in bone repair and regeneration. Bone 2016, 91, 30–38. https://doi.org/10.1016/j.bone.2016.06.013.
87.
Chim, S.M.; Tickner, J.; Chow, S.T.; et al. Angiogenic factors in bone local environment. Cytokine Growth Factor. Rev. 2013, 24, 297–310. https://doi.org/10.1016/j.cytogfr.2013.03.008.
88.
Peng, Y.; Wu, S.; Li, Y.; et al. Type H blood vessels in bone modeling and remodeling. Theranostics 2020, 10, 426–436. https://doi.org/10.7150/thno.34126.
89.
Estilo, C.L.; Fornier, M.; Farooki, A.; et al. Osteonecrosis of the Jaw Related to Bevacizumab. J. Clin. Oncol. 2008, 26, 4037–4038. https://doi.org/10.1200/JCO.2007.15.5424.
90.
Guarneri, V.; Miles, D.; Robert, N.; et al. Bevacizumab and osteonecrosis of the jaw: Incidence and association with bisphosphonate therapy in three large prospective trials in advanced breast cancer. Breast Cancer Res. Treat. 2010, 122, 181–188. https://doi.org/10.1007/s10549-010-0866-3.
91.
Marino, R.; Orlandi, F.; Arecco, F.; et al. Osteonecrosis of the jaw in a patient receiving cabozantinib. Aust. Dent. J. 2015, 60, 528–531. https://doi.org/10.1111/adj.12254.
92.
Suryani, I.R.; Ahmadzai, I.; Shujaat, S.; et al. Non-antiresorptive drugs associated with the development of medication-related osteonecrosis of the jaw: A systematic review and meta-analysis. Clin. Oral. Investig. 2022, 26, 2269–2279. https://doi.org/10.1007/s00784-021-04331-7.
93.
Cegieła, U.; Sliwiński, L.; Kaczmarczyk-Sedlak, I.; et al. In vivo effects of high-dose methotrexate on bone remodeling in rats. Pharmacol. Rep. 2005, 57, 504–514.
94.
Marotte, H.; Pallot-Prades, B.; Grange, L.; et al. A 1-year case-control study in patients with rheumatoid arthritis indicates prevention of loss of bone mineral density in both responders and nonresponders to infliximab. Arthritis Res. Ther. 2007, 9, R61. https://doi.org/10.1186/ar2219.
95.
Xie, Z.; Liu, G.; Tang, P.; et al. Bone-targeted methotrexate–alendronate conjugate inhibits osteoclastogenesis in vitro and prevents bone loss and inflammation of collagen-induced arthritis in vivo. Drug Deliv. 2018, 25, 187–197. https://doi.org/10.1080/10717544.2017.1422295.
96.
Perpétuo, I.P.; Caetano-Lopes, J.; Rodrigues, A.M.; et al. Methotrexate and low-dose prednisolone downregulate osteoclast function by decreasing receptor activator of nuclear factor-κβ expression in monocytes from patients with early rheumatoid arthritis. RMD Open 2017, 3, e000365. https://doi.org/10.1136/rmdopen-2016-000365.
97.
Vajda, F.; Szepesi, Á.; Várady, G.; et al. Comparison of Different Clinical Chemotherapeutical Agents’ Toxicity and Cell Response on Mesenchymal Stem Cells and Cancer Cells. Cells 2022, 11, 2942. https://doi.org/10.3390/cells11192942.
98.
Yu, S.; Ye, J.; Wang, Y.; et al. DNA damage to bone marrow stromal cells by antileukemia drugs induces chemoresistance in acute myeloid leukemia via paracrine FGF10–FGFR2 signaling. J. Biol. Chem. 2023, 299, 102787. https://doi.org/10.1016/j.jbc.2022.102787.
99.
Li, Y.; Jiang, L.; Zhang, S.; et al. Methotrexate attenuates the Th17/IL-17 levels in peripheral blood mononuclear cells from healthy individuals and RA patients. Rheumatol. Int. 2012, 32, 2415–2422. https://doi.org/10.1007/s00296-011-1867-1.
100.
Seitz, M.; Zwicker, M.; Loetscher, P. Effects of methotrexate on differentiation of monocytes and production of cytokine inhibitors by monocytes. Arthritis Rheum. 1998, 41, 2032–2038. https://doi.org/10.1002/1529-0131(199811)41:11<2032::AID-ART19>3.0.CO;2-J.
101.
Fu, Y.; Zhou, J.; Li, H.; et al. Daunorubicin induces procoagulant activity of cultured endothelial cells through phosphatidylserine exposure and microparticles release. Thromb. Haemost. 2010, 104, 1235–1241. https://doi.org/10.1160/TH10-02-0102.
102.
Soultati, A.; Mountzios, G.; Avgerinou, C.; et al. Endothelial vascular toxicity from chemotherapeutic agents: Preclinical evidence and clinical implications. Cancer Treat. Rev. 2012, 38, 473–483. https://doi.org/10.1016/j.ctrv.2011.09.002.
103.
Kim, D.W.; Jung, Y.-S.; Park, H.-S.; et al. Osteonecrosis of the jaw related to everolimus: A case report. Br. J. Oral. Maxillofac. Surg. 2013, 51, e302–e304. https://doi.org/10.1016/j.bjoms.2013.09.008.
104.
Giancola, F.; Campisi, G.; Russo, L.L.; et al. Osteonecrosis of the jaw related to everolimus and bisphosphonate: A unique case report? Ann. Stomatol. 2013, 4, 201.
105.
Marotta, M.; Boffano, P.; Prota, E.; et al. Guselkumab: A new etiological factor of medication related osteonecrosis of the jaw (MRONJ)? A case report. J. Stomatol. Oral. Maxillofac. Surg. 2024, 125, 101985. https://doi.org/10.1016/j.jormas.2024.101985.
106.
Hiraiwa, M.; Ozaki, K.; Yamada, T.; et al. mTORC1 Activation in Osteoclasts Prevents Bone Loss in a Mouse Model of Osteoporosis. Front. Pharmacol. 2019, 10, 684. https://doi.org/10.3389/fphar.2019.00684.
107.
Dai, Q.; Xie, F.; Han, Y.; et al. Inactivation of Regulatory-associated Protein of mTOR (Raptor)/Mammalian Target of Rapamycin Complex 1 (mTORC1) Signaling in Osteoclasts Increases Bone Mass by Inhibiting Osteoclast Differentiation in Mice. J. Biol. Chem. 2017, 292, 196–204. https://doi.org/10.1074/jbc.M116.764761.
108.
Zirngibl, R.A.; Voronov, I. The Role of mTOR in Osteoclasts. Autophagy Health Dis. 2018, 71–85. https://doi.org/10.1007/978-3-319-98146-8_5.
109.
Yago, T.; Nanke, Y.; Kawamoto, M.; et al. IL-23 induces human osteoclastogenesis via IL-17 in vitro, and anti-IL-23 antibody attenuates collagen-induced arthritis in rats. Arthritis Res. Ther. 2007, 9, R96. https://doi.org/10.1186/ar2297.
110.
Razawy, W.; Alves, C.H.; Koedam, M.; et al. IL-23 receptor deficiency results in lower bone mass via indirect regulation of bone formation. Sci. Rep. 2021, 11, 10244. https://doi.org/10.1038/s41598-021-89625-2.
111.
Furuya, H.; Nguyen, C.T.; Gu, R.; et al. Interleukin-23 Regulates Inflammatory Osteoclastogenesis via Activation of CLEC5A (+) Osteoclast Precursors. Arthritis Rheumatol. 2023, 75, 1477–1489. https://doi.org/10.1002/art.42478.
112.
Limones, A.; Sáez-Alcaide, L.M.; Díaz-Parreño, S.A.; et al. Medication-related osteonecrosis of the jaws (MRONJ) in cancer patients treated with denosumab vs. zoledronic acid: A systematic review and meta-analysis. Med. Oral. Patol. Oral. Cir. Bucal 2020, 25, e326–e336. https://doi.org/10.4317/medoral.23324.
113.
Wood, J.; Bonjean, K.; Ruetz, S.; et al. Novel Antiangiogenic Effects of the Bisphosphonate Compound Zoledronic Acid. J. Pharmacol. Exp. Ther. 2002, 302, 1055–1061. https://doi.org/10.1124/jpet.102.035295.
114.
Fournier, P.; Boissier, S.; Filleur, S.; et al. Bisphosphonates inhibit angiogenesis in vitro and testosterone-stimulated vascular regrowth in the ventral prostate in castrated rats. Cancer Res. 2002, 62, 653–844.
115.
Ziebart, T.; Pabst, A.; Klein, M.O.; et al. Bisphosphonates: Restrictions for vasculogenesis and angiogenesis: Inhibition of cell function of endothelial progenitor cells and mature endothelial cells in vitro. Clin. Oral. Investig. 2011, 15, 105–111. https://doi.org/10.1007/s00784-009-0365-2.
116.
Mantovani, A.; Biswas, S.K.; Galdiero, M.R.; et al. Macrophage plasticity and polarization in tissue repair and remodelling. J. Pathol. 2013, 229, 176–185. https://doi.org/10.1002/path.4133.
117.
Scoletta, M.; Arduino, P.G.; Dalmasso, P.; et al. Treatment outcomes in patients with bisphosphonate-related osteonecrosis of the jaws: A prospective study, Oral Surgery, Oral Medicine, Oral Pathology. Oral. Radiol. Endodontology 2010, 110, 46–53. https://doi.org/10.1016/j.tripleo.2010.02.020.
118.
Ji, X.; Pushalkar, S.; Li, Y.; et al. Antibiotic effects on bacterial profile in osteonecrosis of the jaw. Oral. Dis. 2012, 18, 85–95. https://doi.org/10.1111/j.1601-0825.2011.01848.x.
119.
Memar, M.Y.; Yekani, M.; Alizadeh, N.; et al. Hyperbaric oxygen therapy: Antimicrobial mechanisms and clinical application for infections. Biomed. Pharmacother. 2019, 109, 440–447. https://doi.org/10.1016/j.biopha.2018.10.142.
120.
De Wolde, S.D.; Hulskes, R.H.; Weenink, R.P.; et al. The Effects of Hyperbaric Oxygenation on Oxidative Stress. Inflamm. Angiogenesis Biomol. 2021, 11, 1210. https://doi.org/10.3390/biom11081210.
121.
Heck, T.; Lohana, D.; Mallela, D.; et al. Hyperbaric oxygen therapy as an adjunct treatment of periodontitis, MRONJ, and ONJ: A systematic literature review. Clin. Oral. Investig. 2024, 28, 77. https://doi.org/10.1007/s00784-023-05410-7.
122.
Watanabe, T.; Asai, K.; Fukuhara, S.; et al. Effectiveness of surgery and hyperbaric oxygen for antiresorptive agent-related osteonecrosis of the jaw: A subgroup analysis by disease stage. PLoS ONE 2021, 16, e0244859. https://doi.org/10.1371/journal.pone.0244859.
123.
Rupel, K.; Ottaviani, G.; Gobbo, M.; et al. A systematic review of therapeutical approaches in bisphosphonates-related osteonecrosis of the jaw (BRONJ). Oral. Oncol. 2014, 50, 1049–1057. https://doi.org/10.1016/j.oraloncology.2014.08.016.
124.
Sim, I.-W.; Borromeo, G.L.; Tsao, C.; et al. Teriparatide Promotes Bone Healing in Medication-Related Osteonecrosis of the Jaw: A Placebo-Controlled, Randomized Trial. J. Clin. Oncol. 2020, 38, 2971–2980. https://doi.org/10.1200/JCO.19.02192.
125.
Ersan, N.; van Ruijven, L.J.; Bronckers, A.L.J.J.; et al. Teriparatide and the treatment of bisphosphonate-related osteonecrosis of the jaw: A rat model. Dentomaxillofacial Radiol. 2014, 43, 20130144. https://doi.org/10.1259/dmfr.20130144.
126.
Liu, J.; Mattheos, N.; Deng, C.; et al. Management of medication-related osteonecrosis of jaw: Comparison between icariin and teriparatide in a rat model. J. Periodontol. 2021, 92, 149–158. https://doi.org/10.1002/JPER.19-0620.
127.
Park, K.-M.; Lee, N.; Kim, J.; et al. Preventive effect of teriparatide on medication-related osteonecrosis of the jaw in rats. Sci. Rep. 2023, 13, 15518. https://doi.org/10.1038/s41598-023-42607-y.
128.
Cheung, A.; Seeman, E. Teriparatide Therapy for Alendronate-Associated Osteonecrosis of the Jaw. N. Engl. J. Med. 2010, 363, 2473–2474. https://doi.org/10.1056/NEJMc1002684.
129.
Park, K.-S.; Jung, S.M.; Park, Y.-J.; et al. Denosumab-Related Osteonecrosis of the Jaw May Not Be a Subject of Teriparatide Treatment. J. Bone Miner. Res. 2020, 37, 2044–2045. https://doi.org/10.1002/jbmr.4625.
130.
Curi, M.M.; Cossolin, G.S.I.; Koga, D.H.; et al. 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. https://doi.org/10.1016/j.joms.2011.02.078.
131.
Dipalma, G.; Inchingolo, A.M.; Malcangi, G.; et al. Sixty-Month Follow Up of Clinical MRONJ Cases Treated with CGF and Piezosurgery. Bioengineering 2023, 10, 863. https://doi.org/10.3390/bioengineering10070863.
132.
Yüce, M.O.; Adalı, E.; Işık, G. The effect of concentrated growth factor (CGF) in the surgical treatment of medication-related osteonecrosis of the jaw (MRONJ) in osteoporosis patients: A randomized controlled study. Clin. Oral. Investig. 2021, 25, 4529–4541. https://doi.org/10.1007/s00784-020-03766-8.
133.
Urist, M.R. Bone: Formation by Autoinduction. Science 1965, 150, 893–899. https://doi.org/10.1126/science.150.3698.893.
134.
Riley, E.H.; Lane, J.M.; Urist, M.R.; et al. Bone morphogenetic protein-2: Biology and applications. Clin. Orthop. Relat. Res. 1996, 324, 39–46.
135.
Liu, Y.; Lin, D.; Li, B.; et al. BMP-2/CPC scaffold with dexamethasone-loaded blood clot embedment accelerates clinical bone regeneration. Am. J. Transl. Res. 2022, 14, 2874–2893.
136.
Jeon, E.Y.; Um, S.; Park, J.; et al. Precisely Localized Bone Regeneration Mediated by Marine-Derived Microdroplets with Superior BMP-2 Binding Affinity. Small 2022, 18, 2200416. https://doi.org/10.1002/smll.202200416.
137.
Kanatani, M.; Sugimoto, T.; Kaji, H.; et al. Stimulatory effect of bone morphogenetic protein-2 on osteoclast-like cell formation and bone-resorbing activity. J. Bone Miner. Res. 1995, 10, 1681–1690. https://doi.org/10.1002/jbmr.5650101110.
138.
Kaneko, H.; Arakawa, T.; Mano, H.; et al. Direct stimulation of osteoclastic bone resorption by bone morphogenetic protein (BMP)-2 and expression of BMP receptors in mature osteoclasts. Bone 2000, 27, 479–486. https://doi.org/10.1016/S8756-3282(00)00358-6.
139.
Itoh, K.; Udagawa, N.; Katagiri, T.; et al. Bone Morphogenetic Protein 2 Stimulates Osteoclast Differentiation and Survival Supported by Receptor Activator of Nuclear Factor-κB Ligand. Endocrinology 2001, 142, 3656–3662. https://doi.org/10.1210/endo.142.8.8300.
140.
Wang, Y.; Wu, N.-N.; Mu, Y.-Q.; et al. The effect of adenovirus-mediated siRNA targeting BMPR-II on UHMWPE-induced osteoclast formation. Biomaterials 2013, 34, 150–159. https://doi.org/10.1016/j.biomaterials.2012.09.059.
141.
Omi, M.; Kaartinen, V.; Mishina, Y. Activin A receptor type 1–mediated BMP signaling regulates RANKL-induced osteoclastogenesis via canonical SMAD-signaling pathway. J. Biol. Chem. 2019, 294, 17818–17836. https://doi.org/10.1074/jbc.RA119.009521.
142.
Miao, X.; Yuan, J.; Wu, J.; et al. Bone Morphogenetic Protein-2 Promotes Osteoclasts-mediated Osteolysis via Smad1 and p65 Signaling. Pathways 2021, 46, E234–E242. https://doi.org/10.1097/BRS.0000000000003770.
143.
Tachi, K.; Takami, M.; Zhao, B.; et al. Bone morphogenetic protein 2 enhances mouse osteoclast differentiation via increased levels of receptor activator of NF-κB ligand expression in osteoblasts. Cell Tissue Res. 2010, 342, 213–220. https://doi.org/10.1007/s00441-010-1052-y.
144.
Ning, H.; Wu, X.; Wu, Q.; et al. Microfiber-Reinforced Composite Hydrogels Loaded with Rat Adipose-Derived Stem Cells and BMP-2 for the Treatment of Medication-Related Osteonecrosis of the Jaw in a Rat Model. ACS Biomater. Sci. Eng. 2019, 5, 2430–2443. https://doi.org/10.1021/acsbiomaterials.8b01468.
145.
Mikai, A.; Ono, M.; Tosa, I.; et al. BMP-2/β-TCP Local Delivery for Bone Regeneration in MRONJ-Like Mouse Model. Int. J. Mol. Sci. 2020, 21, 7028. https://doi.org/10.3390/ijms21197028.
146.
Dang, A.T.; Ono, M.; Wang, Z.; et al. Local E-rhBMP-2/β-TCP Application Rescues Osteocyte Dendritic Integrity and Reduces Microstructural Damage in Alveolar Bone Post-Extraction in MRONJ-like Mouse Model. Int. J. Mol. Sci. 2024, 25, 6648. https://doi.org/10.3390/ijms25126648.
147.
Tanaka, Y.; Aung, K.T.; Ono, M.; et al. Suppression of Bone Necrosis around Tooth Extraction Socket in a MRONJ-like Mouse Model by E-rhBMP-2 Containing Artificial Bone Graft Administration. Int. J. Mol. Sci. 2021, 22, 12823. https://doi.org/10.3390/ijms222312823.
148.
Brierly, G.I.; Ren, J.; Baldwin, J.; et al. Investigation of Sustained BMP Delivery in the Prevention of Medication-Related Osteonecrosis of the Jaw (MRONJ) in a Rat Model. Macromol. Biosci. 2019, 19, 1900226. https://doi.org/10.1002/mabi.201900226.
149.
Park, J.-H.; Kim, J.-W.; Kim, S.-J. Does the Addition of Bone Morphogenetic Protein 2 to Platelet-Rich Fibrin Improve Healing After Treatment for Medication-Related Osteonecrosis of the Jaw? J. Oral. Maxillofac. Surg. 2017, 75, 1176–1184. https://doi.org/10.1016/j.joms.2016.12.005.
150.
Min, S.-H.; Kang, N.-E.; Song, S.-I.; et al. Regenerative effect of recombinant human bone morphogenetic protein-2/absorbable collagen sponge (rhBMP-2/ACS) after sequestrectomy of medication-related osteonecrosis of the jaw (MRONJ). J. Korean Assoc. Oral. Maxillofac. Surg. 2020, 46, 191–196. https://doi.org/10.5125/jkaoms.2020.46.3.191.
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Volume 1, Issue 1How to Cite
Xu, C., Xiao, Y., Wu, Y., Bakker, A., & Liu, Y. (2024). Impaired Osteoclastogenesis in Medication-Related Osteonecrosis and Potential Clinical Management with BMP-2. Regenerative Medicine and Dentistry, 1(1), 5. https://doi.org/10.53941/rmd.2024.100005
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