Serum levels of RANKL and OPG, and the RANKL/OPG ratio in bisphosphonate-related osteonecrosis of the jaware they useful biomarkers for the advanced stages of osteonecrosis?

  1. Leticia Bagán Debón 1
  2. Yolanda Jiménez Soriano 2
  3. Manuel Leopoldo Rodado 3
  4. A. Rubert 4
  5. José Vicente Bagán Sebastián 5
  1. 1 Associate Professor of Oral Medicine. Universidad Europea de Valencia
  2. 2 Professor of oral manifestations of systemic diseases. Valencia University
  3. 3 Oral and Maxillofacial Surgeon. Consultant. University General Hospital
  4. 4 Associate Professor of Clinical Dentistry. Universidad Europea de Valencia
  5. 5 Professor of Oral Medicine, Valencia University. Head Service of Stomatology and Maxillofacial Surgery, University General Hospital. Fundación para la investigación del Hospital General Universitario de Valencia, Spain
Mostrar afiliaciones +
Revista:
Medicina oral, patología oral y cirugía bucal. Ed. inglesa

ISSN: 1698-6946

Año de publicación: 2017

Volumen: 22

Número: 5

Páginas: 4

Tipo: Artículo

DOI: 10.4317/MEDORAL.22128 DIALNET GOOGLE SCHOLAR lock_openAcceso abierto editor

Otras publicaciones en: Medicina oral, patología oral y cirugía bucal. Ed. inglesa

Resumen

We determined whether serum levels of Receptor Activator for Nuclear Factor κ B Ligand (RANKL), Osteoprotegerin (OPG), and the RANKL/OPG ratio could be useful biomarkers for the severity of oral lesions in bisphosphonate-related osteonecrosis of the jaw (BRONJ). A case-control study in which Group 1 consisted of 41 patients with BRONJ due to intravenous bisphosphonates, and Group 2 consisted of 44 healthy control cases. The plasma levels of RANKL and OPG were analyzed by an ELISA assay. The OPG/RANKL ratio was also calculated. We determined if the mean serum values differed among the different stages of BRONJ. Serum levels of RANKL were lower in Group 1 than in Group 2 (p =0.01), and serum levels of OPG were higher in patients with BRONJ than in the controls (p =0.006). The ratio of RANKL/OPG was greater in the controls than in Group 1 (P >0.01). There were no significant differences in the serum levels of RANKL and OPG among the different stages of osteonecrosis (P > 0.05). Serum levels of RANKL and OPG, and the RANKL/OPG ratio were not valuable biomarkers for determining the severity of oral lesions in patients with BRONJ.

Referencias bibliográficas

  • Marx, RE. (2003). Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg. 61. 1115
  • Ruggiero, SL, Fantasia, J, Carlson, E. (2006). Bisphosphonate-related osteonecrosis of the jaw: background and guidelines for diagnosis, staging and management. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 102. 433
  • Ruggiero, SL, Dodson, TB, Assael, LA, Landesberg, R, Marx, RE, Mehrotra, B. (2009). American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws--2009 update. J Oral Maxillofac Surg. 67. 2-12
  • Allen, MR, Ruggiero, SL. (2009). Higher bone matrix density exists in only a subset of patients with bisphosphonate-related osteonecrosis of the jaw. J Oral Maxillofac Surg. 67. 1373
  • Bagan, JV, Hens-Aumente, E, Leopoldo-Rodado, M, Poveda-Roda, R, Bagan, L. (2012). Bisphosphonate-related osteonecrosis of the jaws: study of the staging system in a series of clinical cases. 19. Oral Oncol. 48. 753
  • Manzaneque, A, Chaguaceda, C, Mensa, M, Bastida, C, Creus-Baró, N. (2017). Use and safety of denosumab in cancer patients. Int J Clin Pharm. 39. 522
  • Hoefert, S, Yuan, A, Munz, A, Grimm, M, Elayouti, A, Reinert, S. (2017). Clinical course and therapeutic outcomes of operatively and non-operatively managed patients with denosumab-related osteonecrosis of the jaw (DRONJ). J Craniomaxillofac Surg. 45. 570
  • Vyas, S, Hameed, S, Murugaraj, V. (2014). Denosumab-associated osteonecrosis of the jaw--a case report. 13. Dent Update. 41. 449
  • Fusco, V, Santini, D, Armento, G, Tonini, G, Campisi, G. (2016). Osteonecrosis of jaw beyond antiresorptive (bone-targeted) agents: new horizons in oncology. Expert Opin Drug Saf. 15. 925
  • Ruggiero, SL, Dodson, TB, Fantasia, J, Goodday, R, Aghaloo, T, Mehrotra, B. (2014). American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw--2014 update. J Oral Maxillofac Surg. 72. 1938
  • Yuan, H, Niu, LN, Jiao, K, Pei, DD, Pramanik, C, Li, JY. (2016). Revival of nitrogen-containing bisphosphonate-induced inhibition of osteoclastogenesis and osteoclast function by water-soluble microfibrous borate glass. Acta Biomater. 31. 312
  • Kimachi, K, Kajiya, H, Nakayama, S, Ikebe, T, Okabe, K. (2011). Zoledronic acid inhibits RANK expression and migration of osteoclast precursors during osteoclastogenesis. Naunyn Schmiedebergs Arch Pharmacol. 383. 297-308
  • Çankaya, M, Cizmeci Şenel, F, Kadioglu Duman, M, Muci, E, Dayisoylu, EH, Balaban, F. (2013). The effects of chronic zoledronate usage on the jaw and long bones evaluated using RANKL and osteoprotegerin levels in an animal model. 17. Int J Oral Maxillofac Surg. 42. 1134
  • Risk factors for medication-related osteonecrosis of the jaws:A systematic review. Oral Dis.
  • Russell, RG, Croucher, PI, Rogers, MJ. (1999). Bisphosphonates: pharmacology, mechanisms of action and clinical uses. Osteoporos Int. 92. 66-80
  • Drake, MT, Clarke, BL, Khosla, S. (2008). Bisphosphonates: mechanism of action and role in clinical practice. Mayo Clin Proc. 83. 1032
  • Parfitt, AM, Mundy, GR, Roodman, GD, Hughes, DE, Boyce, BF. (1996). A new model for the regulation of bone resorption, with particular reference to the effects of bisphosphonates. J Bone Miner Res. 11. 150
  • Nadar, RA, Margiotta, N, Iafisco, M, van den Beucken, JJJP, Boerman, OC, Leeuwenburgh, SCG. (2017). Bisphosphonate-Functionalized Imaging Agents, Anti-Tumor Agents and Nanocarriers for Treatment of Bone Cancer. Adv Healthc Mater. 6.
  • Sandhöfer, B, Meckel, M, Delgado-López, JM, Patrício, T, Tampieri, A, Rösch, F. (2015). Synthesis and preliminary in vivo evaluation of well-dispersed biomimetic nanocrystalline apatites labeled with positron emission tomographic imaging agents. ACS Appl Mater Interfaces. 7. 10623
  • Coxon, FP, Thompson, K, Rogers, MJ. (2006). Recent advances in understanding the mechanism of action of bisphosphonates. Curr Opin Pharmacol. 6. 307
  • Caraglia, M, Santini, D, Marra, M, Vincenzi, B, Tonini, G, Budillon, A. (2006). Emerging anti-cancer molecular mechanisms of aminobisphosphonates. Endocr Relat Cancer. 13. 7-26
  • Cummings, SR, San Martin, J, McClung, MR, Siris, ES, Eastell, R, Reid, IR. (2009). Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 361. 756
  • Bagan, J, Peydró, A, Calvo, J, Leopoldo, M, Jiménez, Y, Bagan, L. (2016). Medication-related osteonecrosis of the jaw associated with bisphosphonates and denosumab in osteoporosis. Oral Dis. 22. 324
  • Marx, RE, Cillo, JE Jr, Ulloa, JJ. (2007). Oral bisphosphonate-induced osteonecrosis: risk factors, prediction of risk using serum CTX testing, prevention, and treatment. J Oral Maxillofac Surg. 65. 2397
  • Kwon, YD, Kim, DY, Ohe, JY, Yoo, JY, Walter, C. (2009). Correlation between serum C-terminal cross-linking telopeptide of type I collagen and staging of oral bisphosphonate-related osteonecrosis of the jaws. J Oral Maxillofac Surg. 67. 2644
  • Bagan, JV, Jiménez, Y, Gómez, D, Sirera, R, Poveda, R, Scully, C. (2008). Collagen telopeptide (serum CTX) and its relationship with the size and number of lesions in osteonecrosis of the jaws in cancer patients on intravenous bisphosphonates. Oral Oncol. 44. 1088
  • Friedlander, AH, Chang, TI, Hazboun, RC, Garrett, NR. (2015). High C-Terminal Cross-Linking Telopeptide Levels Are Associated With a Minimal Risk of Osteonecrosis of the Jaws in Patients Taking Oral Bisphosphonates and Having Exodontia. J Oral Maxillofac Surg. 73. 1735
  • Bagan, J, Sáez, GT, Tormos, MC, Hens, E, Terol, MJ, Bagan, L. (2014). Interleukin-6 concentration changes in plasma and saliva in bisphosphonate-related osteonecrosis of the jaws. Oral Dis. 20. 446
  • Lee, CY, Pien, FD, Suzuki, JB. (2011). Identification and treatment of bisphosphonate-associated actinomycotic osteonecrosis of the jaws. 2. Implant Dent. 20. 331
  • Anavi-Lev, K, Anavi, Y, Chaushu, G, Alon, DM, Gal, G, Kaplan, I. (2013). Bisphosphonate related osteonecrosis of the jaws: clinico-pathological investigation and histomorphometric analysis. 1. Oral Surg Oral Med Oral Pathol Oral Radiol. 115. 660
  • Bagan, J, Sáez, GT, Tormos, MC, Gavalda-Esteve, C, Bagan, L, Leopoldo-Rodado, M. (2014). Oxidative stress in bisphosphonate-related osteonecrosis of the jaws. 6. J Oral Pathol Med. 43. 371
  • Abe, T, Sato, T, Kokabu, S, Hori, N, Shimamura, Y, Sato, T. (2016). 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. 83. 1-7
  • Koch, FP, Merkel, C, Ziebart, T, Smeets, R, Walter, C, Al-Nawas, B. (2012). Influence of bisphosphonates on the osteoblast RANKL and OPG gene expression in vitro. 18. Clin Oral Investig. 161. 79-86
  • Di Nisio, C, Zizzari, VL, Zara, S, Falconi, M, Teti, G, Tetè, G. (2015). RANK/RANKL/OPG signaling pathways in necrotic jaw bone from bisphosphonate-treated subjects. Eur J Histochem. 59. 2455
  • Schiodt, M, Reibel, J, Oturai, P, Kofod, T. (2014). Comparison of nonexposed and exposed bisphosphonate-induced osteonecrosis of the jaws: a retrospective analysis from the Copenhagen cohort and a proposal for an updated classification system. Oral Surg Oral Med Oral Pathol Oral Radiol. 117. 204
  • Mawardi, H, Woo, SB. (2015). Medication-related osteonecrosis of the jaws, stage 0--do we need stage 0 any more?. J Oral Maxillofac Surg. 73. 797
Fuente de los datos: Dialnet