Effects of NSAIDs and environmental oxygen pressure on bone regeneration.

  • Victor Chumpitaz-Cerrate Laboratorio de Fisiología y Farmacología, Facultad de Odontología, Universidad Nacional Mayor de San Marcos, Lima, Perú. Laboratorio de Farmacología, Facultad de Ciencias de la Salud, Universidad Científica del Sur, Lima, Perú
  • Lesly Chávez-Rimache Laboratorio de Fisiología y Farmacología, Facultad de Odontología, Universidad Nacional Mayor de San Marcos, Lima, Perú.
  • César Franco-Quino Laboratorio de Fisiología y Farmacología, Facultad de Odontología, Universidad Nacional Mayor de San Marcos, Lima, Perú. Laboratorio de Farmacología, Facultad de Ciencias de la Salud, Universidad Científica del Sur, Lima, Perú
  • Elías Aguirre-Siancas Laboratorio de Fisiología y Farmacología, Facultad de Odontología, Universidad Nacional Mayor de San Marcos, Lima, Perú. Laboratorio de Embriología e Histología, Facultad de Ciencias de la Salud, Universidad Científica del Sur, Lima, Perú.
  • Victoria Caldas-Cueva Laboratorio de Fisiología y Farmacología, Facultad de Odontología, Universidad Nacional Mayor de San Marcos, Lima, Perú.
  • Eliberto Ruíz-Ramírez Laboratorio de Fisiología y Farmacología, Facultad de Odontología, Universidad Nacional Mayor de San Marcos, Lima, Perú. Laboratorio de Farmacología, Facultad de Ciencias de la Salud, Universidad Científica del Sur, Lima, Perú

Abstract

Objective: To evaluate the effects of administering diclofenac and ketoprofen, as well as the effects of environmental oxygen pressure variation on mandibular bone regeneration. Methods: Thirty-six guinea pigs were distributed into two equal groups. Mandibular bone defects were performed on both groups. Group A was monitored under oxygen pressure at altitude (3320msl, 107mm Hg). Group B was monitored at sea level oxygen pressure (150msl, 157mm Hg). Each group was subdivided into 3 equal groups (A1, A2, A3 and B1, B2, B3). Subgroups A1 and B1 were given diclofenac; subgroups A2 and B2 ketoprofen; subgroups A3 and B3 NaCl. Bone regeneration was evaluated histologically on days 15 and 30. Results: After 15 days in the group controlled at sea level, the level of osteoblasts presented by the control subgroup was significantly higher (28.00±2.65) compared to the diclofenac subgroup (16.00±6.25) and to the ketoprofen subgroup (18.00±4.36); (p=0.041). After 15 days in the group controlled at altitude, the level of osteoblasts was significantly higher in the control subgroup (38.00±5.29) compared to the diclofenac subgroup (21.67±6.35) and to the ketoprofen subgroup (19.33±2.52); p=0.007. After 30 days in the group at sea level there was no difference found in the cell counting; p>0.05. After 30 days in the group controlled at altitude, the level of osteoblast was significantly higher in the control subgroup (58.00±4.58) compared to the diclofenac subgroup (34.33±4.73) and the ketoprofen subgroup (34.00±11.14); (p=0.003). Conclusion: The administration of diclofenac and ketoprofen produced lower mandibular bone regeneration, the effect being significantly more negative at sea level.

References

1. Abou-Khalil R, Colnot C. Cellular and molecular bases of skeletal regeneration: what can we learn from genetic mouse models? Bone. 2014;64:211–21.
2. Luo DJ, Miller C, Jirjis T, Nasir M, Sharma D. The effect of non-steroidal anti-inflammatory drugs on the osteogenic activity in osseointegration: a systematic review. Int J Implant Dent. 2018;4(1):30.
3. Chen YC, Lin YH, Wang SH, Lin SP, Shung KK, Wu CC. Monitoring tissue inflammation and responses to drug treatments in early stages of mice bone fracture using 50 MHz ultrasound. Ultrasonics. 2014;54(1):177–86.
4. García-Martínez O, De Luna-Bertos E, Ramos-Torrecillas J, Manzano-Moreno FJ, Ruiz C. Repercussions of NSAIDS drugs on bone tissue: the osteoblast. Life Sci. 2015;123:72–7.
5. Geusens P, Emans PJ, de Jong JJ, van den Bergh J. NSAIDs and fracture healing. Curr Opin Rheumatol. 2013;25(4):524–31.
6. Inagaki Y, Akahane M, Shimizu T, Inoue K, Egawa T, Kira T, Ogawa M, Kawate K, Tanaka Y. Modifying oxygen tension affects bone marrow stromal cell osteogenesis for regenerative medicine. World J Stem Cells. 2017;9(7):98–106.
7. Lu C, Saless N, Wang X, Sinha A, Decker S, Kazakia G, Hou H, Williams B, Swartz HM, Hunt TK, Miclau T, Marcucio RS. The role of oxygen during fracture healing. Bone. 2013;52(1):220–9.
8. Nicolaije C, van de Peppel J, van Leeuwen JP. Oxygen-induced transcriptional dynamics in human osteoblasts are most prominent at the onset of mineralization. J Cell Physiol. 2013;228(9):1863–72.
9. Asociación Médica Mundial (AMM). Declaración de la amm sobre el uso de animales en la investigación biomédica. Available from:https://www.wma.net/es/policies-post/declaracion-de-la-amm-sobre-el-uso-de-animales-en-la-investigacion-biomedica/
10. Boyan BD, Lohmann CH, Sisk M, Liu Y, Sylvia VL, Cochran DL, Dean DD, Schwartz Z. Both cyclooxygenase-1 and cyclooxygenase-2 mediate osteoblast response to titanium surface roughness. J Biomed Mater Res. 2001;55(3):350–9.
11. Karakawa A, Sano T, Amano H, Yamada S. Inhibitory mechanism of non-steroidal anti-inflammatory drugs on osteoclast differentiation and activation. J Oral Biosci. 2010;52(2):119–24.
12. Lumawig JM, Yamazaki A, Watanabe K. Dose-dependent inhibition of diclofenac sodium on posterior lumbar interbody fusion rates. Spine J. 2009;9(5):343–9.
13. Inal S, Kabay S, Cayci MK, Kuru HI, Altikat S, Akkas G, Deger A. Comparison of the effects of dexketoprofen trometamol, meloxicam and diclofenac sodium on fibular fracture healing, kidney and liver: an experimental rat model. Injury. 2014;45(3):494–500.
14. Sevimli R, Uzel M, Sayar H, Kalender AM, Dökmeci O. The effect of dexketoprofen trometamol on the healing of diaphysis fractures of rat tibia. Acta Orthop Traumatol Turc. 2013;47(6):423–9.
15. Huo MH, Troiano NW, Pelker RR, Gundberg CM, Friedlaender GE. The influence of ibuprofen on fracture repair: biomechanical, biochemical, histologic, and histomorphometric parameters in rats. J Orthop Res. 1991;9(3):383–90.
16. Williams LJ, Pasco JA, Henry MJ, Sanders KM, Nicholson GC, Kotowicz MA, Berk M. Paracetamol (acetaminophen) use, fracture and bone mineral density. Bone. 2011;48(6):1277–81.
17. Zhang Y, Wang X, Qiu Y, Cornish J, Carr AJ, Xia Z. Effect of indomethacin and lactoferrin on human tenocyte proliferation and collagen formation in vitro. Biochem Biophys Res Commun. 2014;454(2):301–7.
18. Hatipoglu MG, Inal S, Kabay S, Cayci MK, Deger A, Kuru HI, Altikat S, Akkas G. The Influence of Different Nonsteroidal Anti-Inflammatory Drugs on Alveolar Bone in Rats: An Experimental Study. Acta Stomatol Croat. 2015;49(4):325–30.
19. Cai WX, Ma L, Zheng LW, Kruse-Gujer A, Stübinger S, Lang NP, Zwahlen RA. Influence of non-steroidal anti-inflammatory drugs (NSAIDs) on osseointegration of dental implants in rabbit calvaria. Clin Oral Implants Res. 2015;26(4):478–83.
20. Nyangoga H, Aguado E, Goyenvalle E, Baslé MF, Chappard D. A non-steroidal anti-inflammatory drug (ketoprofen) does not delay beta-TCP bone graft healing. Acta Biomater. 2010;6(8):3310–7.
21. Wada K, Yu W, Elazizi M, Barakat S, Ouimet MA, Rosario-Meléndez R, Fiorellini JP, Graves DT, Uhrich KE. Locally delivered salicylic acid from a poly(anhydride-ester): impact on diabetic bone regeneration. J Control Release. 2013;171(1):33–7.
22. Vestergaard P, Steinberg TH, Schwarz P, Jørgensen NR. Use of the oral platelet inhibitors dipyridamole and acetylsalicylic acid is associated with increased risk of fracture. Int J Cardiol. 2012;160(1):36–40.
23. Jiang X, Zhang Y, Fan X, Deng X, Zhu Y, Li F. The effects of hypoxia-inducible factor (HIF)-1α protein on bone regeneration during distraction osteogenesis: an animal study. Int J Oral Maxillofac Surg. 2016;45(2):267–72.
24. Oishi S, Shimizu Y, Hosomichi J, Kuma Y, Maeda H, Nagai H, Usumi-Fujita R, Kaneko S, Shibutani N, Suzuki JI, Yoshida KI, Ono T. Intermittent Hypoxia Influences Alveolar Bone Proper Microstructure via Hypoxia-Inducible Factor and VEGF Expression in Periodontal Ligaments of Growing Rats. Front Physiol. 2016;7:416.
25. Wang Y, Li J, Wang Y, Lei L, Jiang C, An S, Zhan Y, Cheng Q, Zhao Z, Wang J, Jiang L. Effects of hypoxia on osteogenic differentiation of rat bone marrow mesenchymal stem cells. Mol Cell Biochem. 2012;362(1-2):25–33.
26. Grayson WL, Zhao F, Izadpanah R, Bunnell B, Ma T. Effects of hypoxia on human mesenchymal stem cell expansion and plasticity in 3D constructs. J Cell Physio. 2006;207(2):331–9.
27. Wagegg M, Gaber T, Lohanatha FL, Hahne M, Strehl C, Fangradt M, Tran CL, Schönbeck K, Hoff P, Ode A, Perka C, Duda GN, Buttgereit F. Hypoxia promotes osteogenesis but suppresses adipogenesis of human mesenchymal stromal cells in a hypoxia-inducible factor-1 dependent manner. PLoS One. 2013;7(9):e46483.
28. Lee JS, Kim SK, Jung BJ, Choi SB, Choi EY, Kim CS. Enhancing proliferation and optimizing the culture condition for human bone marrow stromal cells using hypoxia and fibroblast growth factor-2. Stem Cell Res. 2018;28:87–95.
Published
2019-05-28
How to Cite
CHUMPITAZ-CERRATE, Victor et al. Effects of NSAIDs and environmental oxygen pressure on bone regeneration.. Journal of Oral Research, [S.l.], v. 8, n. 2, p. 152-158, may 2019. ISSN 0719-2479. Available at: <http://www.joralres.com/index.php/JOR/article/view/786>. Date accessed: 20 aug. 2019. doi: https://doi.org/10.17126/jor.v8i2.786.
Section
Articles