13.07.2015 Views

Immunosuppressants: Implications in Orthodontics - Dental Press

Immunosuppressants: Implications in Orthodontics - Dental Press

Immunosuppressants: Implications in Orthodontics - Dental Press

SHOW MORE
SHOW LESS

Create successful ePaper yourself

Turn your PDF publications into a flip-book with our unique Google optimized e-Paper software.

orig<strong>in</strong>al article<strong>Immunosuppressants</strong>: <strong>Implications</strong> <strong>in</strong> orthodonticswho showed greater tooth movement <strong>in</strong> animals subjectedto these medications. As occurs with glucocorticoids,Cyclospor<strong>in</strong>e affects alveolar bone caus<strong>in</strong>gdeleterious periodontal effects that may be due tothe reduction <strong>in</strong> bone volume and number of osteoblasts,and <strong>in</strong>crease <strong>in</strong> osteoclasts. 29 In rats markedg<strong>in</strong>gival growth and bone loss were observed 28 , howevermore uniformly than those observed <strong>in</strong> humanbe<strong>in</strong>gs 13 due to environmental and genetic factors.Recently, Kir<strong>in</strong>o et al 18 <strong>in</strong> a study with animalssubmitted to the application of tacrolimus, observedth<strong>in</strong>ner bone trabeculae, wider medullary cavities 18and <strong>in</strong>crease <strong>in</strong> the number of osteoclasts. 25 Studieshave demonstrated that both Cyclospor<strong>in</strong> and tacrolimusmay <strong>in</strong>duce bone loss both <strong>in</strong> human be<strong>in</strong>gsand <strong>in</strong> experimental animal models, 2 through<strong>in</strong>terleuk<strong>in</strong> gene expression (IL-1, IL-6 and tumornecrosis factor –TNFα), 19 the cytok<strong>in</strong>es that participate<strong>in</strong> bone resorption.Immunosuppressant activity with Rapamic<strong>in</strong>efor long periods 6 or <strong>in</strong> high doses <strong>in</strong>creases bone remodel<strong>in</strong>gand <strong>in</strong>hibits longitud<strong>in</strong>al bone growth, reduc<strong>in</strong>gthe speed of growth by around 30 to 50%, 3 <strong>in</strong>addition to <strong>in</strong>hibit<strong>in</strong>g different cell types, <strong>in</strong>clud<strong>in</strong>gsmooth muscle vascular cells and fibroblasts thatare not part of the immune system. 32 Other immunosuppressantssuch as, Mycophenolate mofetil 10and Azathiopr<strong>in</strong>e 6 showed no deleterious effects onbone m<strong>in</strong>eral density.<strong>Immunosuppressants</strong> represent great advancement<strong>in</strong> the control of different types of diseases, andsuppression of the immune response aga<strong>in</strong>st transplantedorgans, however, a large portion of these medicationsare capable of <strong>in</strong>fluenc<strong>in</strong>g bone metabolismand tooth movement.The orthodontist may frequently encounter patientsthat require prolonged immunosuppressivetherapy and orthodontic treatment. Usually, patients<strong>in</strong> the <strong>in</strong>itial stage of these medications usage maybe advised to delay orthodontic treatment, as therewould be less bone remodel<strong>in</strong>g, or orthodontic activationappo<strong>in</strong>tments should be scheduled at longer<strong>in</strong>tervals. On the other hand, long term medicationtherapy may accelerate tooth movement, thus orthodonticappliances must be adjusted customarily, orwith greater frequency. Medical follow-up with cl<strong>in</strong>icaland densitometry periodic exams are necessary<strong>in</strong> order to obta<strong>in</strong> more predictable and satisfactoryorthodontic results.Conclusion1) <strong>Immunosuppressants</strong> that affect cytok<strong>in</strong>esynthesis (glucocorticoids, cyclospor<strong>in</strong>-CsA,tacrolimus-FK506 and Sirolimus-RAPA) <strong>in</strong>terfere<strong>in</strong> bone metabolism and may <strong>in</strong>fluencetooth movement.2) Interference <strong>in</strong> bone metabolism is dependenton the force applied, dose and duration of immunosuppressanttherapy, <strong>in</strong> addition to the <strong>in</strong>dividualresponse of each patient, except to azathiopr<strong>in</strong>eand Mycophenolate mofetil that haveshown no deleterious effect on bone density.© 2012 <strong>Dental</strong> <strong>Press</strong> Journal of <strong>Orthodontics</strong> 60<strong>Dental</strong> <strong>Press</strong> J Orthod. 2012 Mar-Apr;17(2):55-61


Santos RL, Lacerda MCM, Gonçalves RT, Mart<strong>in</strong>s MA, Souza MMGReferences1. Abbud-Filho M, Ramalho HJ. Revisão/atualização em transplante renal: novosagentes imunossupressores. J Bras Nefrol. 1997;19(2):215-23.2. Abdelhadi M, Ericzon BG, Hultenby K, Sjöden G, Re<strong>in</strong>holt FP, Nordenström J.Structural skeletal impairment <strong>in</strong>duced by immunosuppressive therapy <strong>in</strong> rats:cyclospor<strong>in</strong>e A vs tacrolimus. Transpl Int. 2002;15(4):180-7. Epub 2002 Apr 6.3. Alvarez-Garcia O, Carbajo-Pérez E, Garcia E, Gil H, Mol<strong>in</strong>os I, Rodriguez J, et al.Rapamyc<strong>in</strong> retards growth and causes marked alterations <strong>in</strong> the growth plate ofyoung rats. Pediatr Nephrol. 2007;22(7):954-61. Epub 2007 Mar 17.4. Bol<strong>in</strong>g EP. Secondary osteoporosis: underly<strong>in</strong>g disease and the risk forglucocorticoid-<strong>in</strong>duced osteoporosis. Cl<strong>in</strong> Ther. 2004;26(1):1-14.5. Borel JF, Feurer C, Gubler HU, Stähel<strong>in</strong> H. Biological effects of cyclospor<strong>in</strong> A: a newantilymphocytic agent. Agents Actions. 1976;6(4):468-75.6. Bryer HP, Isserow JA, Armstrong EC, Mann GN, Ruc<strong>in</strong>ski B, Buch<strong>in</strong>sky FJ, et al.Azathiopr<strong>in</strong>e alone is bone spar<strong>in</strong>g and does not alter cyclospor<strong>in</strong> A-<strong>in</strong>ducedosteopenia <strong>in</strong> the rat. J Bone M<strong>in</strong>er Res. 1995;10(1):132-8.7. Canalis E, Giust<strong>in</strong>a A. Glucocorticoid-<strong>in</strong>duced osteoporosis: summary of aworkshop. J Cl<strong>in</strong> Endocr<strong>in</strong>ol Metab. 2001;9(86):5681-5.8. Chung J, Kuo CJ, Crabtree GR, Blenis J. Rapamyc<strong>in</strong>-FKBP specifically blocksgrowth-dependent activation of and signal<strong>in</strong>g by the 70 kd S6 prote<strong>in</strong> k<strong>in</strong>ases. Cell.1992;69(7):1227-36.9. Cipriani RE, Farias ML. Osteoporose após transplante de órgãos sólidos. Arq BrasEndocr<strong>in</strong>ol Metabol. 2005;49(3):369-77.10. Dissanayake IR, Goodman GR, Bowman AR, Ma Y, Pun S, Jee WS, et al.Mycophenolate mofetil: a promis<strong>in</strong>g new immunosuppressant that does not causebone loss <strong>in</strong> the rat. Transplantation. 1998;65(2):275-8.11. Gameiro GH, Pereira-Neto JS, Magnani MB, Nouer DF. The <strong>in</strong>fluence of drugs andsystemic factors on orthodontic tooth movement. J Cl<strong>in</strong> Orthod. 2007;41(2):73-8;quiz 71.12. Goto T, K<strong>in</strong>o T, Hatanaka H, Nishiyama M, Okuhara M, Kohsaka M, et al. Discoveryof FK-506, a novel immunosuppressant isolated from Streptomyces tsukubaensis.Transplant Proc. 1987;19(5 Suppl 6):4-8.13. Guimarães MR, Nassar PO, Andia DC, Nassar CA, Spolidorio DM, Rossa C Jr,et al. Protective effects of Tacrolimus, a calc<strong>in</strong>eur<strong>in</strong> <strong>in</strong>hibitor, <strong>in</strong> experimentalperiodontitis <strong>in</strong> rats. Arch Oral Biol. 2007;52(9):882-8. Epub 2007 Mar 23.14. Hirotani H, Tuohy NA, Woo JT, Stern PH, Clipstone NA. The calc<strong>in</strong>eur<strong>in</strong>/nuclearfactor of activated T cells signal<strong>in</strong>g pathway regulates osteoclastogenesis <strong>in</strong>RAW264.7 cells. J Biol Chem. 2004;279(14):13984-92.15. Holste<strong>in</strong> JH, Kle<strong>in</strong> M, Garcia P, Hist<strong>in</strong>g T, Culemann U, Pizanis A, et al. Rapamyc<strong>in</strong>affects early fracture heal<strong>in</strong>g <strong>in</strong> mice. Br J Pharmacol. 2008;12(14):210-21.16. Hricik DE, Almawi WY, Strom TB. Trends <strong>in</strong> the use of glucocorticoids <strong>in</strong> renaltransplantation. Transplantation. 1994;57(7):979-89.17. Kalia S, Melsen B, Verna C. Tissue reaction to orthodontic tooth movement <strong>in</strong> acuteand chronic corticosteroid treatment. Orthod Craniofac Res. 2004;7(1):26-34.18. Kir<strong>in</strong>o S, Fukunaga J, Ikegami S, Tsuboi H, Kimata M, Nakata N, et al. Regulationof bone metabolism <strong>in</strong> immunosuppressant (FK506)-treated rats. J Bone M<strong>in</strong>er.Metab. 2004 Jun;22(6):554-60.19. Lee WY, Baek KH, Rhee EJ, Tae HJ, Oh KW, Kang MI, et al. Impact of circulat<strong>in</strong>gbone-resorb<strong>in</strong>g cytok<strong>in</strong>es on the subsequent bone loss follow<strong>in</strong>g bone marrowtransplantation. Bone Marrow Transplant. 2004;34(1):89-94.20. Liu J, Farmer JD Jr, Lane WS, Friedman J, Weissman I, Schreiber SL. Calc<strong>in</strong>eur<strong>in</strong> isa common target of cyclophil<strong>in</strong>-cyclospor<strong>in</strong> A and FKBP-FK506 complexes. Cell.1991;66(4):807-15.21. Liu L, Igarashi K, Haruyama N, Saeki S, Sh<strong>in</strong>oda H, Mitani H. Effects of localadm<strong>in</strong>istration of clodronate on orthodontic tooth movement and root resorption <strong>in</strong>rats. Eur J Orthod. 2004;26(5):469-73.22. Makowka L, Chapman F, Cramer DV. Historical development of brequ<strong>in</strong>ar sodiumas a new immunosuppressive drug for transplantation. Transplant Proc. 1993;25(3Suppl 2):2-7.23. Morris RE. Immunopharmacology of new xenobiotic immunosuppressivemolecules. Sem<strong>in</strong> Nephrol. 1992;12(4):304-14.24. Negri AL, Plantalech LC, Russo Picasso MF, Otero A, Sarli M. Post-transplantationosteoporosis. Medic<strong>in</strong>a. 1999;59(6):777-86.25. Santos RL. Ação do tacrolimus no ligamento periodontal e osso alveolar em ratosWistar durante a movimentação ortodôntica [dissertação]. Rio de Janeiro (RJ):Universidade Federal do Rio de Janeiro; 2008.26. Schwartz JE. Ask us: Some drugs affect tooth movement. Am J Orthod DentofacialOrthop. 2005;127(6):644.27. Sobral MC. Avaliação do movimento dentário em coelhos com osteoporose<strong>in</strong>duzida por corticosteróides [dissertação]. Rio de Janeiro (RJ): UniversidadeFederal do Rio de Janeiro; 1999.28. Spolidorio LC, Holzhausen M, Spolidorio DM, Nassar CA, Nassar PO, Muscará MN.Cyclospor<strong>in</strong> but not tacrolimus significantly <strong>in</strong>creases salivary cytok<strong>in</strong>e contents <strong>in</strong>rats. J Periodontol. 2005;76(9):1520-5.29. Spolidorio LC, Marcantonio E Jr, Spolidorio DM, Nassar CA, Nassar PO,Marcantonio RA, et al. Alendronate therapy <strong>in</strong> cyclospor<strong>in</strong>e-<strong>in</strong>duced alveolar boneloss <strong>in</strong> rats. J Periodontal Res. 2007;42(5):466-73.30. Thomson AW, Bonham CA, Zeevi A. Mode of action of tacrolimus (FK506):molecular and cellular mechanisms. Ther Drug Monit. 1995;17(6):584-91.31. Vacca A, Felli MP, Far<strong>in</strong>a AR, Mart<strong>in</strong>otti S, Maroder M, Screpanti I. Glucocorticoidreceptor-mediated suppression of the <strong>in</strong>terleuk<strong>in</strong> 2 gene expression throughimpairment of the cooperativity between nuclear factor of activated T cells andAP-1 enhancer elements. J Exp Med. 1992;175(3):637-46.32. Waller JR, Brook NR, Bicknell GR, Murphy GJ, Nicholson ML. Mycophenolatemofetil <strong>in</strong>hibits <strong>in</strong>timal hyperplasia and attenuates the expression of genesfavour<strong>in</strong>g smooth muscle cell proliferation and migration. Transplant Proc.2005;37(1):164-6.© 2012 <strong>Dental</strong> <strong>Press</strong> Journal of <strong>Orthodontics</strong> 61<strong>Dental</strong> <strong>Press</strong> J Orthod. 2012 Mar-Apr;17(2):55-61

Hooray! Your file is uploaded and ready to be published.

Saved successfully!

Ooh no, something went wrong!