Calcium Hydroxide–Induced Resorption of Deciduous Teeth- A Possible Explanation

Jul-Sep 2012 / Vol 3 | Issue 390 Dental Hypotheses

Introduction

Calcium hydroxide (CaH) was originally introduced to the field of endodontics by Herman in 1920 as root canal filling and antimicrobial agent.[1,2] Since then, CaH has been used for various endodontic procedures including pulp capping, pulpotomy, intracanal medication, apexification, root perforation, and is found in some root canal sealants.[3-5]

The two most important reasons for using CaH in endodontics are its antimicrobial effect and the potential to stimulate mineralized repair of pulp and periapical tissues.[6-9] However, the usage of calcium hydroxide is not routinely recommended for primary dentition because its application frequently results in

the development of chronic pulpal inflammation and internal root resorption.[10-15]

When CaH is placed in permanent teeth, it results in calcific (dentin) bridge formation, but in primary teeth it is likely to cause internal resorption. Though various theories have been proposed and suggested to elucidate this phenomenon, the exact mechanism continues to be obscure. Therefore, the authors present a hypothesis that could possibly provide an explanation.

The Hypothesis

We hypothesize that odontoclasts cause resorption of primary teeth on the placement of CaH and this odontoclastogenesis could be as a result of: CaH-induced chronic inflammatory response which

could influence the macrophages to fuse and form odontoclasts

either through direct stimulation, or indirectly by stimulating stromal odontoblasts/

fibroblasts. A pre-existing predilection of progenitor cells in

deciduous tooth pulp to form odontoclasts. In

Corresponding Author: Dr. R. V. Subramanyam, Department of Oral Pathology, Drs Sudha and Nageswara Rao Siddhartha Insti tute of Dental Sciences, Chinoutapally, Gannavaram521 286, Andhra Pradesh, India. E-mail: [email protected]

ORIGINAL HYPOTHESIS

Calcium hydroxideinduced resorption of deciduous teeth: A possible explanationG. R. Ravi, R. V. Subramanyam1

Departments of Pedodontics, and 1Oral Pathology, Drs Sudha and Nageswara Rao Siddhartha Institute of Dental Sciences, Chinoutapally, Gannavaram, Andhra Pradesh, India

A B S T R A C T

Introduction: Calcium hydroxide (CaH) is customarily used for permanent teeth but not for deciduous dentition because it is known to cause internal resorption in the latter. Though this has been attributed to chronic inflammation and odontoclasts, the exact mechanism has not been elucidated. The Hypothesis: The authors propose an explanation that CaH-induced odontoclastogenesis could be multifactorial. Odontoclasts may result from fusion of cells of monocyte/macrophage series either due to inflammatory mediators or through stimulation by stromal odontoblasts /fibroblasts. Pre-existing progenitor cells of primary tooth pulp because of their inherent propensity may transform into odontoclasts. Evaluation of the Hypothesis: The hypothesis discusses the role of various inflammatory cytokines that may be responsible for CaH-induced transformation of pre-odontoclasts to odontoclasts. Alternatively, pre-existing progenitor cells with proclivity to change into odontoclasts may cause internal resorption. The loss of protective layer of predentin over mineralized dentin may also make the primary tooth more susceptible to resorption.

Key words:Key words: Calcium hydroxide, deciduous, internal resorption, odontoclast, progenitor

Access this article online

Quick Response Code:Website: www.dentalhypotheses.com

DOI: 10.4103/2155-8213.103910

[Downloadedfreefromhttp://www.dentalhypotheses.comonTuesday,July01,2014,IP:37.106.117.73]||ClickheretodownloadfreeAndroidapplicationforthisjournal

https://market.android.com/details?id=comm.app.medknowhttps://market.android.com/details?id=comm.app.medknow

Ravi and Subramanyam: Calcium hydroxide and internal resorption

Jul-Sep 2012 / Vol 3 | Issue 3 91Dental Hypotheses

addition, the loss of predentin could expose mineralized dentin to odontoclasts, making it more vulnerable to resorption. Various mechanisms involved in triggering resorption of deciduous teeth on placement of CaH are illustrated as a schematic flowchart in Figure 1.

Evaluation of the Hypothesis

When CaH was introduced, it was presented as an alternative to formocresol for vital pulp treatment in primary teeth,[16] but it was later found that internal resorption rather than dentine formation occurred in primary teeth.[17] However, some researchers claim that internal resorption following CaH pulpotomies of primary teeth could be caused by pre-existing pulpal inflammation prior to treatment[18] or the presence of an extravascular blood clot intervening between the chemical and the pulp tissue.[19] Nevertheless, internal resorption of primary teeth was still observed even though stringent conditions were taken to avoid clotting.[12]

When CaH is applied directly to the pulp tissue, it produces a limited necrotic zone of superficial liquefaction necrosis that causes a mild irritation,

promoting pulp cells to differentiate into new odontoblasts that place a mineralized dentin bridge on the pulp exposure.[20,21] This is probably because of the high alkaline pH (nearly 12.5) of CaH, which is employed for obtaining the bactericidal action through the release of hydroxyl ions in an aqueous environment.[22-24] Surprisingly, the very properties of CaH that produce healing in permanent teeth, provoke untoward reactions in the pulps of primary teeth.[25] These intense inflammatory responses to high alkaline pH of CaH in deciduous teeth could trigger macrophages to fuse and transform into odontoclasts.

The role of infl ammatory response to calcium hydroxide in odontoclastogenesisChronic inflammatory reaction in deciduous teeth is rapid, diffuse and often results in extensive tissue destruction.[10-12] Various inflammatory cytokines such as tumor necrosis factor- (TNF-), interleukins (IL)-1, IL-, IL-6, IL-11, and IL-17, prostaglandin E2 (PgE2), and tumour growth factor- (TGF-) are all known to stimulate osteoclast differentiation and activation.[26-29] Similarly, in the case of primary teeth, CaH-induced inflammation could activate preodontoclasts and transform them into odontoclasts.

Figure 1: Flowchart depicting the cascade of events and factors that could be responsible for CaH-induced resorption of deciduous teeth (See text for explanation)





Essentially, there are two pathways for odontoclastogenesis to occur. The first involves activation of odontoclastic cells through the ATPP2XR7 (a gene coding for a purinergic ligand-gated ion channel)IL-1 inflammation modulation pathway. Local damage of tissue may result in ATP release, which can activate the receptor P2 R7 on macrophages or other cell types leading to further release of cytokines including IL-1.[30] Such cytokines can recruit more monocytes and macrophages, which may fuse to form odontoclasts and cause resorption [Figure 1a].

The second and more likely pathway involves the RANK (Receptor Activator of Nuclear factor Kappa expressed by odontoclasts)RANKL (RANK ligandexpressed by odontoblasts, pulp, and periodontal ligament (PDL) fibroblasts, as well as by cementoblasts)OPG (osteoprotegerin). RANK-RANKL stimulate odontoclast formation and the OPG, a secreted decoy receptor for RANKL, regulates negatively the odontoclastogenesis. [Figure 1b] The binding of RANKL to RANK is an essential step in the promotion of odontoclast differentiation and resorption.[29,31-33]

The two important factors that could positively impact odontoclast differentiation are RANKL and macrophage colony stimulating factor (M-CSF).[34] M-CSF is known to facilitate osteoclast differentiation by promoting cell survival and proliferation of osteoclast precursors, inducing RANK on hematopoietic cells so they can respond to RANKL, and regulating cytoskeletal changes associated with bone resorption.[35] In a similar fashion, it could expedite odontoclast differentiation and resorption in deciduous teeth. Thus, odontoclastic resorption could be directly related to CaH placement in primary dentition.

The role of pre-existing progenitor cells in odontoclastogenesisIt is a known fact that all deciduous teeth are eventually shed off by 12 years of age. Therefore, it is not surprising to expect predilection for formation of odontoclasts at the time of exfoliation of deciduous teeth. However, it is astonishing to note that there is a high propensity for the formation of odontoclasts well ahead of the eruption of deciduous teeth.[36,37] Even before the eruption of the deciduous teeth into the oral cavity, probably under the influence of various factors like tartrate-resistant acid phosphatase (TRAP), RANK, RANKL, M-CSF, cytokines such as TNF- and interleukins (IL-1, IL-, IL-6, IL-11, IL-17), the progenitor cells could be transformed into pre-odontoclasts which in turn transform into odontoclasts.[29,37,38] Yildrim et al. observed that there is significant expression of RANKL and M-CSF in the primary dental pulp than

in pulpal tissues of permanent teeth, supporting the preferential resorption of primary teeth.[39]

Hence, in the case of deciduous teeth, even before the actual time for exfoliation of deciduous teeth, there is an inherent predilection for the formation of odontoclasts. This pre-existing propensity for transformation could be influenced or hastened by placement of CaHprobably through its high alkaline pH [Figure 1c].

The role high alkaline pH of calcium hydroxideThe high pH of CaH has beneficial effects which include the neutralization of acid products, antimicrobial property, and the activation of alkaline phosphatase.[40] The pH of most calcium hydroxide pastes is approximately 12. The exposure of CaH to blood results in crystalline precipitation due to the intensely differing pH values.[41,42] In the case of permanent dentition, when CaH is applied in direct pulp capping, because of its high alkaline pH, it promotes pulp cells to differentiate into new odontoblast-like cells that generate a mineralized dentin bridge on the area of pulp exposure.[21] This happens because there is an inherent proclivity for odontoblasts to differentiate from undifferentiated mesenchymal cells in the case of permanent teeth. However, when CaH is placed in deciduous teeth, it is very likely that the same high alkaline pH could trigger existing pre-odontoclasts (stromal undifferentiated mesenchymal cells) to transform into odontoclasts.

The role of predentinIt has been well-established by previous studies that resorption can occur when the protective unmineralized tissues such as precementum and predentine are breached or mechanically damaged, allowing osteoclasts/odontoclasts to gain access to calcified dental tissues.[43,44] It is known that the placement of CaH produces a superficial zone of necrosis because of its high alkalinity.[20,21] This could also cause damage to the predentine, which in turn could lead to exposure of the underlying dentin to resting odontoclasts. These odontoclasts, thus activated, could result in tooth resorption [Figure 1d].

Research implicationsResorption of primary teeth due to placement of CaH is multifactorial, which may or may not be mutually exclusive. Though it has been established that odontoclasts that form in response to CaH cause resorption of deciduous teeth, the exact process needs to be probed. Our hypothesis provides an explanation how these events could occur but these




Jul-Sep 2012 / Vol 3 | Issue 3 93Dental Hypotheses

mechanisms need to be substantiated with scientific evidence. Whether the high alkaline pH of CaH can actually result in stimulation of progenitor cells (pre-odontoclasts) to form odontoclasts or not, also requires to be investigated.

References

1. Hermann BW. Calcium hydroxide left as a mean for treatment and filling of the root canals. Wrzburg University, Med Diss V, 29:Sept. 1920

2. Dammaschke T. The history of direct pulp capping. J Hist Dent 2008;56:9-23.

3. Fava LR, Saunders WP. Calcium hydroxide past: Classification and clinical indications. Int Endod J 1999;32:257-82.

4. Ranly DM, Garcia-Godoy F. Current and potential pulp therapies for primary and young permanent teeth. J Dent 2000;28:153-61.

5. Hrsted-Bindslev P, Lvschall H. Treatment outcome of vital pulp Treatment. Endod Top 2002;2:24-34.

6. Safavi KE, Nichols F. Alteration of biological properties of bacterial lipopolysaccharide by calcium hydroxide treatment. J Endod 1994;20:127-9.

7. Schrder U. Effects of calcium hydroxide Containing pulp-capping agents on pulp cell migration, proliferation and differentiation. J Dent Res 1985;64:541-8.

8. Tanomaru Filho M, Leonardo MR, Silva LAB. Effect of irrigating solution and calcium hydroxide root canal dressing on the repair of apical and periapical tissues of teeth with periapical lesion. J Endod 2002;28:295-9.

9. Leonardo MR, Silva LA, Utrilla LS, Leonardo RT, Consolaro A. Effect of intracanal dressings on repair and apical bridging of teeth with incomplete root formation. Endod Dent Traumatol 1993;9:25-30.

10. Law DB. An evaluation of vital pulpotomy technique. J Dent Child 1956;23:40-4.

11. Magnusson B. Therapeutic pulpotomy in primary molarsClinical and histological follow-up. I. Calcium hydroxide paste as a wound dressing. Odontol Revy 1970;21:415-31.

12. Schroder U. A 2-year follow-up of primary molars, pulpotomized with a gentle technique and capped with calcium hydroxide. Scand J Dent Res 1978;86:273-8.

13. Avram CA, Pulver F. Pulpotomy medicaments for vital primary teeth. J Dent Child 1989;56:426-34.

14. Camp J. Pediatric Endodontics: Endodontic treatment for the primary and young permanent dentition. In: Cohen S, Burns RC, editors. Pathways of the pulp. 8th ed. St. Louis: Mosby Year Book; 2002. p. 880-4.

15. Rood H, Waterhaouse P, Fuks A, Fayle S, Moffat M. Pulp therapy for primary molars. Int J Paediatr Dent 2006;16(Suppl 1):S15-23.

16. Doyle WA, McDonald RE, Mitchell DF. Formocresol versus calcium hydroxide in pulpotomy. ASDC J Dent Child 1962;29:86-97.

17. Magnusson B. Therapeutic pulpotomy in primary molarsClinical and histological follow-up. I. Calcium hydroxide paste as a wound dressing. Odontol Revy 1970;21:415-31.

18. Heilig J, Yates J, Siskin M, McKnight J, Turner J. Calcium hydroxide pulpotomy for primary teeth: A clinical study. J Am Dent Assoc 1984;108:775-8.

19. Schroder U. Effect of an extra-pulpal blood clot on healing following experimental pulpotomy and capping with calcium

hydroxide. Odontol Revy 1973;24:257-68.20. Stanley HR. Pulp capping: Conserving the dental pulpCan

it be done? Is it worth it? Oral Surg Oral Med Oral Pathol 1989;68:628-39.

21. Nakamura Y, Hammarstrm L, Lundberg E, Ekdahl H, Matsumoto K, Gestrelius S. Enamel matrix derivative promotes reparative processes in the dental pulp. Adv Dent Res 2001;15:105-7.

22. Bergenholtz G, Reit C. Reactions of the dental pulp to microbial provocation of calcium hydroxide treated dentin. Scand J Dent Res 1980;88:187-92.

23. Tronstad L, Andreasen JO, Hasselgren G, Kristerson L, Riis I. Ph changes in dental tissues after root canal filling with calcium hydroxide. J Endod 1981;7:17-22.

24. Siqueira JF Jr, Lopes HP. Mechanisms of antimicrobial activity of calcium hydroxide: A critical review. Int Endod J 1999;32:361-9.

25. Schroeder U. On internal dentine resorption in deciduous molars treated by pulpotomy and capped with calcium hydroxide. Odontol Revy 1971;22:179-88.

26. Nakashima T, Kobayashi Y, Yamasaki S, Kawakami A, Eguchi K, Sasaki H, et al. Protein expression and functional difference of membrane bound and soluble receptor activator of NF-kappaB ligand: Modulation of the expression by osteotropic factors and cytokines. Biochem Biophys Res Commun 2000;275:768-75.

27. Katagiri T, Takahashi N. Regulatory mechanisms of osteoblast and osteoclast differentiation. Oral Dis 2002;8:147-59.

28. Wang Z, McCauley LK. Osteoclasts and odontoclasts: Signaling pathways to development and disease. Oral Dis 2011;17:129-42.

29. Evlambia HarokopakisHajishengallis. Physiologic root resorption in primary teeth: Molecular and histological events. J Oral Sci 2007;49:1-12.

30. Hartsfield JK Jr. Pathways in external apical root resorption associated with orthodontia. Orthod Craniofac Res 2009;12:236-42.

31. Hartsfield JK Jr, Everett ET, Al-Qawasmi RA. Genetic factors in external apical root resorption and orthodontic treatment. Crit Rev Oral Biol Med 2004;15:115-22.

32. Hasegawa T, Kikuiri T, Takeyama S, Yoshimura Y, Mitome M, Oguchi H, et al. Human periodontal ligament cells derived from deciduous teeth induce osteoclastogenesis in vitro. Tissue Cell 2002;34:44-51.

33. Lossdorfer S, Gotz W, Jager A. Immunohistochemical localization of receptor activator of nuclear factor kappaB (RANK) and its ligand (RANKL) in human deciduous teeth. Calcif Tissue Int 2002;71:45-52.

34. Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature 2003;423:337-42.

35. Negishi-Koga T, Takayanagi H. Ca2+-NFATc1 signaling is an essential axis of osteoclast differentiation. Immunol Rev 2009;231:241-56.

36. Sasaki T, Shimizu T, Watanabe C and Hiyoshi Y. Cellular Roles in Physiological Root Resorption of Deciduous Teeth in the Cat. J Dent Res 1990;69:67.

37. Sahara N. Cellular events at the onset of physiological root resorption in rabbit deciduous teeth. Anat Rec 2001;264:387-96.

38. Takano Y, Ozawa H, Crenshaw MA. Ca-ATPase and ALPase activities at the initial calcification sites of dentin and enamel in the rat incisor. Cell Tissue Res 1986;243:91-9.

39. Yildirim S, Yapar M, Sermet U, Sener K, Kubar A. The role of dental pulp cells in resorption of deciduous teeth. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008;105:113-20.





40. Souza V, Bernabe PF, Holland R, Nery MJ, Mello W, Otoboni Filho JA. Tratamento na-cirurgico de dentes com leses periapicais. Rev Brasil Odont 1989;46:39-46.

41. Nelson Filho P, Silva LA, Leonardo MR, Utrilla LS, Figueiredo F. Connective tissue responses to calcium hydroxide-based root canal medicaments. Int Endod J 1999;32:303-11.

42. Shimizu T, Kawakami T, Ochiai T, Kurihara S, Hasegawa H. Histopathological evaluation of subcutaneous tissue reaction in mice to a calcium hydroxide paste developed for root canal fillings. J Int Med Res 2004;32:416-2.

43. Reitan K. Biomechanical principles and reactions. In: Graber TM, Swain BF, editors. Orthodontics: current principles and techniques. St Louis: C.V. Mosby; 1985. p. 101-92.

Cite this article as: Ravi GR, Subramanyam RV. Calcium hydroxide-induced resorption of deciduous teeth: A possible explanation. Dent Hypotheses 2012;3:90-4.

Source of Support: Nil, Confl ict of Interest: No.

44. Tronstad L. Root resorptionA multidisciplinary problem in dentistry. In: Davidovitch Z, editor. Biological mechanisms in tooth eruption and resorption. Proceedings of the International Conference on Biological Mechanisms of Tooth Eruption and Root Resorption; March 2-4, 1988; Columbus, Ohio: Columbus State University. Columbus, OH: The Ohio State University; 1988; p. 298-302.

Announcement

Android AppA free application to browse and search the journals content is now available for Android based mobiles and devices. The application provides Table of Contents of the latest issues, which are stored on the device for future offline browsing. Internet connection is required to access the back issues and search facility. The application is compatible with all the versions of Android. The application can be downloaded from https://market.android.com/details?id=comm.app.medknow. For suggestions and comments do write back to us.



Calcium Hydroxide–Induced Resorption of Deciduous Teeth- A Possible Explanation

Documents

Transcript of Calcium Hydroxide–Induced Resorption of Deciduous Teeth- A Possible Explanation