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Year : 2010  |  Volume : 21  |  Issue : 4  |  Page : 579-585
Endo-perio lesions: Diagnosis and clinical considerations

Department of Periodontics, A B Shetty Institute of Dental Sciences, Mangalore, India

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Date of Submission20-Sep-2009
Date of Decision26-Jan-2010
Date of Acceptance29-Apr-2010
Date of Web Publication24-Dec-2010


The interrelationship between periodontal and endodontic disease has aroused confusion, queries and controversy. Differentiating between periodontal and endodontic problems can be difficult. A symptomatic tooth may have pain of periodontal and/or pulpal origin. The nature of that pain is often the first clue in determining the etiology of such a problem. Radiographic and clinical evaluation can help clarify the nature of the problem. In some cases, the influence of pulpal pathology may create periodontal involvement. In others, periodontal pathology may create pulpal pathology. This review article discusses the various clinical aspects to be considered for accurately diagnosing and treating endo-perio lesions.

Keywords: Endo-perio lesions, periodontal, pulpal, diagnosis

How to cite this article:
Shenoy N, Shenoy A. Endo-perio lesions: Diagnosis and clinical considerations. Indian J Dent Res 2010;21:579-85

How to cite this URL:
Shenoy N, Shenoy A. Endo-perio lesions: Diagnosis and clinical considerations. Indian J Dent Res [serial online] 2010 [cited 2023 Jan 27];21:579-85. Available from:
The relationship between the pulp and the periodontium has been extensively studied; however, queries regarding the diagnosis, prognosis and treatment are raised time and again. The pathways for the spread of bacteria between pulpal and periodontal tissues have been discussed with controversy. [1],[2],[3] Pulpal infection can drain through the periodontal ligament space and give an appearance of periodontal destruction, termed retrograde periodontitis. Similarly, both pulpal and periodontal infections can coexist in the same tooth, termed combined lesions, where the treatment depends on the degree of involvement of the tissues. Both endodontic and periodontal diseases are caused by a mixed anaerobic infection. This article is an attempt to provide a rational approach to the perio-endo/endo-perio question in order to scientifically diagnose and treat these lesions with predictable success.

The most conventional classification used for endodontic-periodontal lesions was given by Simon et al. (1972), [4] separating lesions involving both periodontal and pulpal tissues into the following groups:

  • Primary endodontic lesions
  • Primary endodontic lesions with secondary periodontal involvement
  • Primary periodontal lesions
  • Primary periodontal lesions with secondary endodontic involvement
  • True combined lesions
  • Classification as recommended by the World Workshop for Classification of Periodontal Diseases (1999)

   Periodontitis Associated with Endodontic Disease Top

  • Endodontic-periodontal lesion
  • Periodontal-endodontic lesion
  • Combined lesion
From the point of view of treating these cases efficaciously, a better clinical classification was provided by Torabinejad and Trope in 1996. [5]

Based on the origin of the periodontal pocket

  • Endodontic origin
  • Periodontal origin
  • Combined endo-perio lesions
  • Separate endodontic and periodontal lesions
  • Lesions with communication
  • Lesions with no communication
Pathways connecting endodontic and periodontal tissues

There are two forms of possible pathways for bacteria and their products connecting the two tissues: Anatomical and Non-physiological [6] [Figure 1].
Figure 1: Pathways for communication between endodontic and periodontal tissues

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Anatomical pathways

The major connections between periodontal and pulpal tissues are the apical foramina. In addition to these main avenues of communication, there are a multitude of branches connecting the main root canal system with the periodontal ligament. In addition to the apical foramina and accessory canals, there is a third possible route for bacteria and their products, the dentinal tubules. [6]

Non-physiological pathways

Iatrogenic root canal perforations: They are serious complications during dental treatment and have a rather poor prognosis. Perforations may be produced by powered rotary instruments during the attempt to gain access to the pulp or during preparation for a post. Improper manipulation of endodontic instruments can also lead to a perforation of the root. [7]

Vertical root fractures: The second group of artificial pathways between periodontal and pulpal tissues are vertical root fractures. Vertical root fractures are caused by trauma and have been reported to occur in both vital and non-vital teeth. In vital teeth, vertical fractures can be continuations of coronal fractures in the "cracked tooth syndrome," or can occur solely on root surfaces. [8]

   Primary Endodontic Lesion Top

An acute exacerbation of a chronic apical lesion on a tooth with a necrotic pulp may drain coronally through the periodontal ligament into the gingival sulcus. This condition may mimic, clinically, the presence of a periodontal

abscess. [9] In reality, it is a sinus tract from pulpal origin that opens through the periodontal ligament area. For diagnosis purposes, it is imperative for the clinician to insert a gutta-percha cone into the sinus tract and to take one or more radiographs to determine the origin of the lesion. When the pocket is probed, it is narrow and lacks width. Primary endodontic diseases usually heal following root canal treatment.

   Primary Endodontic Lesions with Secondary Periodontal Involvement Top

The root canal system primarily becomes infected as a result of dental caries, [10] traumatic injuries and coronal microleakage. [11] Pulp inflammation or necrosis may lead to an inflammatory response in the periodontal ligament at the apical foramen or foramina or at the site of a lateral or accessory canal. The resulting inflammatory lesion can range in extent from a minimal inflammatory process confined to the periodontal ligament to extensive destruction of the periodontal ligament, tooth socket and surrounding bone. Such a lesion may result in a localized or diffuse swelling that may occasionally involve the gingival attachment. A lesion related to pulpal necrosis may also result in a draining sinus tract that drains through the alveolar mucosa or attached gingiva, but may occasionally drain through the gingival sulcus of the involved tooth or through the gingival sulcus of an adjacent tooth. After adequate root canal treatment, lesions resulting from pulpal necrosis resolve an exceptionally high percentage of the time. [12]

The integrity of the periodontium will be reestablished if root canal treatment is done well. If a draining sinus tract through the periodontal ligament is present before root canal treatment, resolution of the defect that can be probed is expected [Figure 2], [Figure 3] and [Figure 4].
Figure 2: Primary endodontic lesion treated endodontically

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Figure 3: Primary endodontic lesion treated endodontically

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Figure 4: Complete healing after 6 months

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   Primary Periodontal Disease Top

These lesions are primarily caused by periodontal pathogens. In this process, chronic periodontitis progresses apically along the root surface. In most cases, pulp tests indicate a clinically normal pulpal reaction. There is frequently an accumulation of plaque and calculus and the pockets are wider. The prognosis depends on the stage of periodontal disease and the efficacy of periodontal treatment. [13]

   Primary Periodontal Disease with Secondary Endodontic Involvement Top

The apical progression of a periodontal pocket may continue until the apical tissues are involved. In this case, the pulp may become necrotic as a result of infection entering via lateral canals or the apical foramen. In single-rooted teeth, the prognosis is usually poor. In molar teeth, the prognosis may be better. [12]

The pulp response to cementum and dentin removal and exposure of patent dentinal tubules by periodontal root planing will vary with the remaining dentin thickness. Unless dentin removal is excessive, pulp response will be negligible. Although the pulp is exposed to a bacterial challenge through patent dentinal tubules, it is quite capable of repair and healing. Production of reparative dentin and reduced canal diameter may result, but pulp tissue remains relatively unaffected.

Unless periodontal disease has progressed to involve the tooth apex, the effect of periodontal disease on the pulp appears to be negligible. [6] Prognosis for a tooth involved with periodontal disease is determined by the outcome expected from periodontal therapy. [9],[12],[13]

   True Combined Disease Top

These lesions occur when an endodontically induced periapical lesion exists at a tooth that is also affected by marginal periodontitis. [9],[12],[13],[14],[15],[16],[17] The two lesions can either merge or exist separately. Merged lesions form by ongoing marginal attachment loss or by exacerbations of apical periodontitis. Teeth with vertical root fractures also belong to this category and have been found to have radiolucencies involving the periodontal ligament in 75% of the cases.

True combined endodontic-periodontal disease occurs less frequently than other endodontic-periodontal problems. The degree of attachment loss in this type of lesion is invariably large and the prognosis isguarded. This is particularly true in single-rooted teeth. In molar teeth, root resection can be considered as a treatment alternative if not all roots are severely involved. Sometimes, supplementary surgical procedures are required. In most cases, periapical healing may be anticipated following successful endodontic treatment. The periodontal tissues, however, may not respond well to treatment and will depend on the severity of the combined disease. The application of guided tissue regeneration (GTR) [18],[19],[20],[21],[22] in periapical surgery has seen an increase in recent years based on favourable outcomes reported in periodontal applications. GTR in combined lesions has been described in numerous case reports, which generally result in clinical improvement.

   Clinical Diagnostic Procedures Top

Visual examination

A thorough visual examination of the lips, cheeks, oral mucosa, tongue, palate and muscles should be carried out. The alveolar mucosa and the attached gingiva are examined for the presence of inflammation, ulcerations or sinus tracts. Frequently, the presence of a sinus tract is associated with a necrotic pulp.


Palpation is performed by applying firm digital pressure to the mucosa covering the roots and apices. With the index finger the mucosa is pressed against the underlying cortical bone. This will detect the presence of periradicular abnormalities or ''hot'' zones that produce painful response to digital pressure. [23]


Although this test does not disclose the condition of the pulp, it indicates the presence of a periradicular inflammation. An abnormal positive response indicates inflammation of the periodontal ligament that may be either from pulpal or periodontal origin. The sensitivity of the proprioceptive fibers in an inflamed periodontal ligament will help identify the location of the pain. This test should be performed gently, especially in highly sensitive teeth.


Tooth mobility is directly proportional to the integrity of the attachment apparatus or to the extent of inflammation in the periodontal ligament. [13] Hypermobility is quite common in cases of primary endodontic involvement and should not be confused with true mobility caused by periodontal destruction. In cases of primary endodontic pathology, the mobility resolves within a week of initiating endodontic therapy.


Interpretation of discrete periapical or lateral lesions and discrete periodontal lesions is of clinical importance in suggesting the cause of the lesion and the proper diagnostic procedures to follow to confirm the cause. [24],[25],[26] Often, the initial phases of periradicular bone resorption from endodontic origin are confined only to cancellous bone. Therefore, it cannot be detected unless the cortical bone is also affected. However, when there is radiographic evidence that bone loss extends from the level of crestal bone to or near the apex of the tooth, the radiograph is of little value in determining the cause. [20],[21],[22]

Fistula tracking

Endodontic or periodontal disease may sometimes develop a fistulous sinus track. Inflammatory exudates may often travel through tissues and structures of minor resistance and open anywhere on the oral mucosa or facial skin. Intraorally, the opening is usually visible on the attached buccal gingiva or in the vestibule. Fistula tracking is done by inserting a semirigid radiopaque material into the sinus track until resistance is met. Commonly used materials include gutta-percha cones or pre-softened silver cones. A radiograph is then taken, which reveals the course of the sinus tract and the origin of the inflammatory process [12],[13] [Figure 5] and [Figure 6].
Figure 5: Clinical view of draining sinus in relation to 44 and 45

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Figure 6: Sinus tracing with gutta-percha cone showing origin of sinus at apex of 44

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Pulp testing

The most commonly used pulp vitality tests are cold test, electric test, blood flow tests and cavity test. The presence or absence of vital tissue in a tooth with a single canal can be determined with confidence with the current pulp-testing procedures. The same degree of confidence cannot be ascribed to positive pulp test responses in a tooth with multiple canals. [23],[27]

   Periodontal Probing Top

Acute or "blow-out" lesions

When a patient presents with a localized swelling that involves the gingival sulcus, it may be difficult to determine whether the swelling is due to a periodontal abscess or an abscess of endodontic origin. [12],[28] The tooth must be non-vital. The swelling is usually on the labial side of the tooth but may occasionally be on the lingual side. As the sulcus is probed, there is usually normal sulcus depth all the way around the tooth until the area of the swelling is probed. At the edge of the swelling the probe drops significantly to a level near the apex of the tooth and the probing depth remains the full width of the swelling. At the opposite edge of the swelling, probing is once again within normal limits. The width of the detached gingiva can be as broad as the entire buccal or lingual surface of the tooth. This swelling can be characterized as having "blown-out" [24] the entire attachment on that side. Endodontic treatment only is indicated. As the result of endodontic management of the swelling, complete periodontal reattachment occurs within 1 week in most cases.

   Typical Periodontal Lesions Top

In periodontal disease, bone loss always begins at the crestal bone level and progresses apically. The typical lesion is conical in contour. The probing may start from a sulcus depth that is within normal limits, then gradually step down a slope to the apical extent of the lesion and then step up again on the other side to a sulcus depth within normal limits. Occasionally, the clinical presentation of a periodontal lesion will have the sloping contour of a conical lesion on one side but a more precipitous, sharp drop-off on the other. Such probing should be considered to be of the "periodontal type" of probing. A periodontal lesion will not resolve in response to root canal treatment even if the associated tooth is pulpless. The prognosis for a tooth with conical-shaped probing must be based on the prognosis for resolving the periodontal lesion. If it can be demonstrated that a tooth is pulpless and if the periodontal prognosis is favorable, root canal treatment should be completed before periodontal therapy. In summary, conical-shaped probing indicates periodontal pathosis.

   Lesions with Narrow Sinus Tract-Type Probing Top

An apparent periodontal lesion may or may not be detectable radiographically. Clinically, a lesion may be probed for some distance down the root surface of the involved tooth but the defect is in fact a sinus tract. Typically, on probing the sulcus depth within normal limits, with the exception of one very narrow area that can be probed some distance down the root surface of the tooth, in many cases it can be probed all the way to the apex of the tooth. Usually, the break in the attachment is only about 1 mm wide, and probing 1 mm to either side of the lesion will be within normal limits. A lesion that probes in this manner is in fact a sinus tract, and the probing represents a typical sinus tract type of probing. The tooth is non-vital. Customary root canal procedures are indicated. There is usually no need for curettage or surgical intervention. It is strictly a sinus tract similar to a sinus tract exiting in the alveolar mucosa or attached gingiva. When a sinus tract occurs over the lateral root surface of a tooth, it will respond to root canal treatment like any other sinus tract. Typically, the orifice into such a sinus tract will close within 1 week after the cleaning and shaping appointment.

Clinical considerations

A deep periodontal defect should always be suspected to harbor bacteria and should therefore be treated endodontically. If the remaining dentition is periodontally healthy and a vertical root fracture has been ruled out, healing of the attachment apparatus can be expected after endodontic treatment without any periodontal treatment.

Lesion characteristics

[Table 1] lists the critical lesion characteristics that significantly contribute to the diagnostic process. A systematic evaluative process goes a long way in accurate diagnosis and treatment planning.
Table 1: Lesion characteristics and diagnostic features of endo-perio lesions

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   Treatment Protocol Top

In general, when primary disease of one tissue, i.e. pulp or periodontium, is present and secondary disease is just starting, treat the primary disease. [12],[13],[15],[16]

When secondary disease is established and chronic, both primary and secondary diseases must be treated. By and large, endodontic therapy precedes periodontal therapy. Periodontal therapy may or may not be required, depending on disease status. The complete healing of destroyed periodontal support can be expected following the treatment of pulpal pathology. The resolution of extensive destruction following the treatment of chronic periodontitis is less predictable. It is important to realize that it is clinically not possible to determine the extent to which one or the other of the two disorders (endodontic or periodontal) has affected the supporting tissues. Therefore, the treatment strategy must be first to focus on the pulpal infection and to perform debridement and disinfection of the root canal system. The second phase includes a period of observation, whereby the extent of periodontal healing resulting from the endodontic treatment is followed. Reduced probing depth can usually be expected within a couple of weeks while bone regeneration may require several months before it can be radiographically detected. Thus, periodontal therapy, including deep scaling with and without periodontal surgery, should be postponed until the result of the endodontic treatment can be properly evaluated.

Sequencing treatment for endo-perio lesions

In acute cases, it is of paramount importance to diagnose the source of the pain and/or swelling and delineate it to be and endodontic or periodontal. This problem should be treated first as a priority. Follow soon after with other treatment.

The debate on which treatment should be initiated first has vexed dentists for long.

Periodontal treatment

It is a known fact that root canal infection significantly affects periodontal healing. Pocket depth reduction is significantly lesser in the presence of canal infection. [29],[30] There is more marginal epithelium over cemental defects if the canals are infected. Removal of cementum will expose dentinal tubules, which means that if there are bacteria in the canal, it could promote inflammatory resorption. It may also expose periodontal tissues to toxic medicaments if used in canal. This is not so critical in areas with recession.

Endodontic treatment

Early initiation of endodontic treatment ensures that the cementum layer is kept intact until root canal infection is eliminated. Because there would be no exposed dentine on the root surface, there is reduced chance of root resorption and improved periodontal healing. On the other hand, if the root canal filling does not have a good seal then the filled canals may be reinfected from periodontal bacteria.

The risk of infection is heightened if periodontal treatment is delayed, especially when a "combined lesion with communication" exists between the two sites. Sterility is more likely while there is a medicated dressing like calcium hydroxide in the canal. Hence, in some cases, it might be prudent to delay the root filling until the periodontal infection has been eliminated.

Treating both lesions concurrently

This would be required when both endodontic and periodontal infection are present simultaneously. Combined endo-perio lesions that exist separately on the same tooth (meaning that they are not physically merged) have recently gained a lot of attention. The true combined endodontic and periodontic lesion requires an accurate diagnosis. This is often a difficult diagnosis and therefore requires reevaluation after either the periodontal or endodontic problems are treated. In such cases, if there is no communication, then complete the endodontic therapy first and initiate periodontal treatment soon after.

When lesions communicate, it makes sense to commence endodontic treatment first and medicate canals until prognosis is known.

Abott, [31] in a detailed analysis on treatment considerations, recommends the following protocol.

Initial management

  • Remove existing restorations and caries
  • Chemomechanically prepare canals
  • Medicate canals (depends on symptoms)
Follow-up management

  • Change intracanal dressing after 3-4 weeks
  • Provide initial periodontal treatment
  • Review healing after 3 months
  • Reassess need for further periodontal treatment
If more periodontal treatment (e.g., surgery) is required,

  • Change intracanal medication again
If healing response is favourable,

  • Complete root canal filling
Longer-term management

  • Defer root filling until after
  • Need for periodontal surgery assessed
  • Surgery completed with satisfactory outcome
Overall prognosis has been assessed to be adequate enough to justify further endodontic and restorative treatment and their costs

   Conclusion Top

Treatment of combined endodontic and periodontal lesions does not differ from the treatment given when the two disorders occur separately. The part of the lesion sustained by the root canal infection can usually be expected to resolve after proper endodontic treatment. The part of the lesion caused by the plaque infection may also heal following periodontal therapy, although little or no regeneration of the attachment apparatus can be expected. This suggests that the larger the part of the lesion caused by the root canal infection, the more favourable the prognosis is for regeneration of the attachment.

   References Top

1.Jansson L, Ehnevid H, Lindskog S, Blomlφf L. The influence of endodontic infection on progression of marginal bone loss in periodontitis. J Clin Periodontol 1995;22:729-73.  Back to cited text no. 1
2.Jansson L, Ehnevid H, Blomlφf L, Weintraub A, Lindskog S. Endodontic pathogens in periodontal disease augmentation. J Clin Periodontol 1995;22:598-602.  Back to cited text no. 2
3.Jansson L, Ehnevid H, Lindskog S, Blomlφf L. Relationship between periapical and periodontal status. A clinical retrospective study. J Clin Periodontol 1993;20:117-23.  Back to cited text no. 3
4.Simon JH, Glick DH, Frank AL. The relationship of endodontic-periodontic lesions. J Periodontol 1972;43:202-8.   Back to cited text no. 4
5.Armitage GC. Development of a classification system for periodontal diseases and conditions. Ann Periodontol 1999;4:1-6.  Back to cited text no. 5
6.Zehnder M, Gold SI, Hasselgren G. Pathologic interactions in pulpal and periodontal tissues. J Clin Periodontol 2002;29:663-71.  Back to cited text no. 6
7.Petersson K, Hasselgren G, Tronstad L. Endodontic treatment of experimental root perforations in dog teeth. Endod Dent Traumatol 1985;1:22-8.   Back to cited text no. 7
8.Chan CP, Lin CP, Tseng SC, Jeng JH. Vertical root fracture in endodontically versus nonendodontically treated teeth. A survey of 315 cases in Chinese patients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;87:504-7.   Back to cited text no. 8
9.Rotstein I, Simon JH. Diagnosis, prognosis and decision-making in the treatment of combined periodontal-endodontic lesions. Periodontol 2000 2004;34:165-203.  Back to cited text no. 9
10.Reeves R, Stanley HR. The relationship of bacterial penetration and pulpal pathosis in carious teeth. Oral Surg Oral Med Oral Pathol 1966;22:59-65.  Back to cited text no. 10
11.Madison S, Wilcox LR. An evaluation of coronal microleakage in endodontically treated teeth. Part III. In vivo study. J Endod 1988;14:455-8.   Back to cited text no. 11
12.Richard E Walton and Mahmoud Torabinejad. Principles and Practice of Endodontics. 3rd Edition Philadelphia W B Saunders Company; 2002 pp. 467-84.   Back to cited text no. 12
13.Rotstein I, Simon JH. Diagnosis, prognosis and decision-making in the treatment of combined periodontal-endodontic lesions. Periodontol 2000 2004;34:165-203.  Back to cited text no. 13
14.Seltzer S, Bender IB, Ziontz M. The interrelationship of pulp and periodontal disease. Oral Surg Oral Med Oral Pathol 1963;16:1474-90.  Back to cited text no. 14
15.Harrington GW, Steiner DR, Ammons WF. The periodontal-endodontic controversy. Periodontol 2000 2002;30:123-30.  Back to cited text no. 15
16.Meng HX. Periodontic-endodontic lesions. Ann Periodontol 1999;4:84-9.  Back to cited text no. 16
17.Lindhe J, Karring T, Lang NP. Clinical Periodontology and Implant Dentistry. 3rd Edition, Copenhagen: Munksgaard; 1997. p. 296-331.   Back to cited text no. 17
18.Pecora G, Baek SH, Rethnam S, Kim S. Barrier membrane technique in endodontic microsurgery. Dent Clin North Am 1997;41:585-602.  Back to cited text no. 18
19.Duff BC. Treatment of an endodontic/periodontic defect using guided tissue regeneration: Report of a case. J Mich Dent Assoc 1993;75:28-30.   Back to cited text no. 19
20.Milano F, Melsen B. Guided tissue regeneration using bioresorbable membranes: what is the limit in the treatment of combined periapical and marginal lesions? Int J Periodontics Restorative Dent 1997;17:416-25.   Back to cited text no. 20
21.Mastromihalis N, Goldstein S, Greenberg M, Friedman S. Applications for guided bone regeneration in endodontic surgery. N Y State Dent J 1999;65:30-2.   Back to cited text no. 21
22.Von Arx T, Cochran DL. Rationale for the application of the GTR principle using a barrier membrane in endodontic surgery: a proposal of classification and literature review. Int J Periodontics Restorative Dent 2001;21;127-39.   Back to cited text no. 22
23.Sigurdsson A. Pulpal diagnosis. Endod Top 2003;5:12-25.  Back to cited text no. 23
24.Bender IB. Factors influencing radiographic appearance of bony lesions. J Endod 1982;8:161-70.  Back to cited text no. 24
25.Lee SJ, Messer HH. Radiographic appearance of artificially prepared periapical lesions confined to cancellous bone. Int Endod J 1986;19:64-72.  Back to cited text no. 25
26.Ehnevid H, Jansson LE, Lindskog SF, Blomlφf LB. Periodontal healing in relation to radiographic attachment and endodontic infection. J Periodontol 1993;64:1199-204.  Back to cited text no. 26
27.Gopikrishna V, Pradeep G, Venkateshbabu N. Assessment of pulp vitality: A Review. Int J Paediatr Dent 2009;19:3-15.   Back to cited text no. 27
28.Harrington GW. The perio-endo question: differential diagnosis. Dent Clin North Am 1979;23:673-90.   Back to cited text no. 28
29.Chen SY, Wang HL, Glickman GN. The influence of endodontic treatment on periodontal wound healing. J Clin Periodontol 1997;24:449-56.   Back to cited text no. 29
30.Jansson L, Ehnevid H, Lindskog S, Blomlφf L. The influence of endodontic infection on progression of marginal bone loss in periodontitis. J Clin Periodontol 1995;22:729-73.   Back to cited text no. 30
31.Abbott P. Endodontic management of combined endodontic-periodontal lesions. J N Z Soc Periodontol 1998;83:15-28.  Back to cited text no. 31

Correspondence Address:
Nina Shenoy
Department of Periodontics, A B Shetty Institute of Dental Sciences, Mangalore
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0970-9290.74238

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]

  [Table 1]

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