Journal of Dental Reports

Dry socket or Alveolar Osteitis (AO) is amongst the most common complications following extraction of teeth in dentistry. A great number of research literature is available to alveolar osteitis with reference to its etiology and pathophysiology. Many studies are available for techniques to prevent AO but controversy still exists regarding the actual etiology, pathophysiology, methods of prevention and treatment. Review of the concepts and controversies surrounding AO is an aim of this article.


Introduction
"Dry socket" was first described in 1896 by Crawford [1]. Many other terms also been referred to these complications, such as septic socket", "localized osteitis "alveolalgia", alveolar osteitis", necrotic socket", "alveolitis sicca dolorosa", "alveolitis", "localized alveolar osteitis" and "fibrinolytic alveolitis" [2,3]. In spite of acceptance of Birn's theory by many authors, the term fibrinolytic osteitis is not commonly used [2,3]. The "alveolar osteitis" is more commonly used while "Dry socket" is referred as general public term. Approximately there are more than eighteen definitions of AO [2]. The most accepted defines AO as "postoperative pain inside and around the extraction site, which increases in severity at any time between the first and third day after the extraction, accompanied by a partial or total disintegrated blood clot within the alveolar socket with or without halitosis" [2] Sever postoperative pain results in excessive use of medications, repeated hospital visits hence increase financial, psychological and physical burden to the patient while delayed recovery period increased cost to the surgeon as well [1,2]. The previous studies regarding pathogenesis of dry socket are yet not well understood [1][2][3]. The studied-on AO are still subject to controversies regarding pathophysiology of risk factors and contributing factors. Birn, labeled it as fibrinolytic alveolitis with reference to understanding of the pathophysiology [4,5]. The pain in empty alveolus is commonly present in all patients with AO [4,6,7]. The other signs and symptoms some time may exaggerate the intensity of AO like radiating pain towards the ear and temporal region [8,9] maxilla, frontal, and ocular regions [4] seldom low-g-rade fever [8,9], inflamed gingival margin [10] greyish discharge [11], bare alveolar bone [10] ipsilateral regional lymphadenopathy [8,9], and halitosis [8,12]. Simple dental extractions reported the incidence of AO has been in the range 0.5% to 5% [13][14][15][16]. In mandibular third molars extraction it varies from 1% to 37.5% [17,18]. While surgical extractions about 10 times higher incidence are reported [2]. About 95-100% of all cases of AO appear within a week [13] generally AO onset is considered to occur 1-3 day after tooth extraction [8,19,20].

Etiology
Birn suggested that the etiology of AO is an increased local fibrinolysis leading to disintegration of the clot [4]. The fibrinolysis is the result of plasminogen pathway activation. The activator substances in AO are direct (physiologic) or indirect (non-physiologic) [5]. Due to trauma to the alveolar bone cells the direct activators are released while bacterial streptokinase release indirect activators. The fibrinolytic activity is limited to local area because initial absorption of plasminogen into the clot limits the activity of plasmin. The active plasmin is inactivated in the general circulation by antiplasmins [21]. Birn and many researchers revealed the local differences in the fibrinolytic activity between different body tissues. Higher fibrinolytic activity was observed with bone and uterine tissues, in comparison to, thyroid tissues, heart, kidney, brain, spleen, liver, lung, and skeletal muscle [22,23]. The factors responsible of triggering fibrinolysis are found to be more ambiguous. The risk factors and contributing factors for development of dry socket has been reviewed by many researchers [4,5,[21][22][23].

Risk factors
The

Systemic disease
Many systemic diseases reported to be associated with AO [4,6]. The most commonly immunocompromised and especially diabetic patients being prone to development of alveolar osteitis due to altered healing [24]. Conditions in Which Pre-existing Alveolar Bone Hypovascularity, such as Vascular or Hematological Disorders, Radiotherapy-induced Osteonecrosis, Cemento-osseous Dysplasia, Osteopetrosis, Paget's Disease the occurrence of AO is controversial.

Oral contraceptives
Oral contraceptive is well known drug associated with dry socket. Oral contraceptives show a significant higher incidence of AO in females [25][26][27]. Estrogen plays a significant role in the fibrinolytic process, Sweet and Butler [28] suggested that increase in the use of oral contraceptives directly correlates with the AO incidence. Studies suggested that oral contraceptives indirectly activate the fibrinolytic activity by increasing factors II, VII, VIII, X, plasminogen hence increase the lysis of blood clot in AO [29]. It has been Abdullah  also found that occurrence of AO enhanced with the increase of estrogen dose in oral contraceptives by Catellani,et. al [30]. To reduce the risk of hormonal cycle's involvement in AO it is suggested for scheduling the elective surgical exodontia [27].

Smoking
A dose dependent relationship between smoking and the occurrence of alveolar osteitis has been studied. 4000 surgically removed mandibular third molars, patients who smoked a half-pack of cigarettes a day had developed AO a four-to five-fold increase (12% versus 2.6%) as compared to non-smokers. AO increased to more than 20% who smoked a pack per day, but it increased to 40% who smoked on the surgery day [31]. However, the exact mechanism like direct local affect including heat or suction for the increase of AO incidence is not very clear [32]. The introduction of foreign substance by means of smoke fumes could act as a contaminant in the extraction wound [33].

Microbial manifestation
It has been documented in most studies that bacterial infections are a major risk factor for the generation and growth of AO. The recurrence of AO increases in patients with risk factors such as poor OH [34] preexisting local infections such as pericoronitis [35] as well as periodontitis. The isolation of the causative organisms has been made via cultures. Rozantis, et. al [36] demonstrated delayed healing of extraction sites after the inoculation of specific microorganisms such as Actinomyces viscosus and Streptococcus mutans, in animal models. Cultures of Treponema denticola, a periodontal disease microorganism, exhibited high plasmin like fibrinolytic projections, according to Nitzan et. al [37]. Catenalli [38] studied bacterial pyrogens in vivo and proposed that they are indirect activators of fibrinolysis.

Excessive cleansing or curettage of socket
Studies have hypothesized that repeated and excessive irrigation of alveolus might hinder the clot formation and that aggressive curettage might also be injurious to the alveolar bone, both of which may lead to the formation of dry socket [4]. However, the literature lacks evidence to certify these claims put forth in the development of AO.

Vasoconstrictors with local infiltration
The use of local anesthesia with vasoconstrictors increases the risk of AO. Lehner [39] studied that because of the poor blood supply due to infiltration anesthesia, a temporary ischemia is induced which increases the frequency of AO. However, followed studies suggested that ischemia lasts for one to two hours and is followed by reactive hyperemia, which is a negligible factor in the disintegration of blood clot [4,40]. Moreover, in a study it was documented that there is no significant difference in the AO of a tooth extracted with infiltration anesthesia versus regional block anesthesia with vasoconstrictor [32]. Therefore, it is currently accepted that local anesthesia with vasoconstrictor has no role in the development of local ischemia which can lead to the formation of AO.

Bony fragment remnants in the wound site
Chow O and H Birn have suggested in their studies that bone/root fragments and debris can lead to delayed wound healing, and consequently aid in the development of AO [2,4]. Simpson, on the other hand, in his study, showed that small bone/root fragments are commonly present after extractions and these fragments do not necessarily cause complications as the epithelium is able to form an external barrier [41].

Design of the flap and suture usage
Some previous literature claims that flap design and the use of sutures affect the development of AO [25]. However, little evidence is found to authenticate such relationship in studies that have recently been conducted [42]. In the absence of any significant evidence, it is practical to assume that these are not major contributing factors [3].

Contributing factors
The contributing factors in pathophysiology of AO

Operator's inexperience
Operator's inexperience is also considered as a major risk factor for the development of AO. A study carried out by Larsen [43] stated that surgeon's lack of experience during the surgical extraction of third molars can lead to deleterious consequences. Alexander and Oginni, et. al [44]. have reported an increased incidence in AO carried out by inexperienced surgeons. Henceforth operator's skills and experience should be considered [3,43,44].

Extraction of mandibular wisdom teeth
Many studies have shown the same pattern of increased AO after extraction of third molar [45,46]. It is a common belief among some authors that increased density of the bone, decreased vascularity, and reduced capacity of formation of granulation tissue can lead to formation of AO [45]. However, no evidence could provide a nexus between AO and reduced blood supply. The reason why surgically extracted third molar are prone for the development of AO is due to surgical trauma, and not for their anatomic location [32].

Patient's gender
In many studies, it has been stated that female gender is more susceptible for the development of AO, despite the use of oral contraceptive pills. MacGregor [14] reported an increase of 50% occurrence of AO in females as compared to men in his study of 4000 extractions, whereas Colby had no difference to show in the same scenario and stated that there is no gender association with the development of AO [14].

Patient's age
There is little evidence to prove the association of incidence of AO with age. The literature supports the general principle of greater risk associated with old age [3]. Blondeau, et. al [47] concluded that surgical removal of impacted mandibular third molars should be carried out well before age of 24 years.

Clot dislodgement
In a contemporary opinion, there is no corroboration that dislodgement of blood clot caused by manipulation or negative Abdullah  pressure is created by sucking a straw as a major contributor AO [32].

Single extraction compared to multiple extractions
Limited data exists indicating a higher prevalence of AO after single extractions [9,12] as compared to multiple extractions. In one study, AO prevalence was 7.3% following single extractions and 3.4% following multiple extractions [32]. This difference could be a possibility due to the fact that patients with single extractions have less pain as compared to the patients with multiple extractions, whose teeth are damaged drastically [48]. Moreover, multiple extractions involving periodontal disease teeth may be less traumatic extraction gave very promising results in prevention of AO [49].

Saliva
A few authors have argued that saliva is a risk factor in the development of AO [50,51]. However, no firm scientific evidence exists to support this claim. Birn found no evidence that saliva plays a role in AO [4].

Trauma due to surgery and difficulty of surgery
Many authors agree on the same point that trauma and difficulty while performing surgery can play a significant role in the development of AO [34,52,53]. This is because traumatic extractions lead to the production of direct tissue activators following bone marrow inflammation [32]. An increase in incidence of AO is seen by 10folds in surgical extraction as compared to non-surgical extractions [24] Lilly, et. al [6] stated that surgical extraction inclusive of a flap design and bone removal are more prone towards the development of AO.

Prevention
Numerous techniques are proposed in existing literature for its prevention. However, no single method has gained solo acceptance. Most common techniques are discussed as under.

Topical antibiotics
The use of topical tetracycline has shown to be an auspicious drug amongst other local antibiotics [59][60][61][62]. Foreign body reactions such as Myospehrulosis have been reported with the application of from petroleumbased tetracycline-hydrocortisone combination [63][64][65]. Study reported a nerve dysesthesia six months after mandibular third molar extraction by the use of medications in the socket [64]. The method of delivery included powder, gauze drain, suspensions and Gelfoam sponges. It has been also suggested that virtually anything into the alveolus, including plain Gelfoam, will result in the improvement in AO symptoms [8].

Para-hydroxybenzoic acid
AO prevention by para-hydroxybenzoic acid (PHBA), an antifibrinolytic agent has been reported [66,67]. PHBA is available in alveolar cone that consists of acetylsalicylic acid and PHBA. A pernyl success in AO Abdullah  proved good, but it is found that it inhibited the bone healing. PHBA has been reported to have good antimicrobial effects [9,68,69]. Aspirin cause local irritation and acute inflammation of the socket [70].

Chlorhexidine
Pre-and perioperative use of 0.12% chlorhexidine decreases appearance of AO after third molar extraction [29,40,71,72]. It has been reported that rinsing with chlorhexidine solution before extraction there is 50% reduction of AO [73]. 0.12% chlorhexidine rinse on the day of extraction gave very promising results in prevention of AO [49].

Polylactic acid
The polylactic acid (PLA), is a biodegradable ester (a clot supporting agent), has been advocated in prevention of AO. PLA provide a stable support for the blood clot, granulation, and osteoid tissue but few follow-up studies failed to support the PLA role in AO Complications and incidence of AO was higher when PLA was used [74,75].

Tranexamic acid
Tranexamic acid (transamin), an antifibrinolytic agent, has been recommended to prevent AO when applied topically or IV after in the extraction [74]. But when compared to a placebo group it did not show a significant reduction in the incidence of AO and local plasminogen inactivation found to be insufficient to cease the appearance of AO [75].

Steroids
Corticosteroid remained in use to decrease postoperative complications but to prevent development of dry socket no promising results found [76]. Topical application of hydrocortisone and antibiotics significantly lessens AO especially after wisdom molar removal [8,77]. It is observed the use of steroids alone without any antibiotic combination is not promising [78].

Eugenol containing dressing
The eugenol containing dressing to prevent development of AO has been very popular [79]. The local irritant effect and the delay in wound healing by eugenol made it be difficult to justify its use in prevention of dry socket [3,80,81].

Lavage
Butler and Sweet [42] reported that tht copious preoperative and intraoperative lavage reduce the incidence of dry socket reported significant reduction in AO, however they found that increase or decrease in the lavage volume do not affect its efficacy. Aminoacrinide 9-aminoacridine is an antiseptic agent; its effectiveness in reducing the incidence of AO is found to be less effective [82].

Use of sterile gloves
The effect of sterile gloves uses instead of clean nonsterile gloves to decrease in the incidence of AO found to be very insignificant [83,84].

Management
The primary aim of dry socket management is pain control and promoting normal healing process. The majority of cases local measures are satisfactory. The systemic analgesics or antibiotics may be necessary or indicated in some cases. The intra- Abdullah  alveolar dressing materials are widly use but may result in delayed healing of extraction socket [81]. Different medicaments combinations of perhaps 18 different ingredients are in use worldwide [4]. Alvogyl in the management of AO contains butamben (anesthetic), eugenol (analgesic), and iodophorm (antimicrobial) is frequently mentioned in the literature. The retardation of healing and inflammation is reported when the sockets were packed with Alvogyl. The use of ZnO eugenol, fibrin substitutes, whitehead varnish and BIPP has also been reported to be effective in management of AO.

Conclusion
The literature postoperative condition of alveolar osteitis is not consistent and often conflicting. The most previous studies are poorly designed, lack of ideal analysis, statistically biased, or consist of very individual opinions. Non established etiology of alveolar osteitis resulted in varying controversial descriptive definitions and diagnostic criterias. The initiation of fibrinolytic process appears to be interfacing multiple independent factors in wound healing of AO [3]. To prevent this complication no single universally acceptable method. Multitudes of intraalveolar medicaments are available on the market however their complications/severe reactions from placed in the socket are rare. The management of this complication should begin with patient education and identifiable risk factors should be informed in detail about this anticipated complication of exodontia. Further welldesigned studies based on latest investigations methodologies are necessary to draw firm conclusions of AO treatments.