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The effect of polylactic acid granules on the incidence of alveolar osteitis after mandibular third molar surgery
The effect of polylactic acid granules on the incidence o f alveolar osteitis after m a n d i b u l a r third molar surgery A prospective randomized study James R. Hooley, DDS, a and Daniel P. Golden, DDS, b Yokosuka, Japan, and Bethesda, Md. NAVY DENTAL CORPS
Objective. To evaluate the effect of polylactic acid granules placed in third molar sockets on the incidence of alveolar osteitis.
Study design. A prospective randomized study with 161 patients (322 bilaterally impacted mandibular third molars). Results. The sockets in which the polylactic acid granules were placed had a significantly higher rate of alveolar osteitis (23.6%) than did the control sockets (13.58%). In all subgroups analyzed, the incidence of alveolar osteitis was higher in the experimental (polylactic acid) group. Conclusion. On the basis of the findings of this study, polylactic acid granules do not reduce the incidence of alveolar osteitis and may actually contribute to a higher incidence of alveolar osteifis. (ORAL SURGORAL MED ORAl. PATHOLORAL RADIOL ENDOD 1995;80:279-83)
Alveolar osteitis (dry socket), as first described by Crawford 1 in 1896, continues to be the most c o m m o n complication associated with the surgical removal of mandibular third molars. The clinical presentation is classic. The patient reports severe throbbing pain not relieved by analgesics that develops or persists several days after surgery. Although polylactic acid has been commercially available for more than a decade, its use as an agent to prevent alveolar osteitis has only been reported twice. On the basis of this data, Brekke et al. 2, 3 have advocated the use of polylactic acid granules injected into mandibular third molar sockets as a method of reducing the incidence of alveolar osteitis. In a 1983 study they used a polylactic acid mesh in 228 patients. 4 When extraction types were divided into soft tissue, partial bony, or full bony, the control and experimental percentages of alveolar osteitis were as follows: 10.8%, 12.9%, and 19.4% for the control and 2.7%, 3.2%, and 3.9% for the experimental side. In their 1986 report, Brekke et al. 3 demonstrated a reduction in the incidence of alveolar osteitis from
The opinions expressed herein are those of the authors and cannot be construed as reflecting the views of the Navy Department or the Naval Service at large. aFormerly Dean and Professor Emeritus, University of California, Los Angeles School of Dentistry; currently Captain, Navy Dental Corps, assigned to the U.S.S. Independence, Yokosuka, Japan. bChairman, Department of Oral and Maxillofacial Surgery, Naval Dental School; Captain, Navy Dental Corps. Received for publication Nov. 3, 1994; revision requested Dec. 12, 1994; accepted for publication March 16, 1994. 7/12/64835
18.1% in the control group tO 2.2% in the group receiving the polylactic acid granules. These results have not been corroborated by any other studies. This investigation is intended to provide additional data concerning the effectiveness of polylactic acid granules injected into third molar sockets to reduce the incidence of alveolar osteitis.
MATERIAL AND METHODS The polylactic acid granules (Drilac) were provided by Osmed, Inc. (Duluth, Minn.). The study included 161 patients. Patients were enrolled in the study if they had bilateral impacted third molars that appeared to be symmetrical on panoramic radiograp h y . All patients were male active-duty military members serving on the aircraft cartier U.S.S. Independence. Patients who had pericoronitis or other infections were excluded. All procedures were performed with patients under intravenous sedation with midazolam and fentanyl. Local anesthesia consisting of lidocaine 2% with 1:100,000 epinephrine and bupivacaine hydrochloride 0.5% with 1;200,000 epinephrine was used. No steroids or antibiotics were used. All procedures required a flap and some bone removal. Bone removal and tooth sectioning were accomplished with a Hall electric drill system (Hall Surgical, Santa Barbara, Calif.) with a 703 burr. A minimum of 175 ml of saline solution was used to irrigate each side. Sutures were not used in most cases, but when necessary one or two 3-0 gut sutures were placed. The polylactic acid granules were placed randomly in either the right or left side as determined by a coin toss. No notation
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Table I. Incidence of alveolar osteitis in smokers and nonsmokers Alveolar osteitis (%)
Smokers Nonsmokers
Number of patients
Control
Polylactic acid
44 117
22.73 10.26
31.82 20.5
was made on the patient's record as to which side the material was inserted. This information was recorded on a separate form that was sealed until completion of the study. All surgery was performed by one board-certified oral and maxillofacial surgeon who also performed all postoperative evaluations. At the postoperative visits it was not possible to determine which side had the polylactic acid granules inserted into the socket; however, it became apparent once the need for a sedative dressing was determined. The data collected included the patient' s name, age, social security number, and smoking status. If the patient smoked cigarettes, the number of cigarettes per day was recorded. The third molars were classified as erupted,, requiring a flap and removal of bone; soft tissue impacted; partially bony impacted; and fully bony impacted. Each surgical procedure was timed. Data were also gathered on other postoperative complications. The patient was given an appointment for postoperative follow-up on the first, fourth, and the seventh days. They were advised to seek postoperative care earlier if there was any sign of infection, hemorrhage, or pain that was not controlled by ibuprofen. Because all patients were living on board an aircraft carrier, compliance with postoperative appointments was 100%. No patients were lost to follow-up. The data were analyzed to compare the number of occurrences of alveolar osteitis in the experimental versus the control group. The data were further analyzed to establish the relationship of various factors, such as the difficulty of the surgery, length of surgery, and smoking status, on the development of alveolar osteitis. The statistical analysis used was the chisquare test. For the purpose of this investigation, the diagnosis of alveolar osteitis was based on clinical symptoms rather than the appearance of the socket. Any patient who reported severe, usually throbbing pain before the seventh day was considered to have the condition. If the pain was not of a throbbing nature but was not relieved by ibuprofen, it was considered to be alveolar osteitis.
RESULTS A total of 161 patients were included in the study. All of the patients were male, between the ages of 18 and 26 years. The average age was 20.45 years. The median age was 20 years. Polylactic acid was placed on the right side in 81 cases and on the left side in 80 cases. Three hundred twenty-two mandibular third molars were surgically removed. The incidence of alveolar osteitis in the control group was 13.58% (22 surgical sites), and in the study group the incidence was 23.6% (38 surgical sites). This difference is statistically significant (chi-square = 4.609 with 1 degree of freedom; p = 0.032) The incidence of alveolar osteitis was higher in the study group for every category analyzed. Forty of the 161 patients were smokers. The incidence of alveolar osteitis was higher than in the 117 nonsmokers (Table I). The incidence of alveolar osteitis in the control group was 22.73% (10 surgical sites), and in the study group the incidence was 31.82% (14 surgical sites). This difference in the incidence between the two groups was not statistically significant (chi-square = 3.224 with 1 degree of freedom; p = 0.073). Eight dry sockets were bilateral, and seven were unilateral. In the nonsmokers, the incidence was 10.26% on the control side and 20.5 % on the study side. Eight dry sockets were bilateral, and 22 were unilateral. A definite correlation was found between the difficulty of the procedure and the incidence of alveolar osteitis (Tables II and III). In the control group no cases of osteitis were found in those patients whose procedures took 2 minutes or less to complete, whereas those patients whose procedures took more than 11 minutes had an incidence of 33%. In the study group no incidence was found in those patients whose procedures lasted 2 minutes or less, and the incidence was 58% for those patients whose procedures lasted 11 minutes or more. Six (3.7%) postoperative infections occurred, all of which resolved after a course of penicillin therapy. No delayed infections occurred. In five patients the polylactic acid granules failed to resorb, and they were subsequently curetted out of the socket. These patients did not have painful symptoms. Five patients in w h o m alveolar osteitis w a s not diagnosed reported significant pain 7 days after the procedure. All five patients were in the study group. DISCUSSION The cause and pathogenesis of alveolar osteitis have been the subject of much study and debate since the condition was first recognized, but no consensus
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Table II. Effect of the length of surgery on the incidence of alveolar osteitis
Table III. The relationship of the predicted difficulty on the incidence of alveolar osteitis
Alveolar osteitis (%)
Time (min)
Number in group
Control
Polylactic acid
1-2 3-4 5-6 7-10 11+
15 32 48 55 11
0 6.25 18.7 10.7 36.3
0 25 20.8 23.2 63.6
exists as to the cause of alveolar osteitis. However, there is some agreement on many factors that may contribute to the development of alveolar osteitis. Hall 5 states that bacterial lysis of the clot is the initiating event. A study by Birn 6 attributes the cause to increased fibrinolytic activity within the alveolus and clot. Trauma is frequently mentioned as a contributing factor. 7 The rate of alveolar osteitis is higher when an inexperienced surgeon is performing the surgery, 8 which further supports the finding that trauma is a contributing cause. Smoking and the use of birth control pills are also considered to be contributing factors.9, 10 In other studies the cause of alveolar osteitis has variously been attributed to inadequacy of the blood supply to the alveolus, 11 infection, 12, 13 a reactivated herpes simplex virus infection, 14, 15 and a variety of other less likely initiating factors including seasonal variation, nutrition, excessive bleeding, and choice of anesthetic. Although alveolar osteitis can occur in any socket, it is almost exclusively .a problem related to mandibular third molars. Numerous agents and methods have been used with some effectiveness for prevention of this condition. Antifibrinolytics 16 and antiinflammatory agents 17 have been used in an effort to stabilize the clot. Other studies h a v e shown that improvment of hygiene and use of antimicrobial rinses have been effective in reducing the incidence of alveolar osteitis in s o m e cases. 18-22 The search for a better understanding of the pathophysiology of this condition continues, and because the mechanism for the development of the condition is poorly understood, the empirical search for new medications and substances will continue. Most current methods of reducing alveolar osteitis are directed at reducing or altering the bacterial population of the third molar region. The methods include the use of topical and systemic antibiotics 23 and antiseptic mouth rinses. Topical tetracycline has proved effective in reducing the incidence of alveolar osteitis. Swanson 24 demonstrated a reduction from 37.5%
Alveolar osteitis (%)
Classification
Number
Control
Polylactic acid
1 2 3 4
14 38 67 42
0 13.1 12 21.4
0 15.8 21 33.3
to 2.6% using Gelfoam saturated with a 50-mg solution of tetracycline. Hall et al. 25 and Sorensen and Preisch 26 also reported excellent results with tetracycline. Chlorhexidine mouth rinses have also shown good results in some studies 22, 27, 28; however, one study showed them to be ineffective. 29 Alveolar osteitis continues to be a significant problem, particularly for patients undergoing mandibular third molar surgery. The incidence of alveolar osteitis in this group of patients is reported to be in the range of 20% to 31%. In this investigation the incidence of 13.58% in the control group appears to be somewhat lower than the average reported in the literature.16, 21, 25, 29, 30 We used a standard buccal approach for the removal of wisdom teeth. Sutures were not usually used, and the wound was irrigated with a minimum of 175 ml of saline solution. Sweet and Butler 31 have found that using 175 ml of saline solution was more effective than lower volumes of saline solution. This represents an extra step in the procedure because irrigation with 175 ml of saline solution takes an extra 30 to 45 seconds during the procedure. No women were included in the study, which m a y have been a factor in the low rate of alveolar osteitis because women are reported to have a higher incidence of alveolar osteitis. 22, 31 In the only previous report on the use of polylactic acid granules injected into third molar sockets for the purpose of prevention of alveolar osteitis, Brekke et al. stated that "alveolar osteitis is the product of postoperative, intrabony ischemia complicated by premature loss of mechanical support provided by a healthy blood clot. ''2 They believed the condition was caused by " v e r y poor intrinsic collateral circulation" and further stated that " w o u n d s protected with polylactic acid d r e s s i n g s . . , successfully tolerate considerably longer durations of surgical trauma than do unprotected wounds. ''2 The p01ylactic acid dressings were believed to provide the fresh blood clot with a stable support system that keeps the newly formed clot in juxtaposition with surviving collateral
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September 1995 circulation. Furthermore, the dressings were believed to reduce the destructive effects of fibrinolysis b y p r o v i d i n g a stable a n d biologically acceptable matrix for future g r a n u l a t i o n tissue development. 2 The theory of Brekke et al. for the pathogenesis of alveolar osteitis is u n s u p p o r t e d by scientific evidence and is in conflict with the b e n c h m a r k findings of Bim, 6 who described the m e c h a n i s m to be high fibrinolytic activity within the socket. Polylactic acid is a biodegradable ester polymer. The material was developed in 1966 b y Kulkarni 32, 33 for surgical implants. Further d e v e l o p m e n t led to its use as an orthopedic i m p l a n t in 1970. 33, 34 Cutright et al. 35 used polylactic acid for m a n d i b u l a r fracture reduction in rhesus m o n k e y s . The material is b e i n g evaluated in h u m a n beings as a nonmetallic resorbable plate for fracture fixation. 36,37 Several other studies attest to the biologic compatibility of polylactic acid w h e n placed i n vivo. 38, 39 A l t h o u g h the material is biocompatible, it does appear to cause a variety of tissue reactions. B e r g s m a et al. 40 reported a u n i f o r m nonspecific f o r e i g n - b o d y reaction w h e n the material was used as a bone, plate, or screw. O l s o n et al.41 reported a m i l d foreign-body reaction w h e n the material was used i n dog extraction wounds. C a m p bell et al. 38 reported that it inhibited carcinoma cell growth. No studies are a v a i l a b l e to describe the biocompatibility of polylactic acid granules in an open w o u n d such as the socket of a m a n d i b u l a r third m o lar. The results of this investigation do not support the findings of Brekke et al. 2, 3 W e are u n a b l e to explain the d i f f e r e n c e in outcomes b e t w e e n the findings of Brekke et al. and the findings of our study. Perhaps it is because of the m a n y differences b e t w e e n the studies, Our study was more rigidly controlled than the Brekke et al. study. All surgery was performed by one surgeon in a tightly controlled institutional setting in our study, c o m p a r e d with three surgeons in three separate private practices in the Brekke et al. study. Our study i n c l u d e d o n l y m e n in a very narrow age range, whereas the Brekke et al. study included w o m e n . I n our study the patients served as their o w n controls in all instances, whereas in the Brekke et al. study this was true for about two thirds of the patients. The Brekke et al. study was not blind, and no m e n tion was made c o n c e r n i n g patients lost to follow-up. Data from the Brekke et al. study were very difficult to interpret, and the n u m e r o u s methodologic problems of the study detracted from the strength of its conclusions. The i n c l u s i o n criteria and the definition of alveolar osteitis were approximately the same for both studies.
CONCLUSION O n the basis of this study, the c o n t i n u e d use of polylactic acid granules for the p r e v e n t i o n of alveolar osteitis cannot be endorsed. The investigational material, polylactic acid, not only did not decrease the incidence of the condition but appeared to actually contribute to its increased incidence. Because this is the first observation of this p h e n o m e n o n , additional studies w o u l d seem to be indicated. This study supports the findings of m a n y other studies in m a n y respects. T h e highest i n c i d e n c e of alveolar osteitis was in patients with difficult i m p a c t i o n s who smoked. We thank Mr. David Langley of Osmed, Inc., for providing the Drilac for this investigation and CDR Brian K. Nicoll, DC, USN, for providing the statistical analysis. REFERENCES
1. Crawford JY. Dry socket. Dental Cosmos 1896;38:929-34. 2. Brekke JH, Bresner M, Reitman MJ. Effect of surgical trauma and polylactate cubes and granules on the incidence of alveolar osteitis in mandibular third molar extraction wounds. J Can Dent Assoc 1986;4:315-9. 3. Brekke JH, Bresner M, Reitman MJ. Surgical dressing material: postoperative therapy for extraction wounds. J Can Dent Assoc 1986;7:599-602. 4. Brekke JH, Olson RAJ, Scully JR, Osbon DB. Influence of polylactic acid mesh on the incidence of localized osteitis. Oral Surg Oral Med Oral Pathol 1983;56:240-5. 5. Hall HD. Effects of chlorhexidine gluconate oral rinse on the incidence of alveolar osteitis in mandibular third molar surgery. J Oral Maxillofac Surg 1990;48:449-55. 6. Birn H. Etiology and pathogenesis of fibrinolytic alveolitis. Int J Oral Maxillofac Surg 1976;2:211-9. 7. Alling CC, Ken D. Trauma as a factor causing delayed repair of dental extraction sites. J Oral Surg 1957;15:3-8. 8. Sisk AL, Hammer WB, Shelton DW, Joy ED. Complications following removal of third molars: the role of the experience of the surgeon. J Oral Maxillofac Surg 1986;44:855-9. 9. Sweet JB, Butler DP. The relationship of smoking to localized osteitis. J Oral Surg 1979;37:732-75. 10. Catellanni JE, Harvey S, Erickson SH. Effect of oral contraceptives on dry socket. J Am Dent Assoc 1980;101:777-88. 11. Huebsch RF. Clinical and histological study of alveolar osteitis. J Oral Surg 1958;16:473-9. 12. Adkisson SR, Harris PF. A statistical study of alveolar osteitis. US Armed Forces Med J 1956;7:1749-56. 13. Brown LR, Merrill SS, Allen RE. Microbiologic study ofintraoral wounds. J Oral Surg 1970;28:89-95. 14. Hedner E, Vahlne A, Kahnberg KE, Hirsch JM. Reactivated herpes simplex virus infection as a possible cause of dry socket after tooth extraction. J Oral Maxillofac Surg 1993;51:370-6. 15. Openshaw H. Reactivated herpes simplex infection as a possible cause of dry socket after tooth extraction. J Oral Maxillofac Surg 1993;51:377-8, 16. Ritzau M, Therkildsen P. Antifibrinolytic prevention of alveolitis sicca dolorosa. Int J Oral Maxillofac Surg 1986;7:53454. 17. Rutledge JL, Marcoot RM. Terracortril/Gelfoam for reduction of the incidence of localized osteitis following mandibular third molar removal. J Oral Pathol Med 1984;39:51-7. 18. Lilly GE, Osbon DB, Raele M, et al. Alveolar osteitis associated with mandibular third molar extractions. J Am Dent Assoc 1974;88:802-9.
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Volume 80, Number 3 19. Schiott CR, Harald LS, Borglure J, et al. The effect of chlorhexidine mouth rinses on the human oral flora. J Periodontal Res 1970;5:84-91. 20. Tjernberg A. Influence of oral hygiene measures on the development of alveolitis sicca dolorosa after surgical removal of mandibular third molars. Int J Oral Maxillofac Surg 1979;8: 430-5. 21. Krekmanov L, Nordenramn A. Postoperative complications after surgical removal of mandibular third molars. Int J Oral Maxillofac Surg 1986;15:25-30. 22. Field EA, Nind D, Varga E, et al. The effect of chlorhexidine irrigation on the incidence of dry socket: a pilot project. Br J Oral Maxillofac Surg !988;26:395-9. 23. Rood JP, Muratroyd J. Metronidazole in the prevention of dry socket. Br J Oral Maxillofac Surg 1979;37:62-9. 24. Swanson AE. Reducing the incidence of dry socket: a clinical appraisal. J Can Dent Assoc 1966;2:25-30. 25. Hall HD, Bildman BS, Hand CD. Prevention of dry socket with local application of tetracycline. J Oral Surg 1971;29:35-7. 26. Sorensen DC, Preisch JW. The effect of tetracycline on the incidence of postextraction alveolar osteitis. J Oral Maxillofac Snrg 1987;45:1029-33. 27. Legarth J, Munkster R, Swendsen J. Klorheksidins virkning pa vdriklingen of alveolitis sicca dolorosa efter operativ fjerneise of visdonstaender i under kaeben [Abstract]. Tanglaegebladet 1977;81:451. 28. Larsen PE. The effect of a chlorhexidine rinse on the incidence of alveolar osteitis following the surgical removal of impacted mandibular third molars. J Oral Maxillofac Surg 1991;49: 932-9. 29. Berwick JE, Lessin ME. Effects of a chlorhexidine glnconate oral rinse on the incidence of alveolar osteitis in mandibular third molar surgery. J Oral Maxillofac Surg 1990;48:444-8. 30. Krekrnanov L. Alveolitis after operative removal of third molars in the mandible. Int J Oral Surg 1981;10:173-7. 31. Sweet JB, Butler DP. Predisposing and operative factors: effect on the incidence of localized osteitis in mandibular third molar surgery. ORAL SURG ORAL MED ORAL PATHOL 1978;46:206-15.
32. Kulkarni RK, Pani C, Neuman C, Leonard F. Biodegradable polylactic acid polymers. J Bi0med Mater Res 1971;5:16981. 33. Kulkarni RK, Pani C, Neuman C, Leonard F. Polylactic acid for surgical implants. Arch Surg 1966;93:839-43. 34. Getter L, et al. A biodegradable intraosseous appliance in the treatment of mandibular fractures. J Oral Surg 1972;30: 344-8. 35. Cutright DE, Hunsuck EL, Beasley J. Fracture reduction using biodegradable material: polylactic acid. J Oral Surg 1971 ;29:393-7. 36. Wittenberg JM, Wittenberg RH, Hipp JA. Biomechanical properties of resorbable poly-L-lactide plates and screws: a comparison with traditional systems. J Oral Maxillofac Surg 1991 ;49:512-7. 37. Suuronen R. Comparison of absorbable self-reinforced polyL-lactide screws and metallic screws in the fixation of mandibular osteotomies: an experimental study in sheep. J Oral Maxillofac Surg 1991;49:989-93. 38. Campbell JH, Edsberg L, Meyer AE. Polylactide inhibition of carcinoma cell growth in vitro. J Oral Maxillofac Surg 1994; 52:49-51. 39. Schliephake H, Newkam FW, Hutmacher D, Becker J. Enhancement of bone ingrowth into a porous hydroxylapatite matrix using a resorbable polylactic membrane. J Oral Maxi11ofac Surg 1994;52:57-63. 40. Bergsma EJ, Rozema FR, Ruud RM, de Bruijn WC. Foreign body reactions to resorbable poly(L-lactide) bone plates and screws used for the fixation of unstable zygomatic fractures. J Oral Maxillofac Surg 1993;51:666-70. 41. Olson RA, Roberts DL, Osbon DB. Comparative study of polylactic acid, Gelfoam, and Surgicel in healing extraction sites. ORAL SURG ORAL MED ORAL PATHOL 1982;53:441-9.
Reprint requests: James R. Hooley, DDS P. O. Box 427 Indianola, WA 98342
Objective. To evaluate the effect of polylactic acid granules placed in third molar sockets on the incidence of alveolar osteitis.
Study design. A prospective randomized study with 161 patients (322 bilaterally impacted mandibular third molars). Results. The sockets in which the polylactic acid granules were placed had a significantly higher rate of alveolar osteitis (23.6%) than did the control sockets (13.58%). In all subgroups analyzed, the incidence of alveolar osteitis was higher in the experimental (polylactic acid) group. Conclusion. On the basis of the findings of this study, polylactic acid granules do not reduce the incidence of alveolar osteitis and may actually contribute to a higher incidence of alveolar osteifis. (ORAL SURGORAL MED ORAl. PATHOLORAL RADIOL ENDOD 1995;80:279-83)
Alveolar osteitis (dry socket), as first described by Crawford 1 in 1896, continues to be the most c o m m o n complication associated with the surgical removal of mandibular third molars. The clinical presentation is classic. The patient reports severe throbbing pain not relieved by analgesics that develops or persists several days after surgery. Although polylactic acid has been commercially available for more than a decade, its use as an agent to prevent alveolar osteitis has only been reported twice. On the basis of this data, Brekke et al. 2, 3 have advocated the use of polylactic acid granules injected into mandibular third molar sockets as a method of reducing the incidence of alveolar osteitis. In a 1983 study they used a polylactic acid mesh in 228 patients. 4 When extraction types were divided into soft tissue, partial bony, or full bony, the control and experimental percentages of alveolar osteitis were as follows: 10.8%, 12.9%, and 19.4% for the control and 2.7%, 3.2%, and 3.9% for the experimental side. In their 1986 report, Brekke et al. 3 demonstrated a reduction in the incidence of alveolar osteitis from
The opinions expressed herein are those of the authors and cannot be construed as reflecting the views of the Navy Department or the Naval Service at large. aFormerly Dean and Professor Emeritus, University of California, Los Angeles School of Dentistry; currently Captain, Navy Dental Corps, assigned to the U.S.S. Independence, Yokosuka, Japan. bChairman, Department of Oral and Maxillofacial Surgery, Naval Dental School; Captain, Navy Dental Corps. Received for publication Nov. 3, 1994; revision requested Dec. 12, 1994; accepted for publication March 16, 1994. 7/12/64835
18.1% in the control group tO 2.2% in the group receiving the polylactic acid granules. These results have not been corroborated by any other studies. This investigation is intended to provide additional data concerning the effectiveness of polylactic acid granules injected into third molar sockets to reduce the incidence of alveolar osteitis.
MATERIAL AND METHODS The polylactic acid granules (Drilac) were provided by Osmed, Inc. (Duluth, Minn.). The study included 161 patients. Patients were enrolled in the study if they had bilateral impacted third molars that appeared to be symmetrical on panoramic radiograp h y . All patients were male active-duty military members serving on the aircraft cartier U.S.S. Independence. Patients who had pericoronitis or other infections were excluded. All procedures were performed with patients under intravenous sedation with midazolam and fentanyl. Local anesthesia consisting of lidocaine 2% with 1:100,000 epinephrine and bupivacaine hydrochloride 0.5% with 1;200,000 epinephrine was used. No steroids or antibiotics were used. All procedures required a flap and some bone removal. Bone removal and tooth sectioning were accomplished with a Hall electric drill system (Hall Surgical, Santa Barbara, Calif.) with a 703 burr. A minimum of 175 ml of saline solution was used to irrigate each side. Sutures were not used in most cases, but when necessary one or two 3-0 gut sutures were placed. The polylactic acid granules were placed randomly in either the right or left side as determined by a coin toss. No notation
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Table I. Incidence of alveolar osteitis in smokers and nonsmokers Alveolar osteitis (%)
Smokers Nonsmokers
Number of patients
Control
Polylactic acid
44 117
22.73 10.26
31.82 20.5
was made on the patient's record as to which side the material was inserted. This information was recorded on a separate form that was sealed until completion of the study. All surgery was performed by one board-certified oral and maxillofacial surgeon who also performed all postoperative evaluations. At the postoperative visits it was not possible to determine which side had the polylactic acid granules inserted into the socket; however, it became apparent once the need for a sedative dressing was determined. The data collected included the patient' s name, age, social security number, and smoking status. If the patient smoked cigarettes, the number of cigarettes per day was recorded. The third molars were classified as erupted,, requiring a flap and removal of bone; soft tissue impacted; partially bony impacted; and fully bony impacted. Each surgical procedure was timed. Data were also gathered on other postoperative complications. The patient was given an appointment for postoperative follow-up on the first, fourth, and the seventh days. They were advised to seek postoperative care earlier if there was any sign of infection, hemorrhage, or pain that was not controlled by ibuprofen. Because all patients were living on board an aircraft carrier, compliance with postoperative appointments was 100%. No patients were lost to follow-up. The data were analyzed to compare the number of occurrences of alveolar osteitis in the experimental versus the control group. The data were further analyzed to establish the relationship of various factors, such as the difficulty of the surgery, length of surgery, and smoking status, on the development of alveolar osteitis. The statistical analysis used was the chisquare test. For the purpose of this investigation, the diagnosis of alveolar osteitis was based on clinical symptoms rather than the appearance of the socket. Any patient who reported severe, usually throbbing pain before the seventh day was considered to have the condition. If the pain was not of a throbbing nature but was not relieved by ibuprofen, it was considered to be alveolar osteitis.
RESULTS A total of 161 patients were included in the study. All of the patients were male, between the ages of 18 and 26 years. The average age was 20.45 years. The median age was 20 years. Polylactic acid was placed on the right side in 81 cases and on the left side in 80 cases. Three hundred twenty-two mandibular third molars were surgically removed. The incidence of alveolar osteitis in the control group was 13.58% (22 surgical sites), and in the study group the incidence was 23.6% (38 surgical sites). This difference is statistically significant (chi-square = 4.609 with 1 degree of freedom; p = 0.032) The incidence of alveolar osteitis was higher in the study group for every category analyzed. Forty of the 161 patients were smokers. The incidence of alveolar osteitis was higher than in the 117 nonsmokers (Table I). The incidence of alveolar osteitis in the control group was 22.73% (10 surgical sites), and in the study group the incidence was 31.82% (14 surgical sites). This difference in the incidence between the two groups was not statistically significant (chi-square = 3.224 with 1 degree of freedom; p = 0.073). Eight dry sockets were bilateral, and seven were unilateral. In the nonsmokers, the incidence was 10.26% on the control side and 20.5 % on the study side. Eight dry sockets were bilateral, and 22 were unilateral. A definite correlation was found between the difficulty of the procedure and the incidence of alveolar osteitis (Tables II and III). In the control group no cases of osteitis were found in those patients whose procedures took 2 minutes or less to complete, whereas those patients whose procedures took more than 11 minutes had an incidence of 33%. In the study group no incidence was found in those patients whose procedures lasted 2 minutes or less, and the incidence was 58% for those patients whose procedures lasted 11 minutes or more. Six (3.7%) postoperative infections occurred, all of which resolved after a course of penicillin therapy. No delayed infections occurred. In five patients the polylactic acid granules failed to resorb, and they were subsequently curetted out of the socket. These patients did not have painful symptoms. Five patients in w h o m alveolar osteitis w a s not diagnosed reported significant pain 7 days after the procedure. All five patients were in the study group. DISCUSSION The cause and pathogenesis of alveolar osteitis have been the subject of much study and debate since the condition was first recognized, but no consensus
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Volume 80, Number 3
Table II. Effect of the length of surgery on the incidence of alveolar osteitis
Table III. The relationship of the predicted difficulty on the incidence of alveolar osteitis
Alveolar osteitis (%)
Time (min)
Number in group
Control
Polylactic acid
1-2 3-4 5-6 7-10 11+
15 32 48 55 11
0 6.25 18.7 10.7 36.3
0 25 20.8 23.2 63.6
exists as to the cause of alveolar osteitis. However, there is some agreement on many factors that may contribute to the development of alveolar osteitis. Hall 5 states that bacterial lysis of the clot is the initiating event. A study by Birn 6 attributes the cause to increased fibrinolytic activity within the alveolus and clot. Trauma is frequently mentioned as a contributing factor. 7 The rate of alveolar osteitis is higher when an inexperienced surgeon is performing the surgery, 8 which further supports the finding that trauma is a contributing cause. Smoking and the use of birth control pills are also considered to be contributing factors.9, 10 In other studies the cause of alveolar osteitis has variously been attributed to inadequacy of the blood supply to the alveolus, 11 infection, 12, 13 a reactivated herpes simplex virus infection, 14, 15 and a variety of other less likely initiating factors including seasonal variation, nutrition, excessive bleeding, and choice of anesthetic. Although alveolar osteitis can occur in any socket, it is almost exclusively .a problem related to mandibular third molars. Numerous agents and methods have been used with some effectiveness for prevention of this condition. Antifibrinolytics 16 and antiinflammatory agents 17 have been used in an effort to stabilize the clot. Other studies h a v e shown that improvment of hygiene and use of antimicrobial rinses have been effective in reducing the incidence of alveolar osteitis in s o m e cases. 18-22 The search for a better understanding of the pathophysiology of this condition continues, and because the mechanism for the development of the condition is poorly understood, the empirical search for new medications and substances will continue. Most current methods of reducing alveolar osteitis are directed at reducing or altering the bacterial population of the third molar region. The methods include the use of topical and systemic antibiotics 23 and antiseptic mouth rinses. Topical tetracycline has proved effective in reducing the incidence of alveolar osteitis. Swanson 24 demonstrated a reduction from 37.5%
Alveolar osteitis (%)
Classification
Number
Control
Polylactic acid
1 2 3 4
14 38 67 42
0 13.1 12 21.4
0 15.8 21 33.3
to 2.6% using Gelfoam saturated with a 50-mg solution of tetracycline. Hall et al. 25 and Sorensen and Preisch 26 also reported excellent results with tetracycline. Chlorhexidine mouth rinses have also shown good results in some studies 22, 27, 28; however, one study showed them to be ineffective. 29 Alveolar osteitis continues to be a significant problem, particularly for patients undergoing mandibular third molar surgery. The incidence of alveolar osteitis in this group of patients is reported to be in the range of 20% to 31%. In this investigation the incidence of 13.58% in the control group appears to be somewhat lower than the average reported in the literature.16, 21, 25, 29, 30 We used a standard buccal approach for the removal of wisdom teeth. Sutures were not usually used, and the wound was irrigated with a minimum of 175 ml of saline solution. Sweet and Butler 31 have found that using 175 ml of saline solution was more effective than lower volumes of saline solution. This represents an extra step in the procedure because irrigation with 175 ml of saline solution takes an extra 30 to 45 seconds during the procedure. No women were included in the study, which m a y have been a factor in the low rate of alveolar osteitis because women are reported to have a higher incidence of alveolar osteitis. 22, 31 In the only previous report on the use of polylactic acid granules injected into third molar sockets for the purpose of prevention of alveolar osteitis, Brekke et al. stated that "alveolar osteitis is the product of postoperative, intrabony ischemia complicated by premature loss of mechanical support provided by a healthy blood clot. ''2 They believed the condition was caused by " v e r y poor intrinsic collateral circulation" and further stated that " w o u n d s protected with polylactic acid d r e s s i n g s . . , successfully tolerate considerably longer durations of surgical trauma than do unprotected wounds. ''2 The p01ylactic acid dressings were believed to provide the fresh blood clot with a stable support system that keeps the newly formed clot in juxtaposition with surviving collateral
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September 1995 circulation. Furthermore, the dressings were believed to reduce the destructive effects of fibrinolysis b y p r o v i d i n g a stable a n d biologically acceptable matrix for future g r a n u l a t i o n tissue development. 2 The theory of Brekke et al. for the pathogenesis of alveolar osteitis is u n s u p p o r t e d by scientific evidence and is in conflict with the b e n c h m a r k findings of Bim, 6 who described the m e c h a n i s m to be high fibrinolytic activity within the socket. Polylactic acid is a biodegradable ester polymer. The material was developed in 1966 b y Kulkarni 32, 33 for surgical implants. Further d e v e l o p m e n t led to its use as an orthopedic i m p l a n t in 1970. 33, 34 Cutright et al. 35 used polylactic acid for m a n d i b u l a r fracture reduction in rhesus m o n k e y s . The material is b e i n g evaluated in h u m a n beings as a nonmetallic resorbable plate for fracture fixation. 36,37 Several other studies attest to the biologic compatibility of polylactic acid w h e n placed i n vivo. 38, 39 A l t h o u g h the material is biocompatible, it does appear to cause a variety of tissue reactions. B e r g s m a et al. 40 reported a u n i f o r m nonspecific f o r e i g n - b o d y reaction w h e n the material was used as a bone, plate, or screw. O l s o n et al.41 reported a m i l d foreign-body reaction w h e n the material was used i n dog extraction wounds. C a m p bell et al. 38 reported that it inhibited carcinoma cell growth. No studies are a v a i l a b l e to describe the biocompatibility of polylactic acid granules in an open w o u n d such as the socket of a m a n d i b u l a r third m o lar. The results of this investigation do not support the findings of Brekke et al. 2, 3 W e are u n a b l e to explain the d i f f e r e n c e in outcomes b e t w e e n the findings of Brekke et al. and the findings of our study. Perhaps it is because of the m a n y differences b e t w e e n the studies, Our study was more rigidly controlled than the Brekke et al. study. All surgery was performed by one surgeon in a tightly controlled institutional setting in our study, c o m p a r e d with three surgeons in three separate private practices in the Brekke et al. study. Our study i n c l u d e d o n l y m e n in a very narrow age range, whereas the Brekke et al. study included w o m e n . I n our study the patients served as their o w n controls in all instances, whereas in the Brekke et al. study this was true for about two thirds of the patients. The Brekke et al. study was not blind, and no m e n tion was made c o n c e r n i n g patients lost to follow-up. Data from the Brekke et al. study were very difficult to interpret, and the n u m e r o u s methodologic problems of the study detracted from the strength of its conclusions. The i n c l u s i o n criteria and the definition of alveolar osteitis were approximately the same for both studies.
CONCLUSION O n the basis of this study, the c o n t i n u e d use of polylactic acid granules for the p r e v e n t i o n of alveolar osteitis cannot be endorsed. The investigational material, polylactic acid, not only did not decrease the incidence of the condition but appeared to actually contribute to its increased incidence. Because this is the first observation of this p h e n o m e n o n , additional studies w o u l d seem to be indicated. This study supports the findings of m a n y other studies in m a n y respects. T h e highest i n c i d e n c e of alveolar osteitis was in patients with difficult i m p a c t i o n s who smoked. We thank Mr. David Langley of Osmed, Inc., for providing the Drilac for this investigation and CDR Brian K. Nicoll, DC, USN, for providing the statistical analysis. REFERENCES
1. Crawford JY. Dry socket. Dental Cosmos 1896;38:929-34. 2. Brekke JH, Bresner M, Reitman MJ. Effect of surgical trauma and polylactate cubes and granules on the incidence of alveolar osteitis in mandibular third molar extraction wounds. J Can Dent Assoc 1986;4:315-9. 3. Brekke JH, Bresner M, Reitman MJ. Surgical dressing material: postoperative therapy for extraction wounds. J Can Dent Assoc 1986;7:599-602. 4. Brekke JH, Olson RAJ, Scully JR, Osbon DB. Influence of polylactic acid mesh on the incidence of localized osteitis. Oral Surg Oral Med Oral Pathol 1983;56:240-5. 5. Hall HD. Effects of chlorhexidine gluconate oral rinse on the incidence of alveolar osteitis in mandibular third molar surgery. J Oral Maxillofac Surg 1990;48:449-55. 6. Birn H. Etiology and pathogenesis of fibrinolytic alveolitis. Int J Oral Maxillofac Surg 1976;2:211-9. 7. Alling CC, Ken D. Trauma as a factor causing delayed repair of dental extraction sites. J Oral Surg 1957;15:3-8. 8. Sisk AL, Hammer WB, Shelton DW, Joy ED. Complications following removal of third molars: the role of the experience of the surgeon. J Oral Maxillofac Surg 1986;44:855-9. 9. Sweet JB, Butler DP. The relationship of smoking to localized osteitis. J Oral Surg 1979;37:732-75. 10. Catellanni JE, Harvey S, Erickson SH. Effect of oral contraceptives on dry socket. J Am Dent Assoc 1980;101:777-88. 11. Huebsch RF. Clinical and histological study of alveolar osteitis. J Oral Surg 1958;16:473-9. 12. Adkisson SR, Harris PF. A statistical study of alveolar osteitis. US Armed Forces Med J 1956;7:1749-56. 13. Brown LR, Merrill SS, Allen RE. Microbiologic study ofintraoral wounds. J Oral Surg 1970;28:89-95. 14. Hedner E, Vahlne A, Kahnberg KE, Hirsch JM. Reactivated herpes simplex virus infection as a possible cause of dry socket after tooth extraction. J Oral Maxillofac Surg 1993;51:370-6. 15. Openshaw H. Reactivated herpes simplex infection as a possible cause of dry socket after tooth extraction. J Oral Maxillofac Surg 1993;51:377-8, 16. Ritzau M, Therkildsen P. Antifibrinolytic prevention of alveolitis sicca dolorosa. Int J Oral Maxillofac Surg 1986;7:53454. 17. Rutledge JL, Marcoot RM. Terracortril/Gelfoam for reduction of the incidence of localized osteitis following mandibular third molar removal. J Oral Pathol Med 1984;39:51-7. 18. Lilly GE, Osbon DB, Raele M, et al. Alveolar osteitis associated with mandibular third molar extractions. J Am Dent Assoc 1974;88:802-9.
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Volume 80, Number 3 19. Schiott CR, Harald LS, Borglure J, et al. The effect of chlorhexidine mouth rinses on the human oral flora. J Periodontal Res 1970;5:84-91. 20. Tjernberg A. Influence of oral hygiene measures on the development of alveolitis sicca dolorosa after surgical removal of mandibular third molars. Int J Oral Maxillofac Surg 1979;8: 430-5. 21. Krekmanov L, Nordenramn A. Postoperative complications after surgical removal of mandibular third molars. Int J Oral Maxillofac Surg 1986;15:25-30. 22. Field EA, Nind D, Varga E, et al. The effect of chlorhexidine irrigation on the incidence of dry socket: a pilot project. Br J Oral Maxillofac Surg !988;26:395-9. 23. Rood JP, Muratroyd J. Metronidazole in the prevention of dry socket. Br J Oral Maxillofac Surg 1979;37:62-9. 24. Swanson AE. Reducing the incidence of dry socket: a clinical appraisal. J Can Dent Assoc 1966;2:25-30. 25. Hall HD, Bildman BS, Hand CD. Prevention of dry socket with local application of tetracycline. J Oral Surg 1971;29:35-7. 26. Sorensen DC, Preisch JW. The effect of tetracycline on the incidence of postextraction alveolar osteitis. J Oral Maxillofac Snrg 1987;45:1029-33. 27. Legarth J, Munkster R, Swendsen J. Klorheksidins virkning pa vdriklingen of alveolitis sicca dolorosa efter operativ fjerneise of visdonstaender i under kaeben [Abstract]. Tanglaegebladet 1977;81:451. 28. Larsen PE. The effect of a chlorhexidine rinse on the incidence of alveolar osteitis following the surgical removal of impacted mandibular third molars. J Oral Maxillofac Surg 1991;49: 932-9. 29. Berwick JE, Lessin ME. Effects of a chlorhexidine glnconate oral rinse on the incidence of alveolar osteitis in mandibular third molar surgery. J Oral Maxillofac Surg 1990;48:444-8. 30. Krekrnanov L. Alveolitis after operative removal of third molars in the mandible. Int J Oral Surg 1981;10:173-7. 31. Sweet JB, Butler DP. Predisposing and operative factors: effect on the incidence of localized osteitis in mandibular third molar surgery. ORAL SURG ORAL MED ORAL PATHOL 1978;46:206-15.
32. Kulkarni RK, Pani C, Neuman C, Leonard F. Biodegradable polylactic acid polymers. J Bi0med Mater Res 1971;5:16981. 33. Kulkarni RK, Pani C, Neuman C, Leonard F. Polylactic acid for surgical implants. Arch Surg 1966;93:839-43. 34. Getter L, et al. A biodegradable intraosseous appliance in the treatment of mandibular fractures. J Oral Surg 1972;30: 344-8. 35. Cutright DE, Hunsuck EL, Beasley J. Fracture reduction using biodegradable material: polylactic acid. J Oral Surg 1971 ;29:393-7. 36. Wittenberg JM, Wittenberg RH, Hipp JA. Biomechanical properties of resorbable poly-L-lactide plates and screws: a comparison with traditional systems. J Oral Maxillofac Surg 1991 ;49:512-7. 37. Suuronen R. Comparison of absorbable self-reinforced polyL-lactide screws and metallic screws in the fixation of mandibular osteotomies: an experimental study in sheep. J Oral Maxillofac Surg 1991;49:989-93. 38. Campbell JH, Edsberg L, Meyer AE. Polylactide inhibition of carcinoma cell growth in vitro. J Oral Maxillofac Surg 1994; 52:49-51. 39. Schliephake H, Newkam FW, Hutmacher D, Becker J. Enhancement of bone ingrowth into a porous hydroxylapatite matrix using a resorbable polylactic membrane. J Oral Maxi11ofac Surg 1994;52:57-63. 40. Bergsma EJ, Rozema FR, Ruud RM, de Bruijn WC. Foreign body reactions to resorbable poly(L-lactide) bone plates and screws used for the fixation of unstable zygomatic fractures. J Oral Maxillofac Surg 1993;51:666-70. 41. Olson RA, Roberts DL, Osbon DB. Comparative study of polylactic acid, Gelfoam, and Surgicel in healing extraction sites. ORAL SURG ORAL MED ORAL PATHOL 1982;53:441-9.
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