Every patient had undergone at least one surgical procedure. A total of 114 surgical procedures in 97 surgeries were performed (Table 7) with a mean and SD of 2.3±1.7 surgeries per patient. One patient of 29 years of age underwent 11 surgeries during the time of our study. If she had been omitted, the mean and SD would have been 2.1±1.0 surgeries. Almost half of the patients had debridement without continuity defect (Table 7).
A total of 67 courses of antibiotics (Table 8) were ordered and received. The largest group of patients (34.3%) received intravenous-targeted antibiotics with or without simultaneous or subsequent oral-targeted antibiotics for at least 4 weeks. Table 8 shows the classification and distribution of antibiotic therapy. Perioperative antibiotics were excluded from this table.
Twenty-five patients (Table 9) had hyperbaric oxygen therapy (HBOT). Sixteen patients (88.9%) with a history of orofacial malignancy and radiotherapy received HBOT. None of the patients who received HBOT recovered fully.
The mean length of follow-up was 13.1±11.3 months. Six patients were followed up for less than 3 months. No deaths were reported in this study. Five patients (11.9%) experienced full recovery; all of them had one risk factor (tooth extraction). Thirty-seven patients (88.1%) achieved limited recovery; the majority of them had malignancy and radiotherapy. There was no significant difference in outcomes when patients who received antibiotics for at least 4 weeks were compared with patients who received antibiotics for less than 4 weeks (P=0.57). The only risk factor associated with osteomyelitis of the jaw that approached statistical significance for an adverse outcome (limited recovery) was orofacial malignancy and radiotherapy (P=0.06). None of these patients (n=18) achieved a full recovery (Table 9). Outcome was not influenced by duration of symptoms (P=0.78), number of surgeries (P=0.33), or type of microorganism isolated during surgery. A good outcome was associated with the female sex, particularly the younger ones (P=0.04). Full recovery was more likely in a younger patient (mean age 40.8±22.1 years) than in an older patient (mean age 60.7±15.7 years; P=0.015). None of the patients with good outcomes had a relapse or complication.
In this retrospective study, we sought to undertake a comprehensive review of osteomyelitis of the jaw as seen in King Abdulaziz University Hospital, Faculty of Dentistry Oral Surgery Clinics, and other medical and dental government centers in Jeddah, Kingdom of Saudi Arabia, in a 10-year period (Table 2). This study is timely because there has been a dearth of studies exploring the full range of this subject in recent years. We anticipate that this study will enhance knowledge about this clinical entity and assist clinicians in the management of osteomyelitis of the jaw. It will also modify the type and modality of treatment. Furthermore, patients will be much more aware of the disease process; hence, they will implement preventive procedures.
Much earlier studies conducted in two centers in Nigeria revealed that patients presented late in the natural history, and the mean age of patients was usually in the second to fourth decade. The major predisposing factor was advanced periodontal disease or odontogenic infection 9,10. More recent studies in the USA had predominantly white patients with mean ages of patients in the fifth and sixth decade, similar to our study, and they recognized the emerging role of osteoradionecrosis 11–13. These previous studies were before the widespread use of bisphosphonates in the management of malignancies. In this study, the major predisposing factors were maxillofacial trauma, odontogenic infections, advanced periodontal diseases, and diabetes mellitus.
The three major risk factors in this study (Table 3) were tooth extraction, radiotherapy for orofacial malignancy, and use of bisphosphonates for the management of malignancies. These risk factors were not mutually exclusive. This is in sharp contrast to the study by Calhoun et al.11, in which the top three risk factors were postradiation therapy (46.7%), post-traumatic infection (25%), and odontogenic infection (21.7%). Another study by Koorbusch et al.13 showed odontogenic infections (36.1%), traumatic infections (fracture related; 36.1%), and radiation and neoplasm (16.7%) as the most common risk factors. Finally, a Korean study in the late 1990s revealed that tooth-related complications (38.5%), postextraction complications (33.3%), and periodontal disease (12.8%) were the most common risk factors 14. Bisphosphonates also have antiangiogenic properties that can delay wound healing 6,15. Bisphosphonate-associated osteonecrosis can develop spontaneously 15. Irradiation affects osteoblasts and consequently decreases collagen formation. Irradiation also affects osteoclast activity initially and causes vascular injury, ultimately leading to sclerosis of bone marrow connective tissues 6,16.
With the compromised bone microenvironment described above in osteonecrosis and osteoradionecrosis and the continued oral contamination, it is not surprising that even small insults such as dental extraction or ill-fitting dentures can result in such a protracted illness (Mortensen et al., 2007 16–18). However, a new hypothesis proposes that osteoradionecrosis arises from a fibroatrophic process, and new considerations for treatment include antioxidants and antifibrotic drugs 16.
The most common symptoms and signs in this study (Table 1) were pain, exposed bone or reconstruction plate, cheek swelling, and discharge/drainage. Fever was seen in a minority of patients. We noted that five of the seven patients with maxillary lesions were on bisphosphonates. This was noted in previous studies as well 18–20. The clinical presentation and site of osteomyelitis are essentially similar to those seen in other studies 11,13,14.
The polymicrobial nature of surgical specimens obtained from osteomyelitis of the jaw has been recognized and largely mimic mouth flora (Table 6). The spectrum of organisms in this study is as seen in earlier studies 4,6,11,13,14. These cultures are deep bone cultures obtained in the operating room. The most common bacteria encountered are the Streptococci spp., Actinomyces spp., and Prevotella spp. Candida spp. is also seen. It is important to note that, although candida, corynbacteria, enterococci, and anaerobic streptococci are common in the mouth, they may not be pathogens in the bone. Calhoun et al.11 had noted that the presence of Candida spp. in cultures did not affect outcome. We found that patient outcome and type of microorganisms recovered during surgery were not statistically significant.
Selecting antibiotics and the treatment rendered is mostly based on isolating bacteria from these cultures 1,2. Empiric antibiotics were started, pending cultures providing adequate coverage for streptococci and anaerobic bacteria such as Actinomyces spp. and Prevotella spp. Penicillin remains the drug of choice 1. Other alternatives that may be used as a combination regimen include clindamycin, fluoroquinolones, metronidazole, a variety of cephalosporins, carbapenems, vancomycin in combination with other antibiotics, and tetracyclines (Table 8). Methicillin-resistant Staphylococcus aureus is noted in only three cultures and does not appear to play a dominant role in this condition. Candida spp. was largely ignored in the selection of antimicrobials.
All 42 patients (100%) presented with positive radiographic findings: 40 (95.2%) with osteolysis, combined with osteosclerosis (Fig. 1), and two (4.8%) with osteosclerosis alone. However, Marx et al. 21 reported on 73.1% of patients presenting with positive radiographic findings: 97.7% of them with osteolysis, combined with osteosclerosis, and 2.3 with osteosclerosis alone.
HBOT is known to enhance collagen synthesis and angiogenesis, leading to improved wound healing in osteoradionecrosis. Therefore, at least theoretically, HBOT was believed to play an adjunctive role in the management of osteoradionecrosis 4,5,16. However, Annane et al.22 in a prospective, multicenter, randomized, double-blind, placebo-controlled trial showed potentially worse outcomes in the HBO arm, and the study was terminated early. Patients with overt mandibular osteoradionecrosis did not benefit from hyperbaric oxygenation 22. Our study confirmed this issue too. None of the 25 patients who had HBOT experienced a full recovery.
Female patients were more likely to have a good outcome. The reason for this is unclear. Full recovery was also more likely in a younger patient, as seen in an earlier study 12. The relationship between a limited recovery and the risk factor of orofacial malignancy and radiotherapy approached statistical significance. In this study, no patient with a risk factor of orofacial malignancy and radiotherapy (n=18) achieved a full recovery. Calhoun and colleagues showed cure to be more likely in the nonradiation group. This agrees with the results of our study in which all the five patients who showed full recovery were those who had undergone tooth extraction. However, this difference disappeared when followed up for more than 6 months 11. There was no statistically significant relationship between the use of bisphosphonates and patient outcome in our study (n=12, all of them achieved limited recovery). The other risk factors associated with osteomyelitis of the jaw did not predict patient outcome. The role of surgery in the management of osteomyelitis has been largely established. The confusion lies in determining the length of antibiotic therapy. Most clinicians use antibiotics empirically for 4–6 weeks. Arguments for longer or shorter courses remain unresolved 7,8,11,23–25. Patient outcome was not affected by length of appropriate antibiotic therapy. Our study did not show any benefit with the use of HBOT. This was obvious in the 25 cases managed with HBOT. Other studies showed similar results 11,16,22.
One male patient was the only patient with more than one episode. He had four episodes during this study. He had a history of osteopetrosis. Osteopetrosis is a heterogenous group of heritable conditions in which there is a defect in bone resorption by osteoclasts resulting in abnormal shape and structure of bone and making the bone very brittle. It also predisposes to osteomyelitis 26. Another patient had symptoms dating back to a subperiosteal implant 29 years before presentation. The implant was ultimately explanted.
In summary, the mean age of patients in this study was 58.3 years. The major risk factors associated with osteomyelitis of the jaw are tooth extraction, radiotherapy for orofacial malignancy, and use of bisphosphonates for the management of malignancies. Most cultures were polymicrobial, and targeted antibiotics were used. However, this study showed that there was no benefit associated with an antibiotic regimen lasting longer than 4 weeks, and patient outcome was not influenced by type of microorganism isolated from operating room cultures. This study also found that a history of orofacial malignancy and radiotherapy was associated with limited recovery, despite HBOT.
In our study we can therefore conclude that osteonecrosis of the jaw that results from odontogenic pyogenic infections has emerged as a significant risk factor associated with the development of osteomyelitis of the jaw. The use of bisphosphonates for the management of malignancies came in the last order. Furthermore, we also conclude that osteoradionecrosis that results from radiotherapy for orofacial malignancy continues to play a significant role as a predisposing factor in the development of osteomyelitis of the jaw. However, bisphosphonates inhibit osteoclast activity, which negatively affects bone resorption and bone remodeling. Bisphosphonates also have antiangiogenic properties that can delay wound healing 6,15. Bisphosphonate-associated osteonecrosis can develop spontaneously 15. Irradiation affects osteoblasts and consequently decreases collagen formation. Irradiation also affects osteoclast activity initially and causes vascular injury, ultimately leading to sclerosis of bone marrow connective tissues 6,16. However, this study showed that no benefit accrued from an antibiotic regimen that lasted longer than 4 weeks, and patient outcome was not influenced by the type of microorganism isolated from operating room cultures. This study also found that a history of orofacial malignancy and radiotherapy was associated with limited recovery despite HBOT. Furthermore, our study did not show any benefit with the use of HBOT.
Our study had some limitations. First, the small number of patients may have failed to unmask potential variables that may have affected patient outcome. Second, this study was carried out at only one academic medical center. A prospective, multicenter study would be useful in confirming our findings and addressing the above points. Third, the lack of adequate documentation of antibiotic therapy in some patient’s charts probably affected the results of our study. Better documentation and a prospective study would address this issue.
On the basis of the radiographic and clinical features of disease, surgical treatment options are suggested. At times, a curative measure can be simply extraction of a tooth with local curettage or removal of the underlying cause, whereas at other times a resection of the affected area may be needed. For purposes of clarification, all marginal debridements are classified as ‘debridement without continuity defect’. This was by far the most widely used surgical treatment both in this study and in the literature. This surgical technique was used when osteomyelitic changes extended through only one cortex of the bone but not both, or if osteomyelitic changes did not advance to the inferior margin of the bone. If pathologic fracture occurred or if clear clinical and radiographic evidence was seen of bicortical osteomyelitis, a resection with continuity defect was often used. Efforts were always made to maintain a continuity of native bone, and this is why the vast majority of cases proved to have debridement without continuity defect.
We anticipate that this study will enhance knowledge about this clinical entity and assist clinicians in the management of osteomyelitis of the jaw. It will also modify the type and modality of treatment. Furthermore, patients will be more aware of the disease process and will thus implement preventive procedures. However, the lack of adequate documentation of antibiotic therapy in some patient’s charts probably affected the results of our study.
The number of cases collected from each center (Table 2) was mentioned separately (of the 3000 cases), which is considered an indicative of healthcare service standards in Kingdom of Saudi Arabia. The number of cases with multiple risk factors was also mentioned, as well as whether the fully recovered cases are among those that could clarify the impact of systemic diseases on treatment outcome.
This project was funded by the Deanship of Scientific Research (DSR), King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia, under Grant No. 462/165/1431. The authors therefore greatly acknowledge DSR technical and financial support.
Conflicts of interest
There are no conflicts of interest.
1. Hudson JW. Osteomyelitis of the jaws: a 50-year perspective. J Oral Maxillofac Surg. 1993;51:1294–1301
2. Marx RE. Chronic osteomyelitis of the jaw. Oral Maxillofac Surg Clin North Am. 1991;3:367–381
3. Bernier S, Clermont S, Maranda G, Turcotte JY. Osteomyelitis of the jaws. J Can Dent Assoc. 1995;61:441–442 445
4. Aitasalo K, Niinikoski J, Grénman R, Virolainen E. A modified protocol for early treatment of osteomyelitis and osteoradionecrosis of the mandible. Head Neck. 1998;20:411–417
5. Kushner GM, Alpert BMiloro M, Ghali GE, Larsen PE, Waite P. Osteomyelitis and osteoradionecrosis. Peterson’s principals of oral and maxillofacial surgery.2nd ed. New York Pmph Usa; 2004
6. Ruggiero SL, Mehrotra B, Rosenberg TJ, Engroff SL. Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases. J Oral Maxillofac Surg. 2004;62:527–534
7. Lew DP, Waldvogel FA. Current concepts: osteomyelitis. N Engl J Med. 1997;336:999–1007
8. Lew PDP, Waldvogel PFA. Osteomyelitis. Lancet. 2004;364:369–379
9. Daramola JO, Ajagbe HA. Chronic osteomyelitis of the mandible in adults: a clinical study of 34 cases. Br J Oral Surg. 1982;20:58–62
10. Ladepo Adekeye E, Cornah J. Osteomyelitis of the jaws: a review of 141 cases. Br J Oral Maxillofac Surg. 1985;23:24–35
11. Calhoun KH, Shapiro RD, Stiernberg CM, Calhoun JH, Mader JT. Osteomyelitis of the mandible. Arch Otolaryngol Head Neck Surg. 1988;114:1157–1162
12. Lobati F, Herndon B, Bamberger D. Osteomyelitis: etiology, diagnosis, treatment and outcome in a public versus a private institution. Infection. 2001;29:333–336
13. Koorbusch GF, Fotos P, Goll KT. Retrospective assessment of osteomyelitis: etiology, demographics, risk factors and management in 35 cases. Oral Surg Oral Med Oral Pathol. 1992;74:149–154
14. Kim SG, Jang HS. Treatment of chronic osteomyelitis in Korea. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2001;92:394–398
15. Migliorati CA, Siegel MA, Elting LS. Bisphosphonate-associated osteonecrosis: a long-term complication of bisphosphonate treatment. Lancet Oncol. 2006;7:508–514
16. Teng MS, Futran ND. Osteoradionecrosis of the mandible. Curr Opin Otolaryngol Head Neck Surg. 2005;13:217–221
17. Melo MD, Obeid G. Osteonecrosis of the jaws in patients with a history of receiving bisphosphonate therapy: strategies for prevention and early recognition. J Am Dent Assoc. 2005;136:1675–1681
18. Mortensen M, Lawson W, Montazem A. Osteonecrosis of the jaw associated with bisphosphonate use: presentation of seven cases and literature review. Laryngoscope. 2007;117:30–34
19. Migliorati CA, Schubert MM, Peterson DE, Seneda LM. Bisphosphonate-associated osteonecrosis of mandibular and maxillary bone: an emerging oral complication of supportive cancer therapy. Cancer. 2005;104:83–93
20. Dimitrakopoulos I, Magopoulos C, Karakasis D. Bisphosphonate-induced avascular osteonecrosis of the jaws: a clinical report of 11 cases. Int J Oral Maxillofac Surg. 2006;35:588–593
21. Marx RE, Sawatari Y, Fortin M, Broumand V. Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: risk factors, recognition, prevention and treatment. J Oral Maxillofac Surg. 2005;63:1567–1575
22. Annane D, Depondt J, Aubert P, Villart M, Géhanno P, Gajdos P, et al. Hyperbaric oxygen therapy for radionecrosis of the jaw: a randomized, placebo-controlled, double-blind trial from the ORN96 study group. J Clin Oncol. 2004;22:4893–4900
23. Mader JT, Shirtliff ME, Bergquist SC, Calhoun J. Antimicrobial treatment of chronic osteomyelitis. Clin Orthop Relat Res. 1999;360:47–65
24. McHenry MC, Easley KA, Locker GA. Vertebral osteomyelitis: long-term outcome for 253 patients from 7 Cleveland-area hospitals. Clin Infect Dis. 2002;34:1342–1350
25. Lazzarini L, Lipsky BA, Mader JT. Antibiotic treatment of osteomyelitis: what have we learned from 30 years of clinical trials? Int J Infect Dis. 2005;9:127–138
© 2012 Egyptian Associations of Oral and Maxillofacial Surgery
26. Tolar J, Teitelbaum SL, Orchard PJ. Mechanisms of disease osteopetrosis. N Engl J Med. 2004;351:2839–2849