Osteomyelitis in the maxillofacial region has been a topic of discussion for many centuries. The unique environment of the oral cavity and dentition in conjunction with a constantly changing intraoral environment has led to several classification schemes for mandibular and maxillofacial osteomyelitis. Newer challenges have emerged with the emergence of osteoradionecrosis of the jaw secondary to radiation to the head and neck, as well as osteonecrosis of the jaw as seen with use of bisphosphonates. These new clinical entities may be different from traditional osteomyelitis in terms of pathogenesis but are managed alike in many respects. The presence of microorganisms in osteoradionecrosis and osteonecrosis is thought to be secondary in their pathogenesis.
Numerous classification systems for osteomyelitis of the jaw exist 1; however, regardless of the classification the goals of treatment remain the same. The goals of therapy are to remove dead bone and eliminate or at least attenuate the proliferating pathogenic microorganisms through a combination of surgery and antibiotics and then give supportive care for healing. It is important to identify the causative or associated pathogens 1–6. Risk factors associated with osteomyelitis of the jaw must be identified and modified if possible. The known risk factors associated with osteomyelitis of the jaws include diabetes mellitus, autoimmune diseases, malignancy, malnutrition, systemic steroids, chemotherapy, radiotherapy, bisphosphonate use, trauma, osteopetrosis, acquired immunodeficiency disease, dental implant, sickle cell anemia, alcoholism, intravenous drug abuse, renal or hepatic failure, chronic hypoxia, old age, and tobacco abuse 1–8.
There has been, however, a paucity of studies on osteomyelitis of the jaws taking into account new risk factors. Hence, a comprehensive review of the management of osteomyelitis of the jaws as seen in different medical and dental centers was performed. The purpose of the present retrospective study was to determine and update the risk factors associated with osteomyelitis of the jaws in the Saudi population. It was also undertaken in an attempt to determine its clinical presentation and microbiological etiology, to assess treatment outcomes and variables that might impact the management of osteomyelitis of the jaw, and evaluate the morbidity and mortality associated with it.
A retrospective chart review was conducted at King Abdulaziz University Hospital and at the Faculty of Dentistry Oral Surgery Clinics, as well as in other government medical and dental centers, particularly King Fahd Military Hospital and King Fahd General Hospital, Jeddah, Kingdom of Saudi Arabia, from January 2000 to December 2010. The most common symptoms and signs of pyogenic osteomyelitis of the jaws determined with the aid of radiographs were used to initially select patients with possible jaw bone involvements (Table 1). From these initially selected patients, charts showing actual inflammatory jaw bone conditions were considered. This category includes the diagnoses of abscess, osteitis, and periostitis. Charts revealing osteomyelitis of the jaws were collected. A definitive diagnosis of osteomyelitis was given for biopsy-proven osteomyelitis. The diagnosis was construed as probable when one of the following three conditions was present: (i) positive cultures were isolated from the jaw during surgical debridement (deep bone cultures), (ii) presence of exposed bone ‘sequestrum’ during examination, or (iii) surgeon’s clinical and radiographic impression of osteomyelitis. Other charts describing other and unspecified diseases of the jaw were excluded. Individual patient charts were then reviewed for study eligibility. The University institutional review board approved the study before the chart review.
Data were collected by reviewing patient charts and computer records [The R4 Dental Management System V 3.24.6; PracticeWorks, a subsidiary of Carestream (Kodak) Health Inc., Herts, UK]. Data collected included demographics, risk factors associated with osteomyelitis, clinical presentation (subjective complaints and physical examination findings), treatment (type of surgery and details of antibiotics), operating room cultures, imaging findings (MRI, computed tomography, and radiograph findings [the software used in the X-ray system is Kodak Dental Imaging Software V 6.10.8, the machine model is Kodak 8000C Pan-Ceph Machine; Trophy, a subsidiary of Carestream (Kodak) Health Inc., Marne-la-Vallée, France], surgical pathology results, and outcomes including complications.
Adequate follow-up for this study was defined as doctor–patient contact for at least 3 months postoperatively. Targeted antibiotics were defined as antibiotic therapy based on culture and sensitivity data (when available). An outcome was classified as follows: ‘full recovery’ was defined as resolution of all signs and symptoms of active infection with no residual disability. ‘Limited recovery’ was defined as resolution of all signs and symptoms of infection but persistence of clinically significant residual disability, such as pain that limited activity or required analgesic therapy. Patients with limited recovery were compared with those who recovered fully. A relapse was defined as recurrence of symptoms of infections after apparent resolution.
Descriptive analysis was used to present a set of data. The χ2-test and the t-test were used for statistical analysis of compared data. Data compared included outcomes and other variables such as risk factors associated with osteomyelitis, antibiotic regimen, duration of symptoms, number of surgeries, and demographic variables.
One thousand patients out of 3000 showed different jaw bone involvements. Three hundred patients out of 1000 showed actual inflammatory jaw conditions. Only 42 patients met the criteria for definite osteomyelitis. Forty-one patients had experienced one episode of osteomyelitis, and one patient had experienced four episodes (Table 2).
Twenty-three patients (54.8%) were female. The mean age of the patients and SD was 58.3±17.5 years (95% confidence interval 53.11–63.21).
The risk factors associated with osteomyelitis in our study are shown in Table 3. The most frequent risk factors were tooth extraction, orofacial malignancy and radiotherapy, use of bisphosphonates, and nicotine abuse. Twenty-nine patients (69.0%) had more than one risk factor for osteomyelitis, whereas 13 (31%) had only one risk factor (Table 4).
Twenty-nine patients (69%) reported pain (Table 1). Other frequently encountered presentations were exposed bone/reconstruction plate and cheek swelling in 42.9 and 38.1% of patients, respectively. Symptoms may also include cellulitis, halitosis, mobile teeth, and trismus. A summary of the clinical presentation is shown in Table 1. Physical findings may include mandibular and/or maxillary bone exposure, pathologic fracture, oral-cutaneous fistula, and clinical infection.
Gross examination revealed a varied amount of exposed, nonvital bone of the maxilla, mandible, or both. The duration of symptoms ranged from 1 week to 29 years. The mean duration was 14.6 months. When the patient with symptoms spanning 29 years was omitted, the longest duration was 3.5 years and the mean and SD was 6.0±8.1 months (95% confidence interval 3.46–8.56). The location of lesions is presented in Table 5. The vast majority of lesions occurred in the mandibular body.
Microbiological samples (Table 6) were obtained during surgery from 45 culture specimens from 34 patients. The most common aerobic isolate was streptococci (46); Actinomyces spp. (12) and Prevotella spp. (11) were the most common anaerobes. The summary of microorganisms is shown in Table 6. Two surgical cultures were reported as normal flora (not included in Table 6). The overwhelming majority (94.1%) of patients had polymicrobial cultures. Thirty-eight cultures (84.4%) contained aerobic Gram-positive bacteria, whereas aerobic Gram-negative bacteria were obtained in 19 cultures (42.2%). Twenty-four cultures (53.3%) included anaerobic Gram-positive bacteria, whereas anaerobic Gram-negative bacteria were seen in 12 cultures (26.7%). Candida spp. was seen in 15 cultures (33.3%).
All 42 patients presented with positive radiographic findings: 40 with osteolysis, combined with osteosclerosis (Fig. 1) and two with osteosclerosis alone. Among the dental radiographic findings was a strong association with a widened periodontal membrane space, particularly at the furcation of the molar teeth (Fig. 2). Osteolysis of the mandible with a pathologic fracture resulted from a tooth removal while the patient received pamidronate bisphosphonate therapy (Fig. 1). Bone loss between the roots of the molar teeth (furcation involvement) is often an early sign of osteonecrosis of the jaws (Fig. 2).
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.
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