Osteoradionecrosis prevention myths
Wahl MJ  International Journal of Radiation Oncology, Biology, PhysicsVolume 64, Issue 3, pages 661-669 (01 March 2006)

Patients undergoing radiation therapy of the head-and-neck region can suffer complications, including osteoradionecrosis (ORN), a nonhealing exposure of bone of at least 6 months’ duration. The most important risk factor for ORN is trauma (including preradiation and postradiation extractions), but ORN can also occur spontaneously. When extractions are necessary, they should be performed as atraumatically as possible. Osteoradionecrosis can be quite painful and debilitating, sometimes requiring surgical resection of the jaw and/or hyperbaric oxygen (HBO) treatments. Most cases of ORN, however, eventually heal without HBO or surgery. There has been much attention given to prevention methods, including preradiation extractions of healthy or restorable teeth and the use of HBO treatments or prophylactic antibiotics for postradiation extractions. Clayman  has shown that, thanks in part to more efficient techniques in radiation therapy, the overall incidence of ORN in pooled studies among radiation patients has dramatically declined since 1968, from 11.8% (391 of 3,312 patients) before 1968 to 5.4% (602 of 11,077 patients) from 1968 to 1992. This incidence includes all cases of ORN and is not limited to cases of preradiation or postradiation extractions. Since 1997, pooled studies have shown an even lower incidence of 3.0% (290 of 9,632 patients) .

The incidence of postradiation extraction ORN has shown a similar decline. For the period 1968–1992, Clayman  reported an incidence of postradiation extraction ORN without prophylactic HBO in pooled studies of 5.8% (32 of 555 patients). Pooled studies since 1986 have shown a rate of 3.1–3.5% (16 of 461–508 patients)

The dose of radiation is an important risk factor for the development of ORN—the higher the dose, the greater the risk. Most cases of ORN occur after doses >60 Gy; very few cases occur after doses <50 Gy. The risk of ORN has historically been considered greater with postradiation than with preradiation extractions or no extractions, but the data from the present review indicate that the risk of developing ORN is approximately the same with preradiation as with postradiation extractions. The typical radiation dose for most oral and head-and-neck tumors is between 50 and 70 Gy . The incidence of ORN is much higher in the mandible than in the maxilla and is higher after mandibular molar extractions in the radiation field than after other extractions, probably because there is less blood supply in the mandible than in the maxilla, although one study of postradiation extractions showed a greater incidence in the maxilla than in the mandible. Alcohol or tobacco use, although common in head-and-neck cancer patients, does not seem to be a cause of osteoradionecrosis. Dental disease before radiation might contribute to the later development of ORN, so needed dental work (including the extraction of nonrestorable teeth) and oral hygiene instructions should be accomplished before radiation therapy.

Although most authorities agree that a time period of 10–14 days should elapse between extractions and irradiation, some recommend a 21-day delay. One study showed that a shorter time interval (<10 days) does not seem to be associated with a higher risk of osteoradionecrosis . The delay of potentially life-saving radiotherapy must be weighed against the potential for ORN. Because the risk of ORN seems to be approximately the same with postradiation than with preradiation extractions, it might be more important not to delay potentially life-saving radiation therapy than to wait for preradiation extraction sites to heal.

Most investigators agree that the risk of postextraction ORN remains years after radiation therapy and possibly for the rest of the patient’s life. The actual risk of ORN probably decreases  over time, but some assert that it might increase. Sulaiman  described the use of a multidisciplinary team approach, whereby every patient receiving radiation is referred to the dental service for an oral examination before treatment. Such collaboration can be invaluable for these patients.

Some of the traditional thinking about preventing ORN is based more on folklore than fact. Although ORN is a serious complication, neither preradiation nor postradiation extractions are associated with a particularly high incidence of ORN. Hyperbaric oxygen is a very costly and time-consuming treatment that has not been proven to prevent ORN. There are serious risks associated with HBO. Prophylactic antibiotics have never been shown to prevent ORN, which might not be an infectious process. There have not been large-scale randomized studies or formal risk/benefit or cost/benefit analyses of HBO or prophylactic antibiotics for the prevention of ORN. To resolve some of the confusion surrounding this issue, three myths regarding the prevention of ORN will be discussed.

Myth 1: Extraction of healthy or restorable teeth before irradiation is a reasonable method of preventing ORN

Because postradiation extractions can cause ORN, and because it is sometimes difficult to predict which teeth might require future extraction, many investigators have recommended the preradiation extraction of healthy or restorable teeth to prevent postradiation ORN. The overall incidence of ORN (from any source) in pooled studies before 1968 was 11.8% (391 of 3,312 patients)

In the past and as late as 1983, many investigators were recommending the extraction of all teeth for most patients before radiotherapy. In 1992, Jansma  recommended removing teeth in the area of the tumor. In 1997, Johnson  recommended removing all mandibular teeth in the radiation field above 60 Gy except in cases of excellent dental health. In 1999, Tong  recommended extracting all second molars, unless the patient has or will have meticulously good oral hygiene, and all molars in patients with poor hygiene. Vissink et al. stated in 2003 that clinicians should be aggressive in extracting teeth before radiotherapy

But preradiation extractions themselves can be a cause of postradiation ORN. Since 1986, the incidence of ORN after preradiation extraction (3.0–3.2%; 23 of 711–756 patients)  was approximately the same as the incidence of ORN after postradiation extraction (3.1–3.5%; 16 of 461–508 patients) in pooled studies.  Osteoradionecrosis can also occur in edentulous patients or spontaneously, and preradiation extractions cannot prevent these. Ulcerations from removable dentures can also be a cause of ORN.

Cancer patients who have undergone radiation therapy are often faced with a litany of medical problems, and adding unnecessary complete or partial edentulousness to this list is a mistake. Ulceration caused by the replacement of these missing teeth with removable dentures can be another cause of ORN. Good nutrition is extremely important in cancer patients, but chewing efficiency can be markedly decreased with unnecessary extractions. Self-esteem can also suffer. When making decisions regarding preradiation extractions, there should be some consideration given to the problems created by these extractions. Most postradiation extractions do not result in ORN. When ORN occurs, most cases heal, improve, or stabilize with conservative treatment and without HBO and surgery . Most investigators therefore no longer recommend the extraction of healthy or restorable teeth before radiation therapy

Myth 2: Prophylactic hyperbaric oxygen for postradiation extractions is a safe, simple, and effective preventive for ORN

Hyperbaric oxygen therapy was thought to be an effective adjunct in the treatment for ORN, so some have thought that it might be helpful as a preventive for ORN. But it is not clear that HBO is effective in treating ORN. A recent prospective, randomized, double-blind, placebo-controlled study has shown no benefit from HBO treatments for ORN

There have only been limited studies of prophylactic HBO. In a randomized, prospective 1985 study, Marx  showed a significantly lower incidence of ORN after postradiation dental extractions in the HBO group vs. the prophylactic antibiotic group. There were 2 cases of ORN in 37 patients (5.4%) receiving HBO undergoing 156 extractions, compared with 11 cases in 37 patients (29.9%) undergoing 135 extractions receiving prophylactic penicillin. A 1999 study showed that of 29 patients who received preextraction HBO, 1 (3.4%) developed ORN; and of 7 patients who did not receive an effective course of HBO, 1 (14.3%) developed ORN. On the basis of these two comparative studies, the investigators recommended prophylactic HBO to prevent ORN in postradiation extraction patients. Many other investigators recommend considering prophylactic HBO therapy for postradiation extractions, with some calling it the “treatment of choice” or the “optimum management” for the prevention of ORN.

In pooled studies of postradiation extractions without HBO since 1986, there was only a 3.1–3.5% incidence of ORN (16 of 461–508 patients), lower than Marx’s 30% without HBO or 5% with HBO. Since 1986 (and therefore not including Marx’s study), pooled studies of postradiation extractions with HBO have actually shown a slightly higher rate of 4.0% (6 of 151 patients)

Hyperbaric oxygen therapy is a time-consuming and costly process. The typical protocol calls for 30 hours of preoperative treatment in 20 90-minute sessions in a hyperbaric chamber, followed by 15 hours of postoperative treatment in 10 90-minute sessions. A physician, chamber operator, and medical assistant are required for each session . The cost of each 90-minute session of HBO has been estimated between $300 and $400, so the cost of the 30 sessions recommended to prevent a case of postextraction ORN is between $9000 and $12,000  The paucity of available HBO chambers could make the multiple visits necessary a hardship for an otherwise healthy patient, even more so for cancer patients. Some cases of ORN occur even after prophylactic HBO therapy.

There are also serious risks involved with HBO therapy. A 1986 study of 90 patients who received HBO for head-and-neck diseases over a 15-year period showed a significant risk of serious complications, including seizure (3.4%), stroke (1.1%), and myocardial infarction (1.1%). There were also 2 cases of eustachian tube dysfunction requiring myringotomy (2.2%). The overall incidence of complications of HBO was 7.8%.

There is a risk of decompression sickness if decompression occurs uncontrollably and a risk of explosion both from the oxygen-rich environment of the hyperbaric chamber and the pressure of the chamber itself. There was a report of five deaths from complications of decompression sickness from an uncontrolled decompression after an HBO chamber door ruptured

Other than the two small studies cited above, Schwartz stated, “All of the other protocols for the use of HBO in post-irradiation patients are entirely empiric, and are not supported by a single clinical trial”. There is insufficient evidence to support the use of HBO to prevent ORN. Until large-scale controlled studies and rigorous risk/benefit and cost/benefit analyses show that the benefits of HBO outweigh their risks and costs, the use of prophylactic HBO should be reconsidered.

Myth 3: Prophylactic antibiotic therapy is a safe, simple, and effective preventive for ORN

Some investigators recommend prophylactic antibiotics for postradiation extractions. Some even consider it unethical not to use prophylactic antibiotics (or HBO) to prevent ORN. In a 2002 British survey, the majority of responding oral surgeons recommended antibiotic prophylaxis in postradiation patients, although there was no consensus on the choice (there were 20 different antibiotics or antibiotic combinations), timing, dosage, and duration of the antibiotic [3 times daily] for 14 days and continued at [twice daily] for as long as the wound or infection is present.” In 1999, Tong  recommended 250 mg penicillin postoperatively four times daily for 1 week or longer. In 2000, Németh recommended a regimen of 1200 mg of clindamycin daily for 21 days, starting 3 days before surgery. Marx et al.’s 1985 regimen  consisted of 1 million intravenous units of aqueous penicillin G just before surgery and 500 mg of phenoxymethyl penicillin four times daily for 10 days after surgery. Despite these large and repeated doses of intravenous antibiotics, 30% of the study patients developed ORN. Although a recent study has shown a multitude of bacterial species associated with osteonecrotic bone, it is not clear that ORN is an infectious process, and there is no evidence that prophylactic antibiotics prevent ORN.

Antibiotics carry risks, including the emergence of resistant organisms, which can be particularly problematic in possibly immunocompromised cancer patients. Other risks include gastrointestinal upset, interactions with other medications, allergy, anaphylaxis, and even death. Antibiotic prophylaxis to prevent infections remains controversial . It is therefore illogical to prescribe antibiotics to prevent possibly noninfectious conditions like ORN.

Although antibiotics can be a valuable aid in the treatment of infections, it is questionable whether antibiotics administered as prophylaxis can truly prevent infections. Case–control studies have shown that prophylactic antibiotics can prevent endocarditis less than half the time . Risk/benefit studies have shown that in some scenarios, the small risk of serious reactions (e.g., gastrointestinal upset, hearing loss, allergy, anaphylaxis, and even death) to antibiotics can actually exceed the even smaller risk that a patient would develop endocarditis . With such controversy surrounding the use of antibiotics to prevent an infectious condition, antibiotics to prevent possibly noninfectious conditions such as ORN should be reconsidered.

Both preradiation and postradiation extractions can be accomplished safely without prophylactic antibiotics or HBO. In many reports, it is difficult to determine whether radiation patients underwent extractions without prophylactic antibiotics or HBO. Some reports are specific as to whether radiation patients received prophylactic antibiotics or prophylactic HBO for dental extractions, but others are not. Of those that do provide such information, the data provided are often sketchy. Still, there have been patients undergoing extractions without HBO or prophylactic antibiotics with low incidences of ORN.

Since 1986, the incidence of ORN in cases in which antibiotics were used in postradiation extractions was approximately the same as the incidence of ORN in cases in which antibiotics were not used. Unfortunately, few details regarding antibiotic use (e.g., choice, timing, dosage) are given in most reports from studies of postradiation extraction, but in those cases reporting antibiotic use, the incidence of ORN after postradiation extractions (3.6%; 11 of 303 patients) was approximately the same as the incidence of ORN in cases without HBO and without antibiotics (antibiotics not reported to have been used or not used routinely) (2.6–3.4%; 5 of 146–193 patients). For preradiation extractions without HBO since 1986, the incidence of ORN without antibiotics (not reported to have been used or not used routinely) (2.6–2.9%; 16 of 561–606 patients) was less than the incidence with antibiotics (4.6%; 9 of 194 patients)

Conclusions

1Patients at risk for ORN should generally be treated like most other dental patients. A preradiation dental evaluation and ongoing collaboration between medical and dental professionals is invaluable.

2 Because dental disease itself might be a risk factor for ORN, necessary dental treatment, including the extraction of nonrestorable teeth, should be completed before radiation commences.

3 Although some investigators recommend a 10–21-day delay of radiation therapy after preradiation extractions, the delay of radiation therapy must be weighed against the potential for ORN. Because the risk of ORN is approximately the same with postradiation as with preradiation extractions, it might be more important not to delay radiation therapy than to wait for preradiation extraction sites to heal.

4 Both prophylactic HBO therapy and prophylactic antibiotics should be reconsidered for the prevention of preradiation or postradiation extraction-induced ORN because neither prophylactic HBO therapy nor prophylactic antibiotics seem to lower the risk of ORN.

5 When ORN occurs, most cases heal, improve, or stabilize without HBO or surgery.

6 A healthy dentition should be maintained in irradiated patients.

7 Extractions in irradiated patients should be performed as atraumatically as possible.