1.3.1 Conservative treatment

It is often the first stage of treatment. In most of the series it associates local application of antiseptic (chlorhexidine), analgesics if necessary, oral hygiene, systemic antibiotics, eventually sequestrectomy and smoothing sharp of bony projections3'4'6'9'33'39'53'67"71. However the optimal scheme of antibiotherapy is not determined and its efficiency has not been demonstrated in controlled studies. Penicilline is often used. Tetracycline is incorporated into bone crystals and then is for Coffin9 the antibiotic of choice for clinical aseptic lesions. Conservative measures allow healing from 15 to 100% of the cases without the adjunct of hyperbaric oxygen therapy, but after several months of treatment3'4'6'9'33'39'53'67-71. In certain series, up to 57 to 100 % of the patients healed, or had lesions stabilized or improved4-6,53. Nevertheless it is difficult to judge the efficiency of conservative treatment because of the lack of standard definition, classification of osteoradionecrosis, and controlled trials.

1.3.2 Surgery

Most of the authors reserve radical surgery to the following indications: intractable pain, fistulae, pathological fracture, no response to conservative treatment3'4'6'9'26'28'31'67'70'72,73. Mandibular resection is necessary in 12 to 40% of patients initially treated with conservative measures without hyperbaric oxygen therapy3'11'13'26'31-33'52'70'74. Hemimandibulectomy with an intra oral approach is the most employed technique, with rapid healing and few complications. Koka73 in a study of 104 hemimandibulectomy for osteoradionecrosis (100 intra oral approach, 4 extra oral approach) found 18 % of post-operative complications: minor sepsis in 8.6 % cases, major sepsis in 2.9 %, hemorrhage in 2.9 %, fistula in 3.8 %. All the complications were effectively controlled. Fracture and pain were the major indications. All the patients who had pain (54 %) and trismus (17%) became asymptomatic following surgery. Alimentation was reestablished within 2-3 weeks in 65 % cases, and for the rest delayed beyond a month.

Multiple techniques of reconstruction have been documented in surgical literature and include myo-osseous or myo-cutaneous flaps; microvascular iliac crest or fibular graft is a more recent technique, with good aesthetic and functional results11'73'75-79.

1.3.3 Hyperbaric oxygen therapy

HBO stimulates angiogenesis, increases neovascularization, cellular levels of oxygen, fibroblast and osteoblast proliferation and collagen formation in irradiated tissues. In an animal model, 20 sessions at 2.4 atmospheres absolute (ata) pressure, 90 minutes each day, significantly increase angiogenesis and cellular density in irradiated mandibles versus normobaric oxygen and air breathing control (p=0.001)80. In an human model, transmucosal oxygen tension in irradiated gingiva increases from 50 to 86 % of the oxygen tension of healthy gingiva after 30 dives (90 minutes/day at 2.4 ata)81. A study showed that angiogenesis rapidly progresses to a plateau at 80 to 85 % of non irradiated tissue vascularity by 20 sessions; transcutaneous oxygen measures remain at that level during several years62. Improvement of angiogenesis and cellular density has been histologically proved too17,62,82.

HBO has been used in the management of ORN since the 1960s. Hart and Mainous suggested as early as 1976 that its action may be due to an enhancement of vascular proliferation69. Several investigators have reported the use of HBO as an adjunct to the conservative treatment or to radical surgery in non controlled trials3'5'28'68'69'71'77'83-86. The modalities of HBO and conservative measures are variable. The rates of healing range from 30% to 100%; all these studies conclude that HBO is an effective adjunct.

Marx82 established a protocol associating surgery and HBO; it consists of three stages. In stage I, after 30 sessions (100% oxygen, 2.4 ata, 90 minutes/day, 5 day/week), wound is re-examined: in case of improvement, the patient completes a full course of 60 sessions. If there is no improvement, the patient is advanced to stage II: a sequestrectomy with primary closure is accomplished, with HBO if healing progresses without complication. If the wound dehisces, the patient is advanced to stage III: a resection is accomplished. In a patient whose initial presentation includes pathologic fracture, orocutaneous fistulae, or radiographic evidence of resorption to the inferior border, an initial course of 30 sessions is given, and the patient directly enters in stage III. In stage III-R, 10 weeks after resection, the patient is given an additional 20 sessions in preparation for bone graft reconstruction. With this technique, resolution was achieved in stage I for 15%, in stage II for 14%, and in stage III (radical surgery) for 70% of the patients (total= 58). The same rates have been retrieved with 268 patients87. London84 using the same protocol showed clinical improvement with decreased pain in all sixteen patients. Marx proposed HBO as an adjunct to bone graft reconstruction too, with a 91.6 % rate of success88.

Recently Annane89 reported on a prospective randomized trial comparing HBO to placebo in the treatment of patients with mandibular ORN. Patients were included in the study if they had (at least 2 months after optimal conservative treatment, including antibiotics, local irrigation, and surgery) one of the following clinical criteria: pain, dysesthesia in the distribution of the inferior alveolar nerve, areas of bone exposure, trismus, fistula; and one of the following radiographic criteria: increased density, periosteal thickening, diffuse radiolucency, mottled areas of osteoporosis, and sclerosis sequestration. Exclusion criteria included fracture or radiographic evidence of bone reabsorption to the inferior border, ongoing cancer, previous treatment with HBO, or contraindication to HBO. Patients were assigned to receive 30 HBO exposures preoperatively at 2.4 ata for 90 minutes or a placebo, and 10 additional HBO sessions postoperatively or a placebo. The hyperbaric sessions were delivered twice daily. Patients received either 100% oxygen without oxygen pauses (active treatment) or a gas containing 9% oxygen and 91% nitrogen (placebo). Before randomization, patients were graded by the same surgeon in group A: areas of exposed bone <20 mm in diameter, no cutaneous fistula, and no a priori need for surgery; and in group B: areas of exposed bone of > 20 mm, cutaneous fistula, or an a priori need for surgery. Sixty eight patients were included. At one year recovery was not significantly different in the two groups. Time to pain relief in the 60 patients who presented with pain at inclusion was similar in the two treatment arms. Of the 54 patients in stage A at enrolment, 26 (48.1%) progressed to stage B, 14 (56%) of 25 in the HBO arm and 12 (41.4%) of 29 in the placebo arm (p=0.41).

In conclusion uncontrolled trials are supporting HBO use in the treatment of ORN. A recent double blind randomized controlled trial did not show positive effect with HBO. However HBO regimen was atypical ( 2 sessions a day to a total of 25 sessions instead of the usual 30 + 10 regimen). At the present time, the efficacy of HBO in the treatment of ORN is unclear and further investigation is warranted. Nevertheless HBO should be useful in patients with more severe ORN.

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