Hyperbaric oxygen therapy as a prevention modality for radiation damage in the mandibles of mice.

BACKGROUND: Radiation therapy (RT) as part head and neck cancer treatment often leads to irradiation of surrounding normal tissue, such as mandibular bone. A reduced reparative capacity of the bone can lead to osteoradionecrosis (ORN). Hyperbaric oxygen therapy (HBOT) is used to treat ORN, based on its potential to raise the oxygen tension in tissues. However, prevention of radiation-induced damage is of great interest. Our purpose was to investigate whether HBOT could prevent radiation-induced damage to murine mandibles. METHODS: Twenty-eight mice were irradiated in the head and neck region with a single dose (15 Gy) and half of them were subsequently subjected to HBOT. Another 14 mice did not receive any treatment and served as controls. Ten and 24 weeks after RT, mandibles were harvested and analysed histologically and by microcomputed tomography (micro-CT). RESULTS: Micro-CT analysis showed a reduction in relative bone volume by RT, which was partly recovered by HBOT. Trabecular thickness and separation were also positively influenced by HBOT. Morphologically, HBOT suppressed the osteoclast number, indicating decreased resorption, and decreased the amount of lacunae devoid of osteocytes, indicating increased bone viability. CONCLUSIONS: HBOT was able to partly reduce radiation-induced effects on microarchitectural parameters, resorption, and bone viability in mouse mandibles. HBOT could therefore potentially play a role in the prevention of radiation-induced damage to human mandibular bone.

The effects of heparan sulphate mimetic RGTA-OTR4120 on irradiated murine salivary glands.

BACKGROUND: This study focuses on the potential of ReGeneraTing Agent OTR4120 (RGTA-OTR4120) to treat radiation-induced damage of salivary glands. RGTAs are biopolymers designed to mimic the effects of heparan sulphate, thereby stimulation tissue repair and regeneration. METHODS: C3H mice were irradiated with a single dose of 15 Gy in the head and neck region. RGTA-OTR4120 was injected 24 h after radiotherapy, followed by weekly injections. At 2, 6 and 10 weeks after radiotherapy, salivary flow rates were measured and animals were sacrificed to obtain parotid and submandibular glands for histology. Periodic acid Schiff stain was performed to visualize mucins that are produced by acinar cells. Amylase and total protein content were measured in saliva samples. RESULTS: Salivary flow rates were increased at 2 weeks, but not at 6 and 10 weeks after radiotherapy with RGTA-OTR4120 administration, compared to irradiated controls. Two and 10 weeks after radiotherapy, the mucin production activity of acinar cells was increased under influence of RGTA administration. RGTA-OTR4120 did not influence amylase or total protein secretion. CONCLUSION: RGTA-OTR4120 administration has a positive effect on salivary flow rates in irradiated mice on the short term. The effect was absent 10 weeks after radiotherapy, while at that time point, mucin producing activity of acinar cells was elevated by RGTA-OTR4120 administration. Given these results and the advantages of RGTA use in irradiated patients, further investigation on the potential of this drug to treat radiation-induced salivary gland damage, alone or in combination with other drugs, such as amifostine, is suggested.

Hyperbaric oxygen therapy in the management of radiation-induced injury in the head and neck region: a review of the literature.

PURPOSE: Radiotherapy is generally used in the treatment of malignant tumors in the head and neck region. It causes a hypoxic, hypocellular, and hypovascular environment that leads to injury to surrounding normal tissue, both acute and chronic, ranging from xerostomia to osteoradionecrosis. These side effects are debilitating and greatly influence quality of life in these patients. Hyperbaric oxygen (HBO) therapy is clinically used to prevent or treat these side effects by enhancing oxygen pressure and thereby regeneration. Although this therapy is widely applied, its mechanism of action is still poorly understood, and controversy exists in the literature about its clinical use. This review therefore aims to analyze the existing experimental and clinical research on this topic. MATERIALS AND METHODS: A systematic search was performed in PubMed for experimental and clinical studies conducted regarding the use of HBO therapy in previously irradiated tissue, in the period from January 1990 to June 2009. RESULTS: Experimental research is scarce, and clinical studies are especially lacking in terms of randomized controlled studies. Although discussions on the subject are ongoing, most studies suggest a beneficial role for HBO in previously irradiated tissue. CONCLUSION: Further research, both experimental and clinical, is necessary to unravel the working mechanism of HBO therapy and validate its clinical use.

Continuous versus discontinuous distraction: evaluation of bone regenerate following various rhythms of distraction.

PURPOSE: To investigate continuous distraction osteogenesis (DO) of the nasal bones in a rabbit model, and to compare data from this continuous DO study with data from a previously conducted discontinuous DO study. In addition, radiographic and ultrasonographic bone-fill scores were determined to investigate whether these scores provided reliable predictive value for the amount of new bone formation in the distraction area. MATERIALS AND METHODS: Skeletally mature female New Zealand White rabbits were subjected to distraction of the nasal bones. A custom-made continuous distractor was used to perform automatic non-stop distraction. Bone data were obtained from radiography, ultrasonography, and microcomputed tomography. Data from this experiment were compared with data from a previous study on discontinuous distraction rhythms. RESULTS: Ultrasonographic bone-fill scores correlated significantly to actual bone volume in contrast to radiographic bone-fill scores. Bone volume was significantly higher in the continuous DO group compared with the discontinuous DO groups. CONCLUSION: Continuous distraction resulted in accelerated osteogenesis compared with discontinuous distraction. Furthermore, bone-fill scores based on ultrasonography showed a significant correlation with actual bone volumes.