The ability of irradiated tissues to support the process of distraction osteogenesis (DO) after clinically relevant doses of external beam radiation is unknown. Anecdotal case reports in the literature have shown mixed results, and animal studies have been small and inconclusive lacking objective measures that would allow adequate analysis of outcomes or efficacy. Radiation therapy is detrimental to bone and soft tissue healing as well as to normal bone remodeling. Negative effects include poor fracture healing
[1–3], impaired growth
, decreased mechanical strength
[5, 6], and bone atrophy due to increased bone resorption and reduced formation. Irradiated bone undergoes a loss of bone cells and fibrosis. Radiation disrupts bone microvasculature causing decreased vascular density and obliteration of small blood vessels that progressively worsens over time
. Recovery of irradiated bone is usually poor and late complications such as osteoradionecrosis can be devastating.
Head and neck cancer (HNC) affects 500,000 people worldwide each year and 52,000 in the United States alone. Many of these patients will require multimodality treatment with surgery, radiation, and chemotherapy. Although radiotherapy has increased survival, it also results in damage to adjacent normal tissues leading to significant morbidity
[8–10]. The corrosive impact of these radiation induced side effects can be unrelenting and their complex management is rarely straightforward. Surgical treatment of HNC poses an ongoing challenge as it is complicated by the severely problematic wound healing issues consequent to adjuvant radiation therapy
[11–17]. Standard of care currently dictates mandibular reconstruction utilizing free tissue transfer, requiring the harvest of bone and tissue from other parts of the body (leg, rib, scapula, or iliac crest).
Advantages of microvascular reconstruction include a rich blood supply, transfer of healthy composite flaps of bone and soft tissue that have not been subject to irradiation
, and a high rate of successful wound closure. Disadvantages include long operative time, significant technical demands, donor site morbidity and the occasional need for two flaps to achieve adequate bone and soft tissue coverage. The significant risks associated with free tissue transfer often exclude their use in both the elderly and the infirm. Perhaps the most troubling clinical consequence of free tissue transfer is that commonly associated wound healing complications can force delays in the initiation of adjuvant therapy jeopardizing prognosis as well as quality of life. A less invasive reconstructive method that would utilize local tissues to restore structural and functional integrity while avoiding donor site morbidity would clearly be desirable.
DO avoids donor site morbidity, generates vascularized endogenous bone and soft tissue, involves a less invasive approach with shorter operative time with the potential of a more rapid recovery and reduction of overall treatment costs. Since DO has already been widely used to treat congenital and traumatic mandibular deficiencies, application of this technique to oncologic reconstruction would be a natural extension of this powerful technology, however, the use of these tissues is currently avoided due to the detrimental effects of irradiation as well as the paucity of local substrate.
Existing animal models of DO following radiation therapy are extremely limited, and results from these animal studies are mixed and largely uncontrolled
[19–21]. Anecdotal case reports concerning the use of mandibular distraction osteogenesis (MDO) in irradiated patients have had variable outcomes without long term follow-up
[22–27]. Furthermore, the spectrum of radiation doses deemed necessary by radiation oncologists for the treatment of the variety of head and neck cancers adds additional uncertainty for outcomes of mandibular reconstruction. For these reasons, the role of MDO in oncologic reconstruction remains ambiguous.
The purpose of this study was to utilize a reproducible rat model of MDO to evaluate, quantify, and document the damaging effects of high dose highly fractionated radiation (XRT) on distraction induced new bone formation. Our hypothesis is that the pathologic effects of radiation on bone formation and healing will lead to a severe and measurable impairment of DO. The specific aim of this investigation is to determine the effects of high dose and highly fractionated radiation on bone formation during MDO utilizing histologic and radiographic outcome measures. The over-arching goal of our work is to generate specific metrics of diminished bone quality within the irradiated mandible and then to develop treatment strategies to assuage the adverse impact of radiation induced injury on new bone formation and healing in order to optimize reconstruction and repair.