Novel Use of Wound Matrix in Mastopexy Complicated by Pyoderma Gangrenosum.

Pyoderma gangrenosum (PG) is a relatively uncommon inflammatory skin disorder that is characterized by rapid onset, ulcerative lesions, and often triggered by trauma or surgery. Although rare, PG of the breast has been well described in the plastic surgery literature, most often reported following breast reductions and reconstructions. The authors present a case of PG that developed in a 56-year-old patient, with a history of essential thrombocytosis, following mastopexy. Her significant full-thickness skin loss was successfully treated with steroids and then reconstructed via serial applications of porcine placental extracellular matrix grafts. Her wounds were completely healed in 3.5 months for the left, and 5 months for the right breast. To the best of the author's knowledge, this is the first published case in which placental grafts have been successfully used to reconstruct pyoderma wounds of the breast. Given their advantageous scarring and lack of donor-site morbidity, placental grafts should be considered for all breast surgery patients afflicted by PG.

Transconjunctival Lower Lid Blepharoplasty with and Without Fat Preservation and Skin Resurfacing.

Transconjunctival lower lid blepharoplasty is a safe and effective procedure with a low complication rate. Success with this procedure depends on proper patient analysis and selection. The lower lid periorbital fat can be resected, or preserved, and draped over the orbital rim or used as free fat grafts, depending on the clinical presentation. The lower lid skin can be resurfaced with a peel, with a laser, or by skin pinch depending on surgeon preference.

Fondaparinux Significantly Reduces Postoperative Venous Thromboembolism After Body Contouring Procedures Without an Increase in Bleeding Complications.

BACKGROUND: It is well established that abdominoplasty confers a uniquely high risk of venous thromboembolism (VTE) complications. However, chemoprophylaxis is not routinely utilized due to the risk of bleeding complications. Fondaparinux, a factor Xa inhibitor FDA approved in 2001 for postoperative VTE prophylaxis, has emerged as a safe option for preventing VTE complications after high-risk surgeries. OBJECTIVES: The goal of this study was to examine the effectiveness and safety of fondaparinux for VTE chemoprophylaxis in patients undergoing abdominoplasty. METHODS: This is a single-center retrospective chart review from January 2008 to December 2014 of 492 patients who underwent abdominoplasty with or without an additional body procedure. Prior to 2011, no VTE chemoprophylaxis was utilized (n = 233). In 2011, the routine employment of postoperative chemoprophylaxis with fondaparinux was implemented (n = 259). Patient demographics and 2005 Caprini scores were evaluated. Primary outcomes included postoperative VTE and bleeding complications. RESULTS: There were no statistical differences in patient demographics or median Caprini score. The treatment group demonstrated a statistically significant reduction in the rate of VTE compared with the nontreatment group (0% vs 2.1%, respectively, P = 0.02). There was no statistically significant difference in the rate of hematoma requiring reoperation between the nontreatment and treatment groups (1.7% vs 2.3%, P = 0.76) or blood loss requiring transfusion (0% vs 0.8%, P = 0.5). CONCLUSIONS: Fondaparinux for VTE chemoprophylaxis after abdominoplasty is efficacious in decreasing the risk of VTE in this susceptible patient population without increasing the risk of postoperative bleeding complications.

Do Patterns of Reconstruction Choices After Mohs Surgery Vary by Specialty? A Pilot Study of Mohs Surgeons and Facial Plastic Surgeons.

BACKGROUND: Differences in approach to repair a specified defect after Mohs micrographic surgery (MMS) between specialties have not been previously examined. OBJECTIVE: To assess the difference in frequency of which reconstruction repairs are selected after MMS, among Mohs surgeons and facial plastic surgeons (FPS), and evaluate whether the level of satisfaction with the final repair outcome differed between specialties. MATERIALS AND METHODS: The study was approved by the Saint Louis University Institutional Review Board. A link to the survey was distributed to members of American College of Mohs Surgery (ACMS) and American Academy of Facial Plastic and Reconstructive Surgery (AAFPRS), between January and May 2016. RESULTS: The reconstructive procedure selected most often ("top choice") was not significantly different between Mohs surgeons and FPS for the majority of the images. There was no material difference in how dermatologists and FPS rate the aesthetic outcome of the 3 presented closure types, with the exception of one closure type-nose with graft. CONCLUSION: Mohs surgeons were found to more likely cluster around a single preference for their reconstruction technique compared with FPS, in which a higher percentage of surgeons also selected other options.

Radioprotection With Amifostine Enhances Bone Strength and Regeneration and Bony Union in a Rat Model of Mandibular Distraction Osteogenesis.

BACKGROUND: Using distraction osteogenesis (DO) to regenerate robust endogenous bone could greatly enhance postoncologic reconstruction of head and neck cancer. However, radiation (XRT) corrosive effects still preclude DO's immense potential. We posit that adjunctive pretreatment with the radioprotectant amifostine (AMF) can optimize wound healing and allow for successful DO with quantifiable enhancements in bony union and strength despite previous surgical bed irradiation. METHODS: Two groups of murine left hemimandibles were exposed to a human equivalent radiation dosage fractionated over 5 daily doses of 7 Gy. AMF-XRT-DO (n = 30) received AMF before radiation, whereas XRT-DO (n = 22) was untreated. All animals underwent left hemimandibular osteotomy and external fixator placement, followed by distraction to a 5.1-mm gap. Left hemimandibles were harvested and mechanically tested for parameters of strength, yield, and breaking load. RESULTS: Radiation-related complications such as severe alopecia were significantly increased in XRT-DO compared with the AMF-treated group (P = 0.001), whereas infection and death were comparable (P = 0.318). Upon dissection, bony defects were grossly visible in XRT-DO distraction gap compared with AMF-XRT-DO, which exhibited significantly more complete unions (P = 0.004). Those results were significantly increased in the specimens prophylactically treated with AMF (yield: 39.41 N vs 21.78 N, P = 0.023; breaking load: 61.74 N vs 34.77 N, P = 0.044; respectively). CONCLUSIONS: Our study revealed that AMF enhances biomechanical strength, regeneration, and bony union after radiation in a murine model of DO. The use of prophylactic AMF in combination with DO offers the promise of an alternative reconstructive option for patients afflicted with head and neck cancer.

Deferoxamine enhances bone regeneration in mandibular distraction osteogenesis.

BACKGROUND: Distraction osteogenesis is a powerful reconstructive technique for bone growth and repair. An angiogenic means of enhancing the efficacy of this metabolically demanding procedure would be beneficial in expanding its therapeutic potential. The authors posit that the angiogenic effect of deferoxamine, an iron chelator that has been shown to increase angiogenesis, will improve bone regeneration by means of augmentations in quality and quantity of bone and bone-producing cells. METHODS: Two groups of rats (n = 12) underwent surgical external fixation and subsequent distraction. During the distraction stage, the experimental deferoxamine group (n = 5) was treated with injections into the distraction gap. After 28 days of consolidation, mandibles were harvested and prepared for histologic analysis. RESULTS: The authors found a proliferation of osteocytes in the deferoxamine-treated group when compared with the regenerate of the control group. Deferoxamine effected a significant increase in osteocytes and an increase in bone volume fraction, with subsequent decreased osteoid volume fraction. The data also demonstrated no significant difference in empty lacunae. CONCLUSIONS: The authors' study demonstrates the effectiveness of deferoxamine treatment to enhance the number of osteocytes within the regenerate in a murine mandibular distraction osteogenesis model. Maintenance of full lacunae supports the authors' finding of a robust cellular response to deferoxamine therapy. These results suggest that the angiogenic capabilities of deferoxamine translate into an increase in the number of bone-forming cells in the regenerate. Deferoxamine may have utility in optimizing bone formation in distraction osteogenesis and lead to superior reconstructive capabilities for craniofacial surgeons in the future.

Amifostine protects vascularity and improves union in a model of irradiated mandibular fracture healing.

BACKGROUND: Pathologic fractures of the mandible can be devastating to cancer patients and are due in large part to the pernicious effects of irradiation on bone vascularity. The authors' aim was to ascertain whether amifostine, a radioprotective drug, will preserve vascularity and improve bone healing in a murine model of irradiated mandibular fracture repair. METHODS: Rats were randomized into three groups: nonirradiated fracture (n = 9), irradiation/fracture (n = 5), and amifostine/irradiation/fracture (n = 7). Animals in the irradiation groups underwent a human equivalent dose of radiation directed at the left hemimandible. Animals treated in the amifostine group received amifostine concomitantly with radiation. All animals underwent unilateral left mandibular osteotomy with external fixation set to a 2.1-mm fracture gap. Fracture healing was allowed for 40 days before perfusion with Microfil. Vascular radiomorphometrics were quantified with micro-computed tomography. RESULTS: When compared with the irradiated/fractured group, amifostine treatment more than doubled the rate of fracture unions to 57 percent. Amifostine treatment also resulted in an increase in vessel number (123 percent; p < 0.05) and a corresponding decrease in vessel separation (55.5 percent; p < 0.05) there was no statistical difference in the vascularity metrics between the amifostine/irradiation/fracture group and the nonirradiated/fracture group. CONCLUSIONS: Amifostine prophylaxis during radiation maintains mandibular vascularity at levels observed in nonirradiated fracture specimens, corresponding to improved unions. These results set the stage for clinical exploration of this targeted therapy alone and in combination with other treatments, to mitigate the effects of irradiation on bone healing and fracture repair.

The effect of Amifostine prophylaxis on bone densitometry, biomechanical strength and union in mandibular pathologic fracture repair.

BACKGROUND: Pathologic fractures (Fx) of the mandibles are severely debilitating consequences of radiation (XRT) in the treatment of craniofacial malignancy. We have previously demonstrated Amifostine's effect (AMF) in the remediation of radiation-induced cellular damage. We posit that AMF prophylaxis will preserve bone strength and drastically reverse radiotherapy-induced non-union in a murine mandibular model of pathologic fracture repair. MATERIALS AND METHODS: Twenty-nine rats were randomized into 3 groups: Fx, XRT/Fx, and AMF/XRT/Fx. A fractionated human equivalent dose of radiation was delivered to the left hemimandibles of XRT/Fx and AMF/XRT/Fx. AMF/XRT/Fx was pre-treated with AMF. All groups underwent left mandibular osteotomy with external fixation and setting of a 2.1mm fracture gap post-operatively. Utilizing micro-computed tomography and biomechanical testing, the healed fracture was evaluated for strength. RESULTS: All radiomorphometrics and biomechanical properties were significantly diminished in XRT/Fx compared to both Fx and AMF/XRT/Fx. No difference was demonstrated between Fx and AMF/XRT/Fx in both outcomes. CONCLUSION: Our investigation establishes the significant and substantial capability of AMF prophylaxis to preserve and enhance bone union, quality and strength in the setting of human equivalent radiotherapy. Such novel discoveries establish the true potential to utilize pharmacotherapy to prevent and improve the treatment outcomes of radiation-induced late pathologic fractures.

Parathyroid hormone therapy mollifies radiation-induced biomechanical degradation in murine distraction osteogenesis.

OBJECTIVE: Descriptions of mandibular distraction osteogenesis for tissue replacement after oncologic resection or for defects caused by osteoradionecrosis have been limited. Previous work demonstrated radiation decreases union formation, cellularity and mineral density in mandibular distraction osteogenesis. The authors posit that intermittent systemic administration of parathyroid hormone will serve as a stimulant to cellular function, reversing radiation-induced damage and enhancing bone regeneration. METHODS: Twenty male Lewis rats were randomly assigned to three groups: group 1 (radiation and distraction osteogenesis, n = 7) and group 2 (radiation, distraction osteogenesis, and parathyroid hormone, n = 5) received a human-equivalent dose of 35 Gy of radiation (human bioequivalent, 70 Gy) fractionated over 5 days. All groups, including group 3 (distraction osteogenesis, n = 8), underwent a left unilateral mandibular osteotomy with bilateral external fixator placement. Distraction osteogenesis was performed at a rate of 0.3 mm every 12 hours to reach a gap of 5.1 mm. Group 2 was injected with parathyroid hormone (60 µg/kg) subcutaneously daily for 3 weeks after the start of distraction osteogenesis. On postoperative day 40, all left hemimandibles were harvested. Biomechanical response parameters were generated. Statistical significance was considered at p ≤ 0.05. RESULTS: Parathyroid hormone-treated mandibles had significantly higher failure load and higher yield than did untreated mandibles. However, these values were still significantly lower than those of nonirradiated mandibles. CONCLUSIONS: The authors have successfully demonstrated the therapeutic efficacy of parathyroid hormone to stimulate and enhance bone regeneration in their irradiated murine mandibular model of distraction osteogenesis. Anabolic regimens of parathyroid hormone, a U.S. Food and Drug Administration-approved drug on formulary, significantly improve outcomes in a model of postoncologic craniofacial reconstruction.

An isogenic model of murine mandibular distraction osteogenesis.

The advent of stem cell-based therapies makes current models of mandibular distraction osteogenesis unwieldy. We thereby designed an isogenic model of distraction osteogenesis whose purpose was to allow for the free transfer of cells and components between rats. As immune response plays a significant role in healing and prevention of infection, an immune-competent mode is desirable rather than an athymic rat/xenograft model. The purposes of this study were as follows: (1) to replicate established models of distraction osteogenesis in a rodent model using an isogenic rat strain, and (2) to characterize the differences between inbred, isogenic rats and outbred rats in mandibular distraction osteogenesis via radiomorphometry and biomechanical response analysis. We demonstrated successful distraction osteogenesis to 5.1 mm in all Lewis (isogenic) rat mandibles as well as all Sprague-Dawley (outbred) rat mandibles, with no significant difference in volume-normalized radiomorphometrics, trending difference in non-volume-normalized radiomorphometrics and significant differences in biomechanical response parameters. We attribute the differences demonstrated to the decreased size of the Lewis rat mandible in comparison to Sprague-Dawley mandibles. We also provide information with caring with the additional needs of the Lewis rat. Given these differences, we find that Lewis rats function as an excellent model for isogenic mandibular distraction osteogenesis, but data procured may not be comparable between isogenic and nonisogenic models.

Role of parathyroid hormone therapy in reversing radiation-induced nonunion and normalization of radiomorphometrics in a murine mandibular model of distraction osteogenesis.

BACKGROUND: The use of mandibular distraction osteogenesis (MDO) for tissue replacement after oncologic resection or for defects caused by osteoradionecrosis has been described but, in fact, has seen limited clinical utility. Previous laboratory work has shown that radiation (XRT) causes decreased union formation, decreased cellularity, and decreased mineral density in an animal model of MDO. Our global hypothesis is that radiation-induced bone damage is partly driven by the pathologic depletion of both the number and function of osteogenic cells. Parathyroid hormone (PTH) is a U.S. Food and Drug Administration-approved anabolic hormonal therapy that has demonstrated efficacy for increasing bone mineral density for the treatment of osteoporosis. We postulate that intermittent systemic administration of PTH will serve as an anabolic stimulant to cellular function that will act to reverse radiation-induced damage and enhance bone regeneration in a murine mandibular model of DO. METHODS: A total of 20 isogenic male Lewis rats were randomly assigned into 3 groups. Group 1 (XRT-DO, n = 7) and group 2 (XRT-DO-PTH, n = 5) received a human bioequivalent dose of 70 Gy fractionated over 5 days. All groups including group 3 (DO, n = 8) underwent a left unilateral mandibular osteotomy with bilateral external fixator placement. Four days later, mandibular DO was performed at a rate of 0.3 mm every 12 hours to reach a maximum gap of 5.1 mm. Group 2 was injected PTH (60 µg/kg) subcutaneously daily for 3 weeks following the start of MDO. On postoperative day 41, all left hemimandibles were harvested. Micro-CT at 45-µm voxel size was performed and radiomorphometrics parameters of bone mineralization were generated. Union quality was evaluated on a 4-point qualitative grading scale. Radiomorphometric data were analyzed using 1-way ANOVA, and union quality assessment was analyzed via the Mann-Whitney test. Statistical significance was considered at p ≤ .05. RESULTS: Groups 1 and 2 appropriately demonstrated clinical signs of radiation-induced stress ranging from alopecia to mucositis. Union quality was significantly higher in PTH-treated XRT-DO animals, compared with XRT-DO group animals (p = .02). Mineralization metrics, including bone volume fraction (BVF) and bone mineral density (BMD), also showed statistically significant improvement. The groups that were treated with PTH showed no statistical differences in union or radiomorphometrics when compared with DO in nonradiated animals. CONCLUSION: We have successfully demonstrated the therapeutic efficacy of PTH to stimulate and enhance bone regeneration in our irradiated murine mandibular model of DO. Our investigation effectively resulted in statistically significant increases in BMD, BVF, and clinical unions in PTH-treated mandibles. PTH demonstrates immense potential to treat clinical pathologies where remediation of bone regeneration is essential.

Stem cell therapy remediates reconstruction of the craniofacial skeleton after radiation therapy.

This study utilized transplanted bone marrow stromal cells (BMSCs) as a cellular replacement therapy to remedy radiation-induced injury and restore impaired new bone formation during distraction osteogenesis (DO). BMSC therapy brought about the successful generation of new bone and significantly improved both the rate and quality of a bony union of irradiated, distracted [X-ray radiation therapy (XRT)/DO] murine mandibles to the level of nonirradiated DO animals. The bone mineral density and bone volume fraction were also significantly improved by the BMSC replacement therapy showing no difference when compared to nonirradiated animals. Finally, a biomechanical analysis examining the yield, failure load, and ultimate load also demonstrated a significantly improved structural integrity in BMSC-treated XRT/DO mandibles over XRT/DO alone. These results indicate that administration of BMSCs intraoperatively to a radiated distraction gap can function as an adequate stimulant to rescue the ability for irradiated bone to undergo DO and produce a healed regenerate of a vastly superior quality and strength. We believe that the fundamental information on the optimization of bone regeneration in the irradiated mandible provided by this work has immense potential to be translated from the bench to the bedside to lead to improved therapeutic options for patients suffering from the disastrous sequelae of radiation therapy.

Raman spectroscopy demonstrates Amifostine induced preservation of bone mineralization patterns in the irradiated murine mandible.

PURPOSE: Adjuvant radiotherapy in the management of head and neck cancer remains severely debilitating. Fortunately, newly developed agents aimed at decreasing radiation-induced damage have shown great promise. Amifostine (AMF) is a compound, which confers radio-protection to the exposed normal tissues, such as bone. Our intent is to utilize Raman spectroscopy to demonstrate how AMF preserves the mineral composition of the murine mandible following human equivalent radiation. METHODS: Sprague Dawley rats were randomized into 3 experimental groups: control (n=5), XRT (n=5), and AMF-XRT (n=5). Both XRT and AMF groups underwent bioequivalent radiation of 70Gy in 5 fractions to the left hemimandible. AMF-XRT received Amifostine prior to radiation. Fifty-six days post-radiation, the hemimandibles were harvested, and Raman spectra were taken in the region of interest spanning 2mm behind the last molar. Bone mineral and matrix-specific Raman bands were analyzed using one-way ANOVA, with statistical significance at p<0.05. RESULTS: The full-width at half-maximum of the primary phosphate band (FWHM) and the ratio of carbonate/phosphate intensities demonstrated significant differences between AMF-XRT versus XRT (p<0.01) and XRT versus control (p<0.01). There was no difference between AMF-XRT and control (p>0.05) in both Raman metrics. Computer-aided spectral subtraction further confirmed these results where AMF-XRT was spectrally similar to the control. Interestingly, the collagen cross-link ratio did not differ between XRT and AMF-XRT (p<0.01) but was significantly different from the control (p<0.01). CONCLUSION: Our novel findings demonstrate that AMF prophylaxis maintains and protects bone mineral quality in the setting of radiation. Raman spectroscopy is an emerging and exceptionally attractive clinical translational technology to investigate and monitor both the destructive effects of radiation and the therapeutic remediation of AMF on the structural, physical and chemical qualities of bone.

Localized deferoxamine injection augments vascularity and improves bony union in pathologic fracture healing after radiotherapy.

BACKGROUND: Medically based efforts and alternative treatment strategies to prevent or remediate the corrosive effects of radiotherapy on pathologic fracture healing have failed to produce clear and convincing evidence of success. Establishing an effective pharmacologic option to prevent or treat the development of non-unions in this setting could have immense therapeutic potential. Experimental studies have shown that deferoxamine (DFO), an iron-chelating agent, bolsters vascularity and subsequently enhances normal fracture healing when injected locally into a fracture callus in long bone animal models. Since radiotherapy is known to impede angiogenesis, we hypothesized that the pharmacologic addition of DFO would serve to mitigate the effects of radiotherapy on new vessel formation in vitro and in vivo. MATERIALS AND METHODS: In vitro investigation of angiogenesis was conducted utilizing HUVEC cells in Matrigel. Endothelial tubule formation assays were divided into four groups: Control, Radiated, Radiated+Low-Dose DFO and Radiated+High-Dose DFO. Tubule formation was quantified microscopically and video recorded for the four groups simultaneously during the experiment. In vivo, three groups of Sprague-Dawley rats underwent external fixator placement and fracture osteotomy of the left mandible. Two groups received pre-operative fractionated radiotherapy, and one of these groups was treated with DFO after fracture repair. After 40 days, the animals were perfused and imaged with micro-CT to calculate vascular radiomorphometrics. RESULTS: In vitro, endothelial tubule formation assays demonstrated that DFO mitigated the deleterious effects of radiation on angiogenesis. Further, high-dose DFO cultures appeared to organize within 2h of incubation and achieved a robust network that was visibly superior to all other experimental groups in an accelerated fashion. In vivo, animals subjected to a human equivalent dose of radiotherapy (HEDR) and left mandibular fracture demonstrated quantifiably diminished µCT metrics of vascular density, as well as a 75% incidence of associated non-unions. The addition of DFO in this setting markedly improved vascularity as demonstrated with 3D angiographic modeling. In addition, we observed an increased incidence of bony unions in the DFO treated group when compared to radiated fractures without treatment (67% vs. 25% respectively). CONCLUSION: Our data suggest that selectively targeting angiogenesis with localized DFO injections is sufficient to remediate the associated severe vascular diminution resulting from a HEDR. Perhaps the most consequential and clinically relevant finding was the ability to reduce the incidence of non-unions in a model where fracture healing was not routinely observed.

Quantitative histologic evidence of amifostine-induced cytoprotection in an irradiated murine model of mandibular distraction osteogenesis.

BACKGROUND: Head and neck cancer management requires adjuvant radiotherapy. The authors have previously demonstrated the damaging effect of a human equivalent dose of radiation on a murine mandibular model of distraction osteogenesis. Using quantitative histomorphometry, the authors' specific aim was to objectively measure amifostine radioprotection of the cellular integrity and tissue quality of an irradiated and distracted regenerate. METHODS: Sprague-Dawley rats were assigned randomly into two groups: radiotherapy/distraction osteogenesis and amifostine/radiotherapy/distraction osteogenesis, which received amifostine before radiotherapy. Both groups received a fractionated human equivalent dose of radiation prior to left mandibular osteotomy with fixator placement. Distraction to 5.1 mm was followed by a 28-day consolidation period. Quantitative histomorphometry was performed on left hemimandibles for osteocytes, empty lacunae, bone volume-to-tissue volume ratio, and osteoid volume-to-tissue volume ratio. RESULTS: Amifostine/radiotherapy/distraction osteogenesis exhibited bony bridging as opposed to radiotherapy/distraction osteogenesis fibrous unions. Quantitative histomorphometry analysis revealed statistically significant higher osteocyte count and bone volume-to-tissue volume ratio in amifostine-treated mandibles compared with irradiated mandibles. There was a corresponding decrease in empty lacunae and the ratio of osteoid volume-to-tissue volume between both groups. CONCLUSIONS: The authors have successfully established the significant osseous cytoprotective and histoprotective capacity of amifostine for distraction osteogenesis in the face of radiotherapy. The amifostine-sparing effect on bone cellularity correlated with increased bony unions and elimination of fibrous union. The authors posit that the demonstration of similar efficacy of amifostine in the clinic may allow the successful implementation of distraction osteogenesis as a viable reconstructive option for head and neck cancer in the future.

Amifostine remediates the degenerative effects of radiation on the mineralization capacity of the murine mandible.

BACKGROUND: Radiotherapy, a cornerstone of head and neck cancer treatment, causes substantial morbidity to normal adjoining bone. The authors assessed the radioprotective effect of amifostine therapy on the mineralization of the mandible using micro-computed tomography. They hypothesized that amifostine would safeguard the mandible from radiation-induced disruption of the mineralization process and the associated failure of new bone creation. METHODS: Male Sprague-Dawley rats were randomized into three groups: control (n = 8), radiation therapy (n = 5), and amifostine (n = 8). Animals in the radiation therapy and amifostine groups underwent human bioequivalent radiation of 70 Gy in five fractions to the left hemimandible. Fifty-six days after irradiation, the hemimandibles were harvested for radiomorphometric analyses. RESULTS: Amifostine-treated animals exhibited less alopecia, mucositis, and weight loss in addition to increased cortical density in comparison with those treated with radiation therapy. Bone and tissue mineral densities showed statistically significant improvement in amifostine versus radiation therapy, and no difference was observed between amifostine and control groups. Detailed micro-computed tomographic analysis further demonstrated significant differences in the mineralization profile when comparing radiation therapy and amifostine. Amifostine maintained regions of lower mineralization consistent with the preservation of normal remodeling. CONCLUSIONS: The authors have successfully demonstrated the ability of amifostine pretreatment to protect the natural mineralization profile of bone. This reflects the capacity of amifostine prophylaxis to safeguard the normal surrounding mandible from the impediments of collateral damage imposed by irradiation. Further study can correlate these findings with the potential use of amifostine to prevent the devastating associated morbidities of radiotherapy such as pathologic fractures and osteoradionecrosis.