Identifying Risk Factors Leading to Unanticipated Postoperative Readmission.

INTRODUCTION: Unanticipated postoperative readmissions are a grading metric directly linked to both the quality of patient care and physician reimbursement. However, little data exist to define factors responsible for these readmissions in the plastic surgery patient population. This study aims to identify patient risk factors contributing to unanticipated postoperative readmissions to optimize perioperative patient care and mitigate negative financial impact upon providers. METHODS: We present an institutional review board-approved study retrospective review of 819 plastic surgery patients undergoing operative procedures performed at our institution between January 1, 2013, and December 31, 2014. All unanticipated readmissions within 30 days of an operation were identified and subjected to statistical analysis in an effort to determine whether these readmissions were associated with identifiable patient risk factors. RESULTS: One hundred forty-nine (18.1%) of the 819 investigated patients underwent readmission, reoperation, or both within 30 postoperative days. Seventy-four (9%) patients required hospital readmission, alone; 55 (6.7%) underwent readmission with operative intervention; and 20 (2.4%) required outpatient operative intervention without readmission. Readmitted patients were significantly more likely to have a positive smoking history (P = 0.009), hypertension (P = 0.0008), congestive heart failure (P = 0.0015), chronic obstructive pulmonary disease (P = 0.023), a higher mean age (P = 0.0001), and a higher Charlson Comorbidity Score (P = 0.0001). CONCLUSIONS: These results identify risk factors associated with unanticipated postoperative readmissions specific to a plastic surgery patient population. With this information, practitioners can allocate appropriate perioperative resources and planning for patients at increased risk for readmission, thereby improving delivery of patient care and satisfying quality metrics linked to practitioner reimbursement.

Significant Differences in the Bone of an Isogenic Inbred Versus Nonisogenic Outbred Murine Mandible: A Study in Rigor and Reproducibility.

Inattention to differences between animal strains is a potential cause of irreproducibility of basic science investigations. Accordingly, the authors' laboratory sought to ensure that cross-comparisons of results generated from studies of mandibular physiology utilizing the Sprague Dawley and Lewis rat strains are valid. The authors specifically investigated baseline histomorphometrics, bone mineral density, and biomechanical strength of the unaltered endogenous mandibles of the inbred, isogenic Lewis rat, and the outbred, nonisogenic Sprague Dawley rat to determine if they are indeed equal. The authors hypothesized that little difference would be found within these metrics.The authors' study utilized 20 male Lewis and Sprague Dawley rats, which underwent no manipulation other than final dissection and analysis. Ten rats from each strain underwent bone mineral density and biomechanical strength analysis. The remaining rats underwent histological analysis. Descriptive and bivariate statistics were computed and the P value was set at 0.05.Lewis rats had a significantly greater number of empty lacunae. Sprague Dawley rats exhibited a significantly greater ratio of bone volume-to-total volume, bone mineral density, tissue mineral density, bone volume fraction, and total mineral content. No differences were found during biomechanical testing.This study demonstrates that differences exist between the Lewis and Sprague Dawley rat within unaltered baseline mandibular tissue. However, these differences appear to have limited functional impact, as demonstrated by similar biomechanical strength metrics. Other specific differences not addressed in this manuscript may exist. However, the authors believe that researchers may confidently cross-compare results between the 2 strains, while taking into account the differences found within this study.

A Comparison of Vascularity, Bone Mineral Density Distribution, and Histomorphometrics in an Isogenic Versus an Outbred Murine Model of Mandibular Distraction Osteogenesis.

PURPOSE: The vascularity, bone mineral density distribution, and histomorphometric data between the inbred, isogenic Lewis rat and the outbred, nonisogenic Sprague Dawley rat within mandibular distraction osteogenesis (MDO) were evaluated to allow future researchers to compare the results generated from these 2 animals. We hypothesized that little difference would be found between the 2 strains within these metrics. MATERIALS AND METHODS: We implemented a comparative study between the Lewis and Sprague Dawley rat strains within MDO. The sample was composed of 17 male Lewis and 17 male Sprague Dawley rats that underwent surgical external fixation and distraction. The rats' hemimandibles were distracted to a total distance of 5.1 mm. After 28 days of consolidation, 9 rats from each group underwent bone mineral density distribution analysis. The remaining rats from each group were analyzed for the vascular and histologic metrics. Descriptive and bivariate statistics were computed, and the P value was set at .05. RESULTS: We demonstrated successful MDO in all the rats, with no significant difference found in the histologic or bone mineral density distribution metrics. No significant differences were found in any of the vascular metrics, with the exception of vascular separation, which was not normalized to the mandibular volume (P = .048). CONCLUSIONS: The results of the present study have demonstrated that little dissimilarity exists between the isogenic Lewis and outbred Sprague Dawley models of MDO. Thus, researchers can confidently compare the gross results between the 2 strains, with consideration of the very small differences between the 2 models. For studies that require an isogenic strain, the Lewis rat is an apt surrogate for the Sprague Dawley strain.

Raman spectroscopy delineates radiation-induced injury and partial rescue by amifostine in bone: a murine mandibular model.

Despite its therapeutic role in head and neck cancer, radiation administration degrades the biomechanical properties of bone and can lead to pathologic fracture and osteoradionecrosis. Our laboratories have previously demonstrated that prophylactic amifostine administration preserves the biomechanical properties of irradiated bone and that Raman spectroscopy accurately evaluates bone composition ex vivo. As such, we hypothesize that Raman spectroscopy can offer insight into the temporal and mechanical effects of both irradiation and amifostine administration on bone to potentially predict and even prevent radiation-induced injury. Male Sprague-Dawley rats (350-400 g) were randomized into control, radiation exposure (XRT), and amifostine pre-treatment/radiation exposure groups (AMF-XRT). Irradiated animals received fractionated 70 Gy radiation to the left hemi-mandible, while AMF-XRT animals received amifostine just prior to radiation. Hemi-mandibles were harvested at 18 weeks after radiation, analyzed via Raman spectroscopy, and compared with specimens previously harvested at 8 weeks after radiation. Mineral (ρ958) and collagen (ρ1665) depolarization ratios were significantly lower in XRT specimens than in AMF-XRT and control specimens at both 8 and 18 weeks. amifostine administration resulted in a full return of mineral and collagen depolarization ratios to normal levels at 18 weeks. Raman spectroscopy demonstrates radiation-induced damage to the chemical composition and ultrastructure of bone while amifostine prophylaxis results in a recovery towards normal, native mineral and collagen composition and orientation. These findings have the potential to impact on clinical evaluations and interventions by preventing or detecting radiation-induced injury in patients requiring radiotherapy as part of a treatment regimen.

Vascular analysis as a proxy for mechanostransduction response in an isogenic, irradiated murine model of mandibular distraction osteogenesis.

INTRODUCTION: Head and neck cancer is a debilitating and disfiguring disease. Although numerous treatment options exist, an array of debilitating side effects accompany them, causing physiological and social problems. Distraction osteogenesis (DO) can avoid many of the pathologies of current reconstructive strategies; however, due to the deleterious effects of radiation on bone vascularity, DO is generally ineffective. This makes investigating the effects of radiation on neovasculature during DO and creating quantifiable metrics to gauge the success of future therapies vital. The purpose of this study was to develop a novel isogenic rat model of impaired vasculogenesis of the regenerate mandible in order to determine quantifiable metrics of vascular injury and associated damage. METHODS: Male Lewis rats were divided into two groups: DO only (n=5) AND Radiation Therapy (XRT)+DO (n=7). Afterwards, a distraction device was surgically implanted into the mandible. Finally, they were distracted a total of 5.1mm. Animals were perfused with a radiopaque casting agent concomitant with euthanasia, and subsequently demineralization, microcomputed tomography, and vascular analysis were performed. RESULTS: Vessel volume fraction, vessel thickness, vessel number, and degree of anisotropy were diminished by radiation. Vessel separation was increased by radiation. CONCLUSION: The DO group experienced vigorous vessel formation during distraction and neovascularization with a clear, directional progression, while the XRT/DO group saw weak vessel formation during distraction and neovascularization. Further studies are warranted to more deeply examine the impairments in osteogenic mechanotransductive pathways following radiation in the murine mandible. This isogenic model provides quantifiable metrics for future studies requiring a controlled approach to immunogenicity.

Quantification and characterization of radiation-induced changes to mandibular vascularity using micro-computed tomography.

OBJECTIVE: Perhaps the most vexing and exigent problem confronting head and neck cancer reconstruction is overcoming the impediments of collateral damage imposed by radiation therapy (XRT) on normal surrounding tissue. Radiation therapy is detrimental to bone and soft tissue repair resulting in an unacceptably high incidence of devastating wound healing complications as well as the associated morbidity of late pathologic fractures, reduced bone healing, and osteoradionecrosis. The consequences of XRT on bone vasculature, long known to be affected by radiation, have been poorly understood. The purpose of this study was to analyze the degree by which irradiation degrades existing bone vascularity using a powerful micro-computed tomography technique to attain highly precise quantitative metrics of the vascular tree. METHODS: Fourteen 400-g male Sprague-Dawley rats underwent 35 Gy of fractionated XRT at 7 Gy/d. The animals were euthanized after 28 days, and the left ventricle was fixed and injected with Microfil (MV-122; Flow Tech, Carver, Mass) contrast. Left hemimandibles were dissected and scanned using high-resolution micro-computed tomography (18-µm voxels). The vessel number, thickness, separation, connectivity, and vessel volume fraction were analyzed for the region of interest, defined to be the volume behind the third molar spanning a total distance of 5.1 mm. RESULTS: Stereologic analysis and subsequent analysis of variance test demonstrated a significant and quantifiable diminution in the irradiated vasculature when compared with control animals. The vessel volume fraction (0.016 vs 0.032, P ≤ 0.003) and vessel thickness (0.042 vs 0.067 mm, P ≤ 0.001) were markedly reduced. Interestingly, further analysis demonstrated no significant differences between vessel separation and vessel number. CONCLUSIONS: The results of our study specifically quantify the corrosive affects of XRT on the vasculature of the mandible. The data from this novel technique go even further and imply retention of blood vessels but a degradation of their quality and size. Further experiments can now be directed at therapeutic interventions to reverse this process and better understand the underlying mechanism of XRT-induced bone injury.

Novel bacterial immobilization compound effectively decreases bacterial counts in healthy volunteers.

Skin flora immobilization technology is similar in efficacy to Iodine-Povidone in healthy volunteers. We did a prospective study in a university clinic with 60 healthy volunteers. Right inguinal skin area on healthy volunteers was used to compare the antimicrobial properties of cyanoacrylate sealant (FloraSeal, Adhesion Biomedical, Wyomissing, PA) versus standard surgical preparation Povidone-iodine (Betadine, Purdue Productions, Stamford, CT). Bacterial counts were measured at different time intervals: 15 minutes, 4 hours, and 24 hours. Bacterial colony forming units were compared between Povidone-iodine and cyanoacrylate sealant. The absolute log reduction was 5.568 for Povidone-iodine (7 absolute CFU); 5.028 for cyanoacrylate (59 absolute CFU); and 5.568 for Povidone-iodine and cyanoacrylate combined (21 absolute CFU). Cyanoacrylate was able to sustain a reduction on bacterial counts at 4 hours and 24 hours of more than 99.8 per cent as compared with the control group. Cyanoacrylate microbial sealant successfully reduces bacterial counts on normal healthy skin. The results were similar to Povidone-iodine alone. We believe this technology may be an excellent means of mitigating incisional surgical site infection by reducing the risk of contamination by skin flora and warrants further testing.

Role of parathyroid hormone in regeneration of irradiated bone in a murine model of mandibular distraction osteogenesis.

BACKGROUND: The purpose of this study was to measure the histologic and histomorphometric effects of parathyroid hormone (PTH) treatment on irradiated bone undergoing distraction osteogenesis (DO). METHODS: Thirty-four rats were divided into 3 groups. The control group underwent DO and the radiation control group underwent radiotherapy (RT) before DO. The PTH group underwent RT and received PTH during DO. Quantitative histology and histomorphometry were performed. RESULTS: RT resulted in a depletion of osteocytes and increase in empty lacunae. Treatment with PTH resulted in an increase in osteocyte counts and decrease in empty lacunae (p < .05), restoring osteocytes to levels seen in nonradiated bone (p = .121). RT decreased bone volume to tissue volume (BV-TV) ratio and increased osteoid volume to tissue volume (OV-TV) ratio, signifying increased immature bone formation. PTH treatment restored OV-TV ratio to that observed in nonradiated bone. CONCLUSION: PTH treatment of irradiated bone enhanced bone regeneration and restored osteocyte counts and OV-TV ratio to levels comparable to nonradiated bone. © 2016 Wiley Periodicals, Inc. Head Neck 39: 464-470, 2017.

Translational treatment paradigm for managing non-unions secondary to radiation injury utilizing adipose derived stem cells and angiogenic therapy.

BACKGROUND: Bony non-unions arising in the aftermath of collateral radiation injury are commonly managed with vascularized free tissue transfers. Unfortunately, these procedures are invasive and fraught with attendant morbidities. This study investigated a novel, alternative treatment paradigm utilizing adipose-derived stem cells (ASCs) combined with angiogenic deferoxamine (DFO) in the rat mandible. METHODS: Rats were exposed to a bioequivalent dose of radiation and mandibular osteotomy. Those exhibiting non-unions were subsequently treated with surgical debridement alone or debridement plus combination therapy. Radiographic and biomechanical outcomes were assessed after healing. RESULTS: Significant increases in biomechanical strength and radiographic metrics were observed in response to combination therapy (p < .05). Importantly, combined therapy enabled a 65% reduction in persisting non-unions when compared to debridement alone. CONCLUSION: We support the continued investigation of this promising combination therapy in its potential translation for the management of radiation-induced bony pathology. © 2015 Wiley Periodicals, Inc. Head Neck 38: E837-E843, 2016.

Prophylactic administration of Amifostine protects vessel thickness in the setting of irradiated bone.

Although often beneficial in the treatment of head and neck cancer (HNC), radiation therapy (XRT) leads to the depletion of vascular supply and eventually decreased perfusion of the tissue. Specifically, previous studies have demonstrated the depletion of vessel volume fraction (VVF) and vessel thickness (VT) associated with XRT. Amifostine (AMF) provides protection from the detrimental effects of radiation damage, allowing for reliable post-irradiation fracture healing in the murine mandible. The purpose of this study is to investigate the prophylactic ability of AMF to protect the vascular network in an irradiated field. Sprague-Dawley rats (n = 17) were divided into 3 groups: control (C, n = 5), radiated (XRT, n = 7), and radiated mandibles treated with Amifostine (AMF XRT, n = 5). Both groups receiving radiation underwent a previously established, human equivalent dose of XRT totaling 35 Gy, equally fractionated over 5 days. The AMF XRT group received a weight dependent (0.5 mg AMF/5 g body weight) subcutaneous injection of AMF 45 min prior to XRT. Following a 56-day recovery period, mandibles were perfused, dissected, and imaged with µCT. ANOVA was used for comparisons between groups and p < 0.05 was considered statistically significant. Stereologic analysis demonstrated a significant and quantifiable restoration of VT in AMF treated mandibles as compared to those treated with radiation alone (0.061 ± 0.011 mm versus 0.042 ± 0.004 mm, p = 0.027). Interestingly, further analysis demonstrated no significant difference in VT between control mandibles and those treated with AMF (0.067 ± 0.016 mm versus 0.061 ± 0.011 mm, p = 0.633). AMF treatment also showed an increase in VVF, however those results were not statistically significant from VVF values demonstrated by the XRT group. Our data support the contention that AMF therapy acts prophylactically to protect vessel thickness. Based on these findings, we support the continued investigation of this treatment paradigm in its potential translation for the prevention of vascular depletion after radiotherapy.

Targeting angiogenesis as a therapeutic means to reinforce osteocyte survival and prevent nonunions in the aftermath of radiotherapy.

BACKGROUND: Radiotherapy (XRT) exerts detrimental collateral effects on bone tissue through mechanisms of vascular damage and impediments to osteocytes, ultimately predisposing patients to the debilitating problems of late pathologic fractures and nonunions. We posit that angiogenic therapy will reverse these pathologic effects in a rat model of radiated fracture healing. METHODS: Three groups of rats underwent mandibular osteotomy. Radiated groups received a fractionated 35-Gy dose before surgery. The deferoxamine (DFO) group received local injections postoperatively. A 40-day healing period was allowed before histology. Analysis of variance (ANOVA; p < .05) was used for group comparisons. RESULTS: Radiated fractures revealed a significantly decreased osteocyte count and corresponding increase in empty lacunae when compared to nonradiated fractures (p = .001). With the addition of DFO, these differences were not appreciated. Further, a 42% increase in bony unions was observed after DFO therapy. CONCLUSION: Targeting angiogenesis is a useful means for promoting osteocyte survival and preventing bone pathology after XRT.

Stem cells rejuvenate radiation-impaired vasculogenesis in murine distraction osteogenesis.

BACKGROUND: Radiotherapy is known to be detrimental to bone and soft-tissue repair. Bone marrow stromal cells have been shown to enhance bone regeneration during distraction osteogenesis following radiation therapy. The authors posit that transplanted bone marrow stromal cells will significantly augment the mandibular vascularity devastated by radiation therapy. METHODS: Nineteen male Lewis rats were split randomly into three groups: distraction osteogenesis only (n = 5), radiation therapy plus distraction osteogenesis (n = 7), and radiation therapy plus distraction osteogenesis with intraoperative placement of 2 million bone marrow stromal cells (n = 7). A mandibular osteotomy was performed, and an external fixator device was installed. From postoperative days 4 through 12, rats underwent a gradual 5.1-mm distraction followed by a 28-day consolidation period. On postoperative day 40, Microfil was perfused into the vasculature and imaging commenced. Vascular radiomorphometric values were calculated for regions of interest. An analysis of variance with post hoc Tukey or Games-Howell tests was used, dependent on data homogeneity. RESULTS: Stereologic analysis indicated significant remediation in vasculature in the bone marrow stromal cell group compared with the radiation therapy/distraction osteogenesis group. Each of five metrics idicated significant improvements from radiation therapy/distraction osteogenesis to the bone marrow stromal cell group, with no difference between the bone marrow stromal cell group and the distraction osteogenesis group. CONCLUSIONS: Bone marrow stromal cells used together with distraction osteogenesis can rejuvenate radiation-impaired vasculogenesis in the mandible, reversing radiation therapy-induced isotropy and creating a robust vascular network. Bone marrow stromal cells may offer clinicians an alternative reconstructive modality that could improve the lifestyle of patients with hypovascular bone.

Amifostine reduces radiation-induced complications in a murine model of expander-based breast reconstruction.

BACKGROUND: Immediate expander-based breast reconstruction after mastectomy is a prevalent option for many women with breast cancer. When coupled with adjuvant radiation therapy, however, radiation-induced skin and soft-tissue injury diminish the success of this reconstructive technique. The authors hypothesize that prophylactic administration of the cytoprotectant amifostine will reduce soft-tissue complications from irradiation, aiding expander-based reconstruction. METHODS: Sprague-Dawley rats were divided into two groups: operative expander placement (expander group) and operative sham (sham group). Expander specimens received a sublatissimus tissue expander with a 15-cc fill volume; shams underwent identical procedures without expanders. Experimental groups were further divided into control specimens receiving no further intervention, radiation therapy-only specimens receiving human-equivalent irradiation, and amifostine plus radiation therapy specimens receiving both amifostine and human-equivalent irradiation. After a 45-day recovery period, animals were evaluated grossly and with ImageJ analysis for skin and soft-tissue complications. RESULTS: None of the control, radiation therapy-alone, or amifostine plus radiation therapy sham specimens showed skin and soft-tissue complications. For expander animals, significantly fewer amifostine plus radiation therapy specimens [four of 13 (30 percent)] demonstrated skin and soft-tissue complications compared with radiation therapy-alone specimens [nine of 13 (69 percent); p = 0.041]. ImageJ evaluation of expander specimens demonstrated a significant increase in skin and soft-tissue necrosis for radiation therapy-alone specimens (12.94 percent) compared with animals receiving amifostine plus radiation therapy (6.96 percent) (p = 0.019). CONCLUSIONS: Amifostine pretreatment significantly reduced skin and soft-tissue complications. These findings demonstrate that amifostine prophylaxis provides protection against radiation-induced skin and soft-tissue injury in a murine model of expander-based breast reconstruction.

Prophylactic amifostine preserves the biomechanical properties of irradiated bone in the murine mandible.

BACKGROUND: The authors have previously demonstrated that amifostine prophylaxis mitigates the pernicious effects of radiation in settings of fracture repair and distraction osteogenesis. Expanding on these studies, the authors examined the biomechanical properties of uninjured bone exposed to both radiation and amifostine. The authors hypothesize that radiation will degrade the biomechanical properties of native bone, and further hypothesize that prophylactic amifostine will preserve biomechanical properties to levels of normal bone and protect against radiation-induced morbidities. METHODS: Rats were randomized into control, irradiated, and amifostine pretreatment plus radiation (amifostine-pretreated) groups. Irradiated animals received a fractionated dosing schedule of 35 Gy, with amifostine-pretreated animals receiving amifostine before irradiation. Hemimandibles were harvested at 8 and 18 weeks for biomechanical testing and micro-computed tomographic analysis. RESULTS: At 8 weeks, irradiated specimens displayed elevations above controls for all biomechanical properties. At 18 weeks, the biomechanical properties of irradiated specimens degraded in comparison with controls; at both time points, amifostine-pretreated specimens were maintained at levels comparable to controls. There was a significant decrease in tissue mineral density from 8- to 18-week irradiated specimens, whereas no such change existed for control and amifostine-pretreated specimens. CONCLUSIONS: The authors' findings demonstrate paradoxical and transient elevations in the initial biomechanical properties of irradiated specimens that were not sustained through the later study time point. Amifostine pretreatment, however, provided uninterrupted preservation of the biomechanical properties of normal, native bone at both time points. This supports the contention that amifostine is capable of providing continuous protection to bone against the untoward effects of radiation therapy.

Deferoxamine administration delivers translational optimization of distraction osteogenesis in the irradiated mandible.

BACKGROUND: The authors' laboratory has previously demonstrated that deferoxamine promotes angiogenesis and bone repair in the setting of radiation therapy coupled with distraction osteogenesis. However, clinically relevant effects of deferoxamine administration on union rate and micro-computed tomographic and biomechanical parameters are unknown. The authors posit that administration of deferoxamine will increase union rate, mineralization, and strength of the regenerate in an irradiated distraction osteogenesis model. METHODS: Sprague-Dawley rats were randomized into three groups: distraction osteogenesis-control, distraction osteogenesis-radiation therapy, and distraction osteogenesis-radiation therapy-deferoxamine. All animals underwent an osteotomy and distraction osteogenesis across a 5.1-mm distraction gap. Irradiated animals received 35-Gy human-equivalent radiation therapy 2 weeks before surgery, and deferoxamine was injected postoperatively in the regenerate site of treatment animals. Animals were killed on postoperative day 40, and mandibles were harvested to determine rates of bony union and micro-computed tomographic and biomechanical parameters. RESULTS: Compared with irradiated mandibles, deferoxamine-treated mandibles exhibited a higher union rate (11 percent versus 92 percent, respectively). Across micro-computed tomographic and biomechanical parameters, significant diminutions were observed with administration of radiation therapy, whereas deferoxamine therapy resulted in significant restoration to levels of controls, with select metrics exhibiting significant increases even beyond controls. CONCLUSIONS: The authors' data confirm that deferoxamine restores clinically relevant metrics of bony union and micro-computed tomographic and biomechanical parameters in a model of irradiated distraction osteogenesis in the murine mandible. Their findings support a potential use for deferoxamine in treatment protocols to allow predictable and reliable use of distraction osteogenesis as a viable reconstructive option in patients with head and neck cancer.

Parathyroid hormone reverses radiation induced hypovascularity in a murine model of distraction osteogenesis.

BACKGROUND: Radiation treatment results in a severe diminution of osseous vascularity. Intermittent parathyroid hormone (PTH) has been shown to have an anabolic effect on osteogenesis, though its impact on angiogenesis remains unknown. In this murine model of distraction osteogenesis, we hypothesize that radiation treatment will result in a diminution of vascularity in the distracted regenerate and that delivery of intermittent systemic PTH will promote angiogenesis and reverse radiation induced hypovascularity. MATERIALS AND METHODS: Nineteen Lewis rats were divided into three groups. All groups underwent distraction of the left mandible. Two groups received radiation treatment to the left mandible prior to distraction, and one of these groups was treated with intermittent subcutaneous PTH (60 µg/kg, once daily) beginning on the first day of distraction for a total duration of 21 days. One group underwent mandibular distraction alone, without radiation. After consolidation, the rats were perfused and imaged with micro-CT angiography and quantitative vascular analysis was performed. RESULTS: Radiation treatment resulted in a severe diminution of osseous vascularity in the distracted regenerate. In irradiated mandibles undergoing distraction osteogenesis, treatment with intermittent PTH resulted in significant increases in vessel volume fraction, vessel thickness, vessel number, degree of anisotropy, and a significant decrease in vessel separation (p < 0.05). No significant difference in quantitative vascularity existed between the group that was irradiated, distracted and treated with PTH and the group that underwent distraction osteogenesis without radiation treatment. CONCLUSIONS: We quantitatively demonstrate that radiation treatment results in a significant depletion of osseous vascularity, and that intermittent administration of PTH reverses radiation induced hypovascularity in the murine mandible undergoing distraction osteogenesis. While the precise mechanism of PTH-induced angiogenesis remains to be elucidated, this report adds a key component to the pleotropic effect of intermittent PTH on bone formation and further supports the potential use of PTH to enhance osseous regeneration in the irradiated mandible.

Deferoxamine expedites consolidation during mandibular distraction osteogenesis.

BACKGROUND: A limitation of mandibular distraction osteogenesis (DO) is the length of time required for consolidation. This drawback subjects patients to possible pin-site infections, as well as a prolonged return to activities of normal daily living. Developing innovative techniques to abridge consolidation periods could be immensely effective in preventing these problematic morbidities. Deferoxamine (DFO) is an angiogenic activator that triggers the HIF-1α pathway through localized iron depletion. We previously established the effectiveness of DFO in enhancing regenerate vascularity at a full consolidation period (28 days) in a murine mandibular DO model. To investigate whether this augmentation in vascularity would function to accelerate consolidation, we progressively shortened consolidation periods prior to µCT imaging and biomechanical testing (BMT). MATERIALS AND METHODS: Three time points (14d, 21d and 28d) were selected and six groups of Sprague-Dawley rats (n = 60) were equally divided into control (C) and experimental (E) groups for each time period. Each group underwent external fixator placement, mandibular osteotomy, and a 5.1 mm distraction. During distraction, the experimental groups were treated with DFO injections into the regenerate gap. After consolidation, mandibles were imaged and tension tested to failure. ANOVA was conducted between groups, and p < 0.05 was considered statistically significant. RESULTS: At 14 days of consolidation the experimental group demonstrated significant increases in bone volume fraction (BVF), bone mineral density (BMD) and ultimate load (UL) in comparison to non-treated controls. The benefit of treatment was further substantiated by a striking 100% increase in the number of bony unions at this early time-period (C:4/10 vs. E:8/10). Furthermore, metrics of BVF, BMD, Yield and UL at 14 days with treatment demonstrated comparable metrics to those of the fully consolidated 28d control group. CONCLUSION: Based on these findings, we contend that augmentation of vascular density through localized DFO injection delivers an efficient means for accelerating bone regeneration without significantly impacting bone quality or strength.