Steven R. Buchman

Volume maintenance of onlay bone grafts in the craniofacial skeleton: Micro-architecture versus embryologic origin

&NA; The superior volume maintenance of membranous over endochondral bone has been shown in several studies and provides the basis for its preferred clinical use as an onlay grafting material in the craniofacial skeleton. The scientific rationale for this seeming embryologic advantage, however, has never been proven. Our hypothesis is that the pattern of onlay bone graft resorption is primarily determined by a grafts micro‐architecture (relative cortical and cancellous composition) rather than its embryologic origin (membranous versus endochondral). Twenty‐five adult New Zealand, White rabbits were used for this study. Eight animals were killed at 3 weeks, eight animals at 8 weeks, and nine animals at 16 weeks. Three graft types were placed onto each rabbit cranium: cortical bone graft of membranous origin and cortical and cancellous bone graft of endochondral origin. Fluorochrome markers were injected into all living rabbits at 1, 6, and 14 weeks. Microcomputed tomography scanning was performed on all of the bone grafts to determine postsacrifice volumes and to obtain detailed information regarding the bone grafts trabecular architecture. In addition, specimens were examined histologically. Volume analysis showed a statistically greater resorption rate in the cancellous endochondral bone graft than in either the endochondral or membranous cortical bone grafts (p < 0.05) for all time points. In addition there was no significant difference in the resorption rates between the endochondral and membranous cortical bone grafts. A post‐test power analysis (alpha = 5 percent) of the volume data comparing the two types of cortical bone grafts showed that a difference in resorption of 8.9 percent would be detected with a 90‐percent probability. Previous studies, which have shown a seeming superiority of membranous over endochondral bone grafts, used composite grafts composed of both cortical and cancellous portions. By separating these components, we have shown that cortical bone grafts maintain their volumes significantly better than cancellous bone grafts. In addition, we found no statistical difference in the resorption rates between the two cortical onlay bone grafts of different embryologic origins, a finding that has never been previously published. From our results, we believe cortical bone to be a superior onlay grafting material, independent of its embryologic origin. We believe these results challenge the currently accepted theories of bone graft dynamics and may lead to a change in the way clinicians approach bone graft selections for craniofacial surgery. (Plast. Reconstr. Surg. 102: 291, 1998.)

Maternal cigarette smoking during pregnancy and the risk of having a child with cleft lip/palate.

Maternal cigarette smoking during pregnancy as a risk factor for having a child with cleft lip/palate has been suggested by several epidemiologic studies. However, most of these studies contained small sample sizes, and a clear association between these two factors could not be established. The U.S. Natality database from 1996 and a case-control study design were used to investigate the association between maternal smoking during pregnancy and having a child with cleft lip/palate. The records of 3,891,494 live births from the 1996 U.S. Natality database were extracted to obtain cleft lip/palate cases and random controls. The National Center for Health Statistics collects maternal and newborn demographic and medical data from the birth certificates of all 50 states. New York (excluding New York City), California, Indiana, and South Dakota did not collect smoking data, and the data from these states were excluded from the analysis. A total of 2207 live births with cleft lip/palate cases were identified, and 4414 controls (1:2 ratio) were randomly selected (using the SAS program) from live births with no congenital defects. Odds ratios and 95 percent confidence intervals were determined from logistic regression models, adjusting for confounding variables, including maternal demographic and medical risk factors. A significant association was found between any amount of maternal cigarette use during pregnancy and having a child with cleft lip/palate [unadjusted odds ratio 1.55 (1.36, 1.76), p < 0.001]. Univariate analysis showed that maternal education level, age, race, and maternal medical conditions (diabetes and pregnancy-associated hypertension) were potential confounders. After adjusting for these confounders, the odds ratio remained significant [Mantel-Haenszel odds ratio 1.34 (1.16, 1.54), p < 0.001]. To determine the dose response of cigarette smoking during pregnancy, the cigarette consumption per day was divided into four groups: none, 1 to 10, 11 to 20, and 21 or more. A dose-response relationship was found when comparing each smoking category with the no smoking reference group: 1.50 (1.28, 1.76), 1.55 (1.23, 1.95), and 1.78 (1.22, 2.59), respectively. This means that increased cigarette smoking during pregnancy resulted in increased odds of having a child with cleft lip/palate. This is the largest study to date to test the association between maternal cigarette smoking during pregnancy and having a newborn with cleft lip/palate. The significant trend in the dose-response relationship strongly suggests the association of smoking tobacco and this common congenital deformity. These results emphasize the public health risks associated with smoking during pregnancy. To prevent this devastating craniofacial anomaly, educational initiatives should be considered that will alert expectant mothers to the association between smoking during pregnancy and the occurrence of cleft lip/palate.

A current 10-year retrospective survey of 199 surgically treated orbital floor fractures in a nonurban tertiary care center

This study characterizes the surgically treated patient population suffering from orbital floor fractures by use of current data from a large series consisting of 199 cases taken from a nonurban setting. Data were gathered through a retrospective chart review of patients surgically treated for orbital floor fractures at the University of Michigan Health System, collected over a 10‐year period. Data regarding patient demographics, signs and symptoms of presentation, cause of injury, nature of injury, associated facial fractures, ocular injury, and associated nonfacial skeleton trauma were collected. In total, there were 199 cases of orbital floor fractures among 189 patients. Male patients outnumbered female patients by a 2:1 ratio and were found to engage in a wider range of behaviors that resulted in orbital floor fractures. Motor vehicle accidents were the leading cause of orbital floor fractures, followed by physical assault and sports‐related mechanisms. The ratio of impure to pure orbital floor fracture was 3:1. The most common signs and symptoms associated with orbital floor fractures, in descending order, were periorbital ecchymosis, diplopia, subconjunctival hemorrhage, and exophthalmos. Associated facial fractures were found in 77.2 percent of patients, the most prevalent of which was the zygoma‐malar fracture. Serious ocular injury occurred in 19.6 percent of patients, with globe rupture being the most prevalent, accounting for 40.5 percent of those injuries. There was a 38.1 percent occurrence of associated nonfacial skeletal trauma; skull fracture and intracranial injury were the most prevalent manifestations. Associated cervical‐spine fractures were rare (0.5 percent). Statistical examination, using odds ratios and chi‐squared analysis, demonstrated significant associations that have not previously been reported. Impure and pure orbital floor fractures revealed striking differences in several demographic aspects, including mechanism of injury, signs and symptoms of presentation, spectrum of associated trauma, and the severity of concomitant trauma. (Plast. Reconstr. Surg. 108: 612, 2001.)

Progressive postnatal craniosynostosis and increased intracranial pressure

Since its first description by Virchow in 1851, craniosynostosis has been known as a potentially serious condition resulting in premature fusion of skull sutures. Traditionally, craniosynostosis has been regarded as an event that occurs early in fetal development, resulting in a skull shape at birth that is determined by the suture or sutures involved. In recent years, a different form of craniosynostosis has been observed. Patients initially come to the attention of physicians because they exhibit midface hypoplasia or occasionally hypertelorism. The affected individuals all have a normal skull shape and open sutures in infancy but develop multiple-suture craniosynostosis postnatally, ultimately requiring surgical correction. These cases are significant because, although the patients do not initially display the physical manifestations of craniosynostosis, they frequently develop increased intracranial pressure, which can have devastating consequences. Unless these patients are recognized and vigilant follow-up monitoring is instituted at an early age, permanent impairment can result. A retrospective chart review study was conducted, and patients with multiple-suture craniosynostosis who developed symptoms of increased intracranial pressure were selected. The patients were divided into two groups, namely, those with normal sutures and/or head shape at birth (progressive craniosynostosis) (n = 15) and those with abnormal head shapes at birth (classic syndromic craniosynostosis) (n = 12). Clinical and radiological findings typically used to monitor the development of increased intracranial pressure were reviewed for both groups and compared. In addition, mutational analyses were performed. All patients with progressive postnatal craniosynostosis demonstrated clinical, radiological, or ophthalmological evidence of increased intracranial pressure, requiring skull expansion. Those patients displayed papilledema, anterior fontanelle bulge, and thumbprinting more often than did the patients with classic craniosynostosis. Thirteen of 15 patients were given the clinical diagnosis of Crouzon syndrome, which raises the question of whether such patients represent a subset of patients with this syndrome. Mutational analyses for the patients with progressive craniosynostosis demonstrated that, of 13 patients tested, 11 had mutations in exon 7 or 9 of FGFR2, which is a common site of mutations in Crouzon syndrome. The traditional indications of increased intracranial pressure used to monitor patients with classic craniosynostosis can be used to monitor patients with progressive postnatal craniosynostosis, particularly anterior fontanelle bulge, papilledema, and thumbprinting. It is thought that regular monitoring of these characteristics may lead to earlier diagnosis and allow for surgical intervention before the development of undesirable outcomes. It is important for clinicians to be aware of this group of patients, because any delay in diagnosis and treatment can result in severe consequences for the patients.

Reasons for Removal of Rigid Internal Fixation Devices in Craniofacial Surgery

Despite the widespread use of rigid fixation techniques in craniofacial surgery, there is a paucity of studies in the literature that serve to better define the reasons for the subsequent removal of plates and screws. The current study appears to be the first to attempt to assess these issues among a broad range of craniofacial surgery patients. Fifty-five patients who underwent hardware removal following craniofacial surgery at the University of Michigan Medical Center between 1989 and 1995 were retrospectively studied via an in-depth chart review. Common reasons for hardware removal included palpable/prominent hardware in 19 patients (34.5%), loosening of plates and screws in 14 patients (25.5%), pain in 14 patients (25.5%), infection in 13 patients (23.6%), wound dehiscence/exposure of hardware in 11 patients (20%), and removal at the time of secondary procedures in 5 patients (9.1%). It is hoped that this study will serve as a tool to define more completely the risk of needing subsequent hardware removal among craniofacial surgery patients treated with rigid internal fixation.

Biomechanical Study of Sternal Closure Using Rigid Fixation Techniques in Human Cadavers

BACKGROUND We believe rigid plate fixation may be superior to wire fixation in sternal closure, as rigid fixation used in the craniofacial skeleton has shown greater stability, lower postoperative pain, and accelerated bone healing. We hypothesize that sterna fixed with titanium plates are more stable mechanically than sterna fixed with wires. METHODS The sterna from human cadavers were used in this two-phased study. Phase I compared wires to four-hole titanium straight plates. Phase II compared wires to four-hole titanium custom H plates. The sterna were tested biomechanically using all fixation methods. RESULTS Phase I showed no statistically significant difference in the stiffness or lateral displacement between the wired and straight plated sterna. Phase II showed a statistically significant greater stiffness (p < 0.05) and less lateral displacement (p < 0.05) in the custom plated sterna over the wired sterna. CONCLUSIONS Our results showed that custom titanium H plates were superior to wire fixation. Furthermore, our results established the importance of plate configuration in sternal fixation. Our study may have beneficial clinical implications, as decreased motion at the sternotomy site could mean less postoperative pain, a decreased incidence of infection, and accelerated bone healing.

Treatment of heterotopic ossification through remote ATP hydrolysis.

Heterotopic ossification induced by injuries and burns is mediated by signaling through the SMAD pathway and can be targeted with topical apyrase. No Bones About It Heterotopic ossification is a painful side effect that can complicate burns, trauma, and some types of surgery. In patients with this condition, small amounts of bone form in abnormal locations throughout the body, causing pain and complicating recovery. Now, Peterson et al. have developed a mouse model of heterotopic ossification, investigated the mechanism of this disorder, and then used their animal model to demonstrate a potential therapeutic intervention: topical application of apyrase. Although apyrase was only applied to the injury site, it decreased the abnormal formation of bone throughout the body. Other therapies, such as celecoxib and a drug called LDN-193189, were effective as well, suggesting the possibility of multiple therapeutic options for preventing heterotopic ossification in injured patients. Heterotopic ossification (HO) is the pathologic development of ectopic bone in soft tissues because of a local or systemic inflammatory insult, such as burn injury or trauma. In HO, mesenchymal stem cells (MSCs) are inappropriately activated to undergo osteogenic differentiation. Through the correlation of in vitro assays and in vivo studies (dorsal scald burn with Achilles tenotomy), we have shown that burn injury enhances the osteogenic potential of MSCs and causes ectopic endochondral heterotopic bone formation and functional contractures through bone morphogenetic protein–mediated canonical SMAD signaling. We further demonstrated a prevention strategy for HO through adenosine triphosphate (ATP) hydrolysis at the burn site using apyrase. Burn site apyrase treatment decreased ATP, increased adenosine 3′,5′-monophosphate, and decreased phosphorylation of SMAD1/5/8 in MSCs in vitro. This ATP hydrolysis also decreased HO formation and mitigated functional impairment in vivo. Similarly, selective inhibition of SMAD1/5/8 phosphorylation with LDN-193189 decreased HO formation and increased range of motion at the injury site in our burn model in vivo. Our results suggest that burn injury–exacerbated HO formation can be treated through therapeutics that target burn site ATP hydrolysis and modulation of SMAD1/5/8 phosphorylation.

A comparison of iliac and cranial bone in secondary grafting of alveolar clefts.

This retrospective study compares the success of iliac versus cranial bone autografts in the secondary grafting of alveolar clefts. The study group was 116 patients with complete records and radiographs from a pool of 186 consecutively grafted patients at Childrens Hospital of Philadelphia. The quality of graft “take” was graded radiologically. Variables potentially influencing outcome were evaluated and included graft type (iliac versus cranial bone), cleft type (unilateral versus bilateral), cleft severity (complete unilateral or bilateral cleft lip and palate versus cleft of the alveolus only), age at grafting, and complications. Although graft “take” versus “nontake” seemed comparable in iliac and cranial bone graft groups, iliac bone showed a statistical superiority over cranial bone, with more radiologically excellent grades (p = 0.04) in all cleft types. Likewise, when the two graft types were compared in more severe clefts (complete unilateral and bilateral cleft lip and palate), iliac bone showed statistical superiority (p = 0.02) over cranial bone. However, they seemed comparable in less severe clefts of the alveolus only (p = 0.22). Recipient-site complications and their sequelae were comparable in iliac versus cranial graft groups, and no age-related differences were noted in children grafted above or below age 10. (Plast. Reconstr. Surg. 96: 789, 1995.)

Early detection of burn induced heterotopic ossification using transcutaneous Raman spectroscopy

INTRODUCTION Heterotopic ossification (HO), or the abnormal formation of bone in soft tissue, occurs in over 60% of major burn injuries and blast traumas. A significant need exists to improve the current diagnostic modalities for HO which are inadequate to diagnose and intervene on HO at early time-points. Raman spectroscopy has been used in previous studies to report on changes in bone composition during bone development but has not yet been applied to burn induced HO. In this study, we validate transcutaneous, in-vivo Raman spectroscopy as a methodology for early diagnosis of HO in mice following a burn injury. METHODS An Achilles tenotomy model was used to study HO formation. Following tenotomy, mice were divided into burn and sham groups with exposure of 30% surface area on the dorsum to 60° water or 30° water for 18s respectively. In-vivo, transcutaneous Raman spectroscopy was performed at early time points (5 days, 2 and 3 weeks) and a late time point (3 months) on both the tenotomized and non-injured leg. These same samples were then dissected down to the bone and ex-vivo Raman measurements were performed on the excised tissue. Bone formation was verified with Micro CT and histology at corresponding time-points. RESULTS Our Raman probe allowed non-invasive, transcutaneous evaluation of heterotopic bone formation. Raman data showed significantly increased bone mineral signaling in the tenotomy compared to control leg at 5 days post injury, with the difference increasing over time whereas Micro CT did not demonstrate heterotopic bone until three weeks. Ex-vivo Raman measurements showed significant differences in the amount of HO in the burn compared to sham groups and also showed differences in the spectra of new, ectopic bone compared to pre-existing cortical bone. CONCLUSIONS Burn injury increases the likelihood of developing HO when combined with traumatic injury. In our in-vivo mouse model, Raman spectroscopy allowed for detection of HO formation as early as 5 days post injury. Changes in bone mineral and matrix composition of the new bone were also evidenced in the Raman spectra which could facilitate early identification of HO and allow more timely therapy decisions for HO patients.

Focal adhesion kinase expression during mandibular distraction osteogenesis: evidence for mechanotransduction.

Distraction osteogenesis is an established treatment strategy in the reconstruction of the craniofacial skeleton. The underlying mechanisms that drive bone formation during this process are largely unknown, but a regulatory role for mechanical force is believed to be critical. The integrin-mediated signal transduction cascade is a primary pathway by which signal transduction of mechanical stimuli (i.e., mechanotransduction) occurs. Focal adhesion kinase (FAK) is a significant regulator in this pathway. The authors hypothesize that mechanical forces created during distraction osteogenesis are responsible for the osteogenic response that takes place, and that these changes arise through integrin-dependent mechanotransduction. Using a rat model of distraction osteogenesis, the authors examined the expression of FAK in critical size defects (n = 15), subcritical size defects (n = 15), and mandibles undergoing distraction osteogenesis (n = 15). Their findings demonstrated FAK immunolocalization in mandibles undergoing distraction osteogenesis, but not in the critical size defects or in subcritical size defects, despite varying degrees of bone formation in the latter two groups. Furthermore, bone sialoprotein mRNA in situ hybridization patterns were found to mirror FAK immunolocalization patterns in mandibles undergoing distraction osteogenesis, demonstrating an association of FAK expression with the osteogenic process specific to distraction osteogenesis. These findings suggest that the bone formation in distraction osteogenesis is regulated by mechanical force by means of integrin-dependent mechanotransduction pathways.