In utero exposure to selective serotonin re-uptake inhibitor affects murine mandibular development.

OBJECTIVES: Antidepressants, specifically Selective Serotonin Re-uptake Inhibitors (SSRIs), that alter serotonin metabolism are currently the most commonly prescribed drugs for the treatment of depression. There is some evidence to suggest these drugs contribute to birth defects. As jaw development is often altered in craniofacial birth defects, the purpose of this study was to interrogate the effects of in utero SSRI exposure in a preclinical model of mandible development. MATERIALS AND METHODS: Wild-type C57BL6 mice were used to produce litters that were exposed in utero to an SSRI, Citalopram (500 µg/day). Murine mandibles from P15 pups were analysed for a change in shape and composition. RESULTS: Analysis indicated an overall shape change with total mandibular length and ramus height being shorter in exposed pups as compared to controls. Histomorphometric analysis revealed that first molar length was longer in exposed pups while third molar length was shorter in exposed as compared to control. Histological investigation of molars and surrounding periodontium revealed no change in collagen content of the molar in exposed pups, some alteration in collagen composition in the periodontium, increased alkaline phosphatase in molars and periodontium and decreased mesenchymal cell marker presence in exposed mandibles. CONCLUSION: The results of this study reveal SSRI exposure may interrupt mandible growth as well as overall dental maturation in a model of development giving insight into the expectation that children exposed to SSRIs may require orthodontic intervention.

A Survey of Bone Grafting Practice Patterns in North American Cleft Surgeons.

INTRODUCTION: Alveolar bone grafting aims to restore bony continuity of the alveolus and provide optimal periodontal support for teeth adjacent to the cleft. We created a survey of cleft surgeons to assess the current standard of care regarding this procedure. METHODS: A multiple choice survey was implemented using Qualtrics software and emailed to a list of 708 surgeons from the ACPA membership directory. Correlation between various provider factors and treatment practices was assessed with Fisher's exact test and likelihood ratio tests. RESULTS: The response rate was 17.5%. Eighty-seven percent of providers preferred to perform grafts prior to secondary canine eruption while 10% favored before central incisor eruption. Eighty-one percent favored palatal expansion prior to bone grafting. Wide variability existed regarding the time to initiate postoperative orthodontics; 43% waited 4 to 6 months. Sixty-four percent of surgeons now utilize cone beam CT to assess graft take. The majority of respondents utilized cancellous bone autograft (92%) from the anterior iliac crest (97%) as graft material. Seventy percent used three or more modalities for post-operative pain control management. Early career surgeons (0-5 years) appeared more likely to use non-autologous materials (p < .01) for grafting. CONCLUSION: Alveolar bone grafting prior to secondary canine eruption remains the most common strategy but other protocols are employed. Surgeons utilize multiple modalities for radiographic evaluation and most often use autologous cancellous bone as the primary grafting material. There is no true consensus on the perioperative timing and sequencing of orthodontic manipulation while principles of multimodal perioperative pain control appear widely accepted.

Patients With a History of Oronasal Fistula Repair Exhibit Lower Oral Health Measured With Patient-Centric Outcomes Measures.

INTRODUCTION: Oronasal fistulae following palatoplasty may affect patients' quality of life by impacting their ability to eat, speak, and maintain oral hygiene. We aimed to quantify the impact of previous oronasal fistula repair on patients' quality of life using patient-reported outcome psychometric tools. METHODS: A cross-sectional study of 8- to 9-year-old patients with cleft palate and/or lip was completed. Patients who had a cleft team clinic between September 2018 and August 2019 were recruited. Participants were divided into 2 groups (no fistula, prior fistula repair). Differences in the individual CLEFT-Q and Child Oral Health Impact Profile-Short Form 19 (COHIP-SF 19) Oral Health scores between the 2 groups were evaluated using a multivariate analysis controlling for Veau classification and syndromic diagnosis. RESULTS: Sixty patients with a history of cleft palate were included. Forty-two (70%) patients had an associated cleft lip. Thirty-two (53.3%) patients had no history of fistula and 28 (46.7%) patients had undergone a fistula repair. CLEFT-Q Dental, Jaw, and Speech Function were all higher in patients without a history of a fistula repair; however, none of these differences were statistically significant. The COHIP-SF 19 Oral Health score demonstrated a significantly lower score in the fistula group, indicating poorer oral health (P = .05). CONCLUSIONS: One would expect that successful repair of a fistula would result in improved function and patient satisfaction, but the consistent trend toward lower CLEFT-Q scores and significantly increased COHIP-SF 19 Oral Health scores in our study group suggests that residual effects linger and that the morbidity of a fistula may not be completely treated with a secondary correction.

Variation in Ontogenetic Facial Suture Fusion Patterns in Catarrhines.

Timing of craniofacial suture fusion is important for the determination of demographics and primate ontogeny. There has been much work concerning the timing of fusion of calvarial sutures over the last century, but little comprehensive work focusing on facial sutures. Here we assess the relationships of facial suture fusion across ontogeny among select catarrhines. Fusion timing patterns for 5 facial sutures were examined in 1,599 crania of Homo, Pan, Gorilla, Pongo, Hylobatidae, Papio, and Macaca. Calvarial volume (early ontogeny) and dental eruption (late ontogeny) were used as indicators of stage of development. General linear models, test for homogeneity of slopes, and ANOVA were used to determine differences in timing of fusion by taxon. For calvarial volume, taxonomic groups segregated by regression slopes, with models for Homo indicating sutural fusion throughout ontogeny, Pongo, Macaca, and Papio representing earlier and more complete suture fusion, and Pan, Gorilla, and Hylobatidae indicating very early facial suture fusion. Similar patterns are observed when dental eruption is used for developmental staging. Only Gorilla and Hylobatidae are observed to, generally, fuse all facial suture sites in adulthood. Finally, Homo appears to be unique in its delay and patency of sutures into late ontogeny. The taxonomic patterns of facial suture closure identified in this study likely reflect important evolutionary shifts in facial growth and development in catarrhines.

Reconstruction of a Calvarial Wound Complicated by Infection: Comparing the Effects of Biopatterned Bone Morphogenetic Protein 2 and Vascular Endothelial Growth Factor.

Bone morphogenetic protein 2 (BMP2) bioprinted on biological matrix induces osseous regeneration in large calvarial defects in rabbits, both uncomplicated and scarred. Healing in unfavorable defects scarred from previous infection is decreased due in part to the lack of vascularity. This impedes the access of mesenchymal stem cells, key to osseous regeneration and the efficacy of BMP2, to the wound bed. The authors hypothesized that bioprinted vascular endothelial growth factor (VEGF) would augment the osseous regeneration achieved with low dose biopatterned BMP2 alone. Thirteen New Zealand white rabbits underwent subtotal calvariectomy using a dental cutting burr. Care was taken to preserve the underlying dura. A 15 mm × 15 mm flap of bone was cut away and incubated in a 1 × 108 cfu/mL planktonic solution of S aureus before reimplantation. After 2 weeks of subsequent infection the flap was removed and the surgical wound debrided followed by 10 days of antibiotic treatment. On postoperative day 42 the calvarial defects were treated with acellular dermal matrix bioprinted with nothing (control), VEGF, BMP2, BMP2/VEGF combined. Bone growth was analyzed with serial CT and postmortem histology. Defects treated with BMP2 (BMP2 alone and BMP2/VEGF combination) showed significantly greater healing than control and VEGF treated defect (P < 0.5). Vascular endothelial growth factor treated defect demonstrated less healing than control and VEGF/BMP2 combination treatments achieved less healing than BMP2 alone though these differences were nonsignificant. Low dose BMP2-patterned acellular dermal matrix improves healing of scarred calvarial defects. Vascular endothelial growth factor at the doses applied in this study failed to increase healing.

Maternal environment and craniofacial growth: geometric morphometric analysis of mandibular shape changes with in utero thyroxine overexposure in mice.

An estimated 3% of US pregnancies are affected by maternal thyroid dysfunction, with between one and three of every 1000 pregnancies being complicated by overactive maternal thyroid levels. Excess thyroid hormones are linked to neurological impairment and excessive craniofacial variation, affecting both endochondral and intramembranous bone. Using a geometric morphometric approach, this study evaluates the role of in utero thyroxine overexposure on the growth of offspring mandibles in a sample of 241 mice. Canonical variate analysis utilized 16 unilateral mandibular landmarks obtained from 3D micro-computed tomography to assess shape changes between unexposed controls (n = 63) and exposed mice (n = 178). By evaluating shape changes in the mandible among three age groups (15, 20 and 25 days postnatal) and different dosage levels (low, medium and high), this study found that excess maternal thyroxine alters offspring mandibular shape in both age- and dosage-dependent manners. Group differences in overall shape were significant (P < 0.001), and showed major changes in regions of the mandible associated with muscle attachment (coronoid process, gonial angle) and regions of growth largely governed by articulation with the cranial base (condyle) and occlusion (alveolus). These results compliment recent studies demonstrating that maternal thyroxine levels can alter the cranial base and cranial vault of offspring, contributing to a better understanding of both normal and abnormal mandibular development, as well as the medical implications of craniofacial growth and development.

Marginal discrepancy of noble metal-ceramic fixed dental prosthesis frameworks fabricated by conventional and digital technologies.

STATEMENT OF PROBLEM: Studies evaluating the marginal adaptation of available computer-aided design and computer-aided manufacturing (CAD-CAM) noble alloys for metal-ceramic prostheses are lacking. PURPOSE: The purpose of this in vitro study was to evaluate the vertical marginal adaptation of cast, milled, and direct metal laser sintered (DMLS) noble metal-ceramic 3-unit fixed partial denture (FDP) frameworks before and after fit adjustments. MATERIAL AND METHODS: Two typodont teeth were prepared for metal-ceramic FDP abutments. An acrylic resin pattern of the prepared teeth was fabricated and cast in nickel-chromium (Ni-Cr) alloy. Each specimen group (cast, milled, DMLS) was composed of 12 casts made from 12 impressions (n=12). A single design for the FDP substructure was created on a laboratory scanner and used for designing the specimens in the 3 groups. Each specimen was fitted to its corresponding cast by using up to 5 adjustment cycles, and marginal discrepancies were measured on the master Ni-Cr model before and after laboratory fit adjustments. RESULTS: The milled and DMLS groups had smaller marginal discrepancy measurements than those of the cast group (P<.001). Significant differences were found in the number of adjustments among the groups, with the milled group requiring the minimum number of adjustments, followed by the DMLS and cast groups (F=30.643, P<.001). CONCLUSIONS: Metal-ceramic noble alloy frameworks fabricated by using a CAD-CAM workflow had significantly smaller marginal discrepancies compared with those with a traditional cast workflow, with the milled group demonstrating the best marginal fit among the 3 test groups. Manual refining significantly enhanced the marginal fit of all groups. All 3 groups demonstrated marginal discrepancies within the range of clinical acceptability.

Improving speech outcomes after failed palate repair: evaluating the safety and efficacy of conversion Furlow palatoplasty.

BACKGROUND: Velopharyngeal insufficiency occurs in a nontrivial number of cases following cleft palate repair. We hypothesize that a conversion Furlow palatoplasty allows for long-term correction of VPI resulting from a failed primary palate repair, obviating the need for pharyngoplasty and its attendant comorbidities. METHODS: A retrospective review of patients undergoing a conversion Furlow palatoplasty between 2003 and 2010 was performed. Patients were grouped according to the type of preceding palatal repair. Velopharyngeal insufficiency was assessed using Pittsburgh Weighted Speech Scale (PWSS). Scores were recorded and compared preoperatively and postoperatively at 3 sequential visits. RESULTS: Sixty-two patients met inclusion criteria and were grouped by preceding repair (straight-line repair (n = 37), straight-line repair with subsequent oronasal fistula (n = 14), or pharyngeal flap (n = 11). Median PWSS scores at individual visits were as follows: preoperative = 11, first postoperative = 3 (mean, 114.0 ± 6.7 days), second postoperative = 1 (mean, 529.0 ± 29.1 days), and most recent postoperative = 3 (mean, 1368.6 ± 76.9 days). There was a significant difference between preoperative and postoperative PWSS scores in the entire cohort (P < 0.001) with overall improvement, and post hoc analysis showed improvement between each postoperative visit (P < 0.05) with the exception of the second to the most recent visit. There were no differences between postoperative PWSS scores in the operative subgroupings (P > 0.05). Eight patients failed to improve and showed no differences in PWSS scores over time (P > 0.05). Patients with a PWSS score of 7 or greater (n = 8) at the first postoperative visit (0-6 months) displayed improvement at the most recent visit (P< 0.05). CONCLUSIONS: Conversion Furlow palatoplasty is an effective means for salvaging speech. Future studies should elucidate which factors predict the success of this technique following failed palate repair.

Bone morphogenetic protein 2­mediated mandible reconstruction successfully heals bony defects but inhibits concurrent inferior alveolar nerve grafting: a rabbit experimental model.

BACKGROUND: Bone morphogenetic protein 2 (BMP-2) has been used to reconstruct mandibular defects. An elegant addition to this reconstruction method would be incorporation of a nerve graft wrapped in a BMP-2 carrier to reconstitute the inferior alveolar nerve (IAN) and restore sensation to the lower face. We developed a rabbit model to determine the effect BMP-2 has on nerve regeneration following neurorrhaphy. METHODS: An inferior border mandibulectomy was created in 16 adult New Zealand white rabbits. The IAN was protected, divided, and repaired with either primary neurorrhaphy or reverse autografts. Bone defects were treated with no treatment controls (n = 2), absorbable collagen sponge (ACS) (vehicle controls) (n = 7), and ACS soaked in BMP-2 (treatment group) (n = 7). Animals underwent computed tomography (CT) 2 days and 6 weeks postoperatively. The percent bone defect healing was calculated using Amira 3D imaging software. At 6 weeks, IANs were harvested mesial to the reconstruction and were evaluated with toluidine blue histology to identify myelinated axons. Reconstructed mandible segments were evaluated with micro-CT and hematoxylin-eosin histology. RESULTS: Bone morphogenetic protein 2-treated animals demonstrated significantly more bone healing than did the ACS and empty defect groups (82%, 38%, 44%, respectively; P < 0.01). One hundred percent of ACS-treated nerves (n = 4) demonstrated axon regrowth, whereas only 25% of BMP-2-treated nerves (n = 4) did. Micro-CT and histology showed BMP-2 caused bone growth around the IAN, but regenerated bone infiltrated the repair site and created a physical barrier to axon growth. CONCLUSIONS: Bone morphogenetic protein 2 can successfully heal bone defects in the rabbit mandible, but ectopic bone growth can inhibit IAN recovery after repair. Level of Evidence: Not gradable.

Selective serotonin re-uptake inhibitors affect craniofacial structures in a mouse model.

Selective serotonin re-uptake inhibitors (SSRI) widely used in the treatment of depression, anxiety, obsessive compulsive disorder, fibromyalgia, and migraine are among the most heavily prescribed drug class in the United States (US). Along with an overall rise in SSRI use, these medications are increasingly used by pregnant individuals and recent preclinical and clinical studies have indicated that SSRIs may increase the prevalence of congenital abnormalities and birth defects of the craniofacial region. Our group has developed pre-clinical models of study, including those that mimic the clinical use of SSRI in mice. Here we designed a study to interrogate a commonly prescribed SSRI drug, Citalopram, for its effects on craniofacial and dental development when introduced in utero. Pre-natal exposure to a clinically relevant dose of citalopram resulted in changes in craniofacial form identified by an increase in endocast volume in SSRI exposed postnatal day 15 mouse pups. More specifically, cranial length and synchondrosis length increased in SSRI exposed pups as compared to control pups of the same age. Additionally, growth center (synchondrosis) height and width and palate length and width decreased in SSRI exposed pups as compared to control un-exposed pups. Effects of SSRI on the molars was minimal. Craniofacial growth and development continue to be an area of interest in the investigation of in utero pharmaceutical drug exposure. Altogether these data indicate that prenatal SSRI exposure affects craniofacial form in multiple tissues and specifically at growth sites and centers of the skull.

Ectocranial suture fusion in primates: as related to cranial volume and dental eruption.

BACKGROUND: Timing of calvarial suture fusion is important in primate ontogeny. Ages at death are difficult to assess especially for museum collections. METHODS: 1550 skulls of Hominoid, Hylobatidae, Macaca and Papio were observed for fusion. Calvarial expansion (early) and dental eruption (late) were utilized as indicators of ontogeny. Homogeneity of slopes and ANOVA were used to determine differences in timing of fusion. RESULTS: For calvarial growth the great apes all showed small levels of calvarial suture remodeling prior to full calvarial expansion. For dental eruption, Homo and Macaca share a common pattern of fusion in late adulthood. The other species show early remodeling. Papio was observed to have distinct patterns for suture fusion progression. CONCLUSIONS: Thus, suture fusion progression although influenced by evolutionary changes in the robusticity of the craniofacial skeleton can be modeled by the phylogeny among this group. Overall, Homo appears to have a distinct pattern of delayed suture fusion progression.

Tissue interactions between craniosynostotic dura mater and bone.

BACKGROUND: Cells within the dura mater have been implicated in the determination of suture patency and fusion. Craniosynostosis (CS), the premature fusion of 1 or more of the cranial sutures, could result from abnormal control over the differentiation of osteoprogenitor cells from the dura mater. This study tested whether dura mater cells derived from rabbits with congenital CS were different from cells derived from normal rabbits and investigated the effects that CS dura mater had on osteogenic differentiation in vitro and in vivo. METHODS: Cells were derived from the dura mater from wild-type rabbits (WT; n = 23) or CS rabbits (n = 16). Cells were stimulated with bone morphogenetic protein 4, and alkaline phosphatase (ALP) expression and cell proliferation were assessed. Dura mater-derived cells were also cocultured with primary rabbit bone-derived cells, and ALP was assessed. Finally, interactions between the dura mater and overlying tissues were manipulated in vivo. RESULTS: Craniosynostotic dura mater-derived cells proliferated faster than did WT cells but were not more ALP positive. Coculture experiments showed that CS dura mater cells induced increased ALP activity in CS bone-derived cells, but not in WT bone-derived cells. In vivo experiments showed that a physical barrier successfully inhibited dura mater-derived osteogenesis. CONCLUSIONS: Coculture of CS bone- and CS dura mater-derived cells evoked an abnormal phenotype in vitro. Covering the CS dura mater led to decreased bone formation in vivo. Further investigations will focus on the signaling molecules involved in the communication between these 2 CS tissue types in vitro and in vivo.

Timing of ectocranial suture activity in Gorilla gorilla as related to cranial volume and dental eruption.

Research has shown that Pan and Homo have similar ectocranial suture synostosis patterns and a similar suture ontogeny (relative timing of suture fusion during the species ontogeny). This ontogeny includes patency during and after neurocranial expansion with a delayed bony response associated with adaptation to biomechanical forces generated by mastication. Here we investigate these relationships for Gorilla by examining the association among ectocranial suture morphology, cranial volume (as a proxy for neurocranial expansion) and dental development (as a proxy for the length of time that it has been masticating hard foods and exerting such strains on the cranial vault) in a large sample of Gorilla gorilla skulls. Two-hundred and fifty-five Gorilla gorilla skulls were examined for ectocranial suture closure status, cranial volume and dental eruption. Regression models were calculated for cranial volumes by suture activity, and Kendall's tau (a non-parametric measure of association) was calculated for dental eruption status by suture activity. Results suggest that, as reported for Pan and Homo, neurocranial expansion precedes suture synostosis activity. Here, Gorilla was shown to have a strong relationship between dental development and suture activity (synostosis). These data are suggestive of suture fusion extending further into ontogeny than brain expansion, similar to Homo and Pan. This finding allows for the possibility that masticatory forces influence ectocranial suture morphology.

An algorithm for application of furlow palatoplasty to the treatment of velocardiofacial syndrome-associated velopharyngeal insufficiency.

Treatment of velocardiofacial syndrome (VCFS)-associated velopharyngeal insufficiency is controversial. Palatoplasties have variable success, and pharyngeal flaps (PPF) increase the obstructive sleep apnea risk. Our center uses Furlow palatoplasties to treat overt clefts and kinetic submucous cleft palates. PPFs are employed to treat akinetic palates and recurrent/persistent velopharyngeal insufficiency after palatoplasty. A retrospective review was performed of patients with VCFS treated according to this algorithm. Twenty-seven patients with VCFS were included: 3.7% (n = 1) had overt clefts; 81.4% (n = 22) underwent Furlow palatoplasties for kinetic submucous cleft palates; 14.8% (n = 4) underwent primary PPFs for akinetic palates. The algorithm was successful in 21 patients (77.7%). Furlow palatoplasty achieved ultimate success in 45% of patients. Secondary PPF was successful in all 7 patients, as was primary PPF in all 4 patients. Furlow palatoplasty represents a first step in treating appropriate VCFS patients that avoids the risk of sleep apnea, but the potential for secondary pharyngoplasty must be considered.

Antibiotic duration and postoperative infection rates in mandibular fractures.

BACKGROUND: Although the use of preoperative antibiotics has been proven effective, the value of postoperative antibiotics in the setting of mandibular fracture remains in question as does the appropriate duration of therapy. METHODS: A retrospective study of all patients 18 years and older who presented with mandibular fractures to St Louis University Hospital between December 2001 and July 2006 was conducted. Collected variables included age, injury severity score, fracture type and location, preoperative antibiotic administration, antibiotic type, duration of antibiotic course, and postoperative infection. Infections were statistically compared with each. RESULTS: Of 253 identified patients, 197 qualified for study inclusion. A total of 9 postoperative infections were documented. When comparing individuals with postoperative infection to those without, age was the only significant difference between infected and uninfected groups, with older patients more likely to acquire infection. Injury severity score, fracture type, duration of antibiotic course, and antibiotic type were not significantly different. CONCLUSIONS: Our findings suggest that patient factors make a greater contribution to postoperative infection when compared with iatrogenic factors in the treatment of mandibular fractures. We found no evidence to support prolonged postoperative antibiotic therapy. Our findings bring into question the need for postoperative antibiotics for the treatment of mandibular fractures.

Outcomes of Furlow Double-Opposing Z-Plasty Palatoplasty for the Treatment of Symptomatic Overt and Occult Submucous Cleft Palate: A Comparison Study.

BACKGROUND: The submucous cleft palate can be overt or occult and may require surgical repair. The double-opposing Z-plasty (Furlow repair) is the authors' center's preferred approach. This study evaluated complication rates, differences in outcome between overt and occult types, and patient factors associated with surgical failure. METHODS: This retrospective study reviewed documentation on all patients who underwent Furlow Z-plasty for submucous cleft palate at a single center between 2004 and 2018. Speech pathology was quantified using the Pittsburgh Weighted Speech Score. RESULTS: A total of 351 patients were included (125 overt and 226 occult cases). Furlow Z-plasty was successful (postoperative Pittsburgh Weighted Speech Score <7 without recommendation for secondary speech surgery) in 291 patients (82.1 percent). Apart from those requiring secondary surgery, there were no documented complications. Occult-type patients were 7.5 years old at palatoplasty with a speech score of 14.1; overt-type patients were 6.5 years old with a score of 15.7. Postoperative speech scores were similar for both groups. Secondary speech surgery patients had a higher preoperative score (16.9 versus 14.2). Age at time of palatoplasty and submucous cleft palate type were not predictive of the need for secondary surgery. Syndromic patients had higher preoperative and postoperative speech scores (15.6 and 7.5, respectively) than nonsyndromic patients (14.3 and 4.3) and needed secondary surgery more often (24.4 percent versus 9.2 percent). V-shaped velar vaulting on preoperative assessment was present in 92 percent of occult-type patients. CONCLUSIONS: Furlow palatoplasty is a safe and effective means of repairing submucous cleft palate. Patients with the occult type presented later with a lower Pittsburgh Weighted Speech Score. High preoperative speech score and syndromic status were associated with the need for secondary speech surgery. V-shaped velar vaulting is a reliable sign of occult submucous cleft palate. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Selective serotonin re-uptake inhibitor sertraline inhibits bone healing in a calvarial defect model.

Bone wound healing is a highly dynamic and precisely controlled process through which damaged bone undergoes repair and complete regeneration. External factors can alter this process, leading to delayed or failed bone wound healing. The findings of recent studies suggest that the use of selective serotonin reuptake inhibitors (SSRIs) can reduce bone mass, precipitate osteoporotic fractures and increase the rate of dental implant failure. With 10% of Americans prescribed antidepressants, the potential of SSRIs to impair bone healing may adversely affect millions of patients' ability to heal after sustaining trauma. Here, we investigate the effect of the SSRI sertraline on bone healing through pre-treatment with (10 mg·kg-1 sertraline in drinking water, n = 26) or without (control, n = 30) SSRI followed by the creation of a 5-mm calvarial defect. Animals were randomized into three surgical groups: (a) empty/sham, (b) implanted with a DermaMatrix scaffold soak-loaded with sterile PBS or (c) DermaMatrix soak-loaded with 542.5 ng BMP2. SSRI exposure continued until sacrifice in the exposed groups at 4 weeks after surgery. Sertraline exposure resulted in decreased bone healing with significant decreases in trabecular thickness, trabecular number and osteoclast dysfunction while significantly increasing mature collagen fiber formation. These findings indicate that sertraline exposure can impair bone wound healing through disruption of bone repair and regeneration while promoting or defaulting to scar formation within the defect site.

Characterization of primary osteocyte-like cells from rat mandibles.

OBJECTIVE: The mandible is continuously undergoing remodeling as a result of mechanobiologic factors, such as chewing forces, tooth loss, orthodontic forces, and periodontitis. The effects of mechanical stress and biologic signals in bone homeostasis have been the focus of many investigations. However, much of this research utilized osteocytes derived from long bones, but little is known about the mandible-derived osteocytes. This study tests a protocol to isolate and grow osteocytes from rat mandible. STUDY DESIGN: Rat mandibles were harvested, sectioned into small pieces, and subjected to a sequence chemical treatment and enzymatic digestion. The treated tissues were cultured for a few weeks while cells emerged. Cells were sorted by using the osteocyte marker podoplanin, an early marker for osteocyte differentiation. The cells were then characterized according to morphology, biochemical markers (osteocalcin, podoplanin, and sclerostin), and alkaline phosphatase activity and compared with an isotype cell line MLO-Y4 cells. RESULTS: The mandibular osteocytic cells had stellate shape and were positive for osteocalcin, podoplanin, and sclerostin and lower alkaline phosphatase activity compared with MLO-Y4 osteocyte-like cells. CONCLUSIONS: The protocol to isolate osteocyte-like cells will allow the investigators to investigate the mechanobiologic differences in biomechanical response between these mandibular and long bone osteocyte-like cells under various conditions.

A Model for Osteonecrosis of the Jaw with Zoledronate Treatment following Repeated Major Trauma.

This study aims to develop a reproducible rat model for post-traumatic bisphosphonate-related osteonecrosis of the jaw (BRONJ). In our previous studies using dental extraction as an inducing factor, only 30%-60% of zoledronate-treated animals fulfilled the definition of clinical BRONJ. We modified the zoledronate regimen and introduced repeated surgical extraction to illicit quantifiable BRONJ in all animals. Eighty retired-breeder female Sprague-Dawley rats were divided between the treatment (i.v. zoledronate; 80 µg/kg/week for 13 weeks) and control (saline) groups. On week 13, the left mandibular first molar was surgically extracted, followed by the second molar a week later. Animals were euthanized at 1-week, 2-weeks, and 8-weeks following extraction. The occurrence and severity of BRONJ were scored in each animal based on gross and MicroCT analysis. Parameters of bone formation and osteoclast functions at the extraction site were compared between groups. All zoledronate-treated animals developed a severe case of BRONJ that fulfilled the clinical definition of the condition in humans. Osteoclast attachment continued to be defective eight weeks after stopping the treatment. There were no signs of kidney or liver toxicity. Our data confirmed that repeated surgical extraction (major trauma) by itself consistently precipitated massive bone necrosis in ZA-treated animals, eliminating the need to induce pre-existing infection or comorbidity. These results will be the basis for further studies examining the in-vivo pathogenesis and prevention of BRONJ.

Nonfatal sport-related craniofacial fractures: characteristics, mechanisms, and demographic data in the pediatric population.

BACKGROUND: Few reports exist on sport-related craniofacial fracture injuries in the pediatric population. Most patients with craniofacial injuries are adults, and most studies on pediatric sport injuries do not focus specifically on craniofacial fractures. The authors' goal was to provide a retrospective, descriptive review of the common mechanisms of sport-related craniofacial injuries in the pediatric population, identifying the characteristics of these injuries and providing a description of the demographics of this population. METHODS: The study population included children between the ages of 0 and 18 years who were seen in the emergency department at Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center between 2000 and 2005. Of the 1508 patients identified, 167 had injuries caused by sport-related trauma (10.6 percent). RESULTS: After evaluation in the emergency department, 45.5 percent were hospitalized, and 15.0 percent of these were admitted to the intensive care unit. The peak incidence of sport-related injuries occurred between the ages of 13 and 15 years (40.7 percent). Nasal (35.9 percent), orbital (33.5 percent), and skull fractures (30.5 percent) were most common, whereas fractures of the maxilla (12.6 percent), mandible (7.2 percent), zygomaticomaxillary complex (4.2 percent), and naso-orbitoethmoid complex (1.2 percent) were observed less frequently. Baseball and softball were most frequently associated with the craniofacial injuries (44.3 percent), whereas basketball (7.2 percent) and football (3.0 percent) were associated with fewer injuries. The most common mechanisms of injury were throwing, catching, or hitting a ball (34.1 percent) and collision with other players (24.5 percent). CONCLUSION: These data may allow targeted or sport-specific craniofacial fracture injury prevention strategies.