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Recombinant human bone morphogenetic protein 2 (rhBMP-2) is used clinically to enhance implant-mediated bone regeneration. However, there are risks associated with the high rhBMP-2 dose that is required in the implant to mitigate diffusional loss over the therapeutic timespan. On-demand, localized control over delivery of rhBMP-2, days after implantation, would therefore be an attractive solution in the area of bone repair and reconstruction, yet this has posed a significant challenge, with little data to support in vivo efficacy to date. To address this, we have developed novel liposome-rhBMP-2 nanocomplexes that release rhBMP-2 in response to non-thermogenic, clinical diagnostic ultrasound exposure. In vitro validation shows that rhBMP-2 release is in proportion to applied ultrasound pressure and duration of exposure. Moreover, here we show in vivo validation of this ultrasound-triggered rhBMP-2 delivery system in a standard mouse bone regeneration model. Implanted into hindleg muscles, the liposome-rhBMP-2 nanocomplexes induced local bone formation only after ultrasound exposure. Such post-implantation control of delivery has potential to improve the safety, efficacy and cost of rhBMP-2 use in bone reconstruction. Furthermore, this first proof-of-concept demonstration of in vivo efficacy for ultrasound-triggered liposomal delivery of rhBMP-2 has broader implications for tunable delivery of a variety of drugs and biologics in medicine and tissue engineering., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Purpose: Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is a severe but extremely rare complication of prolonged treatment with bisphosphonates (BPs). Improper treatment or misdiagnosis can have serious repercussions. In some cases, the treatment of BRONJ can require jaw resection, prolonged use of antibiotics, and long hospitalizations. This study aimed to measure the awareness of dentists in the Province of Ontario, Canada about BRONJ and to identify any gaps in their knowledge of the condition and its treatment. In particular, the study aimed to answer questions about the dentists' knowledge of the current guidelines and their opinions and practices related to performing surgical dental procedures in patients taking BPs., Materials and Methods: The study involved sending a Web-based questionnaire to a random sample of dentists in Ontario, Canada (n = 1,579). Information about their awareness of BPs, their experiences treating patients presenting with ONJ, their experiences with different surgical procedures in patients taking intravenous or oral BPs, and their awareness of the BRONJ guidelines suggested by the American Association of Oral and Maxillofacial Surgeons was collected., Results: A response rate of 30% was achieved. Sixty percent of responding dentists had a good knowledge of BP and BRONJ; however, only 23% followed the guidelines for surgical treatment of a patient taking BPs, and 63% would refer patients if they were taking BPs. Approximately 50% of responding Ontario dentists were not comfortable treating patients with BRONJ at their current knowledge., Conclusion: The finding shows that although 60% of Ontario general dentists and specialists have a good knowledge about BRONJ, most are not comfortable performing oral surgery in patients taking BPs. Those who are comfortable have higher knowledge scores, suggesting greater educational efforts should be made to promote the knowledge of dentists regarding BP, ONJ, and BRONJ., (Copyright © 2015 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: The aims of this study were to 1) calculate rates for maxillofacial (MF) injury-related visits in emergency departments (EDs) and hospitals in Ontario, Canada, 2) identify and rank common causes for MF injuries, 3) investigate the variation and trends in MF injuries according to gender, age, and socioeconomic status, and 4) describe the geographic distribution of MF injuries., Materials and Methods: An 8-year retrospective study design was implemented. The Discharge Abstract Database and the National Ambulatory Care Reporting System datasets were used. After examining demographic and diagnostic information, frequencies, percentages, and rates were calculated. Color-coded maps were created using ArcGIS to display the geographic distribution of MF injuries., Results: From 2004 through 2012, 1,457,990 ED visits and 41,057 hospitalizations occurred as a result of MF injury in Ontario. The mean age of patients for each ED visit was 30.6 years and for each hospitalization was 52.6 years. Rates of ED visits and hospitalizations owing to MF injury show a slight decrease during the 8-year period. MF injuries were most frequent in the evening, during the weekends, and during the summer. Falls were reported as the leading cause of MF injuries. Rural areas had higher rates of ED visits and hospitalizations., Conclusions: This study highlighted the public health impact of MF injuries, offering policy makers important epidemiologic information, which is fundamental to formulate and optimize measures aimed at protecting Canadians from injuries that are largely predictable and preventable. Future injury prevention programs should enhance the population-based approach and focus on high-risk groups such as male youth and elderly women in low-income families., (Copyright © 2015 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Calcium phosphate ceramics such as hydroxyapatite (HA) and biphasic calcium phosphates are used clinically to repair bone defects. These calcium phosphate ceramics can differ by composition, structure, and rate of degradation. This study compared 3 calcium phosphate ceramics, 2 of which have similar structure but different composition: 100% HA (algae derived) and HA/β-tricalcium phosphate (β-TCP) 20/80 (algae derived), and 2 with different structure but similar composition: HA/β-TCP 20/80 (algae derived) and HA/β-TCP 15/85 (synthetic). Calcium phosphate ceramics can be difficult to handle and contour during the surgeries. To improve handling, Poloxamer 407 (P407) was added to the 3 ceramics, and its effect on bone healing was also assessed. Bilateral calvarial defects created in the parietal bones of New Zealand white rabbits were left unfilled or were filled with autograft or one of the ceramics, with and without P407. Six weeks after operation, healing was evaluated qualitatively by histology and quantitatively by micro-computed tomography analysis and histomorphometry. All 3 calcium phosphate ceramics demonstrated osteoconductivity and performed similarly in supporting new bone formation, suggesting that the differences in their composition, structure, or degradation did not significantly affect their ability to promote bone healing in this application. Incorporating P407 did not impede osteoconductivity as HA and biphasic calcium phosphate combined with P407 performed similarly as when used alone for craniofacial defect repair.

To date, there is no objective or reliable means of assessing the severity of degenerative joint disease (DJD) and need for joint replacement surgery. Hence, it is difficult to know when an individual with DJD has reached a point where total arthroplasty is indicated. The purpose of the present study is to determine whether serum levels of Alpha-2 HS-glycoprotein (AHSG) as well as bone morphogenetic proteins (BMP-2, 4, 7) can be used to predict the presence of severe DJD of the hip and/or temporomandibular joint (TMJ) (specifically: joints that require replacement). A total of 30 patients scheduled for arthroplasty (diseased) (15 HIP, 15 TMJ) and 120 age-matched controls (healthy/non-diseased) were included. Blood samples were collected from all patients ≥8 weeks after the last arthroplasty. Concentrations of serum analytes were measured using enzyme-linked immunosorbent assays, and these were compared between the Diseased and Healthy groups, utilizing the Mann-Whitney U-test. Patients with disease had significantly higher levels of BMP-2 and BMP-4 and lower levels of AHSG in serum compared to non-diseased humans (p < 0.01). Higher levels of BMP-2, 4 and reduced levels of AHSG appear to characterize patients who have DJD that is severe enough to require total joint replacement. Perhaps measurements of these proteins can be used to make objective decisions regarding the need for total arthroplasty as opposed to the current subjective approaches., (Copyright © 2012 Orthopaedic Research Society.)

Proteolytic cleavage of precursor bone morphogenetic protein (proBMP) is an important step in generating the active mature BMP. ProBMP-2 contains two proprotein convertase (PC) recognition sites (S1 and S2) and is postulated to be cleaved by PCs at those sites. Cell lines expressing proBMP-2, with a silenced S1 site (mS1) that inhibited PC cleavage, secreted the 20-kDa form BMP-2, while cells expressing wild type (wt) BMP-2 secreted 18- and 20-kDa mature BMP-2 N-terminal isoforms. The mS1 cells secreted 15-fold more mature BMP-2 than the wt, despite their similar mRNA levels. Mutant-secreted BMP-2 demonstrated biological activity in vitro; however, its activity was reduced compared with wt. These data demonstrate that proBMP-2 can be cleaved at an alternative cleavage site without prior S1 site cleavage in cell lines overexpressing BMP-2 and more importantly suggest that the presence of the 2-kDa linker peptide can affect activity and secretion of the mature protein.

To improve recombinant human bone morphogenetic protein-2 (rhBMP-2) yield, cell lines stably expressing hBMP2 were cultured in the presence of polyarginine peptide IND-1 and showed up to 6-fold increase in the yield of mature BMP-2. Repeated addition of IND-1 to cell cultures consistently improved BMP-2 yields over 53 days without affecting cell growth and viability. Investigation of its mechanism of action showed that IND-1 inhibited pro-protein convertase (PC) activity when incubated with cell lysates. However, when intact cells were cultured with IND-1, no change in cellular PC activity was observed. Furthermore, knockdown of furin (a prototypical member of the PCs) in cells did not affect their BMP-2 yields, suggesting furin/PC inhibition is unlikely the mechanism by which IND-1 enhances BMP-2 yields. IND-1 as a medium additive thus enhances BMP-2 production in mammalian cell expression systems.

The aim of this study was to observe the osteogenic activity of native bone morphogenetic proteins (BMPs) obtained from different species including bovine, ostrich and emu sources in order to compare mammalian and avian BMPs. Rat mesenchymal progenitor marrow stromal cells and pre-osteoblastic C2C12 cell cultures, were exposed to the native BMPs and alkaline phosphatase (ALP) and creatine kinase (CK) levels were determined by assay. The results showed that the ALP activity in C2C12 cultures was elevated by bovine BMP by 2- to 10-fold (p < 0.05-0.001) from day 3 during 14 days. There were no significant differences in avian BMP related elevations of ALP activity except with ostrich BMPs at day 14 (p < 0.05). However, exposure of MSCs cultures to BMPs derived from bovine, ostrich or emu sources resulted in elevated ALP from day 3 (p < 0.05). Bovine BMP resulted in more ALP elevation than with either of the avian BMPs. All of BMPs elevated Creatine kinase (CK) activity from day 1 and climbed until peaking at day 7. Compared with control cultures, CK was elevated more with exposure to emu BMP and was more elevated with greater statistical significance than with bovine and ostrich BMP before day 5. These higher levels remained until day 14 (p < 0.05). The results of this study suggest that both bovine and avian BMPs are able to stimulate osteogenesis in mature osteoblasts in vitro. The strongest synergistic effect on osteogenesis was detected in cells stimulated with bovine BMP. Avian BMPs had lower effects on ALP and CK activity, emu BMP being more effective than ostrich BMP., (Copyright © 2011 Wiley Periodicals, Inc.)

Objective: Osteonecrosis of the jaw (ONJ) in association with use of bisphosphonate (BP) has been described primarily in cancer patients receiving high-dose intravenous BP. The frequency of the condition in patients with osteoporosis appears to be low. We evaluated the frequency of BP-associated ONJ in Ontario in the cancer population and in those receiving BP for osteoporosis and metabolic bone disease., Methods: A survey developed by representatives of the Ontario Society of Oral and Maxillofacial Surgeons was mailed to Ontario oral and maxillofacial surgeons (OMFS) in December 2006, asking oral surgeons to provide information on cases of ONJ seen in the previous 3 calendar years (2004 to 2006). OMFS were subsequently contacted by telephone if they had not responded or if they had reported cases of ONJ. The frequency of ONJ in association with BP use was estimated from the number of patients with filled prescriptions for BP in Ontario between 2004 and 2006. The cumulative incidence of ONJ was calculated separately for patients using intravenous (IV) BP for cancer treatment and for patients using oral or IV BP for osteoporosis or other metabolic bone disease., Results: Between 2004 and 2006, 32 ONJ cases were identified. Nineteen patients received IV BP for cancer treatment and 13 patients received oral or IV BP for osteoporosis or metabolic bone disease. Over a 3-year period the cumulative incidence of BP-associated ONJ was 0.442% of cancer patient observations (442 per 100,000) and 0.001% of osteoporosis or other metabolic bone disease observations (1.04 per 100,000). The relative risk of low dose IV/oral BP-associated ONJ was 0.002 (95% CI 0.001, 0.005) compared to high-dose IV BP. Other risk factors for ONJ were present in all cases in whom detailed assessment was available. The median duration of exposure to BP was 42 months (range 36 to 120 mo) and 42 months (range 11 to 79 mo) in osteoporosis patients and cancer patients, respectively., Conclusion: Over a 3-year period, the cumulative incidence for BP-associated ONJ was 0.442% of cancer patient observations (442 per 100,000) and 0.001% of osteoporosis or metabolic bone disease observations (1.04 per 100,000). This study provides an approximate frequency of BP-associated ONJ in Canada. These data need to be quantified prospectively with accurate assessment of coexisting risk factors.

This study aimed to analyze the expression of bone matrix proteins and CD31 by immunohistochemistry after maxillary sinus grafting with different bioimplants in a rabbit model. Rabbit demineralized bone matrix (DBM), partially purified bovine bone morphogenetic proteins (BMP), a mixture of BMP with DBM (BMP/DBM), or particulated autogenous bone was grafted into the maxillary sinuses of 42 rabbits. Animals were sacrificed at 2 and 8 weeks. Immunohistochemistry was used to investigate the expression of type 1 collagen (COL1), osteonectin (ON), osteocalcin (OC), bone sialoprotein (BSP), osteopontin (OPN), and CD31. Sinuses grafted with BMP were filled with trabeculae of woven bone that was strongly immunoreactive for COL1, OC, ON, and BSP. BMP/DBM showed strongly positive immunoreactivity for these proteins within the newly formed bone, but weak immunoreactivity in the DBM particles. Immunoreactivity for COL1, OC, ON, and BSP in DBM sinuses was only seen in the osteoblasts rimming the grafted bone particles. The staining of autogenous bone graft sinuses was similar to those grafted with DBM. OPN staining was detected in autogenous bone graft, BMP/DBM, and BMP bioimplants. CD31 staining was strongest in BMP and BMP/noncollagenous matrix proteins sinuses. These results suggest that exogenous BMP enhances not only osteogenesis but also angiogenesis, an important part of bone repair., (Copyright © 2010 Wiley Periodicals, Inc.)

Objective: This study compared the healing of 2 laser ablation units, erbium YAG and femtosecond lasers versus conventional mechanical cutting with carbide and diamond drills to explore future applications for bone surgery. The effects of laser or mechanical ablation combined with rhBMP-7 were also investigated., Methods and Materials: Following defect standardization, a full-thickness circular defect was created on the parietal bones of 160 mice divided into 4 groups: carbide drill, diamond drill, erbium YAG laser, and femtosecond laser. Each of the 4 ablation groups was treated with and without BMP 7. Hard tissue healing was assessed using microcomputerized tomography at 3 and 12 weeks postsurgical time points., Results: The femtosecond laser created wounds that showed slightly delayed bone healing during the observation period when compared with mechanical drilling, although the difference was not statistically significant. The Er:YAG laser showed a healing rate similar to that of the mechanically ablated groups. When BMP 7 was added to the surgical sites, bone wound closure occurred at a similar rate in all test groups., Conclusions: The femtosecond and Er:YAG lasers are 2 laser modalities suitable for bone ablation that are comparable to mechanical instrumentation in terms of bone healing. This study suggested that BMP-7 may be used to enhance bone healing with success regardless of the ablative modality used, whether laser or mechanical drilling., (Copyright © 2010 Mosby, Inc. All rights reserved.)

Objectives: Recent research has focused on application of growth factors such as bone morphogenetic proteins (BMPs) as alternatives to autogenous bone grafting. Two bone graft substitute bioimplants containing recombinant human BMPs (rhBMPs), Infuse (rhBMP-2) and OP-1 (rhBMP-7), are approved for human application but have never been compared side by side. The aim of this study was to provide a direct comparison of the osteoinductive activity of the 2 commercially available and approved rhBMP-containing bioimplants in their clinically available forms., Study Design: The activity of rhBMP-2 and -7 in solution were compared in vitro using the C2C12 cell-based assay. The activity of Infuse and OP-1 bioimplants containing 52.5 microg of rhBMP-2 or rhBMP-7, respectively, were compared in vivo using a mouse muscle pouch assay and analyzed by microscopic CT (microCT) and histology., Results: The in vitro results showed that rhBMP-2 stimulated greater alkaline phosphatase production than rhBMP-7 over various time points and concentrations. The in vivo results showed that OP-1 induced greater bone volume than Infuse. Both implants induced bone of equivalent quality based on microCT and histologic evaluation., Conclusion: In their clinically available forms, the rhBMP-7-containing OP-1 induced greater bone volume than the rhBMP-2-containing Infuse in the mouse muscle pouch model., (Copyright 2010 Mosby, Inc. All rights reserved.)

Objectives: The aims of this study were to test whether or not the application of an in situ-formed synthetic polyethylene glycol hydrogel (PEG) used as a biodegradable membrane for guided bone regeneration with a variety of graft materials and ambient oxygen or hyperbaric oxygen (HBO) environments would result in enhanced bone regeneration, and to observe the histologic and histomorphometric aspects of bone healing of the calvarial defects with and without a PEG membrane., Study Design: Thirty adult, skeletally mature, male New Zealand white rabbits were randomly divided into 3 groups of 10 animals each. Bilateral 15-mm-diameter critical-size defects were created in the parietal bones of each animal. Group 1 served as a control with unfilled bilateral calvarial defects, group 2 had bilateral calvarial defects filled with morcelized autogenous calvarial bone, and group 3 had bilateral calvarial defects filled with a biphasic calcium phosphate ceramic. One of the calvarial defects was randomly protected with a PEG resorbable liquid membrane in each animal. Five animals from each group underwent a course of HBO treatment (2.4 ATA 100% oxygen for 90 minutes 5 days a week for 4 weeks) and the other 5 served as control and did not receive any supplemental oxygen (normobaric). The animals were killed 6 weeks after their surgery, and their parietal bones were harvested. The specimens were analyzed with microscopic computerized tomography (microCT) scans and histomorphometrics., Results: The unfilled normobaric control bony defects did not heal, proving the critical-size nature of these defects. The presence of autogenous bone or bone ceramic in the defects increased the bone volume fraction and bone mineral density of the defects (P < .001). The presence of a membrane in the ungrafted and autogenous bone grafted defects resulted in a decrease in the corrected bone volume fraction (P = .002) but not in the bone ceramic grafted defects (P = .580). Bony healing of defects where the membrane was unsupported was compromised; the membrane did not maintain the desired bone regeneration volume with the unfilled and autogenous bone grafted groups. The PEG resorbable liquid membrane worked best with the bone ceramic material. HBO did not ameliorate the healing of the autogenous bone graft or ceramic filled defects in the 6-week time period of this study., Conclusions: Although the PEG resorbable liquid membrane is easy to use and forms an occlusive layer, caution is recommended when using the membrane over an unsupported defect. HBO did not ameliorate bony healing with the membrane at the early 6-week time point. The authors recommend future assessment with HBO at the 12-week time point., (Copyright 2010 Mosby, Inc. All rights reserved.)

Objectives: The aim of this study was to assess the possible effect of hyperbaric oxygen (HBO) on the healing of critical-sized defects that were grafted with demineralized bone matrix (DBM) combined with Pluronic F127 (F127) to form a gel or putty, or a commercially available biphasic calcium phosphate (BCP), mixed either with blood or F127 to form a putty., Study Design: Twenty New Zealand White rabbits were randomly divided into 2 groups of 10 animals each. Bilateral 15-mm calvarial defects were created in the parietal bones of each animal, resulting in 40 critical-sized defects. Group I defects were grafted with either DBM putty or DBM gel. Group II defects were grafted with either BCP or BCP putty. Five animals from each group received HBO treatment (100% oxygen, at 2.4 ATA) for 90 minutes per day 5 days a week for 4 weeks. The other 5 animals in each group served as a normobaric (NBO) controls, breathing only room air. All animals were humanely killed at 6 weeks. The calvariae were removed and analyzed by micro computed tomography (mCT) and histomorphometry., Results: mCT analysis indicated a higher bone mineral content (BMC, P < .05), bone volume fraction (BVF; P < .001), and bone mineral density (BMD; P < .001) of the defects grafted with BCP rather than DBM. Furthermore, the voxels that were counted as bone had a higher tissue mineral density (TMD) in the BCP- than in the DBM-filled defects (P < .001). Histologically complete bony union over the defects was observed in all specimens. Histomorphometric analysis showed that DBM-filled defects had more new bone (P < .007) and marrow (P < .001), and reduced fibrous tissue compared with the BCP defects (P < .001) under NBO conditions. HBO treatment reduced the amount of fibrous tissue in BCP filled defects (P < .05), approaching levels similar to that in matching DBM-filled defects. HBO also resulted in a small but significant increase in new bone in DBM-grafted defects (P < .05)., Conclusion: Use of DBM or BCP promoted healing in these critical-sized defects. Hyperbaric oxygen therapy resulted in a slight increase in new bone in DBM-grafted defects and much larger reduction in fibrous tissue and matching increases in marrow in BCP-grafted defects, possibly through increased promotion of angiogenesis., (Copyright 2010 Mosby, Inc. All rights reserved.)

Lemierre syndrome, which can result from a recent oropharyngeal or odontogenic infection, is characterized by clinical or radiographic signs of thrombosis of the internal jugular vein, distant infected emboli and the presence of anaerobic pathogens, usually Fusobacterium necrophorum. The septic emboli resulting from the infected thrombophlebitis of the internal jugular vein give the syndrome its constellation of central nervous system, pulmonary and many other manifestations including septic shock. This condition was so rare that, historically, it became known as the "forgotten disease," but an increasing frequency of reports indicates that Lemierre syndrome may not be so uncommon.

Objective: To evaluate the effectiveness of various bioimplants used for augmentation of the maxillary sinus floor by means of a rabbit model., Materials and Methods: Bone was harvested from the posterior iliac crest of 40 adult New Zealand white rabbits to allow bilateral augmentation of the floor of the maxillary sinus with autogenous bone or other materials. One of the following was grafted to the maxillary sinus of each rabbit: particulated autogenous bone, demineralized bone matrix (DBM), DBM combined with purified bone morphogenetic protein (BMP-DBM bioimplants) and bioimplants consisting of a poloxamer gel with BMP in 1 of 2 different doses. Animals were sacrificed at 2 or 8 weeks. Histologic examination was used to assess biologic healing in the various samples. Histomorphometry was used to demonstrate and quantify bone formation., Results: After 2 weeks, the BMP-containing bioimplants had produced more new bone than any of the other materials. Particulated autogenous bone grafts produced less new bone initially (after 2 weeks), but the amount of bone produced by these grafts gradually increased, to levels comparable to the BMP-containing bioimplants by 8 weeks. For groups in which the poloxamer gel was used as a carrier for BMP or where BMP was used in combination with DBM, the amount of bone generated by 8 weeks was similar to that produced by autogenous bone., Conclusion: The rabbit maxillary sinus model allowed evaluation of multiple types of bioimplants that could be suitable for peri-implant maxillary reconstruction. BMP-containing bioimplants demonstrated promise as alternatives to autogenous bone grafts for sinus-augmentation procedures. These bioimplants had more rapid initial bone production than all other materials, including autogenous bone. In the future, such biomaterials may enable earlier placement of dental implants into augmented maxillary sinuses.

This study investigated the potential use of platelet-rich plasma (PRP) in conjunction with mRNA expression of bone matrix proteins using bioassay and RT-PCR comparing bovine bone morphogenetic proteins (BMP), recombinant human BMP-4 (rhBMP-4) during rat bone marrow stromal cell (Mesenchymal Stem Cell) differentiation at 14 days. The results showed that all three growth factors were associated with significantly elevated alkaline phosphatase activity. PRP and bovine BMP resulted in increased protein content. The mRNA of type I collagen was expressed with all three growth factors and remained consistently elevated. Osteopontin was observed with PRP from days 1 to 7; bone sialoprotein expression was detected on days 1 and 3. PRP, bovine BMP and rhBMP-4 enhanced the steady-state expression of PDGF-A as time-dependent to day 14 and in PRP was the strongest. PTHr was expressed at days 1 and 5. Vascular endothelial growth factor expression was the most highly expressed after day 3. These findings suggest that PRP increases mRNA expression of bone matrix protein, enchances osteogenesis and angiogenesis in vitro.

Objective: To study the expression of bone matrix protein (BMP) induced by bovine bone morphogenetic proteins (BMPs) in vitro., Methods: Type I collagen, osteopontin (OPN), osteonectin (ON), osteocalcin (OC), and bone sialoprotein (BSP) were detected by immunohistochemistry in C2C12 cultured from day 1 to day 28., Results: The signaling of bone matrix protein expression became weaker except for type I collagen, OC and BSP after 5 days. Fourteen days after culture, the positive signaling of type I collagen, OPN, ON, OC, and BSP was gradually declined, and could be detected significantly as compared with that of the negative control on day 28. BMP assay showed that the alkaline phosphatase (ALP) activity was higher in C2C12 culture than in the control during the 14-day culture. Also, total protein and DNA significantly increased during the 14-day culture. High levels of ALP were seen in preosteoblasts and osteoblasts in vivo and in differentiating osteoblasts in vitro. ALP was well recognized as a marker reflecting osteoblastic activity., Conclusion: Native bovine BMP induces conversion of myoblasts into osteoblasts, produces type I collagen, and plays significantly role in osteoinduction and bone matrix mineralization of C2C12 in vitro.

In 2003, the first reports describing osteonecrosis of the jaw (ONJ) in patients receiving bisphosphonates (BP) were published. These cases occurred in patients with cancer receiving high-dose intravenous BP; however, 5% of the cases were in patients with osteoporosis receiving low-dose bisphosphonate therapy. We present the results of a systematic review of the incidence, risk factors, diagnosis, prevention, and treatment of BP associated ONJ. We conducted a comprehensive literature search for relevant studies on BP associated ONJ in oncology and osteoporosis patients published before February 2008.All selected relevant articles were sorted by area of focus. Data for each area were abstracted by 2 independent reviewers. The results showed that the diagnosis is made clinically. Prospective data evaluating the incidence and etiologic factors are very limited. In oncology patients receiving high-dose intravenous BP, ONJ appears to be dependent on the dose and duration of therapy, with an estimated incidence of 1%-12% at 36 months of exposure. In osteoporosis patients, it is rare, with an estimated incidence < 1 case per 100,000 person-years of exposure. The incidence of ONJ in the general population is not known. Currently, there is insufficient evidence to confirm a causal link between low-dose BP use in the osteoporosis patient population and ONJ. We concluded BP associated ONJ is associated with high-dose BP therapy primarily in the oncology patient population. Prevention and treatment strategies are currently based on expert opinion and focus on maintaining good oral hygiene and conservative surgical intervention.

Objectives: This study was undertaken to evaluate the effect of hyperbaric oxygen (HBO) on the repair of critical-sized defects in the presence and absence of a nonvascularized autogenous bone graft., Study Design: Ten New Zealand White rabbits were randomly divided into 2 groups of 5 animals each. Bilateral 15-mm calvarial defects were created in the parietal bones of each animal, resulting in 20 critical-sized defects. Autogenous bone grafts (ABG) were allocated to the left or right defect of each animal. Group 1 received HBO treatment at 2.4 ATA 100% oxygen for 90 minutes per day 5 days a week for 4 weeks. Group 2 served as a normobaric (NBO) control, breathing only room air. The animals in each group were humanely killed at 6 weeks. Calvaria were analyzed by micro-CT and histomorphometry., Results: Micro-CT analysis indicated that as expected there was a higher bone mineral density (BMD) and bone mineral content (BMC) in ABG than unfilled defects (P < .05). However, there was a significant decline in the bone mineral content (BMC) of HBO-treated grafted defects compared to NBO-treated grafted defects (P < .05). Histologically complete bridging of the defect was observed in both NBO and HBO ABG grafted defects. Histomorphometic analysis showed that HBO treatment increased new bone and marrow, and reduced fibrous tissue in the defects (P < .01 for all). Examination of residual graft showed a near significant reduction in residual graft volume (11.2 +/- 4.7 versus 19.1 +/- 7.7, HBO versus NBO P = .085) in the HBO group. The use of a graft increased new bone and marrow in the NBO group (P < .001 for both); however, in the HBO-treated animals the differences between grafted and ungrafted were not significant., Conclusion: HBO enhances bony healing in ungrafted rabbit calvarial critical-sized defects and may increase the rate of residual graft resorption in autogenous bone-grafted defects.

Objective: To investigate the potentially useful of platelet-rich plasma (PRP) on mRNA expression of angiogenesis., Study Design: Adjunct assay and reverse-transcription polymerase chain reaction (RT-PCR) analysis of type I collagen, vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF) in rat bone marrow stromal cells differentiation in 14 days' culture., Results: The PRP significantly elevated alkaline phosphatase activity after day 5 (P < .05), and DNA and protein content increased at culture days 1, 3, and 5 (P < .01) with PRP compared with control. The RT-PCR demonstrated that type I collagen was expressed in all substrates and remained high with PRP during 14 days of culture, and that mRNA expression of VEGF and PDGF were higher over time., Conclusions: This study indicates a potential contribution of PRP as possibly starting the process of angiogenesis, recruiting the endothelial cells which line blood vessels, and beginning the initiation of bone regeneration.

Objective: Following publication of the first reports of osteonecrosis of the jaw (ONJ) in patients receiving bisphosphonates in 2003, a call for national multidisciplinary guidelines based upon a systematic review of the current evidence was made by the Canadian Association of Oral and Maxillofacial Surgeons (CAOMS) in association with national and international societies concerned with ONJ. The purpose of the guidelines is to provide recommendations regarding diagnosis, identification of at-risk patients, and prevention and management strategies, based on current evidence and consensus. These guidelines were developed for medical and dental practitioners as well as for oral pathologists and related specialists., Methods: The multidisciplinary task force established by the CAOMS reviewed all relevant areas of research relating to ONJ associated with bisphosphonate use and completed a systematic review of current literature. These evidence-based guidelines were developed utilizing a structured development methodology. A modified Delphi consensus process enabled consensus among the multidisciplinary task force members. These guidelines have since been reviewed by external experts and endorsed by national and international medical, dental, oral surgery, and oral pathology societies., Results: RECOMMENDATIONS regarding diagnosis, prevention, and management of ONJ were made following analysis of all current data pertaining to this condition. ONJ has many etiologic factors including head and neck irradiation, trauma, periodontal disease, local malignancy, chemotherapy, and glucocorticoid therapy. High-dose intravenous bisphosphonates have been identified as a risk factor for ONJ in the oncology patient population. Low-dose bisphosphonate use in patients with osteoporosis or other metabolic bone disease has not been causally linked to the development of ONJ. Prevention, staging, and treatment recommendations are based upon collective expert opinion and current data, which has been limited to case reports, case series, surveys, retrospective studies, and 2 prospective observational studies., Recommendations: In all oncology patients, a thorough dental examination including radiographs should be completed prior to the initiation of intravenous bisphosphonate therapy. In this population, any invasive dental procedure is ideally completed prior to the initiation of high-dose bisphosphonate therapy. Non-urgent procedures are preferably delayed for 3 to 6 months following interruption of bisphosphonate therapy. Osteoporosis patients receiving oral or intravenous bisphosphonates do not require a dental examination prior to initiating therapy in the presence of appropriate dental care and good oral hygiene. Stopping smoking, limiting alcohol intake, and maintaining good oral hygiene should be emphasized for all patients receiving bisphosphonate therapy. Individuals with established ONJ are most appropriately managed with supportive care including pain control, treatment of secondary infection, removal of necrotic debris, and mobile sequestrate. Aggressive debridement is contraindicated., Conclusion: Our multidisciplinary guidelines, which provide a rational evidence-based approach to the diagnosis, prevention, and management of bisphosphonate-associated ONJ in Canada, are based on the best available published data and the opinion of national and international experts involved in the prevention and management of ONJ.

Infective endocarditis is a rare but life-threatening microbial infection of the heart valves or endocardium, most often related to congenital or acquired cardiac defects. The American Heart Association (AHA) recently updated its recommendations on prophylaxis during dental procedures. The revisions will have a profound impact on both the patient and the dental practitioner. The purpose of this paper is to review the pathogenesis and clinical presentation of infective endocarditis and discuss the 2007 AHA guidelines and their implications for dentists.

Background: Hyperbaric oxygen therapy (HBO) promotes osseous healing, however the mechanism by which this occurs has not been elucidated. HBO may promote angiogenesis, which is vital for bone healing. Vascular endothelial growth factor (VEGF) is one of the key factors that stimulates angiogenesis., Objective: The objective of this study was to investigate whether HBO altered VEGF expression during bone healing., Methods and Materials: Archived samples from calvarial defects of rabbits exposed to HBO (2.4 ATA, 90 minutes a day, 5 days a week for 4 weeks) and normobaric oxygen controls (NBO) were analyzed by immunohistochemistry., Results: VEGF expression in 6-week HBO samples was elevated compared to NBO (P = .012). Staining of the 12-week HBO samples was reduced compared to 6-week HBO (P = .008) and was similar to 6- and 12-week NBO control samples., Conclusion: HBO therapy resulted in increased VEGF expression in the defects even 2 weeks after the termination of treatment (6 weeks postsurgery).

Purpose: The limitations and morbidity associated with autogenous bone grafting have driven the search for predictable bone substitutes and bioimplants. A novel method of reconstruction was tested in this case series., Materials and Methods: Ten patients with major mandibular defects following resection of biopsy-proven ameloblastoma lesions or osteomyelitis of the mandibular body or ramus were included in this study. The resection defects were spanned with rigid reconstruction plates to hold the remaining mandibular segments in the correct position. The defects were filled with a bioimplant containing bone morphogenetic protein-7 (BMP-7) in a demineralized bone matrix (DBM) suspended in a reverse-phase medium to effect sustained BMP delivery., Results: The postoperative course for all 10 patients was uneventful. Radiographic evidence of mandibular bone formation was found in all cases. At the end of 1 year, functional and esthetic reconstruction of the mandible was complete., Conclusion: Bioimplants containing BMP-7 in DBM suspended in a reverse phase medium were successful in restoring major mandibular defects in nonirradiated beds in this series of 10 patients.

Calcium phosphates like hydroxyapatite (HA), beta-tricalcium phosphate (beta-TCP), and their mixtures (biphasic calcium phosphates; BCP) are used clinically to repair bone defects. These materials can be difficult to handle and have no inherent biological activity. Handling properties of other bone substitute materials have been improved by combining them with an inert carrier such as Pluronic F-127 (Pluronic, BASF, Mt. Olive, NJ), while the addition of bone morphogenetic proteins (BMP) with such implants has also been shown to enhance bone repair. This study assessed the impact of adding Pluronic and BMPs to an HA (C-Graft) or a BCP (80/20 HA/beta-TCP ratio; Algisorb) implant's ability of promote bony repair in the rabbit calvarial defect model.Twenty-five New Zealand white rabbits were divided into 5 groups of 5 animals each. Bilateral calvarial defects were made in the parietal bones of each animal. HA or BCP alone or combined with Pluronic and/or BMP were implanted into the defect sites. Animals were euthanized at 6 weeks, postoperatively. Bone regeneration was evaluated quantitatively by histomorphometry. The amount of bone regeneration, which occurred in defects containing HA and BCP, was similar over the time period studied. Incorporating Pluronic increased handling and moldability without compromising osteoconductivity of either calcium phosphate. The addition of BMP significantly increased the amount of new bone formed with all calcium phosphates studied (P < 0.05). These results suggest that Pluronic can be added to calcium phosphates to enhance handling and moldability without any negative effects on their biocompatibility and that healing can be enhanced with the incorporation of BMPs.

Osteopetrosis is one cause of osteosclerosis and may result in such serious oral complications as osteomyelitis and exposed necrotic bone. Dentists should be aware of patients with the disease because of its effect on osteoclast function, which results in impaired wound healing. The purpose of this paper is to review the causes, pathogenesis and differential diagnosis of osteopetrosis and to provide guidance to dentists on the management of patients with osteopetrosis.

Systemic lupus erythematosus (SLE) is a chronic disease with far-reaching systemic implications. The hallmark feature in SLE is chronic inflammation. It can affect the skin, joints, kidneys, lungs, nervous system, serous membranes such as the pleura and pericardium, mucous membranes and other organs of the body. It is imperative that the dental practitioner be familiar with the broad range of systemic and oral implications, including the clinical and biochemical features of SLE. This review article offers an overview of the multiple organ systems affected by this complex heterogeneous disease process that are most relevant to both the general practitioner and the dental specialist. In particular, ways to recognize and manage the oral and dental manifestations of this systemic illness are presented.

Scleroderma, or progressive systemic sclerosis (PSS), an autoimmune rheumatic condition affecting the connective tissues, has a profound impact on oral health. Common orofacial findings include xerostomia, gastroesophageal reflux disease and limited mouth opening. This review article describes scleroderma, or PSS, and its various manifestations. The features of CREST syndrome and morphea are reviewed. Concerns relevant to the prevention of dental disease and the safe delivery of dental care in this group of challenging patients are emphasized.

Bisphosphonate-associated osteonecrosis (BON) may result in serious oral complications, such as osteomyelitis and chronic exposure of necrotic bone. Dentists must be familiar with this disorder and pay special attention to all patients on bisphosphonate therapy due to their defective osteoclast function and reduced osseous tissue vascularity, leading to impaired wound healing. The purpose of this paper is to review the history and pathogenesis of BON, discuss its differential diagnosis, provide guidance to dentists on possible measures to prevent BON and review the management of patients with BON.

Bioimplants containing bone morphogenetic proteins (BMP) such as demineralized bone matrix (DBM) are used clinically to repair bone defects because of their ability to stimulate bone regeneration. Because of handling issues, DBM granules are often combined with an inert carrier, which reduces the DBM content to 40% or less by volume. Recently, Accell DBM100 (Accell, IsoTis OrthoBiologics, Irvine, CA) has been developed, which uses processed DBM as the carrier, resulting in a DBM content of 100%. The purpose of this investigation was to evaluate the use of Accell for bone defect healing.Forty-two athymic male rats were divided into three groups. Bilateral 5 mm calvarial defects were created in each animal. In group 1, one defect was filled with Accell and the other defect was left unfilled (control). In group 2, one defect was filled with OP-1 putty (recombinant human BMP-7 and type I collagen), and the other was left unfilled. In group 3, one defect was filled with Accell and the other with OP-1. Animals were sacrificed at 4 and 8 weeks, postoperatively. Specimens were analyzed by histomorphometry to evaluate bone regeneration quantitatively. Accell and OP-1 both induced significantly more bone at 4 and 8 weeks compared with the unfilled contralateral defects. OP-1-filled defects produced significantly more total reparative tissue (bone + marrow) compared with Accell (P < 0.01); however, the increase in new bone did not reach significance at either time (P = 0.06 at 4 wk; P = 0.10 at 8 wk). In conclusion, these results suggest that Accell DBM100 will be useful in repairing craniofacial bone defects clinically.

Objective: The purpose of this study was to determine whether orthognathic surgical procedures create significant objective postoperative airway compromise or edema., Study Design: A pilot magnetic resonance imaging (MRI) study was performed on 10 patients undergoing orthognathic surgical procedure to determine the time of maximum postoperative swelling, optimum time for scanning, and the anatomical sites of maximum swelling. Anatomical landmarks within the upper airway were determined. A prospective clinical study was then designed to assess the amount of postoperative airway edema in 40 patients undergoing orthognathic surgical procedure at the Toronto General Hospital. All patients received standard anesthetic and postoperative care. Magnetic resonance imaging scan of the upper airway from the hard palate to the subglottis was performed to assess the cross-sectional areas and volumes 24 to 48 hours postoperatively. The anteroposterior and transverse dimensions of the airway were measured at 3 anatomical points: the hyoid bone, the arytenoid cartilages, and the cricoid cartilage. One staff neuroradiologist assessed all MRI scans., Results: The study group consisted of 24 female and 16 male patients, with a range of 15 to 36 years of age, and a mean of 23 years of age. A total of 56 Le Fort I osteotomies (25 advancements, 27 impactions, and 4 extrusions) and 30 bilateral sagittal split osteotomies (13 advancements, 17 setbacks) were included. Seven patients received single-jaw surgical procedures, 16 patients received double-jaw surgical procedures, and 17 patients received double-jaw as well as chin osteotomies. There was no clinical or radiological evidence of postoperative airway edema in any of the 40 patients irrespective of the type or number of osteotomies performed., Conclusions: Orthognathic surgical procedure involving osteotomies of the maxilla, mandible, and/or chin did not cause significant airway compromise or edema in the 40 patients studied. Once patients undergoing orthognathic surgical procedure fulfill postoperative extubation criteria, they can be safely extubated.

Oral and maxillofacial surgeons offer their patients a wide variety of surgical options that may be classified as major or minor surgery. Complications are part of surgery, but major surgery may lead to life-threatening complications that must be managed by the surgical team. Obtaining iliac graft tissue during oral and maxillofacial reconstruction carries the risk of rare but serious complications, such as deep vein thrombosis and fat embolism syndrome. In this paper we describe the latter postoperative complication experienced by a patient undergoing an otherwise routine major oral and maxillofacial reconstructive procedure. A discussion of the factors that stimulate fat embolism during or following surgical procedures is intended to help surgeons prevent this complication.

Facial cellulitis and swellings of the head and neck are worrisome signs of odontogenic infection, which can be life threatening. Most head and neck infections are caused by bacterial pathogens. When treating such infections, dentists must also be aware of possible viral or fungal causes and their associated presentations. This report documents a case of viral infection that initially resembled a bacterial odontogenic infection. It is intended to familiarize dentists with the Ramsay Hunt syndrome and the need for prompt recognition and early definitive treatment.

Purpose: Coating endosseous dental implants with growth factors such as bone morphogenetic proteins (BMPs) may be one way to accelerate and/or enhance the quality of osseointegration. The purpose of this study was to investigate in the murine muscle pouch model whether sintered porous-surfaced titanium alloy implants coated with BMPs would lead to heterotopic bone formation around and within the implant surface geometry., Materials: Porous-surfaced dental implants were coated with partially purified native human BMPs, with or without a carrier of Poloxamer 407 (BASF Corp., Parsippany, NJ), placed in gelatin capsules and implanted into the hindquarter muscles of mice. Mice were euthanized after 28 days. Sections of retrieved specimens were subsequently prepared for morphometric analysis of bone formation using backscatter electron microscopic images., Results: Human BMPs, either with or without the carrier of Poloxamer 407, led to bone formation within and outside of the sintered porous implant surface. When the sintered implant surface region was subdivided into inner and outer halves, similar levels of bone ingrowth and contact were seen in the 2 halves. Evidence of bone formation to the depth of the solid implant core (i.e., the deepest level possible) also was seen., Discussion and Conclusions: Sintered porous-surfaced dental implants can be used as substrate for partially purified BMPs in the murine muscle pouch model. With the addition of these osteoinductive factors, the porous implant surface supported bone formation within the surface porosity provided, in some instances, all the way to the solid implant core. The addition of growth factors to a sintered porous surface may be an efficient method for altering locally the healing sequence and quality of bone associated with osseointegration of bone-interfacing implants.

This study evaluated the repair of critical-sized cranial vault defects in thirty New Zealand white rabbits using various allogeneic and alloplastic bone substitutes designed to provide mechanical protection to the brain as well as osteoinductivity. The strategies employed included demineralized bone matrix (DBM), a putty used in combination with a rigid resorbable plating system as a protective covering and calcium phosphate cement (CPC) combined with native partially purified bone morphogenetic protein (BMP). Bilateral critical-sized defects measuring 15 mm in diameter were created in the parietal bones of 30 adult male New Zealand white rabbits. They were divided into three groups with ten animals in each. Group 1 had one defect left unfilled as a control while autogenous bone was placed in the defect on the other side. In Group 2 a rigid resorbable copolymer membrane, Lactosorb (Lorenz Surgical, Jacksonville, Florida), was placed over both defects to cover them and protect the underlying tissues. The pericranial aspect of one defect was left unfilled while the other defect was filled with DBM putty. Group 3 had a CPC, Mimix (Lorenz Surgical, Jacksonville, Florida), placed into one of the defects while the defect on the other side was filled with the same CPC in combination with BMP in a concentration of 25 mg/mL. Bone healing was assessed clinically, radiographically, and histomorphometrically. All unfilled controlled defects, the defects covered with the resorbable Lactosorb membrane and those filled with calcium phosphate cement alone, healed with a fibrous scar. Defects reconstructed with DBM putty in combination with the resorbable Lactosorb membrane and calcium phosphate in combination with BMP healed with bone bridging the entire defect. This was obvious radiographically where the defects appeared completely filled with a dense radiopaque tissue. Histological analysis demonstrated that specimens where DBM putty was used in combination with the resorbable Lactosorb membrane had 67.7% new bone fill at 6 weeks and 84.0% at 12 weeks. Resorption of DBM particles was evidenced by the presence of osteoclastic activity and by the significant decrease in the size of the demineralized bone particles. In the calcium phosphate groups where BMP was added to the bioimplant there was 45.8% new bone formation at 12 weeks. The utilization of a composite consisting of DBM with resorbable Lactosorb membrane or a composite of calcium phosphate cement composite with BMP promoted complete closure of critical-sized calvarial defects in New Zealand white rabbits with viable new bone at 12 weeks. The complete bone bridging observed with these composites suggests that they could be used to enhance the protection of intracranial contents following craniofacial surgical procedures.

Dentists may be asked to provide consultations for patients who have sustained trauma to their facial structures. Supraorbital rim fractures, although uncommon, must be recognized and promptly referred to an oral and maxillofacial surgeon or other specialist skilled in the management of facial bone fractures. Supraorbital rim fractures commonly coexist with other craniomaxillofacial injuries, especially with fractures of the anterior table of the frontal sinus. In this article, we review the frequency, management and complications associated with the treatment of supraorbital rim fractures in adults. A series of 5 cases was reviewed; 4 of the 5 patients were male, with a mean age of 21.6 years (range 17-28 years). All injuries involved the supraorbital rim and the anterior table of the frontal sinus and occurred concurrently with other facial injuries. Treatment ranged from conservative observation to open reduction and internal fixation of the fractures. No associated perioperative or postoperative complications occurred. The follow-up ranged from 6 months to 26 years, with satisfactory subjective esthetic outcomes in all cases.

Objective: This study was undertaken to evaluate whether the effects of hyperbaric oxygen (HBO) therapy could alter the critical size for spontaneous healing of a bone defect in the rabbit calvarial model., Study Design: An animal trial of 12 weeks duration was conducted using 20 New Zealand white rabbits, which were randomly divided into 2 groups of 10 animals each. Calvarial defects were created in the parietal bones of each animal bilaterally. Defects were critical-sized, 15 mm on one side and supra-critical-sized, 18 mm on the contralateral side. Group 1 received a 90-min HBO treatment sessions at 2.4 absolute atmospheric pressure (ATA) per day for 20 consecutive days. Group 2 served as a control without any HBO treatment sessions. Five animals in each group were sacrificed at 6 and 12 weeks. Data analysis included qualitative assessment of the calvarial specimens, post-sacrifice radiographs, as well as histomorphometric analysis to compute the amount of regenerated bone within the defects. ANOVA and paired sample t test were used for statistical analysis., Results: Both radiographic analysis and histomorphometric analysis demonstrated that HBO-treated animals had significantly more new bone within their defects compared with the control group (P < .001). There was no statistically significant difference between the percentage of new bone forming in the 15-mm and 18-mm HBO-treated defects. There was no difference between the 6-week and the 12-week HBO-treated groups. HBO is effective in enhancing the bony healing of full thickness critical sized as well as supra-critical-sized defects in the rabbit calvarial model., Conclusion: Bone regeneration was significantly greater in the HBO-treated animals regardless of the defect size. HBO may have increased the diameter of the rabbit critical-sized calvarial defect to more than 18 mm.

Purpose: The aim of this study was to compare recovery for oral surgery patients given a deep sedation regimen of midazolam, propofol, and remifentanil with a standard control of fentanyl in place of remifentanil., Materials and Methods: This investigation was designed as a randomized, prospective, single-blinded controlled study. Group 1, the control, received midazolam 0.03 mg/kg, fentanyl 1 microg/kg, and propofol initially at 140 microg/kg/min. Group 2 received midazolam 0.03 mg/kg, remifentanil: propofol (1:500) given at an initial propofol infusion rate of 40 microg/kg/min. Outcome measures included time to response to verbal command, Aldrete score = 9, Postanesthesia Discharge Scoring System = 7, and assessment by the Digit Symbol Substitution Test., Results: Forty-seven subjects were entered in the study. Baseline findings were homogenous between the 2 groups. Subjects in group 2 recovered earlier (P < .005) and required less propofol for both the induction (0.8 +/- 0.4 versus 1.2 +/- 0.6 mg/kg; mean +/- SD, P < .01) and maintenance of deep sedation (46 +/- 9 versus 131 +/- 17 microg/kg/min; P < .005). There were minor differences in vital signs., Conclusions: This study demonstrated that this remifentanil regimen provided significantly more rapid recovery and used significantly less propofol compared with the fentanyl regimen.

Bone morphogenetic proteins (BMPs) are known to promote osteogenesis, and clinical trials are currently underway evaluating the ability of certain BMPs to promote bone graft and fracture healing. To observe the mechanism of osteoinductive and bone formation, 100 microg of bovine BMP was tested during osteogenic differentiation of rat bone marrow stromal cells (MSCs) and C2C12 line culture for 14 and 28 days. We examined alkaline phosphatase (ALP) by assay, immunohistochemical studies for bone matrix proteins, and mRNA expression of bone matrix proteins and osteoblast-related analysis by reverse-transcription polymerase chain reaction. ALP activity in MSC cultures was elevated by bovine BMP by two to fivefold (P < 0.05-0.001). DNA and protein content increased over 14 days. BMP significantly increased the mRNA expression of type I collagen, ALP, osterix, osteocalcin, osteopontin, vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF)-A, and parathyroid hormone receptor time dependently during the osteoblastic differentiation. There was no markedly enhanced mRNA expression of bone sialoprotein (BSP) and glyceraldehyde-3-phosphate dehydrogenase compared with that of control. Immunohistochemical results also showed BMP increased immunoreactive positivity of type I collagen, osteocalcin, osteonectin, osteopontin, and BSP during the C2C12 differentiation. These data indicated that BMP enhances our ability to stimulate the differentiation of osteoblast-like cells and increases osteoinductivity, bone matrix protein formation and mineralization, angiogenesis, and chondrogenesis during osteoblast progenitor cell differentiation in vitro and that the role of chondrogenic is weak.

Objective: To compare the location and multiplicity of mandibular fractures in Kuwait, Canada and Finland during the 1990s., Subjects and Methods: Data were collected from several hospitals in Kuwait (1991-2000), Toronto General Hospital in Canada (1995-2000) and Oulu University Hospital in Finland (1990-1999). The data were analyzed statistically using chi-square test, ANOVA, t test and logistic regression., Results: Condylar fractures were more common in Finnish patients (41%) than Canadian (35%) or Kuwaiti patients (21%). Condylar fractures caused by falls were about 3.4 times more common in Kuwait and Finland compared to Canada. In Finland the risk of road traffic accidents caused by condylar fracture was about 4 times higher than those caused by other etiologies. In Canada male gender was about 2 times higher for the condylar fracture than female gender. Female patients often had more multiple injuries than men in all three countries and multiple fractures were observed especially in traumas caused by falling., Conclusion: Differences in location and multiplicity of mandibular fractures are due to differences in etiologies and demographic patterns.

We studied causes of mandibular fractures treated in oral and maxillofacial units in three countries in years 1990-2000 in Kuwait (n=596), 1995-2000 in Canada (n=228), and 1990-99 in Finland (n=268). Of the Finnish patients, 27% were women. Corresponding percentages in Kuwait and Canada were 13 and 17%, respectively. Traffic crashes were the cause of injury in 55% of the cases in Kuwait and 33% in Oulu, but only 7% in Toronto. In Kuwait, the victims were often young people, which is why more traffic education, more control of speed, and more control of the use of safety belts should be implemented. Assault was the cause in 54% in Toronto, 12% in Kuwait, and 37% in Oulu. Falling was the cause in 22% of the cases in Kuwait. Alcohol was implicated in 21% of cases in Canada and 15% in Finland.

Objective: To observe the activity of repeated extracts of bone matrix and the production of purified bone morphogenetic proteins (BMPs)., Methods: BMPs were extracted 1- 4 times from fresh bovine cortical bone by the modified Urist's method, with each collected precipitate separated and lyophilized as partially purified BMPs. Another fresh bovine bone was extracted three times and the precipitates were mixed and lyophilized. Meanwhile,the alkaline phosphatase (ALP) activity was measured by an in vitro assay employing cultured C2C12 mouse myoblast cells through the osteoinductivity of bovine BMPs extracted four times at days 1, 4, 7, and 14, and the correlation between BMPs quantities and costing during extraction processes was analyzed., Results: The BMPs purified and the cost showed a positive correlation (r=0.969). To separate and lyophilize each collected precipitate as partially purified BMPs raised the cost, and mixed precipitates also cost much. ALP activities of the 1st and mixed extractions of BMPs were shown to be highly osteoinductive and keep a significantly high level (P<0.05-0.01) 4 days after culturing, compared with the 2nd, 3rd and 4th extractions, especially the control group. However, the more times the extraction was done, the less activity of BMPs was shown and more costing was. The x-ray and histological analysis also showed that the 1st extraction of BMPs induced more ossicles and new bone formation., Conclusions: The results indicated that BMPs enhanced the abilities of osteoinductivity in C2C12 culture in vitro. The first extraction of BMPs from bone is fitfull, the second extraction should be enough, while, the 3rd and 4th extractions are unnecessary for they cost more and waste more time, say nothing of mixed extractions.

Native bone morphogenetic proteins (BMPs) extracted from bone have been used clinically to stimulate bone regeneration and repair. However, preparation of purified BMP is a laborious process. This study investigated the yield, activity and cost effectiveness of repeatedly extracting the same bone matrix to produce purified BMP. While repeated extraction was able to increase the yield 62% the activity of the partially purified BMP in later extracts decreased both in vitro and in vivo. This decline in activity appears to be due to an increase in non-BMP contaminants, such as collagen, in the extracts. When the first three extracts were combined and processed together activity was equivalent to that of the first extract. A simple analysis based on the cost of reagents used and the time required for purification indicates that separate processing of the extracts is inefficient while combining the first and second extracts and processing them together would result in a small cost saving. Based on this study we would recommend that the demineralized bone matrix be extracted no more than twice and that the extracts be combined for further processing.

Purpose: The purpose of this investigation was to assess bone regeneration in critical sized defects in the rabbit calvarium using allogeneic and alloplastic bone substitutes., Materials and Methods: Thirty New Zealand White rabbits were divided into 3 groups of 10 animals each. Bilateral 15 mm x 17 mm calvarial defects were made in the parietal bones of each animal. Group 1 had demineralized bone matrix (DBM) gel placed in one defect, while the other defect was left unfilled and served as the control. Group 2 had one defect filled with calcium hydroxide (CaOH)-treated DBM gel and the other defect filled with DBM gel. Group 3, the calcium-phosphate cement group, had Norian CRS (Norian Corp, Cupertino, CA) placed on one side and Bone Source (Howmedica Leibinger, Dallas, TX) placed on the contralateral side. Five animals in each group were killed at 6 and 12 weeks. Data analysis included qualitative assessment of the calvarial specimens and radiographic evaluation. Histomorphometric analysis was used to quantify the amount of new bone within the defects., Results: Histomorphometric analysis showed that DBM gel-treated defects had significantly more new bone at 12 weeks compared with all other groups. There was no significant difference between defects filled with CaOH-treated DBM gel and those filled with DBM gel at 12 weeks. In group 3, Norian CRS- and Bone Source-treated defects were not statistically different from the unfilled controls., Conclusion: DBM gel was an effective allogeneic bone substitute that showed reliable osseous healing of critical size defects in the rabbit calvarium. The addition of CaOH to DBM gel did not significantly improve the bone regenerative capacity of the DBM gel. Both Norian CRS and Bone Source did not promote bone regeneration in this animal model.

Ameloblastic carcinoma is a rare malignant lesion with characteristic histologic features and behaviour that dictates a more aggressive surgical approach than that of a simple ameloblastoma. However, reliable evidence of its biologic activity is currently unavailable due to the scarcity of well-documented cases. It occurs primarily in the mandible in a wide range of age groups; no sex or race predilection has been noted. It may present as a cystic lesion with benign clinical features or as a large tissue mass with ulceration, significant bone resorption and tooth mobility. Because the lesion is usually found unexpectedly after an incisional biopsy or the removal of a cyst, a guide to differential diagnosis is not usually useful. The identifying features of ameloblastic carcinoma must be known and recognized by dental practitioners. Our understanding of the histologic features of ameloblastic carcinoma is somewhat vague. The tumour cells resemble the cells seen in ameloblastoma, but they show cytologic atypia. Moreover, they lack the characteristic arrangement seen in ameloblastoma. The clinical course of ameloblastic carcinoma is typically aggressive, with extensive local destruction. Direct extension of the tumour, lymph node involvement and metastasis to various sites (frequently the lung) have been reported. Wide local excision is the treatment of choice. Regional lymph node dissection should be considered and performed selectively. Radiotherapy and chemotherapy seem to be of limited value for the treatment of ameloblastic carcinomas. At the moment, there are too few reported cases to make a definite recommendation regarding treatment. Close periodic reassessment of the patient is mandatory.

Dental implant failures are still a common occurrence, especially in areas of poor bone quality. The purpose of this study was to observe whether the application of a growth factor, recombinant human transforming growth factor beta-1 (rhTGF-beta1), would improve the healing of bone adjacent to titanium dental implants. Four adult male Yucatan minipigs had four titanium dental implants placed into the inferior border of each hemimandible. On the control side, the implants were placed in standard fashion. On the experimental side, rhTGF-beta1 within a carrier gel was placed into the recipient site before implant placement. After a 6-week healing period, two implants from each side were evaluated by pull-out testing and histomorphometric analysis. The mean pull-out force for experimental implants was 1,124.01 N and 818.12 N (P = 0.5015) for controls. The mean percentage of bone between adjacent threads on the implant surface was 49.74% for the experimental group and 36.50% for controls (P = 0.0783). The mean percentage of bone-implant surface contact was 41.86% for the experimental implant sites and 24.60% for the control implant sites (P = 0.0452). The application of rhTGF-beta1 to implant sites appears to increase the amount of bone healing adjacent to a titanium dental implants in minipig mandibles at the 6-week period. Further studies are required to quantify better the amount of growth factor required and to study its effects over a broader period of time to see whether these differences are maintained.

The clinical use of recombinant bone morphogenetic protein (rBMP) is limited by the lack of a suitable delivery system. The bone morphogenetic protein (BMP) delivery system provided by nature is highly effective, and by studying purified BMP (BMP/NCP) and demineralized bone matrix (DBM), it may be possible to learn how to emulate nature's success. The current study used an in vitro muscle cell model to study the activity of BMP/NCP and DBM and the effects of extracellular matrix on BMP activity. C2C12 cells transiently exposed to recombinant human BMP-4 (rhBMP-4) rapidly increased their alkaline phosphatase (AP) activity to day 5, after which it steadily declined. Cells exposed to BMP/NCP or DBM continued to increase their AP activity over the 14-day culture. If BMP/NCP was treated to remove a 22-kd protein, it became water-soluble and exhibited a similar activity pattern to rhBMP-4. Cells cultured on collagen type I, fibronectin, and hyaluronic-coated surfaces demonstrated increased AP activity when exposed to rhBMP-4 or BMP/NCP compared with cells cultured on bovine serum albumin or poly-l-lysine. These results suggest that the natural BMP delivery system operates both by binding to the BMP molecule and slowly releasing it into the extracellular milieu and by interacting with the responding cells through cell-matrix receptors to enhance the cellular response to BMP.

Purpose: Autogenous bone grafting is well established for use in the maxillofacial skeleton. We present our experience with minimally invasive bone harvesting using a power-driven trephine, with favorable patient and clinical results., Materials and Methods: This retrospective study evaluation patients requiring autogenous bone harvested using a trephine, treated consecutively over a 3-year period. Mean patient age was 27.2 years (range, 8 to 77 years). Only those patients requiring elective surgery and admission on the same day were included in the study. Intraoperative assessment included the description of complications and the quantity and volume of the bone cores harvested. The complications monitored included bleeding, nerve injury, and perforation of the medial or lateral walls of the ilium. Postoperatively, patients were assessed for ambulation, pain, bleeding, and suitability for discharge. The patients were evaluated 1 week after surgery and were examined for wound complications (incision breakdown, infection, paresthesia, pain) and ambulatory deficits. All patients were then surveyed using a questionnaire outlining short-term (1 to 14 days), and long-term (>6 months postoperative) deficits, pain, and general remarks about the procedure., Results: A total of 84 patients underwent bone harvesting using a power-driven trephine. Bone was harvested from a total of 86 anterior iliac crest sites, for a total of 333 cores (3.96 cores per patient). Forty-one patients were discharged on the day of surgery. Intraoperatively, the volume of bone obtained ranged from 3 to 21 mL per harvest site (1 to 7 cores, 4 mm x 30 to 38 mm). The bone volume obtained was dependent on the size of the defect to be filled. Intraoperatively, 1 complication occurred (1 of 333 cores; 0.3%)-a broken instrument-and there were no perforations of the medial or lateral walls of the ilium or excessive bleeding. The complications totaled 3 (3.6%); none of these produced long term effects. Patients surveyed up to 6 months postoperatively noted positive results., Conclusions: The harvesting of bone from the anterior iliac crest using a power driven trephine appears to be safe and results in minimal morbidity and ample bone volume for many maxillofacial procedures, without delaying discharge from hospital.