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Purpose: To compare the outcomes of immediate and delayed implant placement with bone-level tapered implants. Materials and Methods: In this post-market, multicenter prospective randomized controlled study with a primary endpoint of 1 year, 53 patients were randomized to receive either immediate implant placement (test group) or delayed implant placement (control group). The mean crestal bone level changes from implant loading to 12 months postloading were measured using standardized digital periapical radiographs. Changes in facial plate thickness (as measured on CBCT images), implant success and survival, implant stability, soft tissue changes, patient-centered outcomes, and adverse events were measured to assess outcomes between the test and control treatments at 12 months postloading. Results: Of the original 53 patients, 46 patients completed the study (23 in each group). Mean bone changes from loading to the 12-month follow-up were recorded with no statistically significant difference (P = .950) between the groups. The hypothesis was confirmed that immediate implant placement (test) in extraction sockets produces in similar outcomes as delayed placement (control). The test group was found to be similar to the control group (P = .022) in terms of mean changes in facial plate thickness. Implant survival and success were 95.8% in the test group and 92% in the control group. Stability in the control group was superior at the time of surgery, but there was no difference between the groups at implant loading, producing a nonsignificant P value of .563). Conclusions: This randomized controlled multicenter study showed comparable outcomes 1 year after prosthetic loading in the immediate and delayed implant placement groups. [ABSTRACT FROM AUTHOR]

Aberrant lineage commitment of mesenchymal stem cells (MSCs) in marrow contributes to abnormal bone formation due to reduced osteogenic and increased adipogenic potency. While several major transcriptional factors associated with lineage differentiation have been found during the last few decades, the molecular switch for MSC fate determination and its role in skeletal regeneration remains largely unknown, limiting creation of effective therapeutic approaches. Tribbles homolog 3 (Trb3), a member of tribbles family pseudokinases, is known to exert diverse roles in cellular differentiation. Here, we investigated the reciprocal role of Trb3 in the regulation of osteogenic and adipogenic differentiation of MSCs in the context of bone formation, and examined the mechanisms by which Trb3 controls the adipo-osteogenic balance. Trb3 promoted osteoblastic commitment of MSCs at the expense of adipocyte differentiation. Mechanistically, Trb3 regulated cell-fate choice of MSCs through BMP/Smad and Wnt/β-catenin signals. Importantly, in vivo local delivery of Trb3 using a novel gelatin-conjugated caffeic acid-coated apatite/PLGA (GelCA-PLGA) scaffold stimulated robust bone regeneration and inhibited fat-filled cyst formation in rodent non-healing mandibular defect models. These findings demonstrate Trb3-based therapeutic strategies that favor osteoblastogenesis over adipogenesis for improved skeletal regeneration and future treatment of bone-loss disease. The distinctive approach implementing a scaffold-mediated local gene transfer may further broaden the translational use of targeting specific therapeutic gene related to lineage commitment for clinical bone treatment.

Osteonecrosis of the jaw (ONJ), a rare, but potentially severe side effect of anti-resorptive medications, presents as exposed bone in the maxillofacial region lasting for at least 8 weeks. While clinical experience and animal models concur in finding that systemic antiresorptive treatment in conjunction with local risk factors, such as tooth extraction or dental disease may lead to ONJ development, the subclinical molecular changes that precede bone exposure remain poorly understood. The identification of these changes is not only important in understanding disease pathophysiology, but could provide potential for treatment development. Here, we evaluated the early stages of ONJ utilizing a model of experimental periodontitis (EP) in mice treated with two different types of antiresorptives, targeting potential changes in vasculature, hypoxia, oxidative stress, and apoptosis. Antiresorptive treatment in animals with EP increased levels of empty osteocytic lacunae and increased ONJ prevalence compared to Veh animals. The arteriole and venule network seen around EP areas was diminished in animals treated with antiresorptives. Higher levels of vascular endothelial growth factor A (VEGF-A) and vascular cell adhesion protein-1 (VCAM-1) were observed 1-week following EP in treated animals. Finally, levels of hypoxia, oxidative stress, and apoptosis remained high in antiresorptive treated animals with EP through the duration of the experiment. Together, our data point to subclinical vasculature organizational disturbances that subsequently affect levels of hypoxia, oxidative stress, and apoptosis in the area of developing ONJ.

PurposeMedication-related osteonecrosis of the jaw (MRONJ) is a rare but severe side effect of antiresorptive medications. Most animal models use tooth extraction as an instigating local factor to induce MRONJ, with varied results. However, these teeth are healthy and absent of dental disease, a rare finding that does not reflect clinical practices. The authors hypothesized that extraction of teeth with periapical inflammation would lead to MRONJ in rats treated with high-dose bisphosphonates.Materials and methodsRats were pretreated with zoledronic acid (ZA) for 1 week. Pulp exposure (PE) was established by exposing the pulpal chamber of the first and second molars. Experimental periapical disease (EPD) was induced by PE and bacterial inoculation into pulp chambers of the first and second mandibular molars. The mandibular molars were extracted 4 weeks after PE or EPD, and animals were euthanized 4 weeks after tooth extraction. Extraction sockets were assessed clinically, radiographically, and histologically.ResultsClinically, radiographically, and histologically, socket healing was observed in all vehicle-treated animals and in ZA-treated animals after extraction of healthy teeth or teeth with PE. In contrast, bone exposure, lack of socket healing, and osteonecrosis were present in most ZA-treated animals after extraction of teeth with EPD. Bacterial presence was noted in areas of osteonecrotic alveolar bone.ConclusionThese data support a synergistic contribution of severe dental disease and tooth extraction to MRONJ pathogenesis. Importantly, this model is amenable to manipulation of methodologic conditions for the dissection of parameters involved in MRONJ pathogenesis.

ObjectiveThe aim of this study was to explore the radiographic appearance of stage 0 medication-related osteonecrosis of the jaws (MRONJ) and examine 5 radiographic parameters (trabecular sclerosis, cortical erosion, periosteal reaction, sequestration, and crater-like defect) as predictors of progression to bone exposure.Study designTwenty-three patients with a history of antiresorptive therapy, no bone exposure, and nonspecific signs and symptoms were included. Intraoral photographs, panoramic and cone beam computed tomography (CBCT) images at initial visit, and follow-up intraoral photographs were reviewed. Three patients had dental disease (DD), 10 patients with stage 0 MRONJ did not progress to bone exposure (NBE), and 10 patients progressed to bone exposure (BE). Radiographic parameters were scored as absent (0), localized (1), or extensive (2), and their sum formed the composite radiographic index (CRI).ResultsDD patients demonstrated minimal radiographic findings, and their CRI was significantly lower than that of NBE and BE patients. Additionally, BE patients demonstrated a higher radiographic index compared with NBE patients. Intriguingly, sequestration was observed in the initial CBCT of 9 (90%) of 10 BE patients, whereas 80% of NBE patients showed absence of sequestration at initial CBCT examination.ConclusionsCBCT imaging can aid in the differentiation of stage 0 MRONJ from dental disease. Radiographic sequestration at initial presentation can serve as a predictor of future bone exposure in patients with stage 0 MRONJ.

PurposeMedication-related osteonecrosis of the jaws (MRONJ) is a known complication of antiresorptive medications with surgical and nonsurgical treatment options. The aim of this study was to evaluate the effectiveness of nonsurgical therapy using local wound care on management of MRONJ lesions.Materials and methodsThe authors conducted a retrospective cohort study of patients who presented to the University of California-Los Angeles School of Dentistry Oral and Maxillofacial Surgery Clinic for evaluation and treatment of MRONJ. The primary predictor variable was wound care score; secondary predictors were demographics (age, gender), anatomic location, primary condition, and type and time of antiresorptive treatment. Outcomes assessed were disease resolution and time to disease resolution. Statistical analysis was carried out using the Spearman correlation for continuous and ordinal variables or the χ2 test for categorical variables. Time-to-event statistics and Cox proportional hazards models were calculated; a Kaplan-Meier plot was generated to assess time to healing.ResultsOne hundred six patients with 117 MRONJ lesions were treated using local wound care; complete disease resolution was observed 71% of lesions, with an additional 22% of lesions undergoing disease improvement. Wound care score was statistically associated with disease resolution and time to resolution, whereas demographics, anatomic site, condition, and type and time of antiresorptive treatment had no effect on resolution.ConclusionLocal wound care increased the likelihood of MRONJ resolution and decreased the time to disease resolution. This strategy can be used in patients who cannot undergo surgery and should be implemented in all patients with MRONJ lesions who are managed nonsurgically.

Although bone morphogenetic protein-2 (BMP2) has demonstrated extraordinary potential in bone formation, its clinical applications require supraphysiological milligram-level doses that increase postoperative inflammation and inappropriate adipogenesis, resulting in well-documented life-threatening cervical swelling and cyst-like bone formation. Recent promising alternative biomolecular strategies are toward promoting pro-osteogenic activity of BMP2 while simultaneously suppressing its adverse effects. Here, we demonstrated that small molecular phenamil synergized osteogenesis and bone formation with BMP2 in a rat critical size mandibular defect model. Moreover, we successfully elicited the BMP2 adverse outcomes (i.e. adipogenesis and inflammation) in the mandibular defect by applying high dose BMP2. Phenamil treatment significantly improves the quality of newly formed bone by inhibiting BMP2 induced fatty cyst-like structure and inflammatory soft-tissue swelling. The observed positive phenamil effects were associated with upregulation of tribbles homolog 3 (Trib3) that suppressed adipogenic differentiation and inflammatory responses by negatively regulating PPARγ and NF-κB transcriptional activities. Thus, use of BMP2 along with phenamil stimulation or Trib3 augmentation may be a promising strategy to improve clinical efficacy and safety of current BMP therapeutics.

Growth factor-based therapeutics using bone morphogenetic protein 2 (BMP-2) presents a promising strategy to reconstruct craniofacial bone defects such as mandible. However, clinical applications require supraphysiological BMP doses that often increase inappropriate adipogenesis, resulting in well-documented, cyst-like bone formation. Here we reported a novel complementary strategy to enhance osteogenesis and mandibular bone repair by using small-molecule phenamil that has been shown to be a strong activator of BMP signaling. Phenamil synergistically induced osteogenic differentiation of human bone marrow mesenchymal stem cells with BMP-2 while suppressing their adipogenic differentiation induced by BMP-2 in vitro. The observed pro-osteogenic and antiadipogenic activity of phenamil was mediated by expression of tribbles homolog 3 (Trb3) that enhanced BMP-smad signaling and inhibited expression of peroxisome proliferator-activated receptor gamma (PPARγ), a master regulator of adipogenesis. The synergistic effect of BMP-2+phenamil on bone regeneration was further confirmed in a critical-sized rat mandibular bone defect by implanting polymer scaffolds designed to slowly release the therapeutic molecules. These findings indicate a new complementary osteoinductive strategy to improve clinical efficacy and safety of current BMP-based therapeutics.

In a quest to provide best-quality treatment, results, and long-term prognosis, physicians must be well versed in emerging sciences and discoveries to more favorably provide suitable options to patients. Bioengineering and regeneration have rapidly developed, and with them, the options afforded to surgeons are ever-expanding. Grafting techniques can be modified according to evolving knowledge. The basic principles of bioengineering are discussed in this article to provide a solid foundation for favorable treatment and a comprehensive understanding of the reasons why each particular treatment available can be the most adequate for each particular case.

PurposeMedication-related osteonecrosis of the jaws (MRONJ) is a well-described complication of antiresorptive and antiangiogenic medications. Although osteonecrosis can be associated with other inciting events and medications, such as trauma, infection, steroids, chemotherapy, and coagulation disorders, these are rarely reported in the literature.Materials and methodsThis is a six case series of MRONJ associated with medications other than antiresorptive or antiangiogenic drugs.ResultsPatient demographics, inciting event, location, stage, imaging findings, and outcome are reported.ConclusionWith the continued development and clinical use of new biologic medications for diseases such as cancer and rheumatoid arthritis, it is important to continue to evaluate their effects on the oral cavity. The degree of risk for osteonecrosis in patients taking these new classes of drugs is uncertain but warrants awareness and monitoring.

Rheumatoid arthritis (RA), an autoimmune inflammatory disorder, results in persistent synovitis with severe bone and cartilage destruction. Bisphosphonates (BPs) are often utilized in RA patients to reduce bone destruction and manage osteoporosis. However, BPs, especially at high doses, are associated with osteonecrosis of the jaw (ONJ). Here, utilizing previously published ONJ animal models, we are exploring interactions between RA and ONJ incidence and severity. DBA1/J mice were divided into four groups: control, zoledronic acid (ZA), collagen-induced arthritis (CIA), and CIA-ZA. Animals were pretreated with vehicle or ZA. Bovine collagen II emulsified in Freund's adjuvant was injected to induce arthritis (CIA) and the mandibular molar crowns were drilled to induce periapical disease. Vehicle or ZA treatment continued for 8 weeks. ONJ indices were measured by micro-CT (µCT) and histological examination of maxillae and mandibles. Arthritis development was assessed by visual scoring of paw swelling, and by µCT and histology of interphalangeal and knee joints. Maxillae and mandibles of control and CIA mice showed bone loss, periodontal ligament (PDL) space widening, lamina dura loss, and cortex thinning. ZA prevented these changes in both ZA and CIA-ZA groups. Epithelial to alveolar crest distance was increased in the control and CIA mice. This distance was preserved in ZA and CIA-ZA animals. Empty osteocytic lacunae and areas of osteonecrosis were present in ZA and CIA-ZA but more extensively in CIA-ZA animals, indicating more severe ONJ. CIA and CIA-ZA groups developed severe arthritis in the paws and knees. Interphalangeal and knee joints of CIA mice showed advanced bone destruction with cortical erosions and trabecular bone loss, and ZA treatment reduced these effects. Importantly, no osteonecrosis was noted adjacent to areas of articular inflammation in CIA-ZA mice. Our data suggest that ONJ burden was more pronounced in ZA treated CIA mice and that RA could be a risk factor for ONJ development. © 2016 American Society for Bone and Mineral Research.

UnlabelledAlthough adipose-derived stem cells (ASCs) are an attractive cell source for bone tissue engineering, direct use of ASCs alone has had limited success in the treatment of large bone defects. Although bone morphogenetic proteins (BMPs) are believed to be the most potent osteoinductive factors to promote osteogenic differentiation of ASCs, their clinical applications require supraphysiological dosage, leading to high medical burden and adverse side effects. In the present study, we demonstrated an alternative approach that can effectively complement the BMP activity to maximize the osteogenesis of ASCs without exogenous application of BMPs by regulating levels of antagonists and agonists to BMP signaling. Treatment of ASCs with the amiloride derivative phenamil, a positive regulator of BMP signaling, combined with gene manipulation to suppress the BMP antagonist noggin, significantly enhanced osteogenic differentiation of ASCs through increased BMP-Smad signaling in vitro. Furthermore, the combination approach of noggin suppression and phenamil stimulation enhanced the BMP signaling and bone repair in a mouse calvarial defect model by adding noggin knockdown ASCs to apatite-coated poly(lactic-coglycolic acid) scaffolds loaded with phenamil. These results suggest novel complementary osteoinductive strategies that could maximize activity of the BMP pathway in ASC bone repair while reducing potential adverse effects of current BMP-based therapeutics.SignificanceAlthough stem cell-based tissue engineering strategy offers a promising alternative to repair damaged bone, direct use of stem cells alone is not adequate for challenging healing environments such as in large bone defects. This study demonstrates a novel strategy to maximize bone formation pathways in osteogenic differentiation of mesenchymal stem cells and functional bone formation by combining gene manipulation with a small molecule activator toward osteogenesis. The findings indicate promising stem cell-based therapy for treating bone defects that can effectively complement or replace current osteoinductive therapeutics.

Osteonecrosis of the jaws (ONJ) is a significant complication of antiresorptive medications, such as bisphosphonates and denosumab. Antiresorptive discontinuation to promote healing of ONJ lesions remains highly controversial and understudied. Here, we investigated whether antiresorptive discontinuation alters ONJ features in mice, employing the potent bisphosphonate zoledronic acid (ZA) or the receptor activator of NF-κB ligand (RANKL) inhibitor OPG-Fc, utilizing previously published ONJ animal models. Mice were treated with vehicle (veh), ZA, or OPG-Fc for 11 weeks to induce ONJ, and antiresorptives were discontinued for 6 or 10 weeks. Maxillae and mandibles were examined by μCT imaging and histologically. ONJ features in ZA and OPG-Fc groups included periosteal bone deposition, empty osteocyte lacunae, osteonecrotic areas, and bone exposure, each of which substantially resolved 10 weeks after discontinuing OPG-Fc but not ZA. Full recovery of tartrate-resistant acid phosphatase-positive (TRAP+) osteoclast numbers occurred after discontinuing OPG-Fc but not ZA. Our data provide the first experimental evidence demonstrating that discontinuation of a RANKL inhibitor, but not a bisphosphonate, reverses features of osteonecrosis in mice. It remains unclear whether antiresorptive discontinuation increases the risk of skeletal-related events in patients with bone metastases or fracture risk in osteoporosis patients, but these preclinical data may nonetheless help to inform discussions on the rationale for a "drug holiday" in managing the ONJ patient.

PurposeBisphosphonates (BPs) are widely used for the management of bone diseases such as osteoporosis and bone malignancy. However, osteonecrosis of the jaws (ONJ) is a serious complication of BP treatment. ONJ lesions mainly occur after extraction of teeth deemed unrestorable or around teeth with active periodontal or periapical disease. Because socket healing or dental disease shows higher bone turnover, the authors hypothesized that preferentially high BP accumulation would be observed in these areas.Materials and methodsThe authors tested the uptake of fluorescein-labeled zoledronic acid (5-FAM-ZOL) in sites of tooth extraction or experimental periapical disease in mice. Maxillary molars were extracted or the crowns of mandibular molars were drilled to induce pulp exposure. Animals were injected with 5-FAM-ZOL 200 μg/kg at various times after intervention and fluorescence was measured at healthy versus intervention sites. Fluorescein injections were used as controls. Data were analyzed by t test and mixed effects linear models were constructed because the animals had repeated measurements over time and at the 2 sites.ResultsA statistically significant (P≤.001 to .002) time-dependent uptake of 5-FAM-ZOL was detected in the areas of extraction socket and in the alveolar ridge around teeth with periapical disease compared with the healthy contralateral sites of the same animals. For the 2 conditions, the uptake reached a maximum 3 days after experimental intervention and decreased thereafter.ConclusionsThese data suggest that sites with increased bone turnover, such as extraction sites or areas of periapical inflammation, are exposed to higher BP doses than the remaining alveolar ridge and could explain, at least in part, the susceptibility of such areas to ONJ.

Although osteonecrosis of the jaws (ONJ), a serious complication of antiresorptive medications, was reported a decade ago, the exact mechanisms of disease pathophysiology remain elusive. ONJ-like lesions can be induced in animals after antiresorptive treatment and experimental interventions such as tooth extraction or periapical or periodontal disease. However, experimental induction and manipulation of disease progression does not always reflect clinical reality. Interestingly, naturally occurring maxillofacial abscesses, inducing aggressive inflammation of the peri-radicular mucosa with significant osteolysis and alveolar bone expansion, have been reported in mice. Here, we aimed to explore whether osteonecrotic lesions would develop in areas of maxillary peri-radicular infections, in mice on antiresorptive medications with distinct pharmacologic action, thus establishing a novel ONJ animal model. Mice were treated with RANK-Fc or OPG-Fc that bind to RANKL or with the potent bisphosphonate zoledronic acid (ZA). Maxillae were assessed radiographically and histologically. μCT imaging of vehicle mice revealed several maxillae with altered alveolar bone morphology, significant ridge expansion and large lytic areas. However, in RANK-Fc, OPG-Fc and ZA treated animals the extent of bone loss was significantly less, but exuberant bone deposition was noted at the ridge periphery. BV and BV/TV were increased in the diseased site of antiresorptive vs. veh animals. Histologically, extensive inflammation, bone resorption and marginal gingival epithelium migration were seen in the diseased site of vehicle animals. Rank-Fc, OPG-Fc and ZA reduced alveolar bone loss, increased periosteal bone formation, and induced areas of osteonecrosis, and bone exposure that in many animals covered significant part of the alveolar bone. Collectively, our data demonstrate ONJ-like lesions at sites of maxillary peri-radicular infection, indistinguishable in mice treated with RAKL inhibitors vs. zoledronate. This novel mouse model of spontaneous ONJ supports a central role of osteoclast inhibition and infection/inflammation in ONJ pathogenesis and validates and complements existing animal models employing experimental interventions.

Osteonecrosis of the jaws (ONJ) is a complex disease involving multiple tissue and cell-type responses to wound healing or infection. AAOMS defines bisphosphonate related ONJ (BRONJ) as exposed, necrotic bone in the maxillofacial region that has persisted for more than 8 weeks in a patient with current or previous antiresorptive treatment, without a history of radiation therapy to the jaws. Since the first reported ONJ cases in 2003 and 2004, there has been little advancement in understanding the etiology and pathophysiology of ONJ. Many hypotheses have been proposed, including bisphosphonate (BP) toxicity to oral epithelium, altered wound healing after tooth extraction, high turnover of the mandible and maxilla, oral biofilm formation, infection and inflammation, and suppression of angiogenesis and bone turnover. The current classification system of ONJ involves stages 0 to 3 and is based on patient clinical presentation. This report describes a case of stage 0 ONJ in a patient on denosumab and indicates the full-spectrum similarities between BP- and denosumab-associated ONJ clinically, radiographically, and histologically.

Multiple bone augmentation techniques are available to allow implant placement in the atrophic maxilla. However, questions remain, regarding which methods are most predictable and have the best dental implant survival rate (SR) in grafted bone. The aim of this systematic review was to evaluate literature from the last 30 years to determine predictability of bone grafting of the edentulous maxilla for implant placement as well as for implant SR. Materials and Methods: A systematic review was performed of studies conducted during the period 1980 to 2014, specifically focusing on the edentulous maxilla and bone grafting. Surgical techniques discussed in the publications included were guided bone regeneration (GBR), sinus augmentation, onlay bone grafting, nasal floor grafting, and Le Fort I interpositional grafting. All identified articles were evaluated and screened to meet strict inclusion criteria of at least 10 patients, complete maxillary edentulism, 1-year follow-up, and information regarding implant SR. A total of 974 articles were identified with electronic and manual searches. On further evaluation of the titles and abstracts, 44 articles were excluded. Full texts of the articles that met the inclusion criteria were reviewed, of which 40 articles were included in the systematic review. Results: For onlay bone grafting, 16 studies were included and analyzed, and the weighted mean implant SR was 85.2%. For the GBR technique, two studies were included, with a reported SR ranging from 96.1% to 100%. For Le Fort I interpositional grafting, 11 studies were included, with a weighted mean SR of 89.6%. For the sinus augmentation technique, 12 studies were investigated and the weighted mean SR was 91.5%. For the combination technique, six studies were analyzed and the weighted mean SR was 93.6%. Conclusions: All five treatment modalities discussed--onlay bone grafting, GBR, Le Fort I interpositional grafting, maxillary sinus augmentation, and/or nasal floor inlay grafting or the combination approach--can be successfully used to augment edentulous maxillary ridge with high implant SRs. [ABSTRACT FROM AUTHOR]

Purpose: A variety of techniques and materials have been used to establish the structural base of osseous tissue for supporting dental implants. The aim of this systematic review was to identify the most successful technique(s) to provide the necessary alveolar bone to place a dental implant and support long-term survival. Methods: A systematic online review of a main database and manual search of relevant articles from refereed journals were performed between 1980 and 2005. Updates and additions were made from September 2004 to May 2005. The hard tissue augmentation techniques were separated into 2 anatomic sites, the maxillary sinus and alveolar ridge. Within the alveolar ridge augmentation technique, different surgical approaches were identified and categorized, including guided bone regeneration (GBR), onlay/veneer grafting (OVG), combinations of onlay, veneer, inter- positional inlay grafting (COG), distraction osteogenesis (DO), ridge splitting (RS), free and vascularized autografts for discontinuity defects (DO), mandibular interpositional grafting (MI), and socket preservation (SP). All identified articles were evaluated and screened by 2 independent reviewers to meet strict inclusion criteria. Articles meeting the inclusion criteria were further evaluated for data extraction. The initial search identified a total of 526 articles from the electronic database and manual search. Of these, 335 articles met the inclusion criteria after a review of the titles and abstracts. From the 335 articles, further review of the full text of the articles produced 90 articles that provided sufficient data for extraction and analysis. Results: For the maxillary sinus grafting (SG) technique, the results showed a total of 5,128 implants placed, with follow-up times ranging from 12 to 102 months. Implant survival was 92% for implants placed into autogenous and autogenous/composite grafts, 93.3% for implants placed into allogeneic/nonautogenous composite grafts, 81% for implants placed into allo- plast and alloplast/xenograft materials, and 95.6% for implants placed into xenograft materials alone. For alveolar ridge augmentation, a total of 2,620 implants were placed, with follow-up ranging from 5 to 74 months. The implant survival rate was 95.5% for GBR, 90.4% for OVG, 94.7% for DO, and 83.8% for COG. Other techniques, such as DO, RS, SP, and MI, were difficult to analyze because of the small sample size and data heterogeneity within and across studies. Conclusions: The maxillary sinus augmentation procedure has been well documented, and the long-term clinical success/survival (> 5 years) of implants placed, regardless of graft material(s) used, compares favorably to implants placed conventionally, with no grafting procedure, as reported in other systematic reviews. Alveolar ridge augmentation techniques do not have detailed documentation or long-term follow-up studies, with the exception of GBR. However, studies that met the inclusion criteria seemed to be comparable and yielded favorable results in supporting dental implants. The alveolar ridge augmentation procedures may be more technique- and operator-experience-sensitive, and implant survival may be a function of residual bone supporting the dental implant rather than grafted bone. More in-depth, long-term, multi- center studies are required to provide further insight into augmentation procedures to support dental implant survival. INT J ORAL MAXILLOFAC IMPLANTs 2007;22(5uPPL):49-70 [ABSTRACT FROM AUTHOR]

Purpose: The collection of autologous platelet-rich plasma (PRP) has demonstrated favorable affects on wound healing in compromised patients. The purpose of this study was to evaluate the expression of PDGF, bFGF, and TGF-β in irradiated and nonirradiated bone in a rabbit tibia model and the ability of PRP to increase growth factor expression when added to autogenous bone graft in a rabbit cranial defect model. Materials and Methods: Ten New Zealand White rabbit tibiae and calvariae were utilized for this study. Tibiae were irradiated at 60 to 70 cGy and evaluated for expression of PDGF, bFGF, and TGF-β. Rabbit calvariae were also analyzed after grafting with autogenous bone and PRP for determination of growth factor expression. Results: Decreased expression of PDGF, bFGF, and TGF-β was seen in cortical and cancellous bone samples when irradiated bone was compared to nonirradiated rabbit tibiae. An increase in PDGF, bFGF, and TGF-β expression was detected in cortical autogenous bone grafts with PRP at 1 and 2 months compared to autogenous bone alone. Discussion: In this study, growth factors, which were decreased in irradiated cortical and cancellous bone, showed increased expression at 1 and 2 months when PRP was added to autogenous bone grafts. Thus, PRP may have potential therapeutic applications when bone grafting is required in patients with reduced bone vascularity, including patients with previous head and neck irradiation, diabetes, and smoking habits. Conclusions: Decreased expression of PDGF, bFGF, and TGF-β was seen in radiated rabbit tibia as compared to nonirradiated controls, and increased expression of these growth factors was seen in PRP-containing autogenous bone grafts. [ABSTRACT FROM AUTHOR]

Purpose: To guide treatment planning by analyzing the rates of dental implant failure to determine associated risk factors. Materials and Methods: All consecutively treated patients from January 1982 until January 2003 were included in a retrospective cohort study, as defined in the hierarchy of evidence for dental implant literature. Data regarding gender, age, implant location, bone quality, bone volume, and medical history were recorded. Correlations between these data and implant survival were calculated to establish relative risk (RR) ratios. Results: Increasing age was strongly associated with the risk of implant failure. Compared to patients younger than 40 years, patients in the 60-to-79 age group had a significantly higher risk of implant failure (RR = 2.24; P < .05). Gender, hypertension, coronary artery disease, pulmonary disease, steroid therapy, chemotherapy, and not being on hormone replacement therapy for postmenopausal women were not associated with a significant increase in implant failure. Smoking (RR = 1.56), diabetes (RR = 2.75), head and neck radiation (RR = 2.73), and postmenopausal estrogen therapy (RR = 2.55) were correlated with a significantly increased failure rate. Overall, implant failure was 8.16% in the maxilla and 4.93% in the mandible (P < .001). Discussion: Patients who were over age 60, smoked, had a history of diabetes or head and neck radiation, or were postmenopausal and on hormone replacement therapy experienced significantly increased implant failure compared with healthy patients. Conclusion: Overall, dental implant failure is low and there are no absolute contraindications to implant placement. Conditions that were found to be correlated with an increased risk of failure should be considered during treatment planning and factored into the informed consent process. (More than 50 references.) [ABSTRACT FROM AUTHOR]

Purpose: Platelet-rich plasma (PRP) is potentially useful as an adjunct to allograft and xenograft materials in oral and maxillofacial bone and implant reconstructive surgery. This study compares bone healing and formation in 4 cranial defects in rabbits grafted with autogenous bone, xenograft, and xenograft with PRP (with a no-graft group as a control). Materials and Methods: Fifteen New Zealand white rabbits were included in this randomized, blind, prospective pilot study. Four identical 8-mm-diameter defects were created in each rabbit cranium and immediately grafted with the above materials. Five rabbits were evaluated at 1 month, 5 at 2 months, and 5 at 4 months. Radiographs were used to evaluate bone density. Results: Radiographically, sites at which Bio-Oss, autogenous bone, and Bio-Oss + PRP were grafted showed a significant increase in bone density at 1 month (P = .05 for Bio-Oss, P = .02 for autogenous bone, P = .008 for Bio-Oss + PRP) and at 4 months (P = .02 for Bio-Oss, P = .04 for autogenous bone, P = .05 for Bio-Oss + PRP). Autogenous bone sites (P < .001) and Bio-Oss + PRP sites (P < .001) also showed significant increases at 2 months. Histomorphometrically, autogenous bone sites showed a significantly greater increase than control sites (P = .08 at 1 month, P = .03 at 2 months, P = .01 at 4 months), Bio-Oss sites (P < .001 at all 3 evaluation points), or Bio-Oss + PRP sites (P = .009 at 1 month, P = .02 at 2 months, P = .01 at 4 months). Furthermore, Bio-Oss + PRP sites showed a significantly greater increase in bone area at 1, 2, and 4 months than Bio-Oss alone (P = .003 at 1 month, P = .02 at 2 months, P = .006 at 4 months). Discussion: Radiographs showed significantly greater bone density at the Bio-Oss, autogenous bone, and Bio-Oss + PRP sites than at control sites at nearly every point in time evaluated; however, clinical significance is difficult to determine, since all materials appeared dense on the radiograph. Histomorphometry showed that the increase in bone area at autogenous sites was significantly greater than that seen with other grafting materials or at the control sites. Conclusion: This study showed a histomorphometric increase in bone formation with the addition of PRP to Bio-Oss in non-critical-sized defects in the rabbit cranium. [ABSTRACT FROM AUTHOR]