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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]

Objectives: Immediate implant placement and loading is a practice that continues to gain traction in implant dentistry because it reduces treatment time and improves satisfaction. Novel implant designs that facilitate increased primary stability, while not compromising osseointegration and long‐term survival are important to offer immediate solutions for missing teeth. Here, we hypothesize that fully tapered implants can obtain successful osseointegration with high survival rates after immediate loading in fresh extraction sockets and healed sites. Materials and methods: A total of 13 swine with 73 implants were evaluated. Fully tapered or apically tapered implants were placed in extraction sockets and healed sites. Insertion torque and resonance frequency analysis were determined at placement and euthanasia. Animals were evaluated at: placement, and 1‐week and 12‐weeks after placement. Bone to Implant Contact (BIC), Bone Area/Total Area (BA/TA), and first BIC (fBIC) analyses were conducted. Results: The fully tapered implant achieved similar primary stability with lower insertion torque at placement. Apically and fully tapered implants had comparable BIC (50.1% vs 59.4%) and ISQ (82.5 vs 80.3) values by 12 weeks in healed sites. In extraction sockets, BIC and ISQ for the apically tapered implant was 35.8% and 73.2 and 37.8% and 79.2 for the fully tapered implants, respectively. Conclusions: In this short‐term study, immediately loaded fully tapered implants obtained high survival with similar osseointegration ability as apically tapered implants when placed in healed sites and fresh extraction sockets. Fully tapered implants show promise for use in immediate loading and immediate placement. [ABSTRACT FROM AUTHOR]

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]

Purpose: Medication-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 Methods: Rats 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.Results: Clinically, 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.Conclusion: These 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. [ABSTRACT FROM AUTHOR]

Antiresorptive agents, such as bisphosphonates and denosumab, are frequently used for the management of osteoporosis. Indeed, both medications decrease the risk of osteoporotic fractures; however, these medications are associated with rare but potentially severe side effects, such as osteonecrosis of the jaw (ONJ). ONJ, defined as an area of exposed bone in the maxillofacial region that lasts for 8 weeks, often presents with significant pain and infection and can lead to serious complications. Interestingly, other treatments for osteoporosis have been developed, such as antibodies against the osteocyte‐secreted protein, sclerostin. Sclerostin functions to inhibit the Wnt signaling cascade, leading to inhibition of bone formation. In clinical trials, a sclerostin antibody (romosozumab, Amgen Inc., UCB Brussels) increases bone formation and lowers the risk of osteoporotic fractures. However, in conjunction with increased osteoblastic activity, a reduction in bone resorption markers is observed. This antiresorptive effect raises the concern of possible ONJ development in patients treated with sclerostin antibodies. Here, utilizing ligature‐induced experimental periodontitis (EP), we evaluated the effects of sclerostin inhibition on the development of ONJ‐like lesions in ovariectomized rats. Beginning 8 weeks post‐ovariectomy, rats were treated for 22 weeks with weekly injections of vehicle (Veh), 200 μg/kg zoledronic acid (ZA), a potent bisphosphonate at 100‐fold the osteoporosis dose, or 5 mg/kg sclerostin antibody (Scl‐Ab) at the osteoporotic dose. EP was initiated at week 12 and maintained for the remainder of the study. Scl‐Ab treatment transiently increased serum P1NP, a bone formation marker, increased BV/TV, and decreased eroded surfaces in lumbar vertebrae. ZA‐treated rats developed histologic features of ONJ, whereas Veh‐treated controls did not. Scl‐Ab animals lost less periodontal bone in sites with EP. However, these animals presented with no histologic signs of ONJ. In conclusion, sclerostin inhibition enhanced structural bone parameters, without inducing ONJ‐like lesions, in ovariectomized rats with EP. © 2018 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Objective: The 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 Design: Twenty-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).Results: DD 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.Conclusions: CBCT 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. [ABSTRACT FROM AUTHOR]

Purpose: Medication-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 Methods: The 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.Results: One 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.Conclusion: Local 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. [ABSTRACT FROM AUTHOR]

Purpose: Medication-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 Methods: This is a six case series of MRONJ associated with medications other than antiresorptive or antiangiogenic drugs.Results: Patient demographics, inciting event, location, stage, imaging findings, and outcome are reported.Conclusion: With 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. [ABSTRACT FROM AUTHOR]

Hydrogels derived from naturally occurring polymers are attractive matrices for tissue engineering. Here, we report a biofunctional hydrogel for specific use in bone regeneration by introducing Arg–Gly–Asp (RGD)-containing cell adhesive motifs and phosphorylated serine residues, which are prevalent in the native bone extracellular matrix and known to promote osteogenesis by enhancing cell–matrix interactions and hydroxyapatite nucleation, into photopolymerizable methacrylated glycol chitosan (MeGC). Incorporation of phosphoserine into MeGC hydrogels increased the ability of the hydrogels to nucleate minerals on their surfaces. RGD incorporation enhanced cell–matrix interactions by supporting attachment, spreading, and proliferation of bone marrow stromal cells (BMSCs) encapsulated in the hydrogels. Moreover, co-modification of MeGC hydrogels with RGD and phosphoserine synergistically increased the osteogenic differentiation of encapsulated BMSCs in vitro. The bone healing capacity of the modified hydrogels was further confirmed in a mouse calvarial defect model. These findings suggest a promising hydrogel platform with a specific microenvironment tailored to promote osteogenesis for clinical bone repair. [ABSTRACT FROM AUTHOR]

ABSTRACT 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. [ABSTRACT FROM AUTHOR]

The article presents answers to questions concerning the management of the edentulous maxilla, including a question on the importance of clinical practice guidelines for dentistry, the importance of patient communication, and diagnostic criteria when weighing treatment options.

ABSTRACT 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. © 2015 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Purpose Bisphosphonates (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 Methods The 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. Results A 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. Conclusions These 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. [ABSTRACT FROM AUTHOR]

Background: Mandibles (MB) and maxillae possess unique metabolic and functional properties and demonstrate discrete responses to homeostatic, mechanical, hormonal, and developmental stimuli. Osteogenic potential of bone marrow stromal cells (BMSCs) differs between MB versus long bones (LB). Furthermore, MB-versus LB-derived osteoclasts (OCs) have disparate functional properties. This study explores the osteoclastogenic potential of rat MB versus LB marrow in vitro and in vivo under basal and stimulated conditions. Methods: Bone marrow from rat MB and LB was cultured in osteoblastic or osteoclastic differentiation media. Tartrateresistant acid phosphatase (TRAP) staining, resorption pit assays, and real-time polymerase chain reaction were performed. Additionally, osmotic mini-pumps were implanted in animals, mandibles and tibiae were isolated, and multinucleated cells (MNCs) were measured. Results: MB versus LB marrow cultures that were differentiated with receptor activator of nuclear factor-KB ligand (RANKL) and macrophage colony-stimulating factor produced more TRAP+ MNCs and greater resorptive area. To explore MB versus LB BMSC-supported osteoclastogenesis, confluent BMSCs were cultured with parathyroid hormone (PTH), 1,25-dihydroxyvitamin D3 (1,25D3), or PTH-+ 1,25D3. 1,25D3- or PTH-+ 1,25D3-treated LB BMSCs expressed significantly higher RANKL and lower osteoprotegerin (OPG) mRNA and increased RANKL:OPG ratio. When whole marrow was cultured with PTH-+ 1,25D3, more TRAP+ MNCs were seen in LB versus MB cultures, ultimately, rats were infused with PTH-+ 1,25D3, and MB versus tibia MNCs were measured. Hormonal stimulation increased osteoclastogenesis in both MB and tibiae. However, higher TRAP+ MNC numbers were observed in tibiae versus MB under basal and hormonal stimulation. Conclusion: Collectively, these data illustrate differences of both osteoclastogenic potential and OC numbers of MB versus LB marrow. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

ABSTRACT Antiresorptive medications are essential in treating diseases of pathologic osteoclastic bone resorption, including bone cancer and osteoporosis. Bisphosphonates (BPs) are the most commonly used antiresorptives in clinical practice. Although inhibition of bone resorption is important in regulating unwanted malignant and metabolic osteolysis, BP treatment is associated with potential side effects, including osteonecrosis of the jaws (ONJ). Recently, non-BP antiresorptive medications targeting osteoclastic function and differentiation, such as denosumab, have entered the clinical arena. Denosumab treatment results in a similar rate of ONJ as BPs. Animal models of ONJ, using high-dose BP treatment in combination with tooth extraction or dental disease, provide valuable tools and insight in exploring ONJ pathophysiology. However, the ability of other antiresorptives to induce ONJ-like lesions in animal models has not been explored. Such studies would be beneficial in providing support for the role of osteoclast inhibition in ONJ pathogenesis versus a direct BP effect on oral tissues. Here, we tested the ability of the receptor activator of NF-κB ligand (RANKL) inhibitors RANK-Fc (composed of the extracellular domain of RANK fused to the fragment crystallizable [Fc] portion of immunoglobulin G [IgG]) and OPG-Fc (composed of the RANKL-binding domains of osteoprotegerin [OPG] linked to the Fc portion of IgG) to induce ONJ in mice in the presence of periapical disease, but in the absence of dental extractions. We demonstrate radiographic evidence of ONJ in RANK-Fc-treated and OPG-Fc-treated mice, including inhibition of bone loss, increased bone density, lamina dura thickening, and periosteal bone deposition. These findings closely resembled the radiographic appearance of an ONJ patient on denosumab treatment. Histologic examination revealed that RANK-Fc treatment and OPG-Fc treatment resulted in absence of osteoclasts, periosteal bone formation, empty osteocytic lacunae, osteonecrosis, and bone exposure. In conclusion, we have successfully induced ONJ in mice with periapical disease, using potent osteoclast inhibitors other than BPs. Our findings, coupled with ONJ animal models using high-dose BPs, suggest that osteoclast inhibition is pivotal to the pathogenesis of ONJ. © 2014 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

The article presents a study on the role of dental disease in the development of bisphosphonate (BP)-related osteonecrosis of the jaws (BRONJ). It discusses the experiment conducted on a rat model to determine whether periodontal disease and BPs could induce BRONJ. It explores the significance of BP interventions for risk of BRONJ development and osteoporotic patients.

Oxysterols, naturally occurring cholesterol oxidation products, can induce osteoblast differentiation. Here, we investigated short-term 22(S)-hydroxycholesterol + 20(S)-hydroxycholesterol (SS) exposure on osteoblastic differentiation of marrow stromal cells. We further explored oxysterol ability to promote bone healing in vivo. Osteogenic differentiation was assessed by alkaline phosphatase (ALP) activity, osteocalcin (OCN) mRNA expression, mineralization, and Runx2 DNA binding activity. To explore the effects of osteogenic oxysterols in vivo, we utilized the critical-sized rat calvarial defect model. Poly(lactic-co-glycolic acid) (PLGA) scaffolds alone or coated with 140 ng (low dose) or 1400 ng (high dose) oxysterol cocktail were implanted into the defects. Rats were sacrificed at 6 weeks and examined by three-dimensional (3D) microcomputed tomography (microCT). Bone volume (BV), total volume (TV), and BV/TV ratio were measured. Culture exposure to SS for 10 min significantly increased ALP activity after 4 days, while 2 h exposure significantly increased mineralization after 14 days. Four-hour SS treatment increased OCN mRNA measured after 8 days and nuclear protein binding to an OSE2 site measured after 4 days. The calvarial defects showed slight bone healing in the control group. However, scaffolds adsorbed with low or high-dose oxysterol cocktail significantly enhanced bone formation. Histologic examination confirmed bone formation in the defect sites grafted with oxysterol-adsorbed scaffolds, compared to mostly fibrous tissue in control sites. Our results suggest that brief exposure to osteogenic oxysterols triggered events leading to osteoblastic cell differentiation and function in vitro and bone formation in vivo. These results identify oxysterols as potential agents in local and systemic enhancement of bone formation. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:1488-1497, 2007 [ABSTRACT FROM AUTHOR]