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PURPOSE: This review was conducted to systematically assess the impact of bisphosphonates (BPs) and denosumab, used as anti-resorptive therapies, on the incidence of dental implant failure. METHODS: Electronic and manual searches were performed in accordance with the described search protocol. Only articles that met the inclusion criteria were selected. The primary outcome was implant failure, while secondary outcomes included biological complications and comorbidities. Following data extraction, a quality assessment and meta-analysis were conducted. RESULTS: Fourteen eligible studies were included in the analysis following a qualitative evaluation. BP administration, regardless of the timing of anti-resorptive therapy, did not significantly increase the risk of implant failure (odds ratio [OR], 1.40; 95% confidence interval, 0.83-2.34). Subgroup analysis revealed a slightly higher, although statistically insignificant, risk of failure in patients with a follow-up period of 3 years or more compared to those with a follow-up duration of less than 3 years (with ORs of 2.82 and 1.53, respectively). Due to a lack of eligible studies, a meta-analysis for denosumab could not be conducted. CONCLUSIONS: Our findings suggest that BP treatment does not compromise the survival of dental implants. Specifically, in patients with osteoporosis, implant failure rates were not significantly influenced by the administration of BPs before the placement of dental implants, suggesting that low-dose BP therapy may not contraindicate implant placement. Nevertheless, regular check-ups and maintenance periodontal treatment must not be neglected, and concomitant biological factors should be considered to ensure the long-term success of implant rehabilitation.
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Objective: : This systematic review aimed to provide a comparative analysis of the treatment outcomes, including hard and soft tissues, postoperative stability, temporomandibular disorders (TMD), and quality of life (QoL), in patients with facial asymmetry who underwent orthognathic surgery. Methods: : The primary objective was to address the question, "How do different factors related to surgery affect the outcomes and stability of orthognathic surgery in the correction of facial asymmetry?" A meta-analysis was conducted on the outcome parameters, such as skeletal, dental, and soft tissue symmetry, TMD, QoL, and relapse, using the Hartung-Knapp-Sidik-Jonkman method for random-effects models. Subgroup analyses were conducted considering surgery-related factors such as surgical techniques (one-jaw vs. two-jaw), use of the surgery-first approach, utilization of computer simulation, and analytical methods employed to evaluate asymmetry (2D vs. 3D). Results: : Forty-nine articles met the inclusion criteria. The meta-analysis demonstrated a significant improvement in the symmetry of hard and soft tissues. The subgroup analysis indicated that the treatment outcomes showed significant improvement, regardless of the factors related to surgery. Changes in TMD signs and symptoms varied according to the surgical technique used. Quality of life improved in the facial, oral, and social domains. Skeletal relapse was observed during the follow-up. Conclusions: : Our findings support the positive outcomes of orthognathic surgery in the treatment of facial asymmetry in terms of skeletal and soft tissue improvements, stability, relief of TMD symptoms, and enhancement of QoL. However, most of the included studies showed a low certainty of evidence and high heterogeneity.
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OBJECTIVES: This study aimed to investigate the strain in the bone surrounding dental implants supporting a 4-unit bridge and assess the role of excessive strain as a possible risk factor for implant related sequestration (IRS) or peri-implant medication-related osteonecrosis of the jaw (PI-MRONJ). MATERIALS AND METHODS: A 3D-mandibular model was constructed using computed tomography and segmented it into cortical and cancellous bones. The 4-unit implant-supported bridges replacing the mandibular posteriors were constructed, and each featuring two, three, and four implants, respectively. The Young's modulus was assigned based on the quality of the bone. A maximum occlusal force of 200 N was applied to each implant in the axial and in a 30-degree oblique direction. RESULTS: The maximum principal strain of the fatigue failure range (> 3000 µÎµ) in the bone was analyzed. The volume fraction of fatigue failure was higher in poor-quality bone compared to normal bone and oblique load than in axial load. An increasing number of implants may dissipate excessive strain in poor-quality bones. CONCLUSIONS: Occlusal force applied to poor-quality bone can result in microdamage. Given that unrepaired microdamage may initiate medication-related osteonecrosis of the jaw, long-term occlusal force on fragile bones might be a risk factor. CLINICAL RELEVANCE: When planning implant treatment for patients with compromised bone status, clinical modifications such as strategic placement of implants and optimization of restoration morphology should be considered to reduce excessive strain which might be associated with IRS or PI-MRONJ.
Subject(s)
Dental Implants , Osteonecrosis , Humans , Bite Force , Elastic Modulus , MandibleABSTRACT
The mentum plays an important role in the aesthetics of the face, and genioplasty is performed to improve an unbalance of the mentum. Among the various surgical approaches, setback genioplasty is used to create an aesthetic jaw-end appearance by moving the mentum backward when it protrudes more than normal. However, conventional setback genioplasty may be aesthetically disadvantageous because the profile of the mentum could become flat. This case study attempted to overcome the limitations of conventional setback genioplasty by rotating the position of the menton and pogonion. We devised a new method for setback genioplasty by rotating the segment anteroinferiorly. Using virtual surgery, we were able to specify the range of surgery more accurately and easily, and the surgery time was reduced. This case report showed the difference in chin soft tissue responses between conventional setback genioplasty and setback genioplasty with rotation.
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OBJECTIVES: The aim of Working Group 3 was to address the influence of both material- and anti-resorptive drug- related factors on clinical and biological outcomes and complications in implant dentistry. Focused questions were addressed on (a) implant materials other than titanium (alloy)s, (b) transmucosal abutment materials and (c) medications affecting bone metabolism were addressed. MATERIALS AND METHODS: Three systematic reviews formed the basis for discussion in Group 3. Consensus statements and clinical recommendations were formulated by group consensus based on the findings of the systematic reviews. Patient perspectives and recommendations for future research were also conveyed. These were then presented and accepted following further discussion and modifications as required by the plenary. RESULTS: Zirconia is a valid alternative to titanium as material for implant and transmucosal components, allowing soft and hard tissue integration with clinical outcomes-identified by implant survival, marginal bone loss and peri-implant probing depths-up to 5-years comparable to titatnium. However, most of the evidence for zirconia implants is based on 1-piece implants limiting the indication range. Furthermore, based on expert opinion, zirconia transmucosal components might be preferred in the esthetic zone. In patients receiving low-dose bisphosphonate therapy, the rate of early implant failure is not increased, while the long-term effects remain poorly studied. Although it has not been sufficiently addressed, similar outcomes can be expected with low-dose denosumab. A drug holiday is not recommended when considering implant placement in patients treated with low-dose ARD. However, the specific therapeutic window, the cumulative dose and the administration time should be considered. Access to peri-implant supportive care is mandatory to prevent peri-implantitis-related medication-related osteonecrosis of the jaw (MRONJ) or implant-related sequestra (IRS). In patients receiving low-dose anti-resorptive drugs (ARD) therapy, the risk of complications related to implant placement is high, and implant procedures in this specific population should be strictly treated in a comprehensive multidisciplinary center. Finally, healthy dental implants should not be removed before low or high-dose ARD. CONCLUSIONS: Zirconia implants can be an alternative to titanium implants in selected indications. However, the current state of evidence remains limited, especially for 2-piece implant designs. Administration of low-dose ARD did not show any negative impact on early implant outcomes, but careful follow-up and supportive care is recommended in order to prevent peri-implant MRONJ and IRS. Implant placement in high-dose patients must be strictly considered in a comprehensive multidisciplinary center.
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Bone Density Conservation Agents , Dental Implants , Humans , Bone Density Conservation Agents/adverse effects , Titanium , AlloysABSTRACT
OBJECTIVES: To review the current evidence on the relationship between agents that affect bone homeostasis and dental implant failures. MATERIALS AND METHODS: Electronic searches for bisphosphonates, denosumab, methotrexate, corticosteroids, romosozumab, sunitinib, and bevacizumab were performed using PubMed, MEDLINE (OVID), EMBASE (OVID), Cochrane Central Register of Controlled Trials (Cochrane Library), Cochrane Oral Health Group Trials Register (Cochrane Library) and Web of Science (Thomson Reuters). Manual searches were also conducted to complement the digital searches for recent issues. RESULTS: Previous publications suggested that bisphosphonates do not compromise the survival of dental implants. However, one study documented an increased risk of implant failure in patients who had received high-dose of intravenous bisphosphonate therapy after implant rehabilitation. There has been an issue of MRONJ around implants in patients who have successfully received implant therapy before and after antiresorptive therapy, leading to late implant failure. Despite evidence on the detrimental effects of denosumab, methotrexate and corticosteroids on bone metabolism, their role in implant survival is not conclusive. CONCLUSIONS: At present, there is insufficient evidence to establish a potential connection between agents that affects bone homeostasis and implant failure. However, some studies have reported negative results for implant therapy. In addition, implant-related sequestration in patients who received anti-resorptive therapy, despite of successful osseointegration, is also noticeable. Although limited studies are available at present, clinicians should still carefully consider the potential hazards and take appropriate precautions to minimize the risks associated with the medications and implant therapy.
Subject(s)
Denosumab , Methotrexate , Humans , Denosumab/therapeutic use , Homeostasis , DiphosphonatesABSTRACT
BACKGROUND: Risk factors for developing medication-related osteonecrosis of the jaw (MRONJ) include the general condition of the patient, smoking habit, poor oral hygiene, and the type, duration, and administration route of the drug, dentoalveolar surgery, such as implant placement. This study aimed to discuss whether implants may induce osteonecrosis in older patients receiving long-term medication and to analyze the radiological pattern of the bone necrosis. METHODS: This study included 33 patients diagnosed with dental implant-associated medication-related osteonecrosis of the jaw. Data regarding the medical history, type of medication used, durations of administration, laboratory test results, onset of bone necrosis since implant placement, type of opposing teeth, and radiological pattern of the bone necrosis on cone-beam computed tomography were recorded in patients with and without implants. RESULTS: The most commonly used drug was bisphosphonate, with an average duration of use of 61.37 (± 53.72) months. The laboratory results showed average serum C-terminal cross-linking telopeptide (CTX) level of 0.23 ng/mL, vitamin D, 23.42 ng/mL, and osteocalcin, 4.92 ng/mL. Osteonecrosis occurred after an average of 51.03 (± 39.75) months following implant placement. Radiological evaluation revealed obvious sequestration in the implant-absent group, and the formation of a unit sequestration with an implant fixture (en bloc) was observed in the implant-present group. The patients underwent surgical treatment of sequestrectomy and explantation. CONCLUSION: Implant placement, especially loading, may be considered a potential risk factor for the development of osteonecrosis in patients undergoing antiresorptive treatment.
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BACKGROUND: This study aimed to analyze the clinical outcome and complications of narrow-diameter dental implants (NDIs) (diameter ≤3.5 mm). METHODS: The 274 NDIs that met the selection criteria from 2013 to 2018 were included in the retrospective study, and the survival rates (SVR) were compared. Mechanical complications included screw loosening and fractures of the implant components, such as the implant fixture, abutment, and prosthesis. In addition, marginal bone loss (MBL) was measured immediately after surgery and 1 year after loading. RESULTS: The 3-year cumulative SVR was 92.4%. Nineteen fixtures failed during the follow-up. The failure rate was significantly higher (OR=4.573, p<0.05) in smokers and was significantly higher in osteoporosis patients (OR=3.420, p<0.05). The vertical and horizontal values of MBL were 0.33±0.32 mm and 0.18±0.17 mm, respectively. Mechanical complications included screw loosening (5.5%) and porcelain fracture (2.2%), but no fractures of the fixture or components were observed. The choice of titanium and zirconium (TiZr) alloy implant was significantly more frequent in the posterior region. Bone graft was significantly more frequently done in the anterior region. CONCLUSIONS: According to the high SVR and stability of NDIs, the findings of the study suggest that NDIs may be a replacement for regular diameter dental implants (RDIs) and the use of TiZr alloy could extend the indication of NDIs. In the esthetic area, contour augmentation may be a reason for increasing the frequency of bone grafts.
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OBJECTIVES: To investigate the function of enamel matrix derivative (EMD)-liquid compared to EMD-gel (original Emdogain® with polyglycolic acid-carrier) in inducing soft tissue regeneration using a rat dorsal model. MATERIAL AND METHODS: Four subcutaneous pouches were created through dorsal skin incisions in 18 female Wistar rats and randomly allocated to the following groups: (1) sterile saline + non-crosslinked collagen matrix (CM), (2) EMD-gel + CM, and (3) EMD-liquid + CM. After 2 and 4 weeks of healing, the specimens were harvested and stained with Goldner's trichrome, hematoxylin and eosin, and were immunohistochemically stained with an anti-CD31 antibody. RESULTS: The EMD-liquid group showed the thickest connective tissue compared to the other groups, with statistical significance both at 2 (p < 0.001) and 4 weeks (p = 0.011 and 0.023, respectively). The number of multinucleated giant cells was not significantly different among the groups for both periods. Moreover, there was a tendency to have more blood vessels over a longer period, and the highest number of blood vessels was observed in the EMD-liquid group at 4 weeks (p = 0.009 and 0036, respectively). CONCLUSION: EMD-liquid-treated CM is advantageous compared to using CM alone or EMD-gel-treated CM, owing to the histomorphometric results that show significantly increased soft tissue thickness and number of blood vessels when EMD-liquid was pre-primed to CM. CLINICAL RELEVANCE: EMD with a liquid carrier may be an appropriate biologic supplement to provide cell-inducing properties to the CM scaffold and is clinically more beneficial for phenotype modification therapy than CM only and EMD-gel-treated CM.
Subject(s)
Collagen , Dental Enamel Proteins , Rats , Female , Animals , Rats, Wistar , Connective Tissue , Dental Enamel , Dental Enamel Proteins/pharmacology , Wound HealingABSTRACT
Nitrogen-containing bisphosphonates lead to the depletion of geranylgeranyl pyrophosphate involved in the mevalonate pathway. The effect of geranylgeraniol (GGOH) on human osteoblast and osteoclast activities suppressed by zoledronate was investigated in this study. The effect of GGOH on human osteoblasts and osteoclasts subjected to treatment with zoledronate was analyzed by assessing cell viability, osteoclast differentiation, resorption ability, gene expression, and protein synthesis. Cell viability suppressed by bisphosphonates in osteoblasts and osteoprogenitor cells was restored with GGOH. Osteoclast differentiation was analyzed by vitronectin receptor immunofluorescence staining, and the addition of GGOH to zoledronate significantly increased osteoclast differentiation compared with zoledronate alone. A trend of reversal of osteoclast resorption by GGOH was observed; however, it was not significant in all groups. The expression of ALP, type 1 collagen, and RUNX2 in osteoblasts was recovered by the addition of GGOH. Only CALCR expression in osteoclasts was significantly recovered by GGOH addition in the zoledronate group. Although the activities of osteoblasts and osteoclasts were not entirely restored, the possibility that the topical application of GGOH in MRONJ patients or patients with dental problems and bisphosphonates might lessen the risk of development and recurrence of MRONJ is shown.
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The aim of this study was to evaluate the effects of a partial glossectomy on volumetric changes of pharyngeal airway space (PAS) in patients with mandibular setback surgery. Overall, 25 patients showing clinical features related to macroglossia treated with mandibular setback surgery were included in this retrospective study. Subjects were divided into two groups: the control group (G1, n = 13, with BSSRO) and the study group (G2, n = 12, with both BSSRO and partial glossectomy). The PAS volume of both groups was measured by the OnDemand 3D program on CBCT taken shortly before operation (T0), 3 months post-operative (T1), and 6 months post-operative (T2). A paired t-test and repeated analysis of variance (ANOVA) were used for statistical correlation. Total PAS and hypopharyngeal airway space were increased after operation in Group 2 compared to Group 1 (p < 0.05), while oropharyngeal airway space showed no significant statistical difference with the tendency of increasing. The combination of partial glossectomy and BSSRO surgical techniques had a significant effect on increasing the hypopharyngeal and total airway space in class III malocclusion patients (p < 0.05).
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Antibiotic resistance has emerged as a global threat to modern healthcare systems and has nullified many commonly used antibiotics. ß-Lactam antibiotics are among the most successful and occupy approximately two-thirds of the prescription antibiotic market. They inhibit the synthesis of the peptidoglycan layer in the bacterial cell wall by mimicking the D-Ala-D-Ala in the pentapeptide crosslinking neighboring glycan chains. To date, various ß-lactam antibiotics have been developed to increase the spectrum of activity and evade drug resistance. This review emphasizes the three-dimensional structural characteristics of ß-lactam antibiotics regarding the overall scaffold, working mechanism, chemical diversity, and hydrolysis mechanism by ß-lactamases. The structural insight into various ß-lactams will provide an in-depth understanding of the antibacterial efficacy and susceptibility to drug resistance in multidrug-resistant bacteria and help to develop better ß-lactam antibiotics and inhibitors.
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BACKGROUND: As society becomes more complex, the incidence of mandibular fractures is increasing. This study aimed to analyze the incidence and type and identify etiological factors of mandibular fractures to use them in future treatments. MATERIAL AND METHODS: Data were collected from 224 patients who visited the department of oral and maxillofacial surgery at the Kyung Hee Medical Center dental hospital during a 6-year period (2016 to 2021). A logistic regression model was used for data analysis. RESULTS: In a total of 224 patients, 362 fractures were appeared. The average age of the patients was 34.1 years, with the highest incidence in the 20s. And the ratio between male and female was 4.09:1. Symphysis fractures were the most prevalent of all patients (52.7%), followed by unilateral condyle (37.1%), angle (36.2%), bilateral condyle (9.4%), body (8%), and coronoid (2.2%). The most common cause of fracture was daily-life activity (57.6%), followed by violence (30.4%), traffic accidents (8.5%), and syncope (3.6%). Patients with symphysis fracture were at low risk (OR < 1) of angle, body, and unilateral condyle fractures. Similarly, patients with unilateral fracture were at low risk (OR < 1) of symphysis, angle, body, and others site fractures. In contrast, patient with bilateral condyle fracture were at high risk (OR > 1) of coronoid fractures. And younger patients were high risk of mandibular angle fractures. CONCLUSION: Through this study, it was confirmed that etiological factors of mandibular fractures were like those of previous studies.
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Antiresorptives are the most widely prescribed drugs for the treatment of osteoporosis. They are also used in malignant bone metastases, multiple myeloma, and Paget's disease, and provide therapeutic efficacy on those diseases. However, it was reported that the occurrence of osteonecrosis of the jaw (ONJ) could be related to antiresorptive exposures, and there have been many cases regarding this issue. Therefore, a clearer definition and treatment guidelines were needed for this disease. The American Society for Bone and Mineral Research and the Amnerican Association of Oral and Maxillofacial Surgeons reported statements on bisphosphonate-related ONJ (BRONJ), and a revised version was recently presented. In the revised edition, the diagnosis BRONJ was changed to medication-related ONJ (MRONJ), which reflects consideration of the fact that ONJ also occurs for denosumab, a bone resorption inhibitor of the receptor activator of the nuclear factor-κB ligand antibody family, and bevacizumab, an anti-angiogenesis inhibitor. The Korean Society for Bone and Mineral Research and the Korean Association of Oral and Maxillofacial Surgeons had collectively formed a task force for the preparation of an official statement on MRONJ based on a previous position paper in 2015. The task force reviewed current knowledge and coordinated dental and medical opinions to propose the guideline customized for the local Korean situation.
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BACKGROUND: Foreign bodies may be embedded or left behind in the oral cavity during oral surgical procedure. The loss of instruments such as impression material, surgical gauze, and broken injection needles are commonly reported in the dental field. These complications are generally symptomatic and show signs of inflammation, pain, and purulent discharge. Accidental breakage of suture needles is a rare but potentially dangerous event. CASE PRESENTATION: In this report, we present one case of lost suture needle during the procedure of flap operation at local dental clinic and its successful removal under local/general anesthesia administration via CBCT with a help of two reference needles to localize the 6-0 nylon needle and consulting with the clinician. CONCLUSION: CT scanning taken while mouth-closing may not be accurate with regard to real location measurement performed while mouth-opening. If so, other up-to-date radiographic devices and methods to retrieve a needle are recommended.
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The aim of this study was to investigate the effect and timing of recombinant human parathyroid hormone analog (PTH) administration for preventing medication-related osteonecrosis of the jaws (MRONJ) using a murine model. After standardized MRONJ induction using zoledronic acid and dexamethasone injections, 48 female Sprague-Dawley rats were divided into four groups according to the timing of PTH administration before or after dental extraction. Rats were euthanized 3 weeks after dental extraction, followed by clinical and histologic analyses. No clinical improvements were observed in the preoperative and postoperative PTH groups, compared to controls (p = 0.638 and 0.496, respectively). However, on histological analysis, the number of empty lacunae reduced significantly, and the number of blood vessels increased in the preoperative PTH group (p = 0.004 and 0.002, respectively). The postoperative PTH group did not show significant differences for empty lacunae and blood vessels compared to controls (p = 0.075 and 0.194, respectively). The reduction in the empty lacunae and the increase in the blood vessels in the preoperative PTH group were significant compared to other groups, suggesting more viable bone tissue in this group. In perspective, preoperative PTH use may represent a better prophylactic regimen for preventing the occurrence of MRONJ after traumatic dental or surgical procedures, especially in patients with a history of long-term bisphosphonate administration or at high risk of developing MRONJ. However, the findings should be proven in further studies on other animals followed by clinical trials.
Subject(s)
Bisphosphonate-Associated Osteonecrosis of the Jaw , Bone Density Conservation Agents , Animals , Bisphosphonate-Associated Osteonecrosis of the Jaw/etiology , Bisphosphonate-Associated Osteonecrosis of the Jaw/prevention & control , Bone Density Conservation Agents/adverse effects , Diphosphonates/adverse effects , Disease Models, Animal , Female , Humans , Jaw , Mice , Parathyroid Hormone , Rats , Rats, Sprague-DawleyABSTRACT
OBJECTIVES: This study aimed to investigate the association between dental implant therapy and osteonecrosis of the jaw (ONJ) in osteoporotic patients and the relationship between tooth extraction, dental implantation, and ONJ. MATERIAL AND METHODS: This retrospective cohort study used the Customized Health Information Data from the National Health Insurance Corporation in South Korea. The study population included patients older than 70 years with a history of osteoporosis; the cases included patients who had undergone dental implant surgery between July 2014 and July 2016 with specific procedure codes. The case and control cohorts were stratified by tooth extraction because it was the strongest risk factor to consider in this study. Each group of patients was matched using the propensity score. To investigate the relationship between dental implants and ONJ, a Cox proportional hazard model was applied to socio-economic factors, comorbidities, and bisphosphonates (BPs). All analyses were conducted using SAS statistical software. RESULTS: Based on the fully adjusted model, the propensity score-matched osteoporosis patients with dental implants had a 0.51 times hazard ratio of osteonecrosis. On the contrary, tooth extraction was associated with a higher risk of ONJ (HR = 5.89). The patients with rheumatoid arthritis (RA) and those using BPs had a higher HR, respectively, 6.80 and 4.09 HR (p < .001). CONCLUSIONS: Dental implantation was not a risk factor and patients with implants show rather lower ratios. However, older osteoporotic Korean patients who had undergone tooth extraction had higher risks of ONJ. A significantly higher risk of ONJ was associated with RA and BPs as well.
Subject(s)
Bisphosphonate-Associated Osteonecrosis of the Jaw , Bone Density Conservation Agents , Dental Implants , Osteoporosis , Aged , Bisphosphonate-Associated Osteonecrosis of the Jaw/epidemiology , Bisphosphonate-Associated Osteonecrosis of the Jaw/etiology , Cohort Studies , Dental Implants/adverse effects , Diphosphonates , Humans , Osteoporosis/epidemiology , Propensity Score , Republic of Korea/epidemiology , Retrospective Studies , Risk FactorsABSTRACT
Metallo-ß-lactamases (MBLs) hydrolyze almost all ß-lactam antibiotics, including penicillins, cephalosporins, and carbapenems; however, no effective inhibitors are currently clinically available. MBLs are classified into three subclasses: B1, B2, and B3. Although the amino acid sequences of MBLs are varied, their overall scaffold is well conserved. In this study, we systematically studied the primary sequences and crystal structures of all subclasses of MBLs, especially the core scaffold, the zinc-coordinating residues in the active site, and the substrate-binding pocket. We presented the conserved structural features of MBLs in the same subclass and the characteristics of MBLs of each subclass. The catalytic zinc ions are bound with four loops from the two central ß-sheets in the conserved αß/ßα sandwich fold of MBLs. The three external loops cover the zinc site(s) from the outside and simultaneously form a substrate-binding pocket. In the overall structure, B1 and B2 MBLs are more closely related to each other than they are to B3 MBLs. However, B1 and B3 MBLs have two zinc ions in the active site, while B2 MBLs have one. The substrate-binding pocket is different among all three subclasses, which is especially important for substrate specificity and drug resistance. Thus far, various classes of ß-lactam antibiotics have been developed to have modified ring structures and substituted R groups. Currently available structures of ß-lactam-bound MBLs show that the binding of ß-lactams is well conserved according to the overall chemical structure in the substrate-binding pocket. Besides ß-lactam substrates, B1 and cross-class MBL inhibitors also have distinguished differences in the chemical structure, which fit well to the substrate-binding pocket of MBLs within their inhibitory spectrum. The systematic structural comparison among B1, B2, and B3 MBLs provides in-depth insight into their substrate specificity, which will be useful for developing a clinical inhibitor targeting MBLs.
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OBJECTIVES: This study aimed to verify the effectiveness of EMD-liquid in combination with a synthetic bone substitute in a rabbit calvarial model. MATERIAL AND METHODS: Four 7-mm outer diameter circular slits were created in the calvaria of 10 New Zealand white rabbits, and polycarbonate cylinders were inserted into the slits. Two experimental groups were established: (1) EMD-liquid + bone substitute (Osteon III®; biphasic calcium phosphate (BCP), ß-TCP/HA = 40:60) and (2) saline + bone substitute (Osteon III®; BCP). The cylinders were filled with saturated graft materials and covered with polycarbonate caps. Micro-CT and histomorphometric evaluation were conducted. RESULTS: In the histomorphometric analysis, new bone formation was significantly higher in the bone substitute (BS) + EMD-liquid group than in the BS only group at both 5 and 10 weeks (p < 0.01). There were statistically significant differences in the material area between the bone substitute and bone substitute + EMD-liquid groups at only 5 weeks (p < 0.05). The BS + EMD-liquid group demonstrated reduced material area to a greater extent. In micro-CT analysis, the BS + EMD-liquid group (27.04 ± 8.06 at 5 weeks, 28.49 ± 9.22 at 10 weeks) showed a significantly higher percentage of mineralized tissue volume at both 5 and 10 weeks (p < 0.05) than the BS only group. CONCLUSION: EMD-liquid enhances new bone formation when combined with BCP bone substitute in an animal model. Moreover, the EMD-liquid + BS has significantly lesser material area than BS alone, indicating accelerated graft degradation. Further studies on types of graft materials are required to verify the effect of EMD-liquid and to optimize its regenerative potential. CLINICAL RELEVANCE: This study suggests that EMD-liquid may have beneficial effect on bone regeneration with synthetic bone substitute.