Use of a xeno-hybrid bone graft and sticky bone preparation in mandibular regeneration complicated by Actinomyces infection: a case report

Comprehensive Periodontal Therapy: A Statement by the American Academy of Periodontology

Periodontal disease (PD), a chronic inflammatory condition characterized by destruction of the supporting tissues of the teeth, increases the risk of complications in diabetics. Diabetic retinopathy (DR) is a microvascular complication of prolonged hyperglycaemia. There appears to be a similarity in the pathogenesis of DR and PD. Hence, this study aimed to investigate the association, if any, between DR and PD, correlate the severity of DR with the severity of PD, and investigate the association between glycated haemoglobin (HbA1c), serum creatinine and periodontal variables. The periodontal status of 200 adult diabetic patients in the age group of 30–65 years with varying severity of DR was assessed. Evaluation of the severity of PD was assessed by recording clinical parameters. Haematological investigations including glycated haemoglobin (HbA1c) and serum creatinine were estimated before the initiation of treatment for DR. A statistically significant association between the mean duration of diabetes mellitus (DM) and the severity of DR and PD was found. The severity of PD was directly correlated with the severity of DR. There was a significant association between the levels of HbA1c and serum creatinine and severity of DR and PD. There could be a plausible relationship between DR and PD. Further prospective studies on a larger population with longer follow-ups are required to ascertain whether PD and its severity directly affect the progression and severity of DR.

This paper evaluates the prevalence and severity of periodontitis (PD) in patients with rheumatoid arthritis (RA), focusing on the link between the severity of PD with RA disease activity/disability scores, the influence of RA treatment on PD, and levels of vitamin D. A total of 93 RA patients were enrolled in the cross-sectional study and analyzed accordingly as RA-PD (N = 63, 67.8%) and RA-only (N = 30, 32.2%) groups. A number of associations between rheumatological clinical data, i.e., Disease Activity Score (DAS28 CRP), health assessment questionnaires, and PD severity (measured by periodontal outcome parameters) with regard to serum levels of vitamin D were assessed. The outcome variables were compared by parametric and non-parametric tests. A total of 29% of RA patients were diagnosed with severe PD. The RA-PD group presented a higher mean DAS28 CRP score in moderate-severe PD compared to periodontally healthy-initial stage PD subjects (4.49 ± 1.22 vs. 3.86 ± 1.58, p = 0.033). RA patients treated with biologic disease-modifying antirheumatic drugs (bDMARDs) were less likely to be diagnosed with PD (p = 0.022) and revealed significantly lower PD outcome parameters, i.e., bleeding on probing (%) and bone loss (%) (p < 0.05). Vitamin D concentration was significantly lower in RA-PD group with diagnosed advanced severe PD (IV stage) compared to moderate PD (II stage) (39.61 ± 17.12 vs. 52.07 ± 18.23 nmol/l, p = 0.031). The study revealed a high prevalence of severe PD in RA patients, being significantly associated with higher RA disease activity and lower vitamin D level in RA-PD group, while bDMARD treatment was related to lower PD outcome parameters. Key Points • Severe PD is prevalent amongst RA patients and is associated with RA disease activity. The higher RA DAS28 CRP score is associated with moderate-severe PD compared to periodontally healthy-initial stage PD in RA patients. • Biologic DMARDs treatment used for RA is linked to lower PD rates and PD outcome parameters. • Significantly lower vitamin D level is found in advanced severe PD compared to moderate PD stage in RA-PD subjects.

The integration and long-term success of dental implants exploit the unique biology of the oral cavity, which allows for osseous incorporation of a biomaterial and its long-term health within a bacteria-laden oral milieu.1 The delicate balance of defense and repair mechanisms underlying this unique environment may be challenged by various factors that can act both locally and/or systemically, thereby increasing the risk of implant loss and jeopardizing the long-term success of inserted implants. Local risk factors that are present in the oral cavity and systemic risk factors that have the potential to affect oral health on a systemic level can compromise implant treatment at all stages of treatment delivery by: (a) complicating surgical procedures and other invasive measures required during treatment; (b) compromising the process of tissue healing following implant insertion/increasing the risk of wound infection; and (c) contributing to the deterioration of long-term peri-implant health and tissue stability (Table 1). Reduced bone healing Reduced implant stability Reduced bone remodeling Reduced angiogenesis Reduced bone regeneration Acquired immunosuppression Hypovascularity Iatrogenic immunosuppression Reduced tissue regeneration Hypovascularity hypoxia Leukocyte dysfunction Conditions that interfere with invasive procedures, which include poor general health status (https://www.asahq.org/resources/clinical-information/asa-physical-status-classification-system) as a result of severe systemic disease, may impact upon implant surgery, healing, and maintenance. These are mostly cardiovascular conditions that can place the patient at high risk during surgery, irrespective of the nature of the intervention. Bleeding disorders, which may be innate or acquired, as well as attributable to the use of anticoagulants, may also complicate invasive measures. While the former are considered to be relatively rare, the latter may have a significant impact on daily implant treatment in an aging population. All these conditions can also have a negative impact on long-term peri-implant health and maintenance of peri-implant tissues as a result of compromised vascularity, as well as alterations in the immune defense or repair capacity of peri-implant tissues. The increasing patient demand for implant-based treatments in conjunction with a demographic shift of the patient population has resulted in a growing body of literature dealing with an increasing number of patients presenting with medical conditions. A recent cross-sectional analysis indicated that almost 90% of patients aged > 65 years were taking medication for underlying systemic diseases, which could jeopardize implant success.2 The advent of new treatment modalities, such as antiresorptive drugs or monoclonal antibody therapies, adds to the number of potential risk factors,3 leading to an increasing challenge for the provision of implant-based treatments in the future. The aim of this narrative review was therefore to analyze the importance of systemic and local conditions as risk factors for implant loss by critically evaluating the available evidence. During evaluation of the available literature, it was obvious that the term "implant loss" was used to a much lesser degree than "implant failure." Very few reports clearly defined implant failure as implant loss, but the context in which this term has historically been used indicates that implant failure was synonymous for implant loss. It is only in the last decade or so that definitions of implant failure have been published, and not until the 2017 World Workshop on Periodontal and Peri-Implant Disease Classification was an international definition agreed upon.4 One of the major reasons for implant loss is the progressive loss of peri-implant bone support. Therefore, marginal bone loss was also included in the analysis. As progressive crestal bone loss around implants in the absence of clinical signs of soft tissue inflammation is rare,5 reported radiographic bone loss was considered in conjunction with clinical peri-implant parameters (where provided) in the individual reports in order to assess the prognostic relevance of the findings. The effect of cardiovascular conditions on implant treatment has been mostly analyzed in cross-sectional cohort studies. In these reports, 15.6%-37%6-8 of patients were affected by cardiovascular diseases. Two recent multivariate analyses of large cohorts consisting of > 6300 and > 22 000 patients did not identify cardiovascular conditions as significant risk factors for implant loss6 or peri-implant pathology.9 This is in line with other cross-sectional studies of smaller cohorts.10-13 Cardiovascular conditions may, however, be associated with the maintenance of long-term peri-implant tissue health. Patients with diseased implants have shown a higher likelihood of cardiovascular comorbidity,8 and a recent prospective study of 44 patients with fixed mandibular prostheses demonstrated an association between cardiovascular disease and increased radiographic peri-implant bone loss.14 The available evidence currently suggests that cardiovascular conditions are not a major risk factor for implant loss. Although the radiographic bone loss reported had not been classified as progressive, cardiovascular disease should be taken into account in maintenance protocols as a potential comorbidity15 that may affect long-term peri-implant tissue health. Bleeding disorders can be innate, such as hemophilia A/B and von Willebrand–Jürgens Syndrome, or acquired during end stage liver disease, with subsequent deterioration of coagulation factors and platelet counts. The placement of implants in patients with hemophilia is rarely documented in case reports.16, 17 In contrast to this, patients with iatrogenic bleeding disorders as a result of anticoagulation therapy have been studied more frequently. Depending on the underlying disease, anticoagulation therapy may encompass antiplatelet drugs, vitamin K antagonists, or direct oral anticoagulants. There is widespread agreement that anticoagulation therapy with antiplatelet drugs or vitamin K antagonists should not be discontinued for dental surgical procedures, as long as a single drug is used and the level of activity is within the therapeutic range (international normalized ratio 2.5-3.0).18, 19 Some uncertainty exists about the management of patients using direct oral anticoagulants, but it is assumed that no interruption of therapy is required; consulting with the hematologist responsible for the patient's care is always advisable.20 Implant surgery in patients undergoing anticoagulation therapy has been reported in a number of controlled clinical studies, albeit consisting of rather small cohorts.21-24 Follow-up included an immediate postoperative period of 8-10 days. All the authors agreed that implants could be safely placed in patients with anticoagulation therapy without interruption of medication of vitamin K antagonists or direct oral anticoagulants. An exception to this may be dual anticoagulation therapy using two antiplatelet drugs (acetylsalicylic acid and clopidogrel), as is commonly employed following stenting of the coronary arteries. In these cases, postoperative morbidity may occur as a result of the increased risk of postoperative bleeding (Figure 1). Implant surgery should therefore be postponed until dual antiplatelet therapy has returned to single antiplatelet drug use. Depending on the type of stent used, this period may vary from 6 weeks to 6 months. To date, no information is available on implant complications arising in anticoagulated patients beyond the immediate period of surgical wound healing. The management of secondary interventions for soft tissue management or peri-implant diseases has not yet been reported on, but may have an impact on the long-term prognosis of implants, and should be taken into consideration when implants are planned for patients with anticoagulation management. Moreover, it should be noted that the necessity for anticoagulation therapy is commonly an underlying cardiovascular condition that needs to be explored and may require additional action. If anticoagulation therapy is used because of a cardiac condition associated with an increased risk for infective endocarditis, antibiotic prophylaxis is required.25 The necessity for antibiotic prophylaxis has been questioned based on a low risk of bacteremia during implant insertion,26 but adherence to current updates of national guidelines is strongly recommended.27, 28 Osteoporosis is characterized by a loss of structural quality of cancellous bone and a reduction in cortical bone thickness resulting in an overall deterioration of bone density. Approximately 48% of women and 15% of men aged ≥ 75 years are known to be affected.29 Primary osteoporosis can arise because of the loss of osteoanabolic effects of sex hormones (type I) in postmenopausal women (and some 10 years later in men), or because of age-related changes in general metabolism (type II). Osteoporosis may also arise secondary to endocrine diseases (eg, Cushing Syndrome, parathyroid hormone excess) or as a result of medication (eg, corticosteroids). Commonly, the diagnosis is derived from dual energy X-ray absorptiometry of the spine and/or the proximal femur. Dual energy X-ray absorptiometry scans provide a T-score that expresses the deviation of bone mineral density of the patient in standard deviations from the average value of healthy young adults. A T-score of < –2.5 is considered to be indicative of osteoporosis. Osteoporosis has been a concern in implant dentistry from an early stage in the development of the field.30-32 A number of papers have addressed the question of whether reduced skeletal bone density is associated with inferior bone quality in the maxilla or mandible. Subjectively, perceived jaw bone quality did not correlate with documented dual energy X-ray absorptiometry scores.33 Moreover, bone next to implants retrieved from osteoporotic patients did not exhibit a reduced number of bone cells or bone-to-implant contact.34 To identify individuals with reduced skeletal bone density, panoramic indices such as the mandibular cortex width,35 panoramic mandibular index,36 and the Klemetti index37 have been developed. A recent review reported these indices as useful in intercepting patients with reduced bone mineral density (T-score < 1), but did not recommend them to intercept patients with osteopenia/osteoporosis.38 Moreover, a systematic review examining the association between objective measures of jaw bone quality and skeletal bone mineral density was unable to clarify whether skeletal osteoporosis is associated with osteoporosis in the jaw bones.39 The role of osteoporosis in the success of implant treatment and the stability of marginal bone has been evaluated in a number of studies. Recent systematic reviews have found no difference in implant survival rates between patients with and without osteoporosis (risk ratio 1.9, 95% confidence interval 0.93-2.08, P = .11),40 or identified a direct but insignificant effect of osteoporosis on dental implant loss (risk ratio 1.09, 95% confidence interval 0.79-1.52).41 Similarly, earlier reviews and case control studies42-45 did not find evidence for an association between skeletal bone mineral density/osteoporosis and increased implant loss. With regard to peri-implant bone loss, the majority of recent studies (two cross-sectional,46, 47 one prospective,48 and one case control study49) reported no difference in radiographic peri-implant bone loss between patients with and without osteoporosis. Only one cross-sectional study reported significantly increased radiographic loss of marginal bone in osteoporotic patients after 1 year.50 All the patients in this study were part of a maintenance program with low periodontal indices and healthy periodontal conditions. Differences in radiographic bone level changes have been attributed to differences in bone remodeling in osteoporotic patients. The relevance of these findings with regard to long-term implant prognosis remains to be determined. While osteoporosis as such may not play a role in implant failure or loss of peri-implant bone, medications used for osteoporosis therapy may interfere with osseointegration and long-term maintenance of peri-implant health. The drugs prescribed are mostly either bisphosphonates51 or denosumab, a monoclonal antibody against the signaling molecule RANKL that is involved in the recruitment of osteoclasts. Bisphosphonates reduce both the resorptive activity of osteoclasts, as well as the activity of osteoblasts in a dose-dependent manner,52, 53 while denosumab directly reduces osteoclast activity.54 The net effect of the antiresorptive therapy is a decrease in bone turnover and remodeling activity of bone tissues. As remodeling is an essential part of bone regeneration and osseointegration, there has been some concern expressed regarding the capacity of peri-implant bone to incorporate implants inserted under bisphosphonate therapy. Controlled clinical trials have reported implant survival rates of 85.7%-100% in patients taking oral bisphosphonates55, 56 and of 100% for those receiving intravenous bisphosphonates.57 Recent meta-analyses of studies assessing the impact of bisphosphonates on implant treatment concluded that there is insufficient evidence for a negative effect of bisphosphonates on implant survival.58, 59 Besides the effect on implant survival, another aspect of the long-term use of antiresorptive agents is the risk of developing a medication-related necrosis of the jaw.60, 61 Medication-related necrosis of the jaw can be triggered by intra-oral surgical interventions and by bacterial invasion from odontogenic infectious lesions,62 as well as through pressure ulcers resulting from poorly fitting removable dentures.63 Triggering of the onset of medication-related necrosis of the jaw during the insertion of dental implants or through the occurrence of peri-implant infections during follow-up under antiresorptive medication is therefore a significant concern,64-66 and most often requires rather invasive measures for management (Figure 2A-G). The prevalence of medication-related necrosis of the jaw has been considered to depend in part on the route and frequency of bisphosphonate administration, with oral bisphosphonates presenting a lower risk for medication-related necrosis of the jaw than intravenous bisphosphonates. More recent reviews suggest that it is not the route of administration but the dosage of antiresorptive medication that affects the prevalence of medication-related necrosis of the jaw.59 The evidence reported for the occurrence of implant-related medication-related necrosis of the jaw under therapy with either bisphosphonates or denosumab is largely based on case reports64, 67-75 or retrospective case series.63, 76-84 In these reports, the number of cases reported for implant-related medication-related necrosis of the jaw in patients taking oral bisphosphonates is almost as high (n = 74) as in patients receiving intravenous bisphosphonates or denosumab (n = 84), suggesting that it is not the route of administration that is critical for the occurrence of implant-related medication-related necrosis of the jaw. Conversely, a number of case reports and case series reporting on implant treatment with concurrent oral bisphosphonate therapy did not find any cases of medication-related necrosis of the jaw in the patients studied.55, 65, 85-95 The existing level of evidence for an association between implant treatment and the occurrence of medication-related necrosis of the jaw under antiresorptive therapy remains low and needs to be substantiated by appropriately designed randomized controlled trials. Nevertheless, the overall number of reported cases of implant-associated medication-related necrosis of the jaw suggests that antiresorptive drugs need to be considered as a risk factor96 and explained to patients97 prior to the start of the treatment, as part of collecting informed consent. Despite the potential hazards of implant-associated medication-related necrosis of the jaw, implants can help to reduce the occurrence of medication-related necrosis of the jaw, for example, in edentulous patients under antiresorptive drugs by avoiding pressure ulcers resulting from poorly fitting dentures. Therefore, multiple factors need to be considered to inform a balanced decision on whether a patient with antiresorptive drugs is eligible for implant therapy (Table 2). If the majority of these factors indicate a low to moderate risk, implant therapy may also be a valid option in patients with antiresorptive medication. When oral surgical procedures are planned in patients with antiresorptive medication, antibiotic prophylaxis is recommended.98, 99 The ideal protocol for administration of antibiotics has not yet been defined. A clear recommendation is given for preoperative antibiotic coverage,100 however, the dosage and duration of postoperative continuation of antibiotic therapy remain to be determined. Adherence to national guidelines (if available) for the perioperative management of patients with antiresorptive medication is strongly advised. Diabetes mellitus is characterized by a lack of insulin secretion as a result of the loss of insulin-producing beta cells in the Langerhans islands of the pancreas (type 1) or by impaired insulin function because of the failure of insulin receptors to appropriately respond to the stimulation by insulin in the periphery (type 2). This results in constantly elevated blood glucose levels in people with diabetes, which leads to nonenzymatic glycation of numerous proteins to produce advanced glycation end products. An elevated level of advanced glycation end products leads to increased expression and activation of receptors for advanced glycation end products. These receptors are present on many cells (eg, endothelial cells, smooth muscle cells, fibroblasts, and mesanglial cells). Their activation mediates inflammatory reactions, which are considered to be responsible for alterations in the microvasculature and thereby can account for diabetic angiopathy.101 Interaction of advanced glycation end products with receptors for advanced glycation end products on macrophages is considered to be associated with macrophage dysfunction, leading to impaired wound healing in patients with diabetes.102 Moreover, bone regeneration is directly impaired on a molecular level in people with diabetes.103 Clinically, poor glycemic control has been shown to negatively affect the balance of bone growth factors in the peri-implant fluid during implant healing.104 Deterioration of vascularity in conjunction with a less efficient immunologic defense and a decreased regenerative capacity of peri-implant bone may compromise the success of implant treatment in patients with diabetes considerably. The effect of diabetes on implant success and the maintenance of peri-implant tissues has therefore been subject to research for more than 20 years. Numerous reviews have analyzed this relationship.105-115 A recent meta-analysis of 14 controlled clinical trials demonstrated that the risk ratio for implant loss between patients with and without diabetes was 1.07 (95% confidence interval 0.08-1.44), without a significant difference between the groups (P = .65).109 Failure to show an association between the existence of diabetes and an increased loss of dental implants is in line with previous reviews.20, 108, 113, 114, 116 The level of glycemic control as assessed by HbA1c appears to have no effect on implant survival rates, although patients with diabetes have demonstrated a compromised process of implant integration.104, 113, 117-119 Moreover, a recent consensus paper reported only inconclusive evidence for diabetes as a risk factor for peri-implantitis.5 While implant loss and peri-implant tissue health are obviously not affected by the presence of diabetes as such, management of the disease may play a role in the maintenance of peri-implant tissue health. A number of reports and systematic reviews have shown that patients with diabetes and poor glycemic control have an increased risk of peri-implantitis and associated peri-implant bone loss.76, 112, 120 This has been reported to become obvious at 2 years of follow-up compared with healthy individuals.107 However, when HbA1c is within the physiological range and oral hygiene is appropriate, the levels of inflammation have been shown to be reduced to those of healthy patients.121 The prophylactic use of antibiotics in oral surgical procedures in patients with diabetes is still controversial. Data from the scarcely available clinical studies favor the use of antibiotics but the evidence for their benefit is still low.122 The immune system is an indispensable part of tissue healing and repair. This holds true also for bone tissue, where pro-inflammatory cytokines are critical, not only for triggering regeneration but also for orchestrating subsequent bone remodeling.123 Moreover, both nonspecific and specific immune responses are crucial for the defense against bacterial invasion following surgery, as well as during the period of restoration and long-term usage. Immune deficiency can thus be critical for integration of dental implants and for the maintenance of peri-implant tissue health. Immune deficiency can result from a large number of conditions. With the exception of very rare innate immune defects, immune deficiencies are mostly acquired in nature. The nonspecific immune response can be affected by medications (immunosuppression/chemotherapy) and metabolic diseases (eg, diabetes mellitus), or because of chronic malnutrition. Specific immunity can also be reduced by immunosuppressive medication, as well as by hematological diseases and lymphotropic viruses (eg, HIV). Iatrogenic immunosuppression as a result of medications is probably the most frequent cause of immune deficiency in dental implant patients. A major indication for deliberate suppression of the immune response is organ transplantation. Organ transplant patients are treated with a combination of drugs that aim to reduce the proliferation of T-cells and to decrease the number of antigen-presenting cells to avoid rejection of the transplanted organ. Commonly, a combination of monoclonal antibody therapy, inhibitors of that and drugs with of is During the drug are high to immune after which are reduced for maintenance of interventions should not be planned during the of immune The effect of immunosuppression on the success of implant treatment in organ transplant patients has rarely been indicate that the peri-implant bone in a clinical information from a case series on patients with liver reported 100% success after Moreover, two prospective controlled studies found no significant difference in implant survival rates between organ transplant patients and after 1 and years of results without significant differences between groups have also been reported for clinical peri-implant soft tissue and for the of peri-implant The available evidence remains but suggests that the clinical results of implant treatment are and not significantly affected by immunosuppressive drugs used by organ transplant patients. of diseases in which immunosuppressive medication is used is the of diseases. The most for daily clinical are diseases, Syndrome, and disease, as well as conditions of oral and such as oral and systemic with oral or conditions that may largely cause local while such as or disease, may be of concern because of the systemic immunosuppressive medications immunosuppression in and in disease is by a combination of drugs, such as monoclonal against necrosis and drugs are a of agents that include and which are also used for immunosuppression in organ transplant diseases are characterized by and of clinical leading to a level of treatment during their This should be in when treatment for these patients. many patients have medication, the negative of this with regard to bone such as osteoporosis and decreased bone also be taken into osteoporosis is considered to be present at of ≥ These patients should be explored for receiving antiresorptive medication to avoid the There is very information available regarding patients with receiving dental implants. A retrospective evaluation of patients with an implant success of after The success rates but between patients with only and those with tissue diseases The stability of marginal bone by the medication drugs drugs and corticosteroids). The existence of tissue diseases was associated with a significant in peri-implant bone loss and higher bleeding indices compared with patients with an increased of peri-implant tissues to The of authors when examining a smaller cohort of patients with Moreover, a retrospective analysis of a cohort of patients did not identify as a significant risk factor for implant However, an of and systemic may these patients more to marginal peri-implant thus a maintenance The results available for patients with disease are Two cross-sectional analyses and one evaluation of cohorts of were by the examining early and implant loss and the role of implant the study one of the cross-sectional analyses identified a significant association between disease and implant the other cross-sectional study However, the of this is to as the number of patients in this cohort with disease was not diseases with oral Syndrome, systemic and oral in conjunction with dental implants, have largely been reported at an level for almost In and systemic were subject to early case reports years is considered to be critical for implant survival and not only as a result of medication, but more so because of leading to increased and bleeding as well as a higher frequency of As a result of the oral and patients with are often unable to removable and can benefit significantly from implant The level of evidence for the effect of on the success of implant treatment is Two case series and case reports provide into 17 patients with a of 99 implants, with 10 implants after years of Two recent retrospective cohort studies reported success rates of and soft tissues a higher but insignificant in the of patients with compared with healthy The existing thus suggests that implants in patients with are not significantly compromised by either the underlying disease or medication. The for peri-implant in these patients the elevated around in patients with Syndrome, and needs during is a disease associated with general of tissues resulting in reduced with subsequent with and dental has been reported in conjunction with dental implants on an level in individual and for two cases as

Periodontal disease (PD) is more common and severe in people with diabetes than the general population. The presence of severe PD is correlated with decreased survival, since it can potentially affect glycemic control and severity of complications in people with diabetes. We have reported that Medalists (people with T1DM of 50 years or longer duration) may have endogenous protective factors for the development of diabetic nephropathy (DN) and retinopathy (DR). This study assessed the prevalence of PD in the Medalist cohort and correlated it to the known risk factors of PD and diabetic complications. Severity of PD was defined in a subset (n=170) of Medalists with comparable characteristics of the whole cohort, according to the AAP criteria. The prevalence of severe PD was dramatically decreased in Medalists (13.5%) compared with other studies of people with diabetes of similar age, approximately 33%. Clinical parameters, such as male gender, chronological age, age at diagnosis, and total insulin dose were correlated positively with severity of PD (p=0.04, 0.01, 0.03, and 0.02, respectively), while duration of disease, hemoglobin A1c, BMI, and lipid profiles did not exhibit any correlation. Interestingly, detectible plasma C-peptide levels correlated inversely with severity of PD (p=0.04). Systemic inflammatory markers, such as plasma IL-6, clearly correlated positively with the severity of PD (p=0.01). Serum antibody titer against Porphyromonas gingivalis (Pg), a known pathogen of PD, trended with severity of PD (p=0.08). Amongst the various complications, only the prevalence of CVD correlated positively with severity of PD (p=0.02). These results suggest that Medalists are protected from severe PD even with hyperglycemia. The endogenous protective factors for PD could be similar to those for CVD, possibly related to endogenously produced insulin to neutralize the chronic inflammation caused by residual infection with Pg in the gingival tissues. Disclosure T. Shinjo: None. A. Ishikado: Employee; Self; Sunstar Inc.. Employee; Spouse/Partner; Sunstar Inc.. H. Hasturk: None. L.J. Tinsley: None. D.M. Pober: None. I. Wu: None. T.E. Van Dyke: None. R.J. Genco: None. G.L. King: Research Support; Self; Sanofi-Aventis.

Objective: The aim of this work was to review de literature about the role of mesenchymal stem cells in bone regenerative procedures in oral implantology, specifically, in the time require to promote bone regeneration.Study Design: A bibliographic search was carried out in PUBMED with a combination of different key words. Animal and human studies that assessed histomorphometrically the influence of mesenchymal stem cells on bone regeneration procedures in oral implantology surgeries were examined.Reults:- Alveolar regeneration: Different controlled histomorphometric animal studies showed that bone regeneration is faster using stem cells seeded in scaffolds than using scaffolds or platelet rich plasma alone. Human studies revealed that stem cells increase bone regeneration.- Maxillary sinus lift: Controlled studies in animals and in humans showed higher bone regeneration applying stem cells compared with controls.- Periimplantary bone regeneration and alveolar distraction: Studies in animals showed higher regeneration when stem cells are used. In humans, no evidence of applying mesenchymal stem cells in these regeneration procedures was found.Conclusion: Stem cells may promote bone regeneration and be useful in bone regenerative procedures in oral implantology, but no firm conclusions can be drawn from the rather limited clinical studies so far performed. Key words:Mesenchymal stem cells, bone regeneration, dental implants, oral surgery, tissue engineering.

The purpose of this study was to determine whether periodontal disease is associated with endothelial dysfunction and systemic inflammation. Epidemiological studies suggest that severe periodontal disease is associated with increased cardiovascular disease risk, but the mechanisms remain unknown. We assessed flow-mediated dilation and nitroglycerin-mediated dilation of the brachial artery using vascular ultrasound in 26 subjects with advanced periodontal disease and 29 control subjects. The groups were matched for age and sex, and patients with hypercholesterolemia, diabetes mellitus, hypertension, and history of cigarette smoking were excluded. We also examined serum levels of C-reactive protein using an established high-sensitivity method. Subjects with advanced periodontal disease had lower flow-mediated dilation compared with control patients (7.8+/-4.6% versus 11.7+/-5.3%, P=0.005). Nitroglycerin-mediated dilation was equivalent in the two groups. Subjects with advanced periodontitis exhibited higher serum levels of high-sensitivity C-reactive protein compared with healthy controls patients (2.3+/-2.3 versus 1.0+/-1.0 mg/L, P=0.03). Subjects with advanced periodontal disease exhibit endothelial dysfunction and evidence of systemic inflammation, possibly placing them at increased risk for cardiovascular disease.

Background: Hepatocyte growth factor (HGF), endogenous cytokine with pleiotropic repairing and regeneration properties in relation to most tissues and organs, contributes to the progression of periodontal disease (PD). Furthermore, PD is a significant health problem in patients with chronic renal failure (CRF). The role of HGF in the development of PD in this specific population was not a subject of research so far. Material and methods: The following groups were enrolled in the study: (1) 26 chronic hemodialysis (HD) subjects, (2) 26 patients treated by continuous ambulatory peritoneal dialysis (CAPD), (3) 28 predialysis CRF patients, (4) 26 subjects with advanced PD (without coexisting diseases), and (5) 20 healthy subjects without PDs. HGF level in saliva was measured using the immunoenzymatic method. Gingival index, papillary bleeding index, plaque index, and the loss of clinical attachment level were evaluated. Results: The HGF level in saliva of HD patients was twice higher than in that of subjects with healthy periodontium. Direct relationships between proper HGF level in saliva and the indices GI, PBI, and PI in CAPD-treated patients and with more severe PD were shown. It was found that PD is most advanced in HD patients, moderately in CAPD-treated patients and to the smallest extent in predialysis CRF patients. Conclusions: The HGF level in mixed saliva is the index of PD progression in subjects without renal failure and in CAPD-treated patients. PD is common in renal failure patients and is a significant problem concerning general health status.

FRI0059 Evaluation of Periodontitis in 100 Patients with Rheumatoid Artrititis from Argentina

There is a worldwide increase in individuals suffering ≥2 chronic diseases (multimorbidity), and the cause of combinations of conditions remains largely unclear. This pilot study analysed the prevalence of periodontal disease (PD) among (multi)-morbid patients at the outpatient clinic of internal medicine. PD is an inflammatory disease of the tooth supporting tissues and has a negative impact on the overall health. Data were obtained from 345 patients, on demographics, systemic conditions and presence of PD. The possible differences in the distribution of PD status among patients with/without multimorbidity and Medical Subject Headings (MeSH) disease chapters were explored. In total, 180 (52.2%) patients suffered from multimorbidity. The prevalence of severe PD was 16.2%, while the prevalence of mild and severe PD combined (Total PD) was 53.6%. Patients with disease chapter cardiovascular diseases (CVD) had a significantly higher prevalence of severe PD (odds ratio (OR) 2.33; 95% confidence interval (CI) 1.25, 4.33) and Total PD (OR 1.61; 95% CI 1.04, 2.50) than patients without CVD. After subsequent analyses, myocardial infarction was significantly associated with severe PD (OR: 4.68 (95% CI; 1.27 to 17.25)). Those suffering from multimorbidity showed to have a non-significant increased risk for severe (OR 1.27; 95% CI 0.69, 2.34) or Total PD (OR 1.23; 95% CI 0.81, 1.88). In conclusion, PD is highly prevalent in multimorbidity patients. Furthermore, PD was significantly prevalent in patients with CVD. However, larger epidemiological studies are necessary to confirm that the prevalence of PD is significantly increased among multimorbid patients.

Introduction:Over the past century, the dental literature has consistently reflected a controversy related to the effect of periodontal disease on the dental pulp. Nonetheless, practitioners are of the opinion that teeth having deep periodontal pockets show variable pulpal response, which may necessitate root canal treatment. Thus, this study aimed to evaluate the changes in pulp due to advanced periodontal disease.Materials and Methods:Forty caries-free teeth affected with severe periodontitis were collected from patients aged between 18 and 55 years. The collected teeth were stored in formalin for 24 h and were then decalcified and examined histologically after staining with hematoxylin and eosin to note the changes that occurred in pulp.Results:Pulpal calcification (52.62%) and partial necrosis of pulp (52.62%) were found to be the most common findings. Inflammation, which was found in 47.38% of the cases, ranged from mild to severe in most sections and was always chronic. Pulp with complete necrosis was seen in 26.32% of cases. Fibrosis and pulpal edema were seen in 36.84% of cases.Conclusion:In the presence of moderate to severe chronic periodontitis, degenerative changes such as inflammation, fibrosis, edema, calcification and necrosis were observed to variable degree.

Risk factors associated with early implant failure: A 5-year retrospective clinical study

Objective: This narrative review evaluates the therapeutic and regenerative uses of propolis in oral and maxillofacial surgery (OMFS), together with its chemical composition, biological effects, and clinical potential. Materials and Methods: Experimental, clinical, and review studies published between 2000 and 2025 were searched in PubMed, Scopus, and Web of Science using the terms “propolis,” “oral surgery,” “bone regeneration,” “MRONJ,” “implant,” and “wound healing.” Results: Propolis—rich in flavonoids, phenolic acids, and terpenoids—supports oral wound healing and bone regeneration via anti-inflammatory, antioxidant, and antimicrobial mechanisms. Preclinical and limited clinical data report accelerated epithelialization, enhanced osteogenic activity in bone defects, reduced peri-implant inflammation, and a potential protective effect against MRONJ. However, geographic/botanical variability in composition highlights the need for clinical standardization. Conclusion: Propolis is generally well tolerated and exhibits multimodal biological activity, with supportive potential in OMFS for wound healing, bone regeneration, and infection control. Confirmation of clinical efficacy and formulation standardization requires multicenter advanced-phase trials. Keywords: Propolis; Oral and Maxillofacial Surgery; Bone Regeneration; MRONJ; Wound Healing; Dental Implant.

National Trends in the Prevalence and Severity of the Periodontal Diseases

In the present study the function of the neutrophil, which exerts a major role in protection against bacterial infections, was assessed in patients with a family history of diabetes mellitus and severe periodontitis. The neutrophil chemotactic function of two groups of patients was compared, both exhibited severe periodontitis. One group had a family history of diabetes and is therefore classified as individuals with potential for abnormal glucose tolerance (Pot‐AGT Group). The other group had comparable levels of severe periodontal disease but did not have a family history of diabetes. Neither group showed evidence of systemic disease as assessed by an extensive medical history and a battery of clinical laboratory tests including CBC, SMA‐12, prothrombin time, urinalysis and glycosylated hemoglobin levels. The peripheral blood neutrophil chemotactic response of patients in both groups was measured using Boyden chambers charged with the standard chemotactic agents; endotoxin activated serum, E. coli culture supernate and formylmethionylleucylphenylalanine (FMLP), a synthetic chemotactic agent. Patients in both groups were compared on a day‐to‐day basis to systemically and periodontally healthy, age and sex matched controls. Thirteen of the 24 patients in the Pot‐AGT Group exhibited depressed neutrophil chemotaxis. In contrast, neutrophil chemotaxis was either normal or elevated in 19 of 20 patients who had no family history of diabetes, but had severe periodontal disease. One in this group showed depressed chemotaxis. The difference in neutrophil chemotactic function between these two groups was significant at the P &lt; 0.001 level. Hence, the relationship of a positive family history of diabetes and depressed neutrophil chemotaxis was demonstrated. These results support the concept that in subjects with depressed neutrophil function or numbers, severe periodontitis is likely to be seen. These results also raise the possibility that among individuals with adult periodontitis there may be heterogeneity; some may have an underlying host protective dysfunction such as depressed neutrophil chemotactic activity which predisposes them to more severe periodontal disease. Other adults may have normal neutrophil chemotaxis and still have severe periodontal disease which may result from factors such as long term exposure to more virulent periodontopathic organisms, or they may be afflicted with some, as yet undefined, host protective abnormality.