Mario Gabriele

Surgery-triggered and non surgery-triggered Bisphosphonate-related Osteonecrosis of the Jaws (BRONJ): A retrospective analysis of 567 cases in an Italian multicenter study

Invasive local procedures are often reported in clinical history of patients suffering from Bisphosphonates-Related Osteonecrosis of the Jaws (BRONJ) but over 40% of spontaneous forms have been also described in literature. We compared age, gender, underlying bone disorders, bisphosphonate therapy, clinical features and surgical outcome of 205 cases (36.2%) of BRONJ non surgery-triggered (group 1) with 362 (63.8%) cases of surgery-triggered forms (group 2). Differences between group 1 and 2 were analysed using Mann-Whitney U and χ(2) tests. Statistical analysis was performed using STATA 8. Zoledronate was the most used type of bisphosphonate (63.4% versus 69.0%) and the mandible was the most frequently involved site (63.9% versus 63.4%) in both groups. BRONJ in group 1 was more frequently multicentric (9.3% versus 5%, p<0.05), had a lower clinical stage (45.9% versus 13.8% in stage 1, p<0.01) and had a better outcome after surgical therapy (improvement in 74.1% versus 58.6%, p<0.05). The high prevalence of non surgery-triggered forms of BRONJ should be considered by oncologists, haematologists and general physicians who are advised to inform their patients regarding the importance of preventive dental protocols to control the possible causes of osteonecrosis not related to dental invasive procedures.

Activity of human beta-defensin 3 alone or combined with other antimicrobial agents against oral bacteria

ABSTRACT The in vitro activities of human β-defensin 3 (hBD-3) alone or combined with lysozyme, metronidazole, amoxicillin, and chlorhexidine were investigated with the oral bacteria Streptococcus mutans, Streptococcus sanguinis, Streptococcus sobrinus, Lactobacillus acidophilus, Actinobacillus actinomycetemcomitans, and Porphyromonas gingivalis. hBD-3 showed bactericidal activity against all of the bacterial species tested. The bactericidal effect was enhanced when the peptide was used in combination with the antimicrobial agents mentioned above.

Resective surgical approach shows a high performance in the management of advanced cases of bisphosphonate-related osteonecrosis of the jaws: a retrospective survey of 347 cases.

PURPOSE The aim of this study was to evaluate the results of the surgical treatment of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in a large cohort. MATERIALS AND METHODS A retrospective cohort multicenter study was designed. Patients were enrolled if they were diagnosed with BRONJ and received operative treatment. Data on demographic, health status, perioperative, and surgical factors were collected retrospectively. The primary outcome variable was a change in BRONJ staging (improvement, worsening, or no change). Interventions were grouped by local debridement and resective surgery. Data were collected for other variables as cofactors. Univariate analysis and logistic regressions were then performed. RESULTS Of the 347 BRONJ-affected subjects, 59% showed improvement, 30% showed no change, and 11% showed worsening. Improvement was observed in 49% of cases treated with local debridement and 68% of cases treated with resective surgery. Multivariate analysis indicated that maxillary location, resective surgery, and no additional corticosteroid treatment were associated with a positive outcome. CONCLUSIONS Surgical treatment of BRONJ appeared to be more effective when resective procedures were performed. Nonetheless, other factors, such as the absence of symptoms and the types of drug administration, should be taken into account before clinical decisions are made.

Staging of osteonecrosis of the jaw requires computed tomography for accurate definition of the extent of bony disease

Management of osteonecrosis of the jaw associated with antiresorptive agents is challenging, and outcomes are unpredictable. The severity of disease is the main guide to management, and can help to predict prognosis. Most available staging systems for osteonecrosis, including the widely-used American Association of Oral and Maxillofacial Surgeons (AAOMS) system, classify severity on the basis of clinical and radiographic findings. However, clinical inspection and radiography are limited in their ability to identify the extent of necrotic bone disease compared with computed tomography (CT). We have organised a large multicentre retrospective study (known as MISSION) to investigate the agreement between the AAOMS staging system and the extent of osteonecrosis of the jaw (focal compared with diffuse involvement of bone) as detected on CT. We studied 799 patients with detailed clinical phenotyping who had CT images taken. Features of diffuse bone disease were identified on CT within all AAOMS stages (20%, 8%, 48%, and 24% of patients in stages 0, 1, 2, and 3, respectively). Of the patients classified as stage 0, 110/192 (57%) had diffuse disease on CT, and about 1 in 3 with CT evidence of diffuse bone disease was misclassified by the AAOMS system as having stages 0 and 1 osteonecrosis. In addition, more than a third of patients with AAOMS stage 2 (142/405, 35%) had focal bone disease on CT. We conclude that the AAOMS staging system does not correctly identify the extent of bony disease in patients with osteonecrosis of the jaw.

Effects of non‐surgical periodontal therapy on the glomerular filtration rate of the kidney: an exploratory trial

OBJECTIVE To determine whether non-surgical periodontal treatment (PT) would exert, in subjects with generalized chronic periodontitis (GCP), some beneficial effect on renal function as indicated by surrogate measures of the glomerular filtration rate (GFR). MATERIAL AND METHODS Twenty GCP systemically healthy subjects were treated with PT. Serum samples were collected at baseline and 1 day, 7, 30, 90 and 180 days after treatment. GFR was evaluated using cystatin C, a serum marker and modification of diet in renal disease (MDRD), an equation involving creatinine, urea and albumin. Serum markers of systemic inflammation such as C-reactive protein (CRP), D-dimer, serum amyloid A (SAA) and fibrinogen were also assessed. RESULTS The cystatin C level decreased significantly from baseline to the end of the trial (p<0.01). Conversely, MDRD did not vary. A significant inflammatory reaction was produced by PT in the short term. Greater increases were noted for CRP and SAA within 24 h (p<0.001 versus baseline), while D-dimer (p<0.05) and fibrinogen (p<0.01) showed mild variations. The values of inflammatory markers were normalized after 30 days. CONCLUSIONS GFR, as assessed by cystatin C levels, may be positively affected by PT. Because of the exploratory nature of this trial, further research is needed to investigate this preliminary finding.

Clinical performance of access flap surgery in the treatment of the intrabony defect. A systematic review and meta‐analysis of randomized clinical trials

AIM To systematically review the literature and to determine the clinical performance of conservative surgery (CS) for the treatment of intrabony defects (ID). METHODS RCTs on ID treatment with 12 months of follow-up were identified through electronic databases and hand-searched journals. Primary outcomes were tooth survival, clinical attachment (CAL) gain, probing depth (PD) reduction and gingival recession increase (REC). Weighted means and forest plots were calculated for each outcome variable 12 months after surgery. Long-term stability was explored with RCTs of at least 24 months of follow-up. Subgroup analysis was performed according to the type of flap. RESULTS Twenty-seven trials reporting 647 subjects and 734 defects were identified. Twelve months after CS, tooth survival was 98% (IQ: 96.77-100), CAL gain 1.65 mm (95% CI: 1.37-1.94; p < 0.0001), PD reduction 2.80 mm (CI: 2.43-3.18; p < 0.0001) and REC increase 1.26 mm (CI: 0.94-1.49; p < 0.0001). Longer follow-up showed similar findings. CI of CAL gain were 1.44-3.52 for recently introduced papilla preservation flaps and 1.25-1.89 mm for access flaps. CONCLUSIONS The treatment of intrabony defect with CS is associated with high tooth retention and improvement of periodontal clinical parameters. Clinical performance may vary according to the type of surgical flap used.

Up to a quarter of patients with osteonecrosis of the jaw associated with antiresorptive agents remain undiagnosed.

Recent data suggest that the traditional definition of bisphosphonate-associated osteonecrosis of the jaw (ONJ) may exclude patients who present with the non-exposed variant of the condition. To test the hypothesis that a proportion of patients with ONJ remain undiagnosed because their symptoms do not conform to the traditional case definition, we did a secondary analysis of data from MISSION (Multicentre study on phenotype, definition and classification of osteonecrosis of the jaws associated with bisphosphonates), a cross-sectional study of a large population of patients with bisphosphonate-associated ONJ who were recruited in 13 European centres. Patients with exposed and non-exposed ONJ were included. The main aim was to quantify the proportion of those who, according to the traditional case definition, would not be diagnosed with ONJ because they had no exposed necrotic bone. Data analysis included descriptive statistics, median regression, and Fishers exact test. A total of 886 consecutive patients were recruited and 799 were studied after data cleaning (removal or correction of inaccurate data). Of these, 607 (76%) were diagnosed according to the traditional definition. Diagnosis in the remaining 192 (24%) could not be adjudicated, as they had several abnormal features relating to the jaws but no visible necrotic bone. The groups were similar for most of the phenotypic variables tested. To our knowledge this is the first study in a large population that shows that use of the traditional definition may result in one quarter of patients remaining undiagnosed. Those not considered to have ONJ had the non-exposed variant. These findings show the importance of adding this description to the traditional case definition.

Systemic inflammation following non-surgical and surgical periodontal therapy

AIM To describe the kinetics of serum inflammatory markers after a course of treatment comprising surgical and non-surgical treatment of chronic periodontitis (CP). MATERIAL AND METHODS Fourteen CP cases received full-mouth non-surgical treatment and, after 6 months, at least two surgical sessions. Blood samples were collected at various time-points after treatment. Blood markers of systemic inflammation/coagulation including leucocyte counts, C-reactive protein (CRP), serum amyloid-A (SAA) and D-dimers and renal function (cystatin C) were determined using high-sensitivity assays. RESULTS Periodontal treatment resulted in substantial reductions of the number of pockets, gingival bleeding and plaque at 3 and 6 months after non-surgical therapy (p<0.001). Surgical therapy led to an additional reduction of periodontal pockets (p<0.01). Marked increases in the serum levels of CRP and SAA were noted 24 h after non-surgical therapy (p<0.01) and periodontal surgeries (p<0.05). D-dimer levels increased drastically 24 h after non-surgical therapy (p<0.05). The drastic increase of CRP after non-surgical therapy was greater than both the surgical therapy sessions (p<0.05). CONCLUSIONS Patients undergoing periodontal treatment experience perturbations of systemic inflammation of a greater magnitude after non-surgical than surgical periodontal therapy.

Reduced Human Beta Defensin 3 in Individuals with Periodontal Disease

The human beta defensin 3 (hBD3) is widely expressed in the oral cavity and exerts strong antibacterial and immunomodulatory activities. Hence, we hypothesized that hBD3 could play a protective role in the maintenance of periodontal homeostasis, and that it could be found in gingival crevicular fluid (GCF) of healthy individuals and those with periodontitis at levels correlating with the degree of periodontal health. By using an ELISA assay to quantify hBD3 in GCF, we demonstrated that the peptide is present at levels easily detectable in the majority of healthy individuals, but it is drastically reduced in GCF from those with periodontitis. Furthermore, hBD3 levels inversely correlate with the severity of the disease and the degree of colonization by combinations of bacterial species with elevated periodontopathogenic potential. Both genetic factors and host/bacterial proteases released in diseased sites may be responsible for the observed low/null hBD3 levels in GCF from individuals with periodontitis.

Effect of laser micromachining of titanium on viability and responsiveness of osteoblast-like cells.

Objectives:Laser engineering may create hemispherical porosities on titanium surfaces obtaining regular and predetermined rough titanium surfaces. The aim of this study was to assess the viability and the proliferation of primary osteoblast-like cells (OB) to growth factors on titanium surfaces with a different roughness in vitro. Materials and Methods:OB were obtained from volunteers undergoing wisdom tooth removal following a standardized protocol. OB were allowed to attach on 4 different titanium surfaces: sandblasted titanium (SBT) disks, 5-, 10-, and 20-&mgr;m regular laser-engineered micropore titanium disks. A well with no disk was used as control. Cell morphology was evaluated with scanning electron microscopy. Viability was measured with MTT (3[4,5 dimethylthiazol 2yl]2,5 diphenyltetrazolium bromide) assay. Proliferation rate of attached cells was evaluated with Cell Counting Kit-8 48 hours after platelet-released supernatant (PRS) application. Statistical analysiswas performed with analysis of variance test. Results:All surfaces showed OB attachment on scanning electron microscopy. OB appeared more numerous on 20T surfaces. Laser-engineered surfaces showed higher OB viability than SBT (P < 0.01). In terms of proliferation, viability increase was noted for all groups after platelet-released supernatant application. 20T and SBT disks seemed to trigger the higher cellular proliferation (20T vs 10T, P < 0.05). Conclusions:Laser-engineered porous titanium surfaces promote viability and proliferation of OB. In particular, hemispherical porosity of 20 &mgr;m seems to trigger the higher OB response. Further research is needed to confirm these data.