The effect of systemic antibiotics on periodontal regeneration: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: The aim of this systematic review and meta-analysis was to evaluate the clinical efficacy of the use of systemic antibiotics in regenerative periodontal surgery for treating teeth affected by periodontitis. DATA SOURCES: Electronic (MEDLINE, EMBASE, LILACS, Scopus, and Cochrane) and manual literature searches for human randomized controlled trial studies published up to November 2022 were conducted by two reviewers. Meta-analysis was performed to assess probing pocket depth (PPD) reduction and clinical attachment level (CAL) gain in groups receiving systemic antibiotics compared to those not receiving systemic antibiotics. A total of eight studies were included. While treated sites were intrabony defects in six papers, two studies focused on furcation defects. For intrabony defects, the weighted mean difference (WMD) of 0.30 mm (95% CI -0.18 to 0.78) and 0.27 mm (95% CI -0.13 to 0.66) was calculated for PPD reduction and CAL gain, respectively. The differences between antibiotics and non-antibiotics groups for PPD and CAL were not statistically significant. Quantitative analysis could not be performed for furcation defects due to the limited number of studies. However, regardless of the membrane type selection, the existing evidence indicated that antibiotics did not lead to superior clinical outcomes for furcation defects at 9 to 12 months after the regenerative procedures. CONCLUSION: Based on this meta-analysis study's findings, the use of adjunct systemic antibiotics in regenerative periodontal surgery did not appear to achieve more favorable clinical outcomes. Thus, the use of adjunct systemic antibiotics as part of the regenerative periodontal therapy might not be justifiable and should be reconsidered. (Quintessence Int 2023;54:210-219; doi: 10.3290/j.qi.b3648957).

Periodontal Health and Systemic Conditions.

According to the new classification proposed by the recent 2017 World Workshop on Periodontal and Peri-implant Diseases and Conditions, periodontitis, necrotizing periodontal diseases, periodontitis as a manifestation of systemic diseases, and systemic diseases or conditions affecting the periodontal supporting tissues, are considered as separate entities. Scientific evidence has demonstrated that periodontal diseases are not just simple bacterial infections but rather complex diseases of multifactorial complexity that interplay with the subgingival microbes, the host immune, and inflammatory responses. Despite dental plaque biofilm being considered the primary risk factor for periodontitis in the vast majority of patients that dentists encounter on a daily basis, there are other factors that can also contribute and/or accelerate pathologic progressive attachment loss. In this article, the authors aim to briefly review and discuss the present evidence regarding the association between periodontal diseases and systemic diseases and conditions.

Wound Healing Complications Following Guided Bone Regeneration for Ridge Augmentation: A Systematic Review and Meta-Analysis.

PURPOSE: The rate of developing soft tissue complications that accompany guided bone regeneration (GBR) procedures varies widely, from 0% to 45%. The present review was conducted to investigate the rate for resorbable versus nonresorbable membranes and the timing of soft tissue complications. MATERIALS AND METHODS: Electronic and manual literature searches were conducted by two independent reviewers using several databases, including MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Cochrane Oral Health Group Trials Register, for articles published through July 2015, with no language restriction. Articles were included if they were clinical trials aimed at demonstrating the incidence of soft tissue complications following GBR procedures. RESULTS: Overall, 21 and 15 articles were included in the qualitative and quantitative synthesis, respectively. The weighted complication rate of the overall soft tissue complications, including membrane exposure, soft tissue dehiscence, and acute infection/abscess, into the calculation was 16.8% (95% CI = 10.6% to 25.4%). When considering the complication rate based on membrane type used, resorbable membrane was associated with a weighted complication rate of 18.3% (95% CI: 10.4% to 30.4%) and nonresorbable membrane with a rate of 17.6% (95% CI: 10.0% to 29.3%). Moreover, soft tissue lesions were reported as early as 1 week and as late as 6 months based on the included studies. CONCLUSION: Soft tissue complications after GBR are common (16.8%). Membrane type did not appear to significantly affect the complication rate, based on the limited number of data retrieved in this study. Technique sensitivity (ie, soft tissue management) may still be regarded as the main component to avoid soft tissue complications and, hence, to influence the success of bone regenerative therapy.

Recombinant human bone morphogenetic protein 2 outcomes for maxillary sinus floor augmentation: a systematic review and meta-analysis.

AIMS: To study the effect of the recombinant human bone morphogenetic protein 2 (rhBMP-2) on sinus volumetric and histometric changes after sinus floor augmentation compared to a conventional approach of non-biologic bone grafting materials. MATERIALS AND METHODS: An electronic search of 4 databases (January 1990-February 2015), including PubMed/MEDLINE, EMBASE, Web of Science and Cochrane Central, and a hand search of peer-reviewed journals for relevant articles were performed. Human clinical trials with data on comparison of sinus volumetric and/or histometric outcomes with and without the use of rhBMP-2 in sinus grafting procedures, with ≥10 augmentation sites in each study group, and with a follow-up period of at least 6 months, were included. Random-effects meta-analyses were performed to analyze weighted mean difference (WMD) and confidence interval (CI) for the recorded variables according to PRISMA guidelines. RESULTS: Six randomized controlled trials (RCTs) were included. The results of the meta-analyses showed that the WMD of vertical bone height gain was -0.14 mm (95% CI = -1.91 to 1.62 mm, P = 0.87), the WMD of bone density was -142.42 mg/cm3 (95% CI = -310.62-25.78 mg/cm3 , P = 0.10), the WMD of the percentage of vital bone was -4.59% (95% CI = -11.73-2.56%, P = 0.21), and the WMD of the percentage of residual bone grafting materials was -9.90% (95% CI = -26.38-6.58%, P = 0.21). The comparison of implant survival rate presented an overall risk ratio of 1.00 (95% CI = 0.94-1.07). The two approaches (conventional bone grafting compared to BMPs) demonstrated comparable effectiveness for both clinical and histomorphometric measures. CONCLUSIONS: This systematic review revealed that the use of rhBMP-2 in maxillary sinus floor augmentation achieved similar clinical and histometric outcomes when compared to conventional sinus grafting procedures after a healing period of 6-9 months. However, previous studies showed the morbidity and other patient-reported outcomes were improved in rhBMP-2 approaches as compared to bone autograft procedures (both intraoral and extraoral bone harvesting because no donor site is required). Long-term studies are required to determine the cost-benefit of sinus floor augmentation procedures for patients requiring implant reconstruction.

Site specificity of DSP-PP cleavage by BMP1.

Bone morphogenic protein 1 (BMP1), a metalloproteinase, is known to cleave a wide variety of extracellular matrix proteins, suggesting that a consensus substrate cleavage amino acid sequence might exist. However, while such a consensus sequence has been proposed based on P4 to P4' (i.e. the four amino acids flanking either side of the BMP1 cleavage site; P4P3P2P1|P1'P2'P3'P4') sequence homologies between two BMP1 substrates, dentin matrix protein 1 and dentin sialoprotein phosphophoryn (DSP-PP) (i.e. xMQx|DDP), no direct testing has so far been attempted. Using an Sf9 cell expression system, we have been able to produce large amounts of uncleaved DSP-PP. Point mutations introduced into this recombinant DSP-PP were then tested for their effects on DSP-PP cleavage by either Sf9 endogenous tolloid-related protein 1 (TLR-1) or by its human homolog, BMP1. Here, we have measured DSP-PP cleavage efficiencies after modifications based on P4-P4' sequence comparisons with dentin matrix protein 1, as well as for prolysyl oxidase and chordin, two other BMP1 substrates. Our results demonstrate that any mutations within or outside of the DSP-PP P4 to P4' cleavage site can block, impair or accelerate DSP-PP cleavage, and suggest that its BMP1 cleavage site is highly conserved in order to regulate its cleavage efficiency, possibly with additional assistance from its conserved exosites. Thus, BMP1 cleavage cannot be based on a consensus substrate cleavage site.

The efficiency of dentin sialoprotein-phosphophoryn processing is affected by mutations both flanking and distant from the cleavage site.

Normal dentin mineralization requires two highly acidic proteins, dentin sialoprotein (DSP) and phosphophoryn (PP). DSP and PP are synthesized as part of a single secreted precursor, DSP-PP, which is conserved in marsupial and placental mammals. Using a baculovirus expression system, we previously found that DSP-PP is accurately cleaved into DSP and PP after secretion into medium by an endogenous, secreted, zinc-dependent Sf9 cell activity. Here we report that mutation of conserved residues near and distant from the G(447)↓D(448) cleavage site in DSP-PP(240) had dramatic effects on cleavage efficiency by the endogenous Sf9 cell processing enzyme. We found that: 1) mutation of residues flanking the cleavage site from P(4) to P(4)' blocked, impaired, or enhanced DSP-PP(240) cleavage; 2) certain conserved amino acids distant from the cleavage site were important for precursor cleavage; 3) modification of the C terminus by appending a C-terminal tag altered the pattern of processing; and 4) mutations in DSP-PP(240) had similar effects on cleavage by recombinant human BMP1, a candidate physiological processing enzyme, as was seen with the endogenous Sf9 cell activity. An analysis of a partial TLR1 cDNA from Sf9 cells indicates that residues that line the substrate-binding cleft of Sf9 TLR1 and human BMP1 are nearly perfectly conserved, offering an explanation of why Sf9 cells so accurately process mammalian DSP-PP. The fact that several mutations in DSP-PP(240) significantly modified the amount of PP(240) product generated from DSP-PP(240) precursor protein cleavage suggests that such mutation may affect the mineralization process.