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BMC Oral Health Jun 2023Pro- and anti-inflammatory cytokines are acknowledged, during inflammatory bone destruction, as key regulators of osteoclast and osteoblast differentiation and activity.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pro- and anti-inflammatory cytokines are acknowledged, during inflammatory bone destruction, as key regulators of osteoclast and osteoblast differentiation and activity. However, evidence regarding the exact role of pro- and anti-inflammatory cytokines and osteoclastogenesis-related factors in peri-implant diseases is unclear. We aimed to execute a systematic review and meta-analysis about the pro- and anti-inflammatory cytokines and osteoclastogenesis-related factors levels in peri-implant diseases.
METHODS
The focused question was elaborated to summarize the levels of pro-and anti-inflammatory cytokines and osteoclastogenesis-related factors in tissue samples (mRNA) and biofluids (protein levels) of patients with/without peri-implant diseases. Electronic searches of the PubMed, Cochrane Controlled Trials Registry, Web of Science, EMBASE, Scopus and Google scholar databases were conducted for publications up to March 2023. Meta-analysis evaluating the mediator´s levels (protein levels by ELISA) in peri-implant crevicular fluid (PICF) were made. The effect size was estimated and reported as the mean difference. The 95% confidence interval was estimated for each mediator, and the pooled effect was determined significant if two-sided p-values < 0.05 were obtained.
RESULTS
Twenty-two publications were included in the systematic review (qualitative analysis), with nine of these subjected to meta-analyses (quantitative analysis). In the qualitative analysis, higher pro-inflammatory cytokines [Interleukin (IL)-1β, IL-6] and pro-osteoclastogenic mediator [Receptor Activator of Nuclear Factor-Kappa B ligand (RANKL)] levels were observed in PICF of individuals with peri-implant diseases in comparison to healthy individuals. Higher RANKL/osteoprotegerin (OPG) ratios were observed in PICF from individuals with peri-implant diseases in comparison to healthy individuals. Meta-analysis showed higher RANKL levels in diseased groups compared to controls.
CONCLUSIONS
The results showed that the levels of IL-1β, IL-6, IL-10, and RANKL/OPG are not balanced in peri-implant disease, suggesting that these mediators are involved in the host osteo-immunoinflammatory response related to peri-implantitis.
Topics: Humans; Cytokines; Peri-Implantitis; Dental Implants; Interleukin-6; Osteogenesis; Gingival Crevicular Fluid
PubMed: 37355561
DOI: 10.1186/s12903-023-03072-1 -
Frontiers in Endocrinology 2023Circulating adipokines and ghrelin affect bone remodeling by regulating the activation and differentiation of osteoblasts and osteoclasts. Although the correlation... (Meta-Analysis)
Meta-Analysis
CONTEXT
Circulating adipokines and ghrelin affect bone remodeling by regulating the activation and differentiation of osteoblasts and osteoclasts. Although the correlation between adipokines, ghrelin, and bone mineral density (BMD) has been studied over the decades, its correlations are still controversial. Accordingly, an updated meta-analysis with new findings is needed.
OBJECTIVE
This study aimed to explore the impact of serum adipokine and ghrelin levels on BMD and osteoporotic fractures through a meta-analysis.
DATA SOURCES
Studies published till October 2020 in Medline, Embase, and the Cochrane Library were reviewed.
STUDY SELECTION
We included studies that measured at least one serum adipokine level and BMD or fracture risk in healthy individuals. We excluded studies with one or more of the following: patients less than 18 years old, patients with comorbidities, who had undergone metabolic treatment, obese patients, patients with high physical activities, and a study that did not distinguish sex or menopausal status.
DATA EXTRACTION
We extracted the data that include the correlation coefficient between adipokines (leptin, adiponectin, and resistin) and ghrelin and BMD, fracture risk by osteoporotic status from eligible studies.
DATA SYNTHESIS
A meta-analysis of the pooled correlations between adipokines and BMD was performed, demonstrating that the correlation between leptin and BMD was prominent in postmenopausal women. In most cases, adiponectin levels were inversely correlated with BMD. A meta-analysis was conducted by pooling the mean differences in adipokine levels according to the osteoporotic status. In postmenopausal women, significantly lower leptin (SMD = -0.88) and higher adiponectin (SMD = 0.94) levels were seen in the osteoporosis group than in the control group. By predicting fracture risk, higher leptin levels were associated with lower fracture risk (HR = 0.68), whereas higher adiponectin levels were associated with an increased fracture risk in men (HR = 1.94) and incident vertebral fracture in postmenopausal women (HR = 1.18).
CONCLUSIONS
Serum adipokines levels can utilize to predict osteoporotic status and fracture risk of patients.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021224855, identifier CRD42021224855.
Topics: Male; Humans; Female; Adolescent; Bone Density; Leptin; Adipokines; Adiponectin; Ghrelin; Osteoporotic Fractures
PubMed: 37181034
DOI: 10.3389/fendo.2023.1044039 -
The Saudi Dental Journal Mar 2023In spite of bone's healing capacity, critical-size bone defect regeneration and -implant osseointegration are challenging. Tissue engineering provides better outcomes,... (Review)
Review
BACKGROUND AND OBJECTIVES
In spite of bone's healing capacity, critical-size bone defect regeneration and -implant osseointegration are challenging. Tissue engineering provides better outcomes, but requires expensive adjuncts like stem cells, growth factors and bone morphogenic proteins. Vitamin D (Vit.D) regulates calcium and phosphorus metabolism, and helps maintain bone health. Vit.D supplements in deficient patients, accentuates bone healing and regeneration. Therefore the aim of this systematic review was to evaluate the role of adjunctive Vit.D on bone defect regeneration.
METHODS
Comprehensive database search of indexed literature, published between January 1990 and June 2022, was carried out. English language articles fulfilling inclusion criteria (clinical/in vivo studies evaluating bone regeneration including osseointegration and in vitro studies assessing osteogenic differentiation, with adjunct Vit.D) were identified and screened.
RESULTS
Database search identified 384 titles. After sequential title, abstract and full-text screening, 23 studies (in vitro - 9/in vivo - 14) were selected for review. Vit.D as an adjunct with stem cells and osteoblasts resulted in enhanced osteogenic differentiation and upregulation of genes coding for bone matrix proteins and alkaline phosphatase. When used in vivo, Vit.D resulted in early and increased new bone formation and mineralization within osseous defects, and better bone implant contact and osseointegration, around implants. Adjunct Vit.D in animals with induced systemic illnesses resulted in bone defect regeneration and osseointegration comparable to healthy animals. While systemic and local administration of Vit.D resulted in enhanced bone defect healing, outcomes were superior with systemic route.
CONCLUSIONS
Based on this review, adjunct Vit.D enhances bone defect regeneration and osseointegration. In vitro application of Vit.D to stem cells and osteoblasts enhances osteogenic differentiation. Vit.D is a potentially non-invasive and inexpensive adjunct for clinical bone regeneration and osseointegration. Long term clinical trials are recommended to establish protocols relating to type, dosage, frequency, duration and route of administration.
PubMed: 37091280
DOI: 10.1016/j.sdentj.2023.02.002 -
Heliyon Mar 2023There is no consensus in the literature about the best non-cytotoxic antibacterial surface treatment for dental implants. Critically evaluate the existing literature and...
There is no consensus in the literature about the best non-cytotoxic antibacterial surface treatment for dental implants. Critically evaluate the existing literature and answer the question: "which surface treatment for dental implants made of titanium and its alloys has the greatest non-cytotoxic antibacterial activity for osteoblastic cells?" This systematic review was registered in the Open Science Framework (osf.io/8fq6p) and followed the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols. The search strategy was applied to four databases. Articles were selected that evaluated in both studies the properties of 1) antibacterial activity and 2) cytotoxicity on osteoblastic cells of titanium and their alloy dental implants when treated superficially. Systematic reviews, book chapters, observational studies, case reports, articles that studied non-dental implants, and articles that evaluated only the development of surface treatment were excluded. The Joanna Briggs Institute, a quasi-experimental study assessment tool, was adapted to assess the risk of bias. The search strategy found 1178 articles in the databases after removing duplicates in EndNote Web, resulting in 1011 articles to be evaluated by title and abstract, of which 21 were selected for full reading, of which 12 were included by eligibility criteria, and nine were excluded. Quantitative synthesis could not be performed due to the heterogeneity of the data (surface treatment, antibacterial assay, bacteria strain, cell viability assay, and cell type). Risk of bias assessment showed that ten studies were classified as low risk and two studies as moderate risk. The evaluated literature allowed us to conclude that: 1) The literature surveyed did not allow answering the question due to the heterogeneity of the studies; 2) Ten of the 12 studies evaluated presented surface treatments with non-cytotoxic antibacterial activity; 3) Adding nanomaterials, QPEI, BG, and CS, reduce the chances of bacterial resistance by controlling their adhesion by electrical forces.
PubMed: 36895374
DOI: 10.1016/j.heliyon.2023.e13693 -
The Cochrane Database of Systematic... Mar 2023The morbidity and socioeconomic costs of fractures are considerable. The length of time to healing is an important factor in determining a person's recovery after a... (Review)
Review
BACKGROUND
The morbidity and socioeconomic costs of fractures are considerable. The length of time to healing is an important factor in determining a person's recovery after a fracture. Ultrasound may have a therapeutic role in reducing the time to union after fracture by stimulating osteoblasts and other bone-forming proteins. This is an update of a review previously published in February 2014. OBJECTIVES: To assess the effects of low-intensity ultrasound (LIPUS), high-intensity focused ultrasound (HIFUS) and extracorporeal shockwave therapies (ECSW) as part of the treatment of acute fractures in adults. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase (1980 to March 2022), Orthopaedic Proceedings, trial registers and reference lists of articles.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and quasi-RCTs including participants over 18 years of age with acute fractures (complete or stress fractures) treated with either LIPUS, HIFUS or ECSW versus a control or placebo-control.
DATA COLLECTION AND ANALYSIS
We used standard methodology expected by Cochrane. We collected data for the following critical outcomes: participant-reported quality of life, quantitative functional improvement, time to return to normal activities, time to fracture union, pain, delayed or non-union of fracture. We also collected data for treatment-related adverse events. We collected data in the short term (up to three months after surgery) and in the medium term (later than three months after surgery). MAIN RESULTS: We included 21 studies, involving 1543 fractures in 1517 participants; two studies were quasi-RCTs. Twenty studies tested LIPUS and one trial tested ECSW; no studies tested HIFUS. Four studies did not report any of the critical outcomes. All studies had unclear or high risk of bias in at least one domain. The certainty of the evidence was downgraded for imprecision, risk of bias and inconsistency. LIPUS versus control (20 studies, 1459 participants) We found very low-certainty evidence for the effect of LIPUS on Health-related quality of life (HRQoL) measured by SF-36 at up to one year after surgery for lower limb fractures (mean difference (MD) 0.06, 95% confidence interval (CI) -3.85 to 3.97, favours LIPUS; 3 studies, 393 participants). This result was compatible with a clinically important difference of 3 units with both LIPUS or control. There may be little to no difference in time to return to work after people had complete fractures of the upper or lower limbs (MD 1.96 days, 95% CI -2.13 to 6.04, favours control; 2 studies, 370 participants; low-certainty evidence). There is probably little or no difference in delayed union or non-union up to 12 months after surgery (RR 1.25, 95% CI 0.50 to 3.09, favours control; 7 studies, 746 participants; moderate-certainty evidence). Although data for delayed and non-union included both upper and lower limbs, we noted that there were no incidences of delayed or non-union in upper limb fractures. We did not pool data for time to fracture union (11 studies, 887 participants; very low-certainty evidence) because of substantial statistical heterogeneity which we could not explain. In upper limb fractures, MDs ranged from 0.32 to 40 fewer days to fracture union with LIPUS. In lower limb fractures, MDs ranged from 88 fewer days to 30 more days to fracture union. We also did not pool data for pain experienced at one month after surgery in people with upper limb fractures (2 studies, 148 participants; very low-certainty evidence) because of substantial unexplained statistical heterogeneity. Using a 10-point visual analogue scale, one study reported less pain with LIPUS (MD -1.7, 95% CI -3.03 to -0.37; 47 participants), and the effect was less precise in the other study (MD -0.4, 95% CI -0.61 to 0.53; 101 participants). We found little or no difference in skin irritation (a possible treatment-related adverse event) between groups but judged the certainty of the evidence from this small study to be very low (RR 0.94, 95% CI 0.06 to 14.65; 1 study, 101 participants). No studies reported data for functional recovery. Data for treatment adherence were inconsistently reported across studies, but was generally described to be good. Data for costs were reported for one study, with higher direct costs, as well as combined direct and indirect costs, for LIPUS use. ECSW versus control (1 study, 56 participants) We are uncertain whether ECSW reduces pain at 12 months after surgery in fractures of the lower limb (MD -0.62, 95% CI -0.97 to -0.27, favours ECSW); the difference between pain scores was unlikely to be clinically important, and the certainty of the evidence was very low. We are also uncertain of the effect of ECSW on delayed or non-union at 12 months because the certainty of this evidence is very low (RR 0.56, 95% CI 0.15 to 2.01; 1 study, 57 participants). There were no treatment-related adverse events. This study reported no data for HRQoL, functional recovery, time to return to normal activities, or time to fracture union. In addition, no data were available for adherence or cost.
AUTHORS' CONCLUSIONS
We were uncertain of the effectiveness of ultrasound and shock wave therapy for acute fractures in terms of patient-reported outcome measures (PROMS), for which few studies reported data. It is probable that LIPUS makes little or no difference to delayed union or non-union. Future trials should be double-blind, randomised, placebo-controlled trials recording validated PROMs and following up all trial participants. Whilst time to union is difficult to measure, the proportion of participants achieving clinical and radiographic union at each follow-up point should be ascertained, alongside adherence with the study protocol and cost of treatment in order to better inform clinical practice.
Topics: Adult; Humans; Adolescent; Extracorporeal Shockwave Therapy; High-Energy Shock Waves; Fractures, Stress; Ultrasonography; Pain; Randomized Controlled Trials as Topic
PubMed: 36866917
DOI: 10.1002/14651858.CD008579.pub4 -
Journal of Functional Biomaterials Jan 2023(1) Background: Different compositions of biodegradable materials are being investigated to successfully replace non-resorbable ones in bone tissue regeneration in... (Review)
Review
(1) Background: Different compositions of biodegradable materials are being investigated to successfully replace non-resorbable ones in bone tissue regeneration in dental surgery. The systematic review tried to address the question, "Can biodegradable polymers act as a replacement for conventional materials in dental surgery procedures?" (2) Methods: An electronic search of the PubMed and Scopus databases was conducted in October 2022. The following keywords were used: (lactide polymers) and (hydroxyapatite or fluorapatite) and (dentistry) and (regeneration). Initially, 59 studies were found. Forty-one studies met the inclusion criteria and were included in the review. (3) Results: These usually improved the properties and induced osteogenesis, tissue mineralisation and bone regeneration by inducing osteoblast proliferation. Five studies showed higher induction of osteogenesis in the case of biomaterials, UV-HAp/PLLA, ALBO-OS, bioresorbable raw particulate hydroxyapatite/poly-L-lactide and PLGA/Hap, compared to conventional materials such as titanium. Four studies confirmed improvement in tissue mineralisation with the usage of biomaterials: hydroxyapatite/polylactic acid (HA/PLA) loaded with dog's dental pulp stem cells (DPSCs), Coll/HAp/PLCL, PDLLA/VACNT-O:nHAp, incorporation of hydroxyapatite and simvastatin. Three studies showed an acceleration in proliferation of osteoblasts for the use of biomaterials with additional factors such as collagen and UV light. (4) Conclusions: Lactide polymers present higher osteointegration and cell proliferation rate than the materials compared. They are superior to non-biodegradable materials in terms of the biocompability, bone remodelling and healing time tests. Moreover, because there is no need of reoperation, as the material automatically degrades, the chance of scars and skin sclerosis is lower. However, more studies involving greater numbers of biomaterial types and mixes need to be performed in order to find a perfect biodegradable material.
PubMed: 36826882
DOI: 10.3390/jfb14020083 -
Neurosurgery Aug 2023Many clinicians associate nicotine as the causative agent in the negative and deleterious effects of smoking on bone growth and spine fusion. Although nicotine is the...
BACKGROUND
Many clinicians associate nicotine as the causative agent in the negative and deleterious effects of smoking on bone growth and spine fusion. Although nicotine is the primary driver of physiological addiction in smoking, isolated and controlled use of nicotine is one of the most effective adjuncts to quitting smoking.
OBJECTIVE
To explore the relationship between nicotine and noncombustion cigarette products on bone growth.
METHODS
One thousand five studies were identified, of which 501 studies were excluded, leaving 504 studies available for review. Of note, 52 studies were deemed to be irrelevant. Four hundred fifty-two studies remained for eligibility assessment. Of the remaining 452, 218 failed to assess study outcomes, 169 failed to assess bone biology, 13 assessed 5 patients or fewer, and 12 were deemed to be ineligible of the study criteria. Forty studies remained for inclusion within this systematic review.
RESULTS
Of the 40 studies identified for inclusion within the study, 30 studies were classified as "Animal Basic Science," whereas the remaining 10 were categorized as "Human Basic Science." Of the 40 studies, 11 noted decreased cell proliferation and boney growth, whereas 8 showed an increase. Four studies noted an increase in gene expression products, whereas 11 noted a significant decrease.
CONCLUSION
The results of this study demonstrate that nicotine has a variety of complex interactions on osteoblast and osteoclastic activities. Nicotine demonstrates dose-dependent effects on osteoblast proliferation, boney growth, and gene expression. Further study is warranted to extrapolate the effects of solitary nicotine on clinical outcomes.
Topics: Animals; Humans; Nicotine; Smoking; Osteogenesis; Calcification, Physiologic; Tobacco Products
PubMed: 36815769
DOI: 10.1227/neu.0000000000002412 -
Acta Orthopaedica Belgica Sep 2022Approximately 5 to 10% of all patients with fractures experience deficient fracture healing that results in fracture nonunions. Previous studies have shown that nitric...
INTRODUCTION
Approximately 5 to 10% of all patients with fractures experience deficient fracture healing that results in fracture nonunions. Previous studies have shown that nitric oxide production from arginine could improve fracture healing by improving local blood supply, supplementing growth factors, and improving collagen synthesis. Apart from its simple oral mode of administration, this amino acid provides a non-toxic and inexpensive option for fracture healing. To date, no systematic reviews regarding oral L-arginine supplementation for fracture healing are available. We present the first systematic review of oral L-arginine supplementation for fracture healing.
METHODS
A systematic literature search was carried out using PubMed, Google Scholar, and ScienceDirect until February 1, 2021 using a combination of text words. No date limits were set. Studies investigating the use of oral L-arginine supplementation for fracture healing were included. Reference lists of relevant publications were assessed for additional references. In addition, bibliographies from other reviews were searched.
RESULTS
Four studies were included. Of these, 3 were animal studies, and the other one was an in vitro study. Animals that were given oral L-arginine supplementation had significantly increased angiogenesis, reduced defect area, higher osteoblasts and osteoclasts, and higher rate of bone formation compared to controls.
CONCLUSIONS
The available preclinical studies suggest that oral L-arginine supplementation is a potential new therapy for fracture healing. This amino acid supplement is not only affordable and non-toxic; it is also simple. Further clinical studies are required to investigate the optimal dose of oral L-arginine supplementation for fracture healing in human subjects.
Topics: Animals; Humans; Arginine; Fracture Healing; Amino Acids; Fractures, Bone; Dietary Supplements
PubMed: 36791716
DOI: 10.52628/88.3.7541 -
BioMed Research International 2023Stem cells provided new opportunity to treat various diseases, including liver disorders. Stem cells are unspecialized cells, stimulating influential research interest... (Review)
Review
Stem cells provided new opportunity to treat various diseases, including liver disorders. Stem cells are unspecialized cells, stimulating influential research interest be indebted to their multipotent self-renewal capacity and differentiation characteristics into several specialized cell types. Many factors contribute to their differentiation into different cell types such as insulin producing cells, osteoblast, and hepatocytes. Accordingly, wide range methods and materials have been used to transform stem cells into hepatocytes, but effectiveness of differentiation is different and depends on several factors such as cell-to-cell adhesion, cell-to-cell contact, and cell biological change. Search was done in PubMed, Scopus, and WOS to evaluate results of studies about stem cells differentiation for higher efficacy. Among more than 28000 papers, 51 studies were considered eligible for more evaluations. Results indicated that most studies were performed on mesenchymal stem cells compared with other types. Acute liver failure was the most investigated liver disorder, and tissue engineering was the most investigated differentiation methods. Also, functional parameters were the most evaluated parameters in assessing differentiation efficacy. We summarize recent advances in increasing efficiency of stem cells differentiation using varied materials, since promising results of this review, further studies are needed to assess efficiency and safety of these cells transplantation in some liver disease treatment.
Topics: Humans; Hepatocytes; Liver Failure, Acute; Cell Differentiation; Stem Cells; Liver
PubMed: 36685673
DOI: 10.1155/2023/4868048 -
Bioengineering (Basel, Switzerland) Jan 2023Bone healing is a multifarious process involving mesenchymal stem cells, osteoprogenitor cells, macrophages, osteoblasts and -clasts, and chondrocytes to restore the... (Review)
Review
Bone healing is a multifarious process involving mesenchymal stem cells, osteoprogenitor cells, macrophages, osteoblasts and -clasts, and chondrocytes to restore the osseous tissue. Particularly in long bones including the tibia, clavicle, humerus and femur, this process fails in 2-10% of all fractures, with devastating effects for the patient and the healthcare system. Underlying reasons for this failure are manifold, from lack of biomechanical stability to impaired biological host conditions and wound-immanent intricacies. In this review, we describe the cellular components involved in impaired bone healing and how they interfere with the delicately orchestrated processes of bone repair and formation. We subsequently outline and weigh the risk factors for the development of non-unions that have been established in the literature. Therapeutic prospects are illustrated and put into clinical perspective, before the applicability of biomarkers is finally discussed.
PubMed: 36671657
DOI: 10.3390/bioengineering10010085