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International Endodontic Journal Jul 2014The aim of this review was to examine current knowledge of the role of interleukin-6 (IL-6) in apical periodontitis (AP) pathogenesis as an inflammatory or... (Review)
Review
The aim of this review was to examine current knowledge of the role of interleukin-6 (IL-6) in apical periodontitis (AP) pathogenesis as an inflammatory or pro-inflammatory cytokine. It also looked at whether IL-6 could serve as a measure for differential diagnosis or as a biomarker that can further predict the progression of bone resorption. A systematic review relating to AP and IL-6 was made via PubMed, BIOSIS, Cochrane, EMBASE and Web of Science databases using keywords and controlled vocabulary. Two independent reviewers first screened titles and abstracts and then the full texts. The reference lists of the identified publications were examined for additional titles. Eighteen papers were studied in total. In vitro studies (n = 6) revealed that IL-6 is present in AP, and its levels are proportional to the size of the periapical lesions. Neutrophils and macrophages resident in these lesions can produce IL-6 in vitro after a bacterial stimulus. Animal studies (n = 5) showed that IL-6 is present in AP and that osteoblasts can produce IL-6 in vivo. On the other hand, two studies using IL-6 knockout mice revealed larger periapical lesions when compared with control groups, demonstrating IL-6's role as an anti-inflammatory cytokine. In human studies (n = 7), IL-6 was identified in AP, and its levels were higher in symptomatic, epithelialized and large lesions than in asymptomatic and small lesions. These data lead to the conclusion that IL-6 may play a pro-inflammatory role, increasing its levels and reabsorbing bone in the presence of infections. When IL-6 is not present, other cytokines such as IL-1 and TNF-α induce bone resorption. Further studies about the relationship between AP development and the cytokine network must be performed to establish the exact role of each cytokine in the inflammatory process.
Topics: Animals; Humans; Interleukin-6; Periapical Periodontitis
PubMed: 24224782
DOI: 10.1111/iej.12196 -
American Journal of Human Biology : the... Nov 2022Bone is a dynamic organ under continual turnover influenced by life history stage, energy dynamics, diet, climate, and disease. Bone turnover data have enormous...
OBJECTIVES
Bone is a dynamic organ under continual turnover influenced by life history stage, energy dynamics, diet, climate, and disease. Bone turnover data have enormous potential in biological anthropology for testing evolutionary and biocultural hypotheses, yet few studies have integrated these biomarkers. In the present article we systematically review the current availability, future viability, and applicability of measuring bone turnover markers (BTMs) in dried blood spot (DBS) samples obtained from finger prick whole blood.
METHODS
Our review considers clinical and public health relevance, biomarker stability in DBS, assay availability, and cost. We consider biomarkers of bone formation such as osteocalcin (bone matrix protein), PINP (N-terminal propeptide of type I collagen), and alkaline phosphatase (osteoblast enzyme), as well as biomarkers of bone resorption such as CTX (marker of collagen breakdown) and TRACP5b (tartrate-resistant acid phosphatase 5b; osteoclast enzyme).
RESULTS
Two BTMs have been validated for DBS: osteocalcin (formation) and TRACP5b (resorption). Prime candidates for future development are CTX and PINP, the formation and resorption markers used for clinical monitoring of response to osteoporosis treatment.
CONCLUSION
BTMs are a field-friendly technique for longitudinal monitoring of skeletal biology during growth, reproduction and aging, combining minimized risk to study participants with maximized ease of sample storage and transport. This combination allows new insights into the effects of energy availability, disease, and physical activity level on bone, and questions about bone gain and loss across life history and in response to environmental factors; these issues are important in human biology, paleoanthropology, bioarchaeology, and forensic anthropology.
Topics: Humans; Osteocalcin; Tartrate-Resistant Acid Phosphatase; Bone Remodeling; Biomarkers; Anthropology
PubMed: 36214251
DOI: 10.1002/ajhb.23816 -
Endocrine Apr 2024Runx2 and osteocalcin have pivotal roles in bone homeostasis. Polymorphism of these two genes could alter the function of osteoblasts and consequently bone mineral... (Meta-Analysis)
Meta-Analysis
PURPOSE
Runx2 and osteocalcin have pivotal roles in bone homeostasis. Polymorphism of these two genes could alter the function of osteoblasts and consequently bone mineral density (BMD). Attempts to understand the relationship between these polymorphisms and BMD in postmenopausal women across a variety of populations have yielded inconsistent results. This meta-analysis seeks to define the relationship between these polymorphisms with BMD in postmenopausal women.
METHODS
Eligible studies were identified from three electronic databases. Data were extracted from the eligible studies (4 studies on Runx2 and 6 studies on osteocalcin), and associations of Runx2 T > C and osteocalcin HindIII polymorphisms with BMD in postmenopausal women were assessed using standard difference in means (SDM) and 95% confidence intervals (CI) as statistical measures.
RESULTS
A significant difference in the lumbar spine (LS) BMD in postmenopausal women was observed between the TT and CC homozygotes for the Runx2 T > C (SDM = -0.445, p-value = 0.034). The mutant genotypes (CC) showed significantly lower LS BMD in comparison to wild type genotypes under recessive model of genetic analysis (TC + TT vs. CC: SDM = -0.451, p-value = 0.032). For osteocalcin, HindIII polymorphism, the mutant genotypes (HH) was associated with significantly higher BMD for both LS and femoral neck (FN) than the wild type (hh) homozygotes (SDM = 0.152, p-value = 0.008 and SDM = 0.139, p-value = 0.016 for LS and FN, respectively). There was no association between total hip (TH) BMD and the osteocalcin HindIII polymorphism.
CONCLUSIONS
Runx2 T > C and osteocalcin HindIII polymorphisms influence the level of BMD in postmenopausal women and may be used as predictive markers of osteoporosis.
Topics: Female; Humans; Bone Density; Osteocalcin; Postmenopause; Polymorphism, Genetic; Osteoporosis; Genotype; Osteoporosis, Postmenopausal
PubMed: 38055125
DOI: 10.1007/s12020-023-03621-2 -
International Journal of Molecular... Apr 2021Patients receiving orthopedic implants are at risk of implant-associated infections (IAI). A growing number of antibiotic-resistant bacteria threaten to hamper the...
Patients receiving orthopedic implants are at risk of implant-associated infections (IAI). A growing number of antibiotic-resistant bacteria threaten to hamper the treatment of IAI. The focus has, therefore, shifted towards the development of implants with intrinsic antibacterial activity to prevent the occurrence of infection. The use of Ag, Cu, and Zn has gained momentum as these elements display strong antibacterial behavior and target a wide spectrum of bacteria. In order to incorporate these elements into the surface of titanium-based bone implants, plasma electrolytic oxidation (PEO) has been widely investigated as a single-step process that can biofunctionalize these (highly porous) implant surfaces. Here, we present a systematic review of the studies published between 2009 until 2020 on the biomaterial properties, antibacterial behavior, and biocompatibility of titanium implants biofunctionalized by PEO using Ag, Cu, and Zn. We observed that 100% of surfaces bearing Ag (Ag-surfaces), 93% of surfaces bearing Cu (Cu-surfaces), 73% of surfaces bearing Zn (Zn-surfaces), and 100% of surfaces combining Ag, Cu, and Zn resulted in a significant (i.e., >50%) reduction of bacterial load, while 13% of Ag-surfaces, 10% of Cu-surfaces, and none of Zn or combined Ag, Cu, and Zn surfaces reported cytotoxicity against osteoblasts, stem cells, and immune cells. A majority of the studies investigated the antibacterial activity against . Important areas for future research include the biofunctionalization of additively manufactured porous implants and surfaces combining Ag, Cu, and Zn. Furthermore, the antibacterial activity of such implants should be determined in assays focused on prevention, rather than the treatment of IAIs. These implants should be tested using appropriate in vivo bone infection models capable of assessing whether titanium implants biofunctionalized by PEO with Ag, Cu, and Zn can contribute to protect patients against IAI.
Topics: Copper; Humans; Osteoblasts; Oxidation-Reduction; Porosity; Prostheses and Implants; Silver; Staphylococcal Infections; Staphylococcus aureus; Stem Cells; Titanium; Zinc
PubMed: 33917615
DOI: 10.3390/ijms22073800 -
Nephrology (Carlton, Vic.) Oct 2018As the GFR loss aggravates, the disturbed mineral metabolism worsens the bone microstructure and remodelling - scenario, which is known as CKD-mineral bone disease...
As the GFR loss aggravates, the disturbed mineral metabolism worsens the bone microstructure and remodelling - scenario, which is known as CKD-mineral bone disease (MBD). CKD-MBD is characterized by : (i) abnormal metabolism of calcium, phosphorus, parathyroid hormone (PTH), or vitamin D; (ii) abnormalities in bone turnover, mineralization, volume linear growth or strength; (iii) soft-tissue calcifications, either vascular or extra-osseous. Uremic vascular calcification and osteoporosis are the most common complications related to CKD-MBD. Disregulated bone turnover by uremic toxin or secondary hyperparathyroidism disturbed bone mineralization and makes it difficult for calcium and inorganic phosphate to enter into bone, resulting in increased serum calcium and inorganic phosphate. Vascular calcification worsens by hyperphosphatemia and systemic inflammation. Since vitamin D deficiency plays an important role in renal osteodystrophy, supplement of nutritional vitamin D is important in treating uremic osteoporosis and vascular calcification at the same time. Its pleotropic effect improves the bone remodeling initiated by osteoblast and alleviates the risk factors for vascular calcification with less hypercalcemia than vitamin D receptor analogs. Therefore, nutritional vitamin D should be considered in managing CKDMBD.
Topics: Animals; Arteries; Bone Remodeling; Chronic Kidney Disease-Mineral and Bone Disorder; Dietary Supplements; Humans; Kidney; Osteogenesis; Prognosis; Risk Factors; Vascular Calcification; Vitamin D; Vitamin D Deficiency
PubMed: 30298663
DOI: 10.1111/nep.13457 -
Clinical Chemistry and Laboratory... 2007Hyperhomocysteinemia (HHCY) has been suggested as a new risk factor for osteoporosis. Recent epidemiological, clinical and experimental studies provide a growing body of... (Review)
Review
Hyperhomocysteinemia (HHCY) has been suggested as a new risk factor for osteoporosis. Recent epidemiological, clinical and experimental studies provide a growing body of data, which is reviewed in this article. Epidemiological and (randomized) clinical trials suggest that HHCY increases fracture risk, but has minor effects on bone mineral density. Measurement of biochemical bone turnover markers indicates a shift of bone metabolism towards bone resorption. Animal studies confirm these observations showing a reduced bone quality and stimulation of bone resorption in hyperhomocysteinemic animals. Homocysteine (HCY) has been found to accumulate in bone by collagen binding. Cell culture studies demonstrate that high HCY levels stimulate osteoclasts but not osteoblasts, indicating again a shift of bone metabolism towards bone resorption. Regarding B-vitamins, only a few in vivo studies with equivocal results have been published. However, two large cell culture studies confirm the results obtained with exogenous HCY administration. In addition, HHCY seems to have adverse affects on extracellular bone matrix by disturbing collagen crosslinking. In conclusion, existing data suggest that HHCY (and possibly B-vitamin deficiencies) adversely affects bone quality by a stimulation of bone resorption and disturbance of collagen crosslinking.
Topics: Animals; Bone Density; Folic Acid Deficiency; Fractures, Bone; Humans; Hyperhomocysteinemia; Osteoporosis; Vitamin B 12; Vitamin B 6; Vitamin B Deficiency
PubMed: 18067447
DOI: 10.1515/CCLM.2007.362 -
International Journal of Implant... Oct 2018Non-steroidal anti-inflammatory drugs are commonly used in implant dentistry for management of post-operative pain. The objective of this systematic review was to... (Review)
Review
Non-steroidal anti-inflammatory drugs are commonly used in implant dentistry for management of post-operative pain. The objective of this systematic review was to analyse the effect of non-steroidal anti-inflammatory drugs on the osteogenic activity of osteoblasts with an emphasis on its effect on osseointegration. A systematic literature search for in vitro, animal models, and clinical trials was conducted using Ovid, PubMed, Scopus, and Web of Science databases. Articles published since the introduction of selective COX-2 inhibitors, between January 1999 and July 2018, were selected. The integrated search followed the PRISMA statement with the following key terms: non-steroidal anti-inflammatory drug/s, titanium, osseointegration, and osteoblast. The review is registered at PROSPERO database: CRD42016051448. The titles and abstracts of each research article in the initial search (n = 875) were independently screened by two reviewers. A third independent reviewer reviewed the articles that were included by one but excluded by the other reviewer. This resulted in the cataloguing of 79 full-text manuscripts where the articles were assessed for the following criteria: the study investigates the effects of NSAIDs on osteoblasts, explores the COX pathway and its effect on osteogenic activity, and compares the effects of NSAIDs on osteoblasts with a control group. A total of 13 articles have been included for qualitative synthesis. There is a lack of consensus in the literature to explicitly conclude that there is a relationship between the use of post-operative NSAIDs and failed osseointegration; however, osseointegration does not appear to be negatively affected by NSAIDs in the human clinical studies.
PubMed: 30298361
DOI: 10.1186/s40729-018-0141-7 -
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 -
Biological Trace Element Research Sep 2011The present review is based on a survey of 21 studies on the cytocompatibility of medical biomaterials containing nickel, as assessed by cell culture of human and animal... (Review)
Review
The present review is based on a survey of 21 studies on the cytocompatibility of medical biomaterials containing nickel, as assessed by cell culture of human and animal osteoblasts or osteoblast-like cells. Among the biomaterials evaluated were stainless steel, NiTi alloys, pure Ni, Ti, and other pure metals. The materials were either commercially available, prepared by the authors, or implanted by various techniques to generate a protective layer of oxides, nitrides, acetylides. The observation that the layers significantly reduced the initial release of metal ions and increased cytocompatibility was confirmed in cell culture experiments. Physical and chemical characterization of the materials was performed. This included, e.g., surface characterization (roughness, wettability, corrosion behavior, quantity of released ions, microhardness, and characterization of passivation layer). Cytocompatibility tests of the materials were conducted in the cultures of human or animal osteoblasts and osteoblast-like cells. The following assays were carried out: cell proliferation and viability test, adhesion test, morphology (by fluorescent microscopy or SEM). Also phenotypic and genotypic markers were investigated. In the majority of works, it was found that the most cytocompatible materials were stainless steel and NiTi alloy. Pure Ni was rendered and less cytocompatible. All the papers confirmed that the consequence of the formation of protective layers was in significant increase of cytocompatibility of the materials. This indicates the possible further modifications of the manufacturing process (formation of the passivation layer).
Topics: Animals; Biocompatible Materials; Cell Proliferation; Cell Survival; Humans; Nickel; Osteoblasts
PubMed: 20703824
DOI: 10.1007/s12011-010-8798-7 -
EFORT Open Reviews Jan 2022Patients with Gorham-Stout disease (GSD) present progressive destruction and resorption of bone. Typical bone-related symptoms include swelling, pain and functional... (Review)
Review
Patients with Gorham-Stout disease (GSD) present progressive destruction and resorption of bone. Typical bone-related symptoms include swelling, pain and functional impairment in the region involved. The three aspects of GSD etiopathology are osteoclasts, angiogenesis/lymphangiogenesis and osteoblast function. Multi-targeted pharmacological approach includes innovative options and represent milestones of treatment, sometimes associated with radiotherapy. Surgery is mainly used to treat complications: pathologic/impending fractures, spinal instability or deformities and chylothorax. In this narrative review, we highlight current standards in diagnosis, clinical management and therapeutic strategies.
PubMed: 35076412
DOI: 10.1530/EOR-21-0083