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Metabolism: Clinical and Experimental May 2017Vitamin K is a liposoluble vitamin. The predominant dietary form, phylloquinone or vitamin K1, is found in plants and green vegetables; whereas menaquinone, or vitamin... (Review)
Review
Vitamin K is a liposoluble vitamin. The predominant dietary form, phylloquinone or vitamin K1, is found in plants and green vegetables; whereas menaquinone, or vitamin K2, is endogenously synthesized by intestinal bacteria and includes several subtypes that differ in side chain length. Aside from its established role in blood clotting, several studies now support a critical function of vitamin K in improving bone health. Vitamin K is in fact required for osteocalcin carboxylation that in turn regulates bone mineral accretion; it seems to promote the transition of osteoblasts to osteocytes and also limits the process of osteoclastogenesis. Several observational and interventional studies have examined the relationship between vitamin K and bone metabolism, but findings are conflicting and unclear. This systematic review aims to investigate the impact of vitamin K (plasma levels, dietary intake, and oral supplementation) on bone health with a particular interest in bone remodeling, mineral density and fragility fractures.
Topics: Aged; Bone and Bones; Female; Fractures, Bone; Humans; Male; Nutrition Assessment; Osteoporosis; Vitamin K
PubMed: 28403946
DOI: 10.1016/j.metabol.2017.01.032 -
PloS One 2021Drug research with animal models is expensive, time-consuming and translation to clinical trials is often poor, resulting in a desire to replace, reduce, and refine the...
Drug research with animal models is expensive, time-consuming and translation to clinical trials is often poor, resulting in a desire to replace, reduce, and refine the use of animal models. One approach to replace and reduce the use of animal models is to use in vitro cell-culture models. To study bone physiology, bone diseases and drugs, many studies have been published using osteoblast-osteoclast co-cultures. The use of osteoblast-osteoclast co-cultures is usually not clearly mentioned in the title and abstract, making it difficult to identify these studies without a systematic search and thorough review. As a result, researchers are all developing their own methods, leading to conceptually similar studies with many methodological differences and, as a consequence, incomparable results. The aim of this study was to systematically review existing osteoblast-osteoclast co-culture studies published up to 6 January 2020, and to give an overview of their methods, predetermined outcome measures (formation and resorption, and ALP and TRAP quantification as surrogate markers for formation and resorption, respectively), and other useful parameters for analysis. Information regarding these outcome measures was extracted and collected in a database, and each study was further evaluated on whether both the osteoblasts and osteoclasts were analyzed using relevant outcome measures. From these studies, additional details on methods, cells and culture conditions were extracted into a second database to allow searching on more characteristics. The two databases presented in this publication provide an unprecedented amount of information on cells, culture conditions and analytical techniques for using and studying osteoblast-osteoclast co-cultures. They allow researchers to identify publications relevant to their specific needs and allow easy validation and comparison with existing literature. Finally, we provide the information and tools necessary for others to use, manipulate and expand the databases for their needs.
Topics: Animals; Bone Resorption; Cell Differentiation; Coculture Techniques; Databases, Factual; Drug Discovery; Humans; Models, Animal; Osteoblasts; Osteoclasts; RANK Ligand
PubMed: 34735456
DOI: 10.1371/journal.pone.0257724 -
Maturitas Jan 2017A systematic review of studies was undertaken to evaluate the potential effect of intake of tocotrienols or circulating levels of tocotrienols on parameters associated... (Review)
Review
OBJECTIVES
A systematic review of studies was undertaken to evaluate the potential effect of intake of tocotrienols or circulating levels of tocotrienols on parameters associated with successful ageing, specifically in relation to cognitive function, osteoporosis and DNA damage.
METHODS
Following PRISMA guidelines a systematic review of epidemiological observational studies and clinical trials was undertaken. Inclusion criteria included all English language publications in the databases PubMed and Scopus, through to the end of July 2016.
RESULTS
Evidence from prospective and case-control studies suggested that increased blood levels of tocotrienols were associated with favorable cognitive function outcomes. A clinical trial of tocotrienol supplementation for 6 months suggested a beneficial effect of intake on DNA damage rates, but only in elderly people. Regarding osteoporosis, only in vitro studies with cultures of human bone cells were identified, and these demonstrated significant inhibition of osteoclast activity and promotion of osteoblast activity.
CONCLUSIONS
Research in middle-aged and elderly humans suggests that tocotrienols have a potential beneficial anti-ageing action with respect to cognitive impairment and DNA damage. Clinical trials are required to elucidate these effects.
Topics: Aged; Aging; Bone and Bones; Cognition; Cognition Disorders; Dietary Supplements; Humans; Osteoblasts; Osteoclasts; Osteoporosis; Prospective Studies; Tocotrienols
PubMed: 27889054
DOI: 10.1016/j.maturitas.2016.11.003 -
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 -
Current Osteoporosis Reports Oct 2019Bone turnover is a regulated process. Osteoglycin is suggested to have an important impact on bone function but may also affect cardiovascular and metabolic functions....
PURPOSE OF REVIEW
Bone turnover is a regulated process. Osteoglycin is suggested to have an important impact on bone function but may also affect cardiovascular and metabolic functions. This review investigates the action of osteoglycin in bone as well as its potential endocrine effects.
RECENT FINDINGS
Osteoglycin is expressed by several tissues including bone and muscle. Some studies suggest that osteoglycin increases osteoblast differentiation whereas others suggest that osteoglycin decreases osteoblast differentiation. Thus, findings on the influence of osteoglycin in bone are conflicting. A recent study found increased bone mass in osteoglycin deficient mice. Another study reported that osteoglycin is a marker of low bone mineral density and vertebral fractures in women with type 2 diabetes. Furthermore, clinical studies link osteoglycin to insulin resistance and cardiovascular disease. Osteoglycin may be a novel marker of a muscle, pancreatic, and bone axis. However, current evidence is limited and further research investigating osteoglycin in both a pre-clinical and a clinical setting is needed.
Topics: Animals; Biomarkers; Bone Density; Bone Remodeling; Cardiovascular Diseases; Cell Differentiation; Humans; Insulin Resistance; Intercellular Signaling Peptides and Proteins
PubMed: 31396918
DOI: 10.1007/s11914-019-00523-z -
Association Between Obstructive Sleep Apnea and Osteoporosis: A Systematic Review and Meta-Analysis.International Journal of Endocrinology... Jul 2016Hypoxia reduces osteoblast growth resulting in bone thinning and osteoporosis. Although obstructive sleep apnea (OSA) with recurrent hypoxia might be a contributing... (Review)
Review
CONTEXT
Hypoxia reduces osteoblast growth resulting in bone thinning and osteoporosis. Although obstructive sleep apnea (OSA) with recurrent hypoxia might be a contributing factor for osteoporosis development, whether OSA is a risk or protective factor for osteoporosis has not been demonstrated.
OBJECTIVES
This systematic review and meta-analysis evaluated the association between OSA and osteoporosis using published observational studies.
DATA SOURCES
PubMed/MEDLINE and EMBASE databases.
STUDY SELECTION
We completed a systematic review and meta-analysis of published observational studies that evaluated incidence or prevalence of osteoporosis or bone mineral density in obstructive sleep apnea compared with controls. Severity of OSA was characterized using the apnea-hypopnea index (AHI).
DATA EXTRACTION
Primary outcomes were incidence, prevalence, or odds ratio of having osteoporosis, defined as bone mineral density T-score < -2.5 SD.
RESULTS
Of 353 articles, 344 articles were excluded, 9 underwent full-length review and data were extracted from 7 studies consisting of 113,558 patients. Finally, 3 extracted studies were included in the meta-analysis of osteoporosis. Among cohort studies, the pooled odds ratio of osteoporosis in patients with OSA was 1.92 (95% confidence interval [CI]: 1.24 - 2.97) compared with controls. Among cross-sectional studies, odds of osteoporosis was higher in controls compared with patients with OSA (OR = 0.60, 95% CI: 0.42 - 0.87). In subgroup analysis by gender and study design, in both sexes, only cohort studies had higher odds of osteoporosis compared with controls.
CONCLUSIONS
There was significant association between OSA and osteoporosis in studies with cohort design. Further prospective studies with large numbers of patients adjusted for the effects of age, sex, or BMI are required to comprehensively determine whether OSA is a risk factor for osteoporosis.
PubMed: 27942262
DOI: 10.5812/ijem.36317 -
Current Genomics Apr 2019Microgravity (μG) negatively influences bone metabolism by affecting normal osteoblast and osteoclast function. μG effects on bone metabolism has been an extensive... (Review)
Review
BACKGROUND
Microgravity (μG) negatively influences bone metabolism by affecting normal osteoblast and osteoclast function. μG effects on bone metabolism has been an extensive field of study in recent years, due to the challenges presented by space flight.
METHODS
We systematically reviewed research data from genomic studies performed in real or simulat-ed μG, on osteoblast and osteoclast cells. Our search yielded 50 studies, of which 39 concerned cells of the osteoblast family and 11 osteoclast precursors.
RESULTS
Osteoblastic cells under μG show a decreased differentiation phenotype, proved by diminished expression levels of Alkaline Phosphatase (ALP) and Osteocalcin (OCN) but no apoptosis. Receptor Activator of NF-κB Ligand (RANKL)/ Osteoprotegerine (OPG) ratio is elevated in favor of RANKL in a time-dependent manner, and further RANKL production is caused by upregulation of Interleukin-6 (IL-6) and the inflammation pathway. Extracellular signals and changes in the gravitational environment are perceived by mechanosensitive proteins of the cytoskeleton and converted to intracellular signals through the Mitogen Activated Protein Kinase pathway (MAPK). This is followed by changes in the ex-pression of nuclear transcription factors of the Activator Protein-1 (AP-1) family and in turn of the NF-κB, thus affecting osteoblast differentiation, cell cycle, proliferation and maturation. Pre-osteoclastic cells show increased expression of the marker proteins such as Tryptophan Regulated Attenuation Protein (TRAP), cathepsin K, Matrix Metalloproteinase-9 (MMP-9) under μG conditions and become sensitized to RANKL.
CONCLUSION
Suppressing the expression of fusion genes such as syncytine-A which acts independently of RANKL, could be possible future therapeutic targets for microgravity side effects.
PubMed: 31929726
DOI: 10.2174/1389202920666190422142053 -
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 -
Osteoporosis International : a Journal... Feb 2021Methotrexate (MTX)-related osteopathy is rare, defined by the triad of pain, osteoporosis, and "atypical fractures" when it was first described in the 1970s in children... (Review)
Review
INTRODUCTION
Methotrexate (MTX)-related osteopathy is rare, defined by the triad of pain, osteoporosis, and "atypical fractures" when it was first described in the 1970s in children treated with high doses MTX for acute leukemia. Since then, several cases have been reported in patients treated with low-dose MTX for inflammatory diseases.
METHODS
A systematic research of cases of MTX-related osteopathy was performed in records of Rheumatology Department of Rennes University Hospital. Data collection focused on demographic data, corticosteroid doses, MTX doses and intake method, cumulative doses, year of diagnosis, fracture location, bone densitometry value, and osteoporosis treatment if necessary. A literature review was also conducted to identify other cases in literature and try to understand the pathophysiological mechanisms of this rare entity.
RESULTS
We report 5 cases identified between 2011 and 2019, which represents the largest cohort described excluding oncology cases. Fracture locations were atypical for osteoporotic fractures. All patients improved in the following months with MTX withdrawal. All patients except one were treated with antiresorptives (bisphosphonates, denosumab). Two patients, treated with bisphosphonates, had a recurrence of fracture, once again of atypical location. Twenty-five cases were collected in literature with similar clinical presentation. The cellular studies that investigated the bone toxicity of MTX mainly showed a decrease in the number of osteoblasts, osteocytes, and chondrocytes in the growth plate and an increase in the number and activity of osteoclasts. In vitro, consequences of mechanical stimulation on human trabecular bone cells in the presence of MTX showed an alteration in mechano-transduction, with membrane hyperpolarization, acting on the integrin pathway. In contrast with our report, the cases described in the literature were not consistently associated with a decrease in bone mineral density (BMD).
CONCLUSION
MTX osteopathy while rare must be known by the rheumatologist, especially when using this treatment for inflammatory conditions. The mechanisms are still poorly understood, raising the question of a possible remnant effect of MTX on osteo-forming bone cells, potentially dose-dependent. Methotrexate (MTX) osteopathy, described as a clinical triad, pain, osteoporosis, and atypical stress fractures, while rare, must be known by the rheumatologist. Our cohort of 5 cases represent the largest series of the literature. Pathophysiological studies raised the question of a dose-dependent remnant effect of MTX on osteo-forming bone cells.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Bone Density; Bone Diseases; Child; Humans; Methotrexate; Osteoporosis
PubMed: 33128074
DOI: 10.1007/s00198-020-05664-x -
The Journal of Oral Implantology Dec 2016Polyetheretherketone (PEEK) has been suggested as an alternative to replace titanium as a dental implant material. However, PEEK's bioactivity and osseointegration are... (Comparative Study)
Comparative Study Review
Polyetheretherketone (PEEK) has been suggested as an alternative to replace titanium as a dental implant material. However, PEEK's bioactivity and osseointegration are debatable. This review has systematically analyzed studies that have compared PEEK (or PEEK-based) implants with titanium implants so that its feasibility as a possible replacement for titanium can be determined. The focused question was: "Are the bioactivity and osseointegration of PEEK implants comparable to or better than titanium implants?" Using the key words "dental implant," "implant," "polyetheretherketone," "PEEK," and "titanium" in various combinations, the following databases were searched electronically: PubMED/MEDLINE, Embase, Google Scholar, ISI Web of Knowledge, and Cochrane Database. 5 in vitro and 4 animal studies were included in the review. In 4 out of 5 in vitro studies, titanium exhibited more cellular proliferation, angiogenesis, osteoblast maturation, and osteogenesis compared to PEEK; one in vitro study observed comparable outcomes regardless of the implant material. In all animal studies, uncoated and coated titanium exhibited a more osteogenic behavior than did uncoated PEEK, while comparable bone-implant contact was observed in HA-coated PEEK and coated titanium implants. Unmodified PEEK is less osseoconductive and bioactive than titanium. Furthermore, the majority of studies had multiple sources of bias; hence, in its unmodified form, PEEK is unsuitable to be used as dental implant. Significantly more research and long-term trials must focus on improving the bioactivity of PEEK before it can be used as dental implant. More comparative animal and clinical studies are warranted to ascertain the potential of PEEK as a viable alternative to titanium.
Topics: Animals; Benzophenones; Dental Implants; Ketones; Osseointegration; Polyethylene Glycols; Polymers; Titanium
PubMed: 27560166
DOI: 10.1563/aaid-joi-D-16-00072