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Journal of Orthopaedic Surgery and... Nov 2023The OPG/RANKL signal pathway was important regulation mechanism of bone remodeling cycle, but the effect of osteoprotegerin (OPG) and RANKL in osteoporosis was... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The OPG/RANKL signal pathway was important regulation mechanism of bone remodeling cycle, but the effect of osteoprotegerin (OPG) and RANKL in osteoporosis was uncertain. We did a systematic review with meta-analysis to assess the association between serum OPG/RANKL and osteoporosis.
METHODS
The systematic search, data extraction, critical appraisal, and meta-analysis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Randomized controlled studies were searched in PubMed, OvidMedline, Embase (1946 to present). Standard mean difference (SMD), and associated credible interval (CI) were calculated using RevMan statistical software to assess the continuous data. Heterogeneity in studies was measured by I values. Subgroup analysis was performed based on different bone turnover.
RESULTS
A total of 5 randomized controlled studies met the inclusion criteria. Both OPG and RANKL had no significant differences between the osteoporosis and control group, and the statistical heterogeneity was high in meta-analysis. However, RANKL had significant differences between the osteoporosis group with low bone turnover and control group (SMD = - 1.17; 95% CI - 1.77 to 0.57; P value < 0.01) in subanalysis. Furthermore, the OPG/RANKL ratio was significant lower in the osteoporosis group than in the control group (SMD = - 0.29; 95% CI - 0.57 to - 0.02; P value < 0.05), and the statistical heterogeneity was very low (Chi = 0.20, P = 0.66, I = 0%).
CONCLUSIONS
Our meta-analysis study supported OPG and RANKL were important modulatory factors of bone formation and resorption in bone turnover, respectively. Although the serum level of both OPG and RANKL were not associated with osteoporosis, but the OPG/RANKL ratio was associated with osteoporosis. In future, standardizing the test method and unit was good to clinical application.
Topics: Humans; Osteoprotegerin; Osteoporosis; Bone Remodeling; Osteogenesis; RANK Ligand; Bone Density
PubMed: 37932757
DOI: 10.1186/s13018-023-04179-5 -
Clinical Rheumatology Oct 2017This study aimed to systemically review the evidence regarding the relationship between the circulating blood osteoprotegerin (OPG) level and rheumatoid arthritis (RA),... (Meta-Analysis)
Meta-Analysis Review
This study aimed to systemically review the evidence regarding the relationship between the circulating blood osteoprotegerin (OPG) level and rheumatoid arthritis (RA), as well as the potential influential factors. Research related to plasma/serum OPG levels in RA patients and healthy controls were gathered using PubMed, EMBASE, and The Cochrane Library database (up to Jan. 1, 2017). Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by fixed-effects or random-effect model analysis. Heterogeneity test was performed by the Q statistic and quantified using I , and publication bias was evaluated using a funnel plot and Egger's linear regression test. After searching databases, 443 articles were obtained, and 11 studies with 710 RA patients and 561 controls were finally included. Meta-analysis revealed that, compared with the control group, the OPG level was significantly higher in the RA group (P < 0.001), with the SMD of 1.02 and 95%CI (0.20, 1.84). Subgroup analyses showed that race, disease duration, body mass index (BMI), and disease activity score based on the assessment of 28 joints (DAS28) were positively associated with OPG level in RA patients. Our meta-analysis revealed a significantly higher circulating OPG level in RA patients, and it was influenced by race, disease duration, BMI, and DAS28.
Topics: Adult; Aged; Arthritis, Rheumatoid; Body Mass Index; Case-Control Studies; Cross-Sectional Studies; Ethnicity; Female; Humans; Linear Models; Male; Middle Aged; Osteoprotegerin; Severity of Illness Index; Time Factors
PubMed: 28698901
DOI: 10.1007/s10067-017-3747-x -
Immunological Investigations Feb 2021: Type 1 diabetes mellitus (T1D) has been disclosed to be associated with an elevated risk of cardiovascular disease (CVD), as well as increased risks of losing bone... (Meta-Analysis)
Meta-Analysis
: Type 1 diabetes mellitus (T1D) has been disclosed to be associated with an elevated risk of cardiovascular disease (CVD), as well as increased risks of losing bone mass and progression of osteoporosis (OP). Osteoprotegerin (OPG), as a decoy receptor, has been demonstrated to play a critical role in bone metabolism homeostasis and vascular atherosclerotic diseases. This meta-analysis aimed to investigate the associations between OPG levels and T1D. : Related literatures were searched and identified from the database of the Cochrane Library database, PubMed and EMbase inception to August 3, 2019 in English. The pooled standard mean difference (SMD) with its 95% confidence interval (CI) was calculated in using random-effect model analysis. Chi-square statistic and test were performed to evaluate and quantified the presence of heterogeneity. : Twelve studies with 1288 subjects (794 T1D patients and 494 healthy controls) were finally included. The incorporated results indicated that T1D patients have higher plasma/serum OPG levels than in healthy individuals (SMD = 0.64, 95% CI: 0.06, 1.22). Subgroup analyses suggested that Caucasian and glycosylated hemoglobin A1c (HbA1c) <8.5% groups showed higher OPG levels, however, there was no significant differences of OPG levels regarding subgroups of BMI ≥ or <25, children-adolescents or adults and HbA1c ≥8.5%. : The current evidence suggested that circulating OPG levels are significantly higher in T1D than in healthy controls, and the increase of OPG levels are influenced by factors of race and HbA1c.
Topics: Age Factors; Biomarkers; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Humans; Osteoprotegerin; Racial Groups; Up-Regulation
PubMed: 31920120
DOI: 10.1080/08820139.2019.1710531 -
Immunological Investigations Feb 2019Currently published data regarding the potential role of osteoprotegerin (OPG), osteocalcin (OCN) and osteopontin (OPN) for the discrimination between rheumatoid... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Currently published data regarding the potential role of osteoprotegerin (OPG), osteocalcin (OCN) and osteopontin (OPN) for the discrimination between rheumatoid arthritis (RA) and osteoarthritis (OA) are contradictory. To derive a more precise evaluation, a meta-analysis was performed.
METHODS
Published literatures comparing plasma/serum OPG, OCN and OPN levels between RA group and OA controls were searched in PubMed, Embase and the Cochrane Library. The Newcastle-Ottawa Scale was used to assess the study quality. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by random-effect model analysis. Heterogeneity test was performed by the Q statistic and quantified using I.
RESULTS
Nine studies including 438 RA patients and 255 OA patients were finally incorporated in the meta-analysis after examining title, type, abstracts and full text. The results showed that RA patients had higher plasma/serum OPN (pooled SMD = -2.57, 95% CI = -4.72 to -0.41) levels when compared to OA patients. No significant difference in plasma/serum OPG (pooled SMD = -0.29, 95% CI = -1.07‒0.49) and OCN (pooled SMD = -0.09, 95% CI = -0.48‒0.31) levels were found between RA patients and OA patients. Subgroup analysis indicated that plasma/serum OPG levels had no significant differences between RA patients and OA patients in Europe and Asian.
CONCLUSIONS
Overall, there is no significant difference in circulating OPG and OCN levels between RA patients and OA patients. However, plasma/serum OPN level is significantly higher in RA patients compared with OA patients.
Topics: Arthritis, Rheumatoid; Biomarkers; Diagnosis, Differential; Humans; Osteoarthritis; Osteocalcin; Osteopontin; Osteoprotegerin; Prognosis; Publication Bias
PubMed: 30188218
DOI: 10.1080/08820139.2018.1510957 -
BMJ Open Jun 2023Metformin is associated with osteoblastogenesis and osteoclastogenesis. This study aims to investigate the impacts of metformin therapy on bone mineral density (BMD) and... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Metformin is associated with osteoblastogenesis and osteoclastogenesis. This study aims to investigate the impacts of metformin therapy on bone mineral density (BMD) and bone turnover markers.
DESIGN
Systematic review and meta-analysis of randomised controlled trials.
METHODS
Searches were carried out in PubMed, EMBASE, Web of science, Cochrane library, ClinicalTrials.gov from database inception to 26 September 2022. Two review authors assessed trial eligibility in accordance with established inclusion criteria. The risk of bias was assessed using the Cochrane Risk of Bias tool (RoB V.2.0). Data analysis was conducted with Stata Statistical Software V.16.0 and Review Manager Software V.5.3.
RESULTS
A total of 15 studies with 3394 participants were identified for the present meta-analysis. Our pooled results indicated that metformin had no statistically significant effects on BMD at lumbar spine (SMD=-0.05, 95% CI=0.19 to 0.09, p=0.47, participants=810; studies=7), at femoral (MD=-0.01 g/cm, 95% CI=-0.04 to 0.01 g/cm, p=0.25, participants=601; studies=3) and at hip (MD=0.01 g/cm, 95% CI=0.02 to 0.03 g/cm, p=0.56, participants=634; studies=4). Metformin did not lead to significant change in osteocalcin, osteoprotegerin and bone alkaline phosphatase. Metformin induced decreases in N-terminal propeptide of type I procollagen (MD=-6.09 µg/L, 95% CI=9.38 to -2.81 µg/L, p=0.0003, participants=2316; studies=7) and C-terminal telopeptide of type I collagen (MD=-55.80 ng/L, 95% CI=97.33 to -14.26 ng/L, p=0.008, participants=2325; studies=7).
CONCLUSION
This meta-analysis indicated that metformin had no significant effect on BMD. Metformin decreased some bone turnover markers as N-terminal propeptide of type I procollagen and C-terminal telopeptide of type I collagen. But the outcomes should be interpreted with caution due to several limitations.
Topics: Humans; Bone Density; Metformin; Lumbar Vertebrae; Bone Remodeling
PubMed: 37355276
DOI: 10.1136/bmjopen-2023-072904 -
Progress in Orthodontics Dec 2014This systematic review aimed to generate evidence on role of potent markers of inflammation [cytokines, chemokines, their associated receptors and antagonists] following... (Review)
Review
This systematic review aimed to generate evidence on role of potent markers of inflammation [cytokines, chemokines, their associated receptors and antagonists] following the application of orthodontic forces. Subsequent to registration with PROSPERO, literature search followed a predetermined search strategy to key databases along with hand search (HS). Seventy-seven articles from PubMed (P), 637 from Scopus (S), 51 from Embase (E), and 3 from hand search (HS) were identified. A total of 39 articles were shortlisted that met strict inclusion and exclusion criteria and quality assessment. Each study was evaluated for participant characteristics, study design, oral hygiene regimen, and gingival crevicular fluid (GCF) handling. Among these studies, biomarkers in the order of frequency were interleukin (IL)-1β (N=21), tumor necrosis factor (TNF)-α (N=10), IL-8,IL-6(N=8), receptor activator of nuclear factor kappa-B ligand (RANKL) (N=7), monocyte chemoattractant protein (MCP)-1 (N=3), IL-2 (N=4), IL-4, IL-10, RANTES (N=2), IL-1, IL-5, IL-1α, IP-10, osteopontin (OPN) (N=1) and receptors and their antagonists in the order of osteoprotegerin (OPG) (N=8), IL-1RA (N=5), and RANK (N=1). Results revealed an immediate release of inflammatory bone-resorptive mediators, IL-1β and TNF-α, where IL-1β increased as early as 1 min to 1 h reaching peak at 24 h while TNF-α increased at 1 h or 1 day. This was accompanied by a fall in bone-protective mediator (OPG) levels at 1 h and 24 h after orthodontic force application. Continuous forces were accompanied by a decrease in mediator levels after attaining peak levels (most commonly at 24 h) while repeated activations in interrupted force upregulated their secretion. Significant correlations of IL-1β levels with pain intensity, rate of orthodontic tooth movement (OTM) and of activity index (AI) (IL-1β/IL-1RA) with velocity of tooth movement and growth status of individuals have also been deduced. A greater AI and RANKL/OPG ratio was seen in juveniles as compared to adults or non-growers that were associated with faster rate of OTM in juveniles. None of the studies addressed the effect of estrous cycle in female subjects. Lack of homogeneity in several parameters calls for a better controlled research on the biology of OTM.
Topics: Biomechanical Phenomena; Cytokines; Gingival Crevicular Fluid; Humans; Inflammation Mediators; Receptors, Cytokine; Stress, Mechanical; Tooth Movement Techniques
PubMed: 25487828
DOI: 10.1186/s40510-014-0065-6 -
Journal of the American Heart... Aug 2018Background Osteoprotegerin is a cytokine involved in bone metabolism as well as vascular calcification and atherogenesis. Although circulating osteoprotegerin levels are... (Meta-Analysis)
Meta-Analysis
Background Osteoprotegerin is a cytokine involved in bone metabolism as well as vascular calcification and atherogenesis. Although circulating osteoprotegerin levels are robustly associated with incident cardiovascular disease ( CVD ) in the general population, its relevance as a biomarker among populations at high CVD risk is less clear. Methods and Results Three independent reviewers systematically searched PubMed, EMBASE , and Web of Science to identify prospective studies that had recruited participants on the basis of having conditions related to high CVD risk. A total of 19 studies were eligible for inclusion, reporting on 27 450 patients with diabetes mellitus (2 studies), kidney disease (7 studies), preexisting heart disease (5 studies), or recent acute coronary syndromes (5 studies) at baseline. Over a mean follow-up of 4.2 years, 4066 CVD events were recorded. In a random-effects meta-analysis, the pooled risk ratio for CVD events comparing people in the top versus the bottom tertile of osteoprotegerin concentration was 1.30 (95% confidence interval, 1.12-1.50; P<0.001; I=68.3%). There was evidence for presence of publication bias ( P value from Egger's test=0.013). Correction for publication bias using the trim-and-fill method reduced the risk ratio to 1.21 (95% confidence interval, 1.03-1.42; P<0.001). The risk ratios did not vary significantly by population type, geographical region, statistical adjustment, sample or assay type, age, sex, or length of follow-up. Conclusions In populations at high CVD risk, elevated circulating osteoprotegerin levels are associated with a higher risk for future CVD events. The magnitude of association appears weaker than in the general population.
Topics: Acute Coronary Syndrome; Angina Pectoris; Biomarkers; Cardiovascular Diseases; Comorbidity; Diabetes Mellitus; Heart Diseases; Humans; Kidney Diseases; Myocardial Infarction; Myocardial Revascularization; Osteoprotegerin; Risk; Stroke
PubMed: 30369329
DOI: 10.1161/JAHA.118.009012 -
Clinical Orthopaedics and Related... Dec 2014Identification of biomarkers associated with wear and tribocorrosion in joint arthroplasty would be helpful to enhance early detection of aseptic loosening and/or... (Review)
Review
BACKGROUND
Identification of biomarkers associated with wear and tribocorrosion in joint arthroplasty would be helpful to enhance early detection of aseptic loosening and/or osteolysis and to improve understanding of disease progression. There have been several new reports since the last systematic review (which covered research through mid-2008) justifying a new assessment.
QUESTIONS/PURPOSES
We sought to determine which biomarkers have the most promise for early diagnosis and monitoring of aseptic loosening and/or osteolysis related to wear or corrosion in total joint arthroplasty.
METHODS
We performed a systematic review using MEDLINE and EMBASE databases, covering the period through December 2013, and identified 1050 articles. We restricted the definition of biomarker to biomolecules and imaging parameters useful for diagnosis and monitoring of disease progression, only including articles in English. We chose 65 articles for full review, including 44 from the original search and 21 from subsequent hand searches. We used the 22 articles in which patients with total joint arthroplasty who had aseptic loosening and/or periimplant osteolysis unrelated to sepsis had been compared with patients with total joint arthroplasty with stable implants. There were 90 comparisons of these two patient populations involving 35 different biomarkers.
RESULTS
Diagnostic accuracy was assessed in nine of the 90 comparisons with the highest accuracy found for tartrate-resistant acid phosphatase 5b (0.96), although a separate comparison for this biomarker found a lower accuracy (0.76). Accuracy of > 0.80 was also found for crosslinked n-telopeptide of type I collagen, osteoprotegerin, and deoxypyridinoline. The most studied markers, tumor necrosis factor-α and interleukin-1β, were found to differ in the affected and control groups in < 30% of the comparisons. Thirty of the 35 biomarkers were studied in four or fewer separate comparisons with nearly half of the biomarkers (17) studied in only one comparison. Many of the comparisons were not able to eliminate a number of confounding variables, and there was only one prospective study.
CONCLUSIONS
Currently, there are no validated biomarkers for early diagnosis and monitoring of the biological sequelae of wear or tribocorrosion, although there are some promising leads, including markers of bone turnover.
Topics: Arthroplasty, Replacement; Biomarkers; Biomechanical Phenomena; Corrosion; Diagnostic Imaging; Humans; Joint Prosthesis; Joints; Osteolysis; Predictive Value of Tests; Prosthesis Design; Prosthesis Failure; Risk Factors; Stress, Mechanical; Treatment Outcome
PubMed: 24668073
DOI: 10.1007/s11999-014-3580-3 -
Journal of Dentistry Jul 2024To perform a comprehensive quantitative and qualitative analysis of the findings from previously published meta-analyses and to assess existing biases. (Review)
Review
OBJECTIVES
To perform a comprehensive quantitative and qualitative analysis of the findings from previously published meta-analyses and to assess existing biases.
DATA/SOURCES
A search was conducted for meta-analyses of observational studies investigating the association between any risk factor and peri‑implantitis in PubMed, Scopus, Cochrane Database of Systematic Reviews, and Epistemonikos, from inception until October 2023 (PROSPERO: CRD42024512408).
STUDY SELECTION
From a total of 5002 publications, 51 full-text articles were evaluated for eligibility, and 12 articles that described 41 unique meta-analyses evaluating the association between risk factors and periimplantitis were selected. Among 41 associations, 24 associations were significant. None of the associations were graded as convincing evidence. Two associations, presence of periodontitis (OR = 3.84 [95 % CI 2.58,5.72]) and cigarette smoking (RR=2.07 [95 % CI 1.41,3.04]) were graded as highly suggestive. Eight associations, diabetes mellitus, hyperglycaemia, lack of prophylaxis, history of chronic periodontal disease, ongoing or history of periodontal disease, implants located in the anterior region of the jaw (maxillary and mandibular), osteoprotegerin (OPG) gene polymorphisms, and lack of keratinized mucosal width were graded as suggestive evidence.
CONCLUSIONS
Periodontitis and cigarette smoking are highly suggestive risk factors for peri‑implantitis. The remaining risk factors which are suggestive require more high-quality studies to be performed to upgrade the level of evidence.
CLINICAL SIGNIFICANCE
The highly suggestive and suggestive risk factors for peri‑implantitis summarized in this umbrella review should be rigorously assessed, monitored and managed by clinicians to reduce the risk peri‑implantitis, as well as to form part of the preoperative consent process.
Topics: Humans; Peri-Implantitis; Risk Factors; Observational Studies as Topic; Meta-Analysis as Topic; Dental Implants; Periodontitis; Bias
PubMed: 38762079
DOI: 10.1016/j.jdent.2024.105065