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Heart (British Cardiac Society) Jun 2019Vascular stiffness (VS) and vascular calcification (VC) are surrogate markers of vascular health associated with cardiovascular events. Vitamin K-dependent proteins... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Vascular stiffness (VS) and vascular calcification (VC) are surrogate markers of vascular health associated with cardiovascular events. Vitamin K-dependent proteins (VKDP) are associated with VS and VC and require vitamin K for activity. We conducted a systematic review and meta-analysis of: (1) the effect of vitamin K supplementation on VS and VC and (2) association of inactive VKDP levels with incident cardiovascular disease and mortality.
METHODS
Two authors searched MEDLINE and Embase databases and Cochrane and ISRCTN registries for studies of vitamin K clinical trials that measured effects on VC, VS or VKDP and longitudinal studies assessing effect of VKDP on incident CVD or mortality. Random effects meta-analyses were performed.
RESULTS
Thirteen controlled clinical trials (n=2162) and 14 longitudinal studies (n=10 726) met prespecified inclusion criteria. Vitamin K supplementation was associated with significant reduction in VC (-9.1% (95% CI -17.7 to -0.5); p=0.04) and VKDP (desphospho-uncarboxylated matrix Gla protein; -44.7% (95% CI -65.1 to -24.3), p<0.0001) and uncarboxylated osteocalcin; -12.0% (95% CI -16.7 to -7.2), p<0.0001) compared with control, with a non-significant improvement in VS. In longitudinal studies with median follow-up of 7.8 (IQR 4.9-11.3) years, VKDP levels were associated with a combined endpoint of CVD or mortality (HR 0.45 (95% CI 0.07 to 0.83), p=0.02).
CONCLUSIONS
Supplementation with vitamin K significantly reduced VC, but not VS, compared with control. The conclusions drawn are limited by small numbers of studies with substantial heterogeneity. VKDP was associated with combined endpoint of CVD or mortality. Larger clinical trials of effect of vitamin K supplementation to improve VC, VS and long-term cardiovascular health are warranted.
TRIAL REGISTRATION NUMBER
CRD42017060344.
Topics: Biomarkers; Dietary Supplements; Humans; Vascular Calcification; Vascular Diseases; Vitamin K; Vitamins
PubMed: 30514729
DOI: 10.1136/heartjnl-2018-313955 -
Journal of Clinical Medicine Jun 2019This study seeks to evaluate the long-term effects of pharmacologic therapy on the bone markers and bone mineral density of transgender patients and to provide a basis... (Review)
Review
This study seeks to evaluate the long-term effects of pharmacologic therapy on the bone markers and bone mineral density of transgender patients and to provide a basis for understanding its potential implications on therapies involving implant procedures. Following the referred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and well-defined PICOT (Problem/Patient/Population, Intervention, Comparison, Outcome, Time) questionnaires, a literature search was completed for articles in English language, with more than a 3 year follow-up reporting the long-term effects of the cross-sex pharmacotherapy on the bones of adult transgender patients. Transgender demographics, time under treatment, and treatment received were recorded. In addition, bone marker levels (calcium, phosphate, alkaline phosphatase, and osteocalcin), bone mineral density (BMD), and bone turnover markers (Serum Procollagen type I N-Terminal pro-peptide (PINP), and Serum Collagen type I crosslinked C-telopeptide (CTX)) before and after the treatment were also recorded. The considerable variability between studies did not allow a meta-analysis. All the studies were completed in European countries. Transwomen (921 men to female) were more frequent than transmen (719 female to male). Transwomen's treatments were based in antiandrogens, estrogens, new drugs, and sex reassignment surgery, meanwhile transmen's surgeries were based in the administration of several forms of testosterone and sex reassignment. Calcium, phosphate, alkaline phosphatase, and osteocalcin levels remained stable. PINP increased in transwomen and transmen meanwhile, CTX showed contradictory values in transwomen and transmen. Finally, reduced BMD was observed in transwomen patients receiving long-term cross-sex pharmacotherapy. Considering the limitations of this systematic review, it was concluded that long-term cross-sex pharmacotherapy for transwomen and transmen transgender patients does not alter the calcium, phosphate, alkaline phosphatase, and osteocalcin levels, and will slightly increase the bone formation in both transwomen and transmen patients. Furthermore, long-term pharmacotherapy reduces the BMD in transwomen patients.
PubMed: 31159456
DOI: 10.3390/jcm8060784 -
Biomarkers in Body Fluids as Indicators of Skeletal Maturity: A Systematic Review and Meta-analysis.Rambam Maimonides Medical Journal Aug 2023This review aimed to critically appraise the evidence for biomarkers in blood serum, gingival crevicular fluid (GCF), saliva, and urine in comparison with standard... (Review)
Review
OBJECTIVES
This review aimed to critically appraise the evidence for biomarkers in blood serum, gingival crevicular fluid (GCF), saliva, and urine in comparison with standard radiographic indices for skeletal maturation assessment.
MATERIALS AND METHODS
A thorough literature search in multiple databases was conducted for biomarkers in body fluids for skeletal maturation assessed with cervical vertebrae in lateral cephalograms or on hand-wrist radiographs. Different combinations including free text, MeSH terms, and Boolean operators were used. Two researchers used strict inclusion and exclusion criteria to screen title, abstract, and full text, and used the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 instrument for risk of bias assessment of individual studies. Meta-analysis was performed on eligible studies using RevMan 5 software.
RESULTS
A total of 344 articles were screened, of which 33 met the inclusion criteria and quality assessment. The skeletal maturity indicators included insulin-like growth factors (IGF-1), alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BALP), dehydroepiandrosterone sulfate (DHEAS), vitamin D binding protein (DBP), parathormone-related protein (PTHrP), osteocalcin, metalloproteins, and serotransferrin (TF) along with different metabolites. At puberty, a significant rise was seen in IGF-1, DBP, ALP, osteocalcin, TF, and BALP. However, the serum DHEAS and PTHrP increased from pre-pubertal to post-pubertal stages. Due to the data heterogeneity, a meta-analysis could be performed on seven studies in total on IGF-1 in serum and blood. Of these, five were included for data in males and six in females, and four studies on IGF-1 in serum and blood. A significant difference in IGF-1 levels was seen between stages of peak pubertal growth spurt (CS3 and CS4) and decelerating pubertal growth (CS5) compared with growth initiation stage (CS2).
CONCLUSIONS
Pubertal growth spurts were correlated with peak serum IGF-1 and BALP in both sexes individually. Peak ALP levels in GCF were correlated with the pubertal spurt in a combined sample of males and females. Standard biofluid collection protocols and homogeneity in sampling and methodology are strongly recommended for future research.
PubMed: 37669407
DOI: 10.5041/RMMJ.10506 -
The Cochrane Database of Systematic... Jun 2020Malabsorption and deficiency of fat-soluble vitamins K may occur in cystic fibrosis, a genetic disorder affecting multiple organs. Vitamin K is known to play an...
BACKGROUND
Malabsorption and deficiency of fat-soluble vitamins K may occur in cystic fibrosis, a genetic disorder affecting multiple organs. Vitamin K is known to play an important role in both blood coagulation and bone formation, hence the role of supplementation of vitamin K in this category needs to be reviewed. This is an updated version of the review.
OBJECTIVES
To assess the effects of vitamin K supplementation in people with cystic fibrosis and to investigate the hypotheses that vitamin K will decrease deficiency-related coagulopathy, increase bone mineral density, decrease risk of fractures and improve quality of life in people with CF. Also to determine the optimal dose and route of administration of vitamin K for people with CF (for both routine and therapeutic use).
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Most recent search: 12 August 2019.
SELECTION CRITERIA
Randomised controlled trials of all preparations of vitamin K used as a supplement compared to either no supplementation (or placebo) at any dose or route and for any duration, in patients with cystic fibrosis.
DATA COLLECTION AND ANALYSIS
Two authors independently screened papers, extracted trial details and assessed their risk of bias. The quality of the evidence was assessed using the GRADE criteria.
MAIN RESULTS
Three trials (total 70 participants, aged 8 to 46 years) assessed as having a moderate risk of bias were included. One trial compared vitamin K to placebo, a second to no supplementation and the third compared two doses of vitamin K. No trial in either comparison reported our primary outcomes of coagulation and quality of life or the secondary outcomes of nutritional parameters and adverse events. Vitamin K versus control Two trials compared vitamin K to control, but data were not available for analysis. One 12-month trial (n = 38) compared 10 mg vitamin K daily or placebo in a parallel design and one trial (n = 18) was of cross-over design with no washout period and compared 5 mg vitamin K/week for four-weeks to no supplementation for four-weeks. Only the 12-month trial reported on the primary outcome of bone formation; we are very uncertain whether vitamin K supplementation has any effect on bone mineral density at the femoral hip or lumbar spine (very low-quality evidence). Both trials reported an increase in serum vitamin K levels and a decrease in undercarboxylated osteocalcin levels. The cross-over trial also reported that levels of proteins induced by vitamin K absence (PIVKA) showed a decrease and a return to normal following supplementation, but due to the very low-quality evidence we are not certain that this is due to the intervention. High-dose versus low-dose vitamin K One parallel trial (n = 14) compared 1 mg vitamin K/day to 5 mg vitamin K/day for four weeks. The trial did report that there did not appear to be any difference in serum undercarboxylated osteocalcin or vitamin K levels (very low-quality evidence). While the trial reported that serum vitamin K levels improved with supplementation, there was no difference between the high-dose and low-dose groups.
AUTHORS' CONCLUSIONS
There is very low-quality evidence of any effect of vitamin K in people with cystic fibrosis. While there is no evidence of harm, until better evidence is available the ongoing recommendations by national CF guidelines should be followed.
Topics: Adolescent; Adult; Biomarkers; Blood Coagulation; Bone Density; Child; Cystic Fibrosis; Dietary Supplements; Fractures, Bone; Humans; Middle Aged; Osteocalcin; Osteogenesis; Protein Precursors; Prothrombin; Quality of Life; Randomized Controlled Trials as Topic; Vitamin K; Vitamin K Deficiency; Vitamins
PubMed: 32497260
DOI: 10.1002/14651858.CD008482.pub6 -
Iranian Journal of Public Health Feb 2022Vitamin D plays an essential role in the regulation of bone metabolism. The current meta-analysis aimed to assess the effectiveness of vitamin D fortification on special... (Review)
Review
BACKGROUND
Vitamin D plays an essential role in the regulation of bone metabolism. The current meta-analysis aimed to assess the effectiveness of vitamin D fortification on special bone biomarkers.
METHODS
Five main databases (PubMed/Medline, ISI Web of Knowledge, Science Direct, Scopus, Cochrane Library as well as Science Direct, and Scopus) were considered for this systematic review, until Jan 2020. All randomized controlled trials were included to evaluate the probable relationship between consumption of vitamin D fortification products and bone biomarkers profile in this review.
RESULTS
Among serum bone biomarkers (osteocalcin and telopeptides of type-1 collagen) investigated, only the level of telopeptides of type-1 collagen significantly decreased after fortification of vitamin D in the intervention group. A significant increase in vitamin D was seen in those older than 18 yr old, while the increase in younger children was not statistically significant between intervention and control groups.
CONCLUSION
Vitamin D fortification was not associated with a significant improvement in bone mass density (BMD), while it resulted in decreased PTH levels. Vitamin D fortified foods have some benefits on bone health due to increase in the level of vitamin D and IGF-1; and decreasing PTH and CTx levels.
PubMed: 35866135
DOI: 10.18502/ijph.v51i2.8681 -
The Application of Statins in the Regeneration of Bone Defects. Systematic Review and Meta-Analysis.Materials (Basel, Switzerland) Sep 2019This systematic review aims to analyze the effect of the local application of statins in the regeneration of non-periodontal bone defects. A systematic study was... (Review)
Review
This systematic review aims to analyze the effect of the local application of statins in the regeneration of non-periodontal bone defects. A systematic study was conducted with the Pubmed/Medline, Embase, Cochrane Library and Scielo databases for in vivo animal studies published up to and including February 2019. Fifteen articles were included in the analysis. The local application of the drug increased the percentage of new bone formation, bone density, bone healing, bone morphogenetic protein 2, vascular endothelial growth factor, progenitor endothelial cells and osteocalcin. Meta-analyses showed a statistically significant increase in the percentage of new bone formation when animals were treated with local statins, in contrast to the no introduction of filling material or the introduction of polylactic acid, both in an early (4-6 weeks) and in a late period (12 weeks) (mean difference 39.5%, 95% confidence interval: 22.2-56.9, <0.001; and mean difference 43.3%, 95% confidence interval: 33.6-52.9, < 0.001, respectively). Basing on the animal model, the local application of statins promotes the healing of critical bone size defects due to its apparent osteogenic and angiogenic effects. However, given the few studies and their heterogenicity, the results should be taken cautiously, and further pilot studies are necessary, with radiological and histological evaluations to translate these results to humans and establish statins' effect.
PubMed: 31527399
DOI: 10.3390/ma12182992 -
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 -
Annals of Palliative Medicine Oct 2022Postmenopausal women are one of the most vulnerable groups to osteoporosis. Romosozumab is a newly monoclonal drug that inhibits the activity of sclerostin. Since it has... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Postmenopausal women are one of the most vulnerable groups to osteoporosis. Romosozumab is a newly monoclonal drug that inhibits the activity of sclerostin. Since it has been on the market for only 3 years, there is a lack of systematic analysis on postmenopausal women and the efficacy is not clear. In this study, we compared randomized controlled trials to assess the effects of blosozumab versus placebo in perimenopausal and postmenopausal women.
METHODS
This meta-analysis has been registered in the PROSPERO registry (number CRD42020145839). The PubMed, Cochrane Library, ClinicalKey, and Embase databases were searched from inception date to July 01, 2021. We used the keywords "osteoporosis", "decreased bone mass", and "blosozumab" to retrieve studies on the relationship between blosozumab and osteoporosis in each database. The inclusion criteria were: (I) randomized controlled trials (RCTs) comparing the treatment of osteoporosis with blosozumab and a placebo or without treatment, (II) studies on postmenopausal women aged over 50 years, and (III) studies providing bone mineral density data. The quality of all randomized controlled trials included in this study was independently assessed by two researchers according to the Cochrane risk manual and was divided into high, medium and low quality. The main results analyzed were bone mineral density (BMD) and T-score. Our results mainly include BMD and procollagen type I N-terminal propeptide (P1NP), C-terminal telopeptide of type I collagen (CTX), bone-specific alkaline phosphatase (BSAP), and osteocalcin (OC).
RESULTS
Three RCTs with 105 patients were selected from 157 retrieved articles. Due to high heterogeneity [BMD: Tau2=2.79; Chi2=11.70, degrees of freedom (df) =1 (P=0.0006); I2=91%], we could not perform statistical analysis of BMD. The results of BMD were then evaluated systematically. Three RCT studies were included in the evaluation. Compared with that of the placebo, blosozumab increased levels of the BMD biomarker osteocalcin [mean deviation (MD) 12.55; 95% confidence interval (CI), 8.18, 16.91; P<0.00001]. None of the 3 RCTs presented a risk of bias during the meta-analysis.
CONCLUSIONS
The results suggested that blosozumab could be used as a target drug to improve BMD in postmenopausal women. This will provide a reference for the clinical treatment of postmenopausal women with osteoporosis.
Topics: Female; Humans; Middle Aged; Bone Density Conservation Agents; Osteocalcin; Osteoporosis; Osteoporosis, Postmenopausal; Postmenopause; Randomized Controlled Trials as Topic
PubMed: 36367007
DOI: 10.21037/apm-22-998 -
European Journal of Medical Research Jul 2023Dental pulp stem cells (DPSCs) are adult stem cells with multi-directional differentiation potential derived from ectoderm. Vitro experiments have shown that adding... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Dental pulp stem cells (DPSCs) are adult stem cells with multi-directional differentiation potential derived from ectoderm. Vitro experiments have shown that adding cytokines can help DPSCs to be transformed from multipotent stem cells to osteoblasts. TGF-β has been proved to have an effect on the proliferation and mineralization of bone tissue, but its effect on the osteogenesis and proliferation of dental pulp stem cells is still uncertain. We aim to determine the effect of TGF-β on the osteogenesis and proliferation of dental pulp stem cells.
METHODS
We have identified studies from the Cochrane Central Register of Controlled Trials, PubMed, Embase, and China national knowledge infrastructure (CNKI) for studies interested in TGF-β and proliferation and differentiation of dental pulp stem cells in the following indicators: A490 (an index for evaluating cell proliferation), bone sialoprotein (BSP), Col plasmid-1 (Col-1), osteocalcin (OCN), runt-related transcription factor 2 (Runx-2); and the number of mineralized nodules. Any language restrictions were rejected. Furthermore, we drew a forest plot for each outcome. We conducted a sensitivity analysis, data analysis, heterogeneity, and publication bias test. We evaluate the quality of each study under the guidance of Cochrane's tool for quality assessment.
RESULTS
The pooled data showed that TGF-β could promote the proliferation and ossification of dental pulp stem cells. All the included results support this conclusion except for the number of mineralized nodules: TGF-β increases the A490 index (SMD 3.11, 95% CI [0.54-5.69]), promotes the production of BSP (SMD 3.11, 95% CI [0.81-6.77]), promotes the expression of Col-1 (SMD 4.71, 95% CI [1.25-8.16]) and Runx-2 (SMD 3.37, 95% CI [- 0.63 to 7.36]), increases the content of OCN (SMD 4.32, 95% CI [1.20-7.44]) in dental pulp, and has no significant effect on the number of mineralized nodules (SMD 3.87, 95% CI [- 1.76 to 9.51]) in dental pulp stem cells.
CONCLUSIONS
TGF-β promotes the proliferation and osteogenesis of dental pulp stem cells.
Topics: Humans; Cell Differentiation; Cell Proliferation; Cells, Cultured; Dental Pulp; Osteogenesis; Stem Cells; Transforming Growth Factor beta
PubMed: 37501191
DOI: 10.1186/s40001-023-01227-y -
Diseases (Basel, Switzerland) Feb 2022Periodontitis is the most prevalent inflammatory disease worldwide. Its inflammatory levels spread systemically, which can be associated with chronic kidney disease.... (Review)
Review
Periodontitis is the most prevalent inflammatory disease worldwide. Its inflammatory levels spread systemically, which can be associated with chronic kidney disease. Biomarkers have the potential to diagnose and correlate periodontitis and chronic kidney disease, helping to monitor systemic inflammation. Thereby, this study aimed to analyze the association between chronic kidney disease and periodontitis by conducting a biomarker analysis on blood and saliva. An electronic search through PubMed/MEDLINE, EMBASE, and Web of Science databases was conducted to identify clinical studies published in the last ten years, with no language restrictions. Twelve articles met all the inclusion criteria, two randomized controlled trials, one cohort study, and nine observational studies. The studies included a total of 117 patients for saliva biomarkers, with a mean age of approximately 57 years old, and 56.68% of the subjects were female. After analyzing all the included studies, it was possible to verify the following biomarkers assessed: CRP, WBC, fibrinogen, IL-4 and -6, cardiac troponin T, NOx, ADMA, albumin, osteocalcin, cystatin C, PGLYRP1, cholesterol, HDL, LDL, triglycerides, and hemoglobin. A direct cause-effect association between periodontitis and CKD could not be established. However, it was possible to conclude that there was a correlating effect present, through the analyzed biomarkers.
PubMed: 35225864
DOI: 10.3390/diseases10010012