-
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 -
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 -
Journal of Diabetes Research 2018Undercarboxylated osteocalcin (ucOC) increases insulin release and insulin resistance in mice. In humans, evidence is scarce but a correlation of ucOC and total... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Undercarboxylated osteocalcin (ucOC) increases insulin release and insulin resistance in mice. In humans, evidence is scarce but a correlation of ucOC and total osteocalcin (tOC) with glycemic status markers has been demonstrated. The relationship of ucOC and tOC with gestational diabetes mellitus (GDM) has been even less characterized.
OBJECTIVE
To assess the mean difference of tOC and ucOC serum concentrations among nondiabetic pregnant women and women diagnosed as GDM in the second trimester of pregnancy and to determine the possible intrinsic and extrinsic contributors to this difference.
METHODS
A systematic search was performed to identify relevant studies published in English and Spanish using PubMed, SCOPUS, ISI Web of Knowledge, and PROSPERO database for meta-analysis. Observational studies measuring mean serum levels of osteocalcin among GDM, with at least 10 subjects analyzed in each group were selected. Mean difference (MD) by random effects model was used. Heterogeneity between studies was assessed using Cochran's Q, H, and statistics.
RESULTS
From 38 selected studies, 5 were retained for analysis for a total of 1119 pregnant women. Serum concentrations of tOC were not significantly different among women with GDM and nondiabetic pregnant controls (MD: 1.56; 95% CI: -0.70 to 3.82; = 0.175). Meanwhile, ucOC serum levels were significantly higher among women with GDM (MD: 1.17; 95% CI: 0.24 to 2.11; = 0.013). The only factor influencing tOC was the UV index, showing a reduction in mean difference between GDM and controls when exposed to higher concentrations of UV rays.
CONCLUSIONS
This meta-analysis provides evidence to support the use of ucOC as a potential marker for GDM rather than tOC, yielding very little variability among studies and no difference among methods or brands used for its analysis.
Topics: Bias; Biomarkers; Blood Glucose; Diabetes, Gestational; Female; Humans; Insulin; Insulin Resistance; Osteocalcin; Pregnancy; Pregnancy Complications; Prospective Studies; Regression Analysis; Retrospective Studies; Risk
PubMed: 30693288
DOI: 10.1155/2018/4986735 -
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 -
Scientific Reports Jul 2018To study supplementation effect of vitamin K (VK) alone or combined with other nutrients administered to pregnant women, we searched Cochrane Pregnancy and Childbirth... (Meta-Analysis)
Meta-Analysis
To study supplementation effect of vitamin K (VK) alone or combined with other nutrients administered to pregnant women, we searched Cochrane Pregnancy and Childbirth Group's Trials Register (till 22 January 2016, updated on 28 February 2018) including other resources. Two review authors independently assessed randomised or quasi-randomised controlled trials for inclusion, data extraction, accuracy, and risk of bias. We included older trials from high-income countries (six; 21,493 women-newborns), judged mostly as high or unclear bias risk. We could not assess high-risk e.g. epileptic women, but healthy women (different gestational ages) received varying VK dosages and duration. We meta-analysed neonatal bleeding (RR 1.16, 95% CI 0.59 to 2.29; P = 0.67) and maternal plasma VK1 (MD 2.46, 95% CI 0.98 to 3.93; P = 0.001). We found many outcomes were un-assessed e.g. perinatal death, maternal bleeding, healthcare utilization. Mostly newborns were included where VK found significantly effective for e.g. serum VK (mother-newborn), maternal breast milk VK. Few trials reported neonatal adverse side effects. The GRADE evidence quality was very low i.e. neonatal bleeding, neonatal jaundice, maternal plasma VK1. The intervention was favourable for maternal sera VK1 but remained uncertain for neonatal bleeding and other outcomes. The existing literature gaps warrant future investigations on un-assessed or inadequately reported outcomes.
Topics: Dietary Supplements; Female; Humans; Infant, Newborn; Milk, Human; Osteocalcin; Pregnancy; Pregnancy Outcome; Publication Bias; Risk; Vitamin K
PubMed: 30061633
DOI: 10.1038/s41598-018-29616-y -
Journal of Oral Biology and... 2018The objective of the study was to conduct a systematic review of the literature so as to evaluate and summarize the diagnostic and prognostic potential of GCF. Included...
The objective of the study was to conduct a systematic review of the literature so as to evaluate and summarize the diagnostic and prognostic potential of GCF. Included studies were systematically analyzed based on PRISMA (Preferred Reporting Items For Systematic Reviews and Meta Analyses) and studies were identified based on the-PICO (Glossary of evidence based terms 2007): 1)Patients with chronic periodontitis.2)Intervention- NSPT (Non-SurgicalPeriodontal therapy); NSPT + Chemotherapeutics.3)Comparison between treated v/s non treated sites.4)Outcomes measured: Analysis of variation in constituents of GCF. Electronic database search of Pubmed, Medline, Google Scholar and Scopus was performed using (MeSH) terms- Gingival Crevicular fluid and Cytokines, MMP's, NE, PGE-2, A2M, B2M, ALP, AST, Osteocalcin and Calprotectin. Articles published between year 2000-2016 were reviewed and were included based on inclusion and exclusion criteria. Based on this systematic review of literature, it can be concluded that analysis of constituents of GCF can be used as an effective and efficient diagnostic tool of periodontal diseases. These biomarkers in turn with their prognostic significance could act as a valuable tool in the combat of periodontal disease.
PubMed: 29892530
DOI: 10.1016/j.jobcr.2018.02.002 -
Journal of Cancer Research and... 2018The number of people living with and beyond cancer is at an all time high. These survivors are not necessarily living well, as adverse side effects from cancer and its... (Meta-Analysis)
Meta-Analysis Review
The number of people living with and beyond cancer is at an all time high. These survivors are not necessarily living well, as adverse side effects from cancer and its treatment can last up to 5 years and leave patients at a higher risk of developing secondary cancers and other chronic illnesses. Exercise has been proven to be a safe and effective method of intervention to decrease mortality and overall improve health outcomes. The biological mechanism through which this occurs is an area of research that is in its infancy and not well defined. A systematic search was conducted of four databases for relevant randomized controlled trials (RCTs) published between January 2004 and December 2014. Studies had to include any blood/urine biological markers as an outcome measure to a physical activity intervention for cancer survivors posttreatment. Fifteen relevant articles were identified (12 RCTs). It was shown that randomized controlled trials of exercise for cancer survivors posttreatment may results in changes to circulating levels of insulin, insulin related pathways (insulin like growth factor II [IGF II], IGF binding protein 3), high density lipoprotein, total cholesterol, leptin, and osteocalcin. Due to small sample sizes, the evidence is still preliminary and therefore more research is warranted in this area in the form of larger, statistically powered RCTs for cancer survivors.
Topics: Biomarkers; Cancer Survivors; Exercise; Humans; Neoplasms; Outcome Assessment, Health Care
PubMed: 29516906
DOI: 10.4103/0973-1482.191036 -
The Cochrane Database of Systematic... Aug 2017Cystic fibrosis is a genetic disorder which can lead to multiorgan dysfunction. Malabsorption of fat and fat-soluble vitamins (A, D, E, K) may occur and can cause... (Review)
Review
BACKGROUND
Cystic fibrosis is a genetic disorder which can lead to multiorgan dysfunction. Malabsorption of fat and fat-soluble vitamins (A, D, E, K) may occur and can cause subclinical deficiencies of some of these vitamins. Vitamin K is known to play an important role in both blood coagulation and bone formation. Supplementation with vitamin K appears to be one way of addressing the deficiency, but there is very limited agreement on the appropriate dose and frequency of use of these supplements. This is an updated version of the review.
OBJECTIVES
To assess the effects of vitamin K supplementation in people with cystic fibrosis and to determine the optimal dose and route of administration of vitamin K 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: 30 January 2017.
SELECTION CRITERIA
Randomised and quasi-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 children or adults diagnosed with cystic fibrosis (by sweat test or genetic testing).
DATA COLLECTION AND ANALYSIS
Two authors independently screened papers, extracted trial details and assessed their risk of bias.
MAIN RESULTS
Two trials (total of 32 participants) each lasting one month were included in the review and were assessed as having a moderate risk of bias. One was a dose-ranging parallel group trial in children (aged 8 to 18 years); and the other (with an older cohort) had a cross-over design comparing supplements to no treatment, but no separate data were reported for the first intervention period. Neither of the trials addressed any of the primary outcomes (coagulation, bone formation and quality of life). Both trials reported the restoration of serum vitamin K and undercarboxylated osteocalcin levels to the normal range after one month of daily supplementation with 1 mg of vitamin K.
AUTHORS' CONCLUSIONS
Evidence from randomised controlled trials on the benefits of routine vitamin K supplementation for people with CF is currently weak and limited to two small trials of short duration. However, no harm was found and until further evidence is available, the present recommendations should be adhered to.
Topics: Adolescent; Adult; Blood Coagulation; Child; Cystic Fibrosis; Dietary Supplements; Humans; Osteogenesis; Quality of Life; Randomized Controlled Trials as Topic; Vitamin K; Vitamin K Deficiency; Vitamins
PubMed: 28829533
DOI: 10.1002/14651858.CD008482.pub5 -
Frontiers in Endocrinology 2017Osteocalcin (OC) is an intriguing hormone, concomitantly being the most abundant non-collagenous peptide found in the mineralized matrix of bone, and expanding the...
BACKGROUND
Osteocalcin (OC) is an intriguing hormone, concomitantly being the most abundant non-collagenous peptide found in the mineralized matrix of bone, and expanding the endocrine function of the skeleton with far-reaching extra-osseous effects. A new line of enquiry between OC and vascular calcification has emerged in response to observations that the mechanism of vascular calcification resembles that of bone mineralisation. To date, studies have reported mixed results. This systematic review and meta-analysis aimed to identify any association between OC and vascular calcification and atherosclerosis.
METHODS AND RESULTS
Databases were searched for original, peer reviewed human studies. A total of 1,453 articles were retrieved, of which 46 met the eligibility criteria. Overall 26 positive, 17 negative, and 29 neutral relationships were reported for assessments between OC (either concentration in blood, presence of OC-positive cells, or histological staining for OC) and extent of calcification or atherosclerosis. Studies that measured OC-positive cells or histological staining for OC reported positive relationships (11 studies). A higher percentage of Asian studies found a negative relationship (36%) in contrast to European studies (6%). Studies examining carboxylated and undercarboxylated forms of OC in the blood failed to report consistent results. The meta-analysis found no significant difference between OC concentration in the blood between patients with "atherosclerosis" and control ( = 0.13, = 1,197).
CONCLUSION
No definitive association was determined between OC and vascular calcification or atherosclerosis; however, the presence of OC-positive cells and histological staining had a consistent positive correlation with calcification or atherosclerosis. The review highlighted several themes, which may influence OC within differing populations leading to inconclusive results. Large, longitudinal studies are required to further current understanding of the clinical relevance of OC in vascular calcification and atherosclerosis.
PubMed: 28824544
DOI: 10.3389/fendo.2017.00183 -
Journal of Bone and Mineral Research :... Dec 2015Diet-induced weight loss has been suggested to be harmful to bone health. We conducted a systematic review and meta-analysis (using a random-effects model) to quantify... (Meta-Analysis)
Meta-Analysis Review
Diet-induced weight loss has been suggested to be harmful to bone health. We conducted a systematic review and meta-analysis (using a random-effects model) to quantify the effect of diet-induced weight loss on bone. We included 41 publications involving overweight or obese but otherwise healthy adults who followed a dietary weight-loss intervention. The primary outcomes examined were changes from baseline in total hip, lumbar spine, and total body bone mineral density (BMD), as assessed by dual-energy X-ray absorptiometry (DXA). Secondary outcomes were markers of bone turnover. Diet-induced weight loss was associated with significant decreases of 0.010 to 0.015 g/cm(2) in total hip BMD for interventions of 6, 12, or 24 (but not 3) months' duration (95% confidence intervals [CIs], -0.014 to -0.005, -0.021 to -0.008, and -0.024 to -0.000 g/cm(2), at 6, 12, and 24 months, respectively). There was, however, no statistically significant effect of diet-induced weight loss on lumbar spine or whole-body BMD for interventions of 3 to 24 months' duration, except for a significant decrease in total body BMD (-0.011 g/cm(2); 95% CI, -0.018 to -0.003 g/cm(2)) after 6 months. Although no statistically significant changes occurred in serum concentrations of N-terminal propeptide of type I procollagen (P1NP), interventions of 2 or 3 months in duration (but not of 6, 12, or 24 months' duration) induced significant increases in serum concentrations of osteocalcin (0.26 nmol/L; 95% CI, 0.13 to 0.39 nmol/L), C-terminal telopeptide of type I collagen (CTX) (4.72 nmol/L; 95% CI, 2.12 to 7.30 nmol/L) or N-terminal telopeptide of type I collagen (NTX) (3.70 nmol/L; 95% CI, 0.90 to 6.50 nmol/L bone collagen equivalents [BCEs]), indicating an early effect of diet-induced weight loss to promote bone breakdown. These data show that in overweight and obese individuals, a single diet-induced weight-loss intervention induces a small decrease in total hip BMD, but not lumbar spine BMD. This decrease is small in comparison to known metabolic benefits of losing excess weight.
Topics: Absorptiometry, Photon; Adult; Aged; Bone Density; Bone Diseases, Metabolic; Bone Remodeling; Bone and Bones; Clinical Trials as Topic; Collagen Type I; Diet, Reducing; Female; Humans; Lumbar Vertebrae; Male; Middle Aged; Obesity; Osteocalcin; Overweight; Peptides; Randomized Controlled Trials as Topic; Weight Loss
PubMed: 26012544
DOI: 10.1002/jbmr.2564