-
BioFactors (Oxford, England) Jan 2020Diabetes mellitus and pre-diabetes are prevalent endocrine disorders associated with substantial morbidity and premature mortality. Vitamin K is known to have several...
Diabetes mellitus and pre-diabetes are prevalent endocrine disorders associated with substantial morbidity and premature mortality. Vitamin K is known to have several beneficial effects on complications of diabetes and pre-diabetes. However, systematic consolidation of evidence is required to quantify these effects in order to inform clinical practice and research. A systematic search in PubMed, Scopus, Embase, ProQuest, and Google Scholar databases was undertaken from database inception up to October 2018 to evaluate functional roles of different forms of vitamin K on diabetes and pre-diabetes. From 3,734 identified records, nine articles met the inclusion criteria and were evaluated. Vitamin K supplementation was found to be associated with significant reductions in blood glucose (six studies), increased fasting serum insulin (four studies), reduced hemoglobin A1c (three studies), reduced homeostatic model assessment-insulin resistance index (HOMA-IR) (two studies), and increased ß-cell function (two studies) in diabetic animal studies. Following 2-hour oral glucose tolerance test, vitamin K supplementation was observed to be effective in reducing blood glucose and insulin levels in the pre-diabetic population. However, no evidence of effect was observed for fasting blood sugar, insulin, HOMA-IR, and homeostatic model assessment-β-cell function index (two studies). A statistically significant effect was also noted with vitamin K in improving dyslipidemia (three studies) as well as oxidative stress and inflammatory markers (five studies) in diabetic animals. In conclusion, clinical trials and animal studies confirm that vitamin K supplementation may improve both clinical features and complications of diabetes and pre-diabetes. However, quantification of clinical efficacy in the pre-diabetic population and among individuals with comorbidities requires further investigation.
Topics: Animals; Diabetes Complications; Dietary Supplements; Humans; Prediabetic State; Vitamin K; Vitamins
PubMed: 31573736
DOI: 10.1002/biof.1569 -
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 -
Annals of the New York Academy of... Dec 2019The current study presents a comprehensive systematic review and meta-analysis of randomized controlled trials (RCTs) on resveratrol and bone health biomarkers. PubMed,... (Meta-Analysis)
Meta-Analysis
The current study presents a comprehensive systematic review and meta-analysis of randomized controlled trials (RCTs) on resveratrol and bone health biomarkers. PubMed, Scopus, and Web of Science (until September 2018) were searched to identify the potential RCTs with information on resveratrol supplementation and bone metabolism biomarkers. Mean differences (MD) were analyzed using a random-effects model. Pooling six RCTs (eight treatment arms with 264 subjects) together identified no significant reduction of serum Ca, osteocalcin, C-terminal telopeptide of type I collagen, and procollagen I N-terminal propeptide values after resveratrol supplementation over placebo treatment. However, a significant increase in serum alkaline phosphatase (ALP) (MD: 5.69 mg/mL, 95% CI: 3.58-7.80, I = 95.7%, P < 0.001) and bone alkaline phosphatase (BAP) (MD: 10.57 mmHg, 95% CI: 5.36-15.78, I = 99.2%, P < 0.001) values was observed after resveratrol treatment relative to placebo. The findings of this study indicate that resveratrol supplementation increased some key bone biomarkers, such as ALP and BAP. Further precise clinical trials of the effects of resveratrol supplementation on bone health should be conducted.
Topics: Alkaline Phosphatase; Antioxidants; Biomarkers; Bone Density; Bone and Bones; Calcium; Collagen Type I; Enzyme Inhibitors; Humans; Osteocalcin; Parathyroid Hormone; Peptide Fragments; Peptides; Procollagen; Randomized Controlled Trials as Topic; Resveratrol
PubMed: 31490554
DOI: 10.1111/nyas.14226 -
Osteoporosis International : a Journal... Dec 2019To assess the time from fracture until bone turnover markers (BTM), which are biochemical markers reflecting in vivo bone formation and resorptive activity, have...
To assess the time from fracture until bone turnover markers (BTM), which are biochemical markers reflecting in vivo bone formation and resorptive activity, have returned to a stable level since BTM have been shown to be at least as good as bone mineral density in monitoring the effect of anti-resorptive treatment in osteoporosis. This study searched for articles in PUBMED, CINAHL, Medline, EM-BASE, and Cochrane, and identified 3486 unique articles. These articles were screened based on predefined inclusion and exclusion criteria. Seven articles addressing time to normalization of either CTX, PINP, osteocalcin, or bone-specific alkaline phosphatase after a recent fracture were identified and these were analyzed qualitatively. CTX appeared to return to baseline within 6 months. PINP appeared to return to baseline within 6 months and interestingly dip below baseline after a year. Osteocalcin was elevated throughout the first year after a fracture, with most changes in the first 6 months. Bone-specific alkaline phosphatase (BAP) was increased for up to a year, however with a discrepancy between used assays. Seven studies were identified, showing CTX and PINP to return to baseline within 6 months. OC was elevated for 12 months. BAP was increased for up to a year. However, none of these studies had fasting patients and a long follow-up period with regular measurements. The studies could indicate that the BTM CTX and PINP have returned to baseline within 6 months; however, further studies are needed assessing pre-analytical factors while having a long follow-up. Bone turnover markers appear as good as or better than bone mineral density in monitoring the effect of anti-resorptive medication in osteoporosis. This study tries to identify the time from fracture until BTM are back at baseline. Most studies did not however take pre-analytical variation into consideration. Further research is therefore needed.
Topics: Alkaline Phosphatase; Biomarkers; Bone Remodeling; Collagen Type I; Fractures, Bone; Humans; Osteocalcin; Peptide Fragments; Peptides; Procollagen
PubMed: 31446441
DOI: 10.1007/s00198-019-05132-1 -
Scandinavian Cardiovascular Journal :... Dec 2019Circulating osteocalcin (OC), a marker which is central in bone mineralization, may be involved in the atherosclerotic process and influence the risk of developing... (Meta-Analysis)
Meta-Analysis
Circulating osteocalcin (OC), a marker which is central in bone mineralization, may be involved in the atherosclerotic process and influence the risk of developing cardiovascular disease (CVD). We conducted a systematic review and meta-analysis of published observational evidence, to assess and quantify the associations of circulating OC (total, undercarboxylated, and carboxylated OC) with cardiovascular outcomes (clinical CVD endpoints and intermediate cardiovascular phenotypes). Relevant studies were identified in a literature search of MEDLINE, EMBASE, and reference lists of relevant studies to March 2019. Mean differences and risk ratios with 95% CIs were aggregated using random-effects models. Thirty-three observational studies (prospective and retrospective cohort, case-control, and cross-sectional) with data on 21,021 unique participants were eligible. The pooled risk ratio in a comparison of extreme fourths of total OC levels was 0.98 (95% CI 0.89, 1.08) for composite CVD. Circulating total OC levels were significantly lower in patients with cardiovascular conditions compared with those without these conditions -2.58 ng/ml (95% CI -3.85, -1.32; .001). Prospective and cross-sectional data showed significant inverse associations between total OC and traits such as aortic or coronary calcification, coronary atherosclerosis or calcification, carotid intima-media thickness, and plaque score. There was limited data on carboxylated and undercarboxylated OC, with no evidence of associations. Observational evidence generally supports inverse associations of circulating total OC with risk of atherosclerotic outcomes and CVD endpoints; however, the data were mostly based on cross-sectional evaluations. Large-scale prospective data are needed.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Cardiovascular Diseases; Female; Humans; Male; Middle Aged; Observational Studies as Topic; Osteocalcin; Phenotype; Predictive Value of Tests; Prognosis; Risk Factors
PubMed: 31397589
DOI: 10.1080/14017431.2019.1655166 -
Human Reproduction Update Sep 2019Polycystic ovary syndrome (PCOS) has reproductive and metabolic aspects that may affect bone health. Controversial results from different studies regarding the risk of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Polycystic ovary syndrome (PCOS) has reproductive and metabolic aspects that may affect bone health. Controversial results from different studies regarding the risk of fractures, bone mineral density (BMD) or bone markers led to uncertainty whether PCOS might improve or deteriorate bone health.
OBJECTIVE AND RATIONALE
This study aimed to investigate the impact of PCOS on bone markers, BMD and fracture risk.
SEARCH METHODS
A systematic review and a meta-analysis were carried out. PubMed, EMBASE and Cochrane databases were searched for eligible studies from 1st of January of 1990 to 9th of October of 2018. Eligible studies enrolled women older than 18 years with PCOS, which should be diagnosed according to the Rotterdam Consensus, the Androgen Excess Society, the National Institutes of Health Consensus or the International Classification of Diseases. The studies were grouped according to patient mean BMI: <27 kg/m2 or ≥27 kg/m2. The results were polled as mean difference (MD), standardized MD (SMD) and hazard ratio (HR).
OUTCOMES
Overall, 921 studies were retrieved, and 31 duplicated studies were removed. After screening the titles and abstracts, 80 studies were eligible for full text reading. Of those, 23 studies remained for qualitative synthesis. With the exception of one study, all studies were considered high quality based on the Newcastle-Ottawa scale (NOS; score ≥6). Meta-analysis was performed in 21 studies, with a total of 31 383 women with PCOS and 102 797 controls. Women with PCOS with BMI <27 kg/m2 had lower BMD of the total femur (MD, -0.04; 95% CI, -0.07 to 0.00; I2 = 31%; P = 0.22) and spine (MD, -0.07; 95% CI, -0.13 to -0.01; I2 = 70%; P < 0.01) when compared with the control group, whereas for women with BMI ≥27 kg/m2 no difference was observed (femur: MD, 0.02; 95% CI, -0.02 to 0.05; I2 = 20%, P = 0.29; spine: MD, 0.02; 95% CI, -0.06 to 0.05; I2 = 0%; P = 0.84). Osteocalcin was remarkably reduced in women with PCOS with BMI <27 kg/m2 (SMD, -2.68; 95% CI, -4.70 to -0.67; I2 = 98%; P < 0.01), but in women with BMI ≥27 kg/m2, there were no differences between PCOS and controls. Few studies (n = 3) addressed the incidence of bone fractures in women with PCOS. The HR for total bone fractures did not identify differences between women with PCOS and controls.
WIDER IMPLICATIONS
On the basis of the available evidence, it is possible to assume that PCOS in women with BMI <27 kg/m2 is associated with reduced BMD in the spine and femur, and decreased bone formation, as manifested by lower levels of circulating osteocalcin. These findings suggest that bone parameters in PCOS may be linked, to some extent, to adiposity. These studies included premenopausal women, who have already achieved peak bone mass. Hence, further prospective studies are necessary to clarify the existence of increased risk of fractures in women with PCOS.
Topics: Bone Density; Female; Femur; Fractures, Bone; Humans; Incidence; Obesity; Osteocalcin; Osteogenesis; Osteoporosis; Polycystic Ovary Syndrome; Prospective Studies; Spine
PubMed: 31374576
DOI: 10.1093/humupd/dmz020 -
Critical Reviews in Food Science and... 2020Osteoporosis is a common bone disease characterized by reduced bone mass resulting from continuous bone resorption. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Osteoporosis is a common bone disease characterized by reduced bone mass resulting from continuous bone resorption.
METHODS
PubMed, Scopus, and Embase were searched to find published trials on the effect of soy isoflavones on bone mineral density (BMD) and bone turnover markers (bone-specific alkaline phosphatase, osteocalcin, osteoprotegerin, pyridinoline, deoxypyridinoline, C-telopeptide, and N-telopeptide). Random-effects inverse-variance model was used to calculate the pooled effects.
RESULTS
A total of 5313 articles were found, screened, and assessed for eligibility, and finally 52 trials were included in the meta-analysis. Consumption of soy isoflavones caused significant improvement in BMD of lumbar spine (mean difference (MD) = 0.76%; 95% CI: 0.09, 1.42%; = 0.03), hip (MD = 0.22%; 95% CI: 0.02, 0.42%; = 0.04), and femoral neck (MD = 2.27%; 95% CI: 1.22, 3.31%; < 0.001). Subgroup analysis showed that in all 3 sites, the improvement was significant in normal weight subjects and interventions longer than a year, although trial location and dosage were also factors influencing isoflavones' impact on BMD. Among markers of bone turnover, osteoprotegerin (MD = 5.79; 95% CI: 3.08, 8.51 pg/ml; < 0.001), pyridinoline (MD = -5.13; 95% CI: -7.76, -2.50 nmol/mmol; < 0.001), and C-telopeptides (MD = -0.08; 95% CI: -0.16, -0.00 ng/ml; = 0.04) were favorably affected by isoflavones while osteocalcin and bone alkaline phosphatase did not change. Subgroup analysis of bone markers showed that in overweight/obese individuals and dosages <90 mg/day, isoflavones are more effective.
CONCLUSIONS
Soy isoflavones prevent osteoporosis-related bone loss in any weight status or treatment duration. They increase BMD in normal weight subjects and diminish bone resorption in overweight/obese individuals. Although bone resorption may be decelerated over short-term isoflavone consumption, periods longer than a year are probably needed to affect BMD. Isoflavones also appear benefits on bone in any dose or subjects' ethnicity.
Topics: Bone Density; Bone Resorption; Humans; Isoflavones; Osteoporosis; Randomized Controlled Trials as Topic; Glycine max
PubMed: 31290343
DOI: 10.1080/10408398.2019.1635078 -
Hormone and Metabolic Research =... Jun 2019A meta-analysis was performed to summarize the evidence from observational studies regarding the association between serum osteocalcin (OC) and C-reactive protein (CRP).... (Meta-Analysis)
Meta-Analysis
A meta-analysis was performed to summarize the evidence from observational studies regarding the association between serum osteocalcin (OC) and C-reactive protein (CRP). A systemic research of the literature databases including PubMed, SCOPUS, and Google Scholar was performed to identify the relevant studies up to March 2018. We used the random-effects model by the method of DerSimonian and Laird to calculate the overall effect size. Q-test and -statistics were used to assess between-study heterogeneity. In addition, we did subgroup analysis to detect possible sources of heterogeneity based on BMI range, gender, type of study population and age. We identified 21studies of association between serum osteocalcin and CRP eligible for the meta-analysis. The overall effect size showed a significant inverse association between OC and CRP (Fisher's z=-0.127; 95% CI: -0.166, -0.088, p<0.0001). However, the significant chi-squared statistic result, indicates a heterogeneity of effect sizes ( =61.6, df=20, p<0.0001). The subgroup analysis found BMI range, type of study population, and age were the potential sources of heterogeneity. In addition, the strongest correlation was observed in the subgroup of obese subjects (Fisher's z=-0.264, p=0.002), less than 40 years old (Fisher's z=-0.115, p<0.0001) and healthy subjects (Fisher's z=-0.115, p<0.0001). These findings suggest that there is a significant inverse association between serum OC and CRP levels in the adult population.
Topics: Biomarkers; Bone Diseases; C-Reactive Protein; Humans; Incidence; Inflammation; Osteocalcin; Prognosis
PubMed: 31207656
DOI: 10.1055/a-0897-844 -
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 -
European Journal of Nutrition Sep 2019We conducted a meta-analysis to systematically assess the prospective association between vitamin K and cardiovascular disease (CVD) events and all-cause mortality. (Meta-Analysis)
Meta-Analysis
PURPOSE
We conducted a meta-analysis to systematically assess the prospective association between vitamin K and cardiovascular disease (CVD) events and all-cause mortality.
METHODS
We searched PubMed and EMBASE through January 2019 for prospective studies that reported the association of vitamin K (assessed by dietary intake or circulating concentration) with CVD events [including total CVD, CVD mortality, total coronary heart disease (CHD), fatal CHD, nonfatal myocardial infarction (MI), and stroke] and all-cause mortality. Multivariable-adjusted hazard ratios (HRs) comparing top versus bottom tertiles of vitamin K were combined using random-effects meta-analysis.
RESULTS
Twenty-one articles were included with 222,592 participants. A significant association was found between dietary phylloquinone and total CHD (pooled HR 0.92; 95% CI 0.84, 0.99; I = 0%; four studies), as well as menaquinone and total CHD (0.70; 95% CI 0.53, 0.93; I = 32.1%; two studies). No significant association was observed between dietary vitamin K and all-cause mortality, CVD mortality, or stroke. Elevated plasma desphospho-uncarboxylated MGP (dp-ucMGP), a marker of vitamin K deficiency, was associated with an increased risk of all-cause mortality (1.84; 95% CI 1.48, 2.28; I = 16.8%; five studies) and CVD mortality (1.96; 95% CI 1.47, 2.61; I = 0%; two studies). No significant association was observed between circulating total osteocalcin and all-cause mortality or total CVD.
CONCLUSIONS
Our findings showed that higher dietary vitamin K consumption was associated with a moderately lower risk of CHD, and higher plasma dp-ucMGP concentration, but not total circulating osteocalcin, was associated with increased risks of all-cause and CVD mortality. However, causal relations cannot be established because of limited number of available studies, and larger prospective studies and randomized clinical trials are needed to validate the findings.
Topics: Cardiovascular Diseases; Death; Diet; Humans; Risk Factors; Vitamin K
PubMed: 31119401
DOI: 10.1007/s00394-019-01998-3