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The Cochrane Database of Systematic... Jan 2015Cystic 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.
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: 08 October 2014.
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: 25879106
DOI: 10.1002/14651858.CD008482.pub4 -
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 -
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 -
Archives of Osteoporosis Sep 2020Osteocalcin, the osteoblast-derived protein, has been shown to be modulated in patients with problematic glucose metabolism. Our systematic review and meta-analysis... (Meta-Analysis)
Meta-Analysis
UNLABELLED
Osteocalcin, the osteoblast-derived protein, has been shown to be modulated in patients with problematic glucose metabolism. Our systematic review and meta-analysis found that in humans, higher blood osteocalcin level is associated with lower body indices of fat.
PURPOSE/INTRODUCTION
Osteocalcin (OC) was found to be inversely correlated with measures of glucose and energy metabolism, with some groups suggesting the undercarboxylated form (ucOC) to be metabolically active, although the link is not clear, especially in humans. Given obesity is a major risk factor for metabolic disorders, we aimed to assess the correlation between OC and two measures of body weight: body mass index (BMI) and percentage body fat (%BF).
METHODS
MEDLINE and EMBASE were searched to identify observational studies in adult populations that reported the crude correlation coefficients (r) between OC and BMI and %BF. Pool r were obtained using random-effects models.
RESULTS
Fifty-one publications were included in this analysis. Both total OC (TOC) (pooled r = - 0.151, 95% CI - 0.17, - 0.130; I = 52%) and ucOC (pooled r = - 0.060, 95% CI - 0.103, - 0.016; I = 54%) were inversely correlated with BMI. The pooled r between TOC and BMI in Caucasian-and-other-regions (r = - 0.187) were stronger than those in Asian populations (r = - 0.126; intra-group p = 0.002; R = 0.21). The mean/median BMI of the reported cohort was the major contributor to between-study heterogeneity in correlation between TOC/ucOC and BMI (R = 0.28 and 0.77, respectively). Both TOC and ucOC were also inversely correlated with %BF (TOC: pooled r = - 0.185, 95% CI - 0.257 to - 0.112; ucOC: pooled r = - 0.181, 95% CI - 0.258 to - 0.101).
CONCLUSION
Higher OC and ucOC were correlated with lower BMI and %BF. The inverse correlations between TOC/ucOC and BMI appear to be affected by ethnicity and obesity status.
Topics: Adiposity; Adult; Body Mass Index; Body Weight; Humans; Obesity; Observational Studies as Topic; Osteocalcin
PubMed: 32945990
DOI: 10.1007/s11657-020-00812-6 -
Journal of Bone and Mineral Metabolism Sep 2022Vitamin K2 supplementation has been revealed to be effective in the prevention and treatment of osteoporosis in Japan, but further proof for the effectiveness of this... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Vitamin K2 supplementation has been revealed to be effective in the prevention and treatment of osteoporosis in Japan, but further proof for the effectiveness of this practice is still needed.
OBJECTIVE
To investigate whether vitamin K2 supplementation plays a role in maintaining bone mineral density (BMD) and reducing the incidence of fractures for postmenopausal women with osteoporosis at a long-term follow-up.
MATERIALS AND METHODS
We searched systematically throughout the databases of PubMed, Cochrane library, and EMBASE from the dates of their inception to November 16 2021 in this meta-analysis and systematic review, using keywords vitamin K2 and osteoporosis.
RESULTS
Nine RCTs with 6853 participants met the inclusion criteria. Vitamin K2 was associated with a significantly increased percentage change of lumbar BMD and forearm BMD (WMD 2.17, 95% CI [1.59-2.76] and WMD 1.57, 95% CI [1.15-1.99]). There were significant differences in undercarboxylated osteocalcin (uc-OC) reduction (WMD -0.96, 95% CI [-0.70 to 0.21]) and osteocalcin (OC) increment (WMD 26.52, 95% CI [17.06-35.98]). Adverse reaction analysis showed that there seemed to be higher adverse reaction rates in the vitamin K2 group (RR = 1.33, 95% CI [1.11-1.59]), but no serious adverse events related to vitamin K2 supplementation.
CONCLUSION
This meta-analysis and systematic review seemed to support the hypothesis that vitamin K2 plays an important role in the maintenance and improvement of BMD, and it decreases uc-OC and increases OC significantly at a long-term follow-up. Vitamin K2 supplementation is beneficial and safe in the treatment of osteoporosis for postmenopausal women.
Topics: Bone Density; Bone Density Conservation Agents; Female; Humans; Osteocalcin; Osteoporosis; Osteoporosis, Postmenopausal; Postmenopause; Vitamin K 2
PubMed: 35711002
DOI: 10.1007/s00774-022-01342-6 -
Calcified Tissue International Feb 2023There exists a marked circadian variation for several bone markers (BM), which is influenced by endogenous as well as exogenous factors including hormones, physical... (Review)
Review
There exists a marked circadian variation for several bone markers (BM), which is influenced by endogenous as well as exogenous factors including hormones, physical activity, and fasting. Consequently, was the aim of this review to provide an overview of the knowledge of the circadian variation of BM and which factors influence this rhythmicity. A systematic search of PubMed was performed for studies evaluating the circadian variation of BM and which factors influence this rhythmicity. The studies were screened for eligibility by a set of predetermined criteria including a list of relevant BM and a minimum study duration of 24 h with at least 3 blood samples of which two should be at least 6 h apart. In total were 29 papers included. There exists a marked circadian variation for most BM including Carboxy-terminal Cross-Linked Telopeptide of Type I Collagen (CTX) and osteocalcin (OC) with nighttime or early morning peak. Pro-collagen Type I N-terminal Propeptide (PINP) and PTH also showed circadian rhythm but with less amplitude. The inter-osteoblast-osteoclast regulatory markers such as OPG, RANKL, FGF23, and sclerostin showed no circadian rhythm. The markers were differently affected by exogenous factors like fasting, which greatly reduced the circadian variation of CTX but did not affect PINP or OC. The marked circadian variation and the factors which influence the rhythmicity, e.g., fasting are of great consequence when measuring BM. To reduce variation and heighten validity should circadian variation and fasting be kept in mind when measuring BM.
Topics: Circadian Rhythm; Bone and Bones; Collagen Type I; Biomarkers; Osteocalcin
PubMed: 35305134
DOI: 10.1007/s00223-022-00965-1 -
Hormone and Metabolic Research =... Oct 2015Studies on the association between serum total osteocalcin level and type 2 diabetes mellitus (T2DM) had reported controversial results. The aim of this study was to... (Meta-Analysis)
Meta-Analysis Review
Studies on the association between serum total osteocalcin level and type 2 diabetes mellitus (T2DM) had reported controversial results. The aim of this study was to comprehensively assess this association through a meta-analysis. Eligible articles were identified in electronic databases from their inception through May 1, 2015. To assess the relationship between serum total osteocalcin and T2DM, a meta-analysis was performed to determine whether total osteocalcin differed obviously between individuals with and without T2DM, and whether serum total osteocalcin level was associated with the risk of T2DM. The standardized mean difference (SMD) and their 95% confidence intervals (95% CIs) for total osteocalcin between individuals with and without T2DM, and pooled odds ratios (ORs) and their 95% CI for the T2DM risk were calculated by meta-analysis. Twenty-four papers fulfilled the inclusion criteria. From the pooled data, the total osteocalcin level was significantly lower among T2DM patients than controls (SMD: - 2.87; 95% CI-3.76 to - 1.98; p<0.00001), and high total osteocalcin level was significantly and independently associated with decreased risk of T2DM (OR=0.70, 95% CI 0.56-0.88; p=0.002). There was no evidence for publication bias. Serum total osteocalcin level is significantly lower in T2DM patients than controls, and total osteocalcin is inversely associated with the development of T2DM.
Topics: Aged; Case-Control Studies; Diabetes Mellitus, Type 2; Female; Humans; Male; Middle Aged; Osteocalcin; Publication Bias
PubMed: 26372899
DOI: 10.1055/s-0035-1564134 -
EClinicalMedicine Mar 2024Childhood obesity is a pressing health crisis of epidemic proportions. Bariatric surgery (BS) is an effective weight loss solution however its role in the paediatric...
BACKGROUND
Childhood obesity is a pressing health crisis of epidemic proportions. Bariatric surgery (BS) is an effective weight loss solution however its role in the paediatric population is contentious owing to the paucity of weight specific and generalised health outcomes. This systematic review and meta-analysis aimed to assess the impact of paediatric BS on bone health.
METHODS
This prospectively registered systematic review (PROSPERO ID: CRD42023432035) was performed in accordance with PRISMA guidelines. We searched MEDLINE (1946-1928 September 2023), EMBASE (1947-1928 September 2023) via the Ovid platform, and the Cochrane Review Library to identify scientific publications reporting bone outcome measures in patients under the age of 18 years who underwent BS. Meta-analysis was undertaken on post-operative weight and bone parameters in paediatric patients following BS. Outcomes were reported as weighted or standardized mean difference with 95 percent confidence intervals. Subgroup analysis by intervention, quality scoring and risk of bias were assessed.
FINDINGS
Twelve studies with 681 patients across 5 countries (mean age 17 ± 0.57 years) were included. The quality of included studies was rated as high and there was substantial between-study heterogeneity for most factors included in the meta-analysis ( from 0% to 99.1%). Patients underwent Roux-en-Y gastric bypass (RYGB, n = 216), sleeve gastrectomy (SG, n = 257), gastric band (n = 184) or intragastric balloon placement (n = 24). BS was associated with significant weight reduction, body mass index (BMI) -12.7 kg/m (95% CI -14.5 to -10.9, p < 0.001), with RYGB being most effective, BMI -16.58 kg/m (95% CI -19.6 to -13.6, p < 0.001). Patients who underwent SG or RYGB had significantly lower lumbar bone mineral density, -0.96 g/cm (95% CI -0.1 to -0.03, p < 0.001), Z score, -1.132 (95% CI -1.8 to -0.45, p < 0.001) and subtotal body bone mineral density, -0.7 g/cm (95% CI -1.2 to -0.2, p < 0.001) following surgery. This was accompanied with higher markers of bone resorption, C-terminal telopeptide of type 1 collagen 0.22 ng/ml (95% CI 0.12-0.32, p < 0.001) and osteocalcin, 10.83 ng/ml (95% CI 6.01-15.67, p < 0.001). There was a significant reduction in calcium levels following BS, -3.78 mg/dl (95% CI -6.1 to -1.5, p < 0.001) but no difference in 25-hydroxyvitamin D, phosphate, bone alkaline phosphatase, procollagen type 1 N propeptide or parathyroid hormone.
INTERPRETATION
BS effectively reduces weight in paediatric patients, but RYGB and SG may have adverse effects on bone health in the medium term. It is crucial to monitor and support bone health through appropriate nutritional supplementation and judicious follow-up. Long-term data is needed to fully understand the clinical implications of these findings on bone outcomes.
FUNDING
Medical Research Council (MRC), United Kingdom.
PubMed: 38333369
DOI: 10.1016/j.eclinm.2024.102462 -
Bone Reports Dec 2022To clarify the role of mediators of ectopic mineralization as biomarkers for arterial calcifications. (Review)
Review
AIM
To clarify the role of mediators of ectopic mineralization as biomarkers for arterial calcifications.
METHODS
MEDLINE and Embase were searched for relevant literature, until January 4th 2022. The investigated biomarkers were: calcium, phosphate, parathyroid hormone, vitamin D, pyrophosphate, osteoprotegerin, receptor activator of nuclear factor-kappa B ligand (RANKL), fibroblast growth factor-23 (FGF-23), Klotho, osteopontin, osteocalcin, Matrix Gla protein (MGP) and its inactive forms and vitamin K. Studies solely performed in patients with kidney insufficiency or diabetes mellitus were excluded.
RESULTS
After screening of 8985 articles, a total of 129 articles were included in this systematic review. For all biomarkers included in this review, the results were variable and more than half of the studies for each specific biomarker had a non-significant result. Also, the overall quality of the included studies was low, partly as a result of the mostly cross-sectional study designs. The largest body of evidence is available for phosphate, osteopontin and FGF-23, as a little over half of the studies showed a significant, positive association. Firm statements for these biomarkers cannot be drawn, as the number of studies was limited and hampered by residual confounding or had non-significant results. The associations of the other mediators of ectopic mineralization with arterial calcifications were not clear.
CONCLUSION
Associations between biomarkers of ectopic mineralization and arterial calcification are variable in the published literature. Future longitudinal studies differentiating medial and intimal calcification could add to the knowledge of biomarkers and mechanisms of arterial calcifications.
PubMed: 35769144
DOI: 10.1016/j.bonr.2022.101599 -
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