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Endocrine Regulations Oct 2019The bones form the framework of our body. We know that bones protect our vital organs, regulate calcium and phosphorous homeostasis, and function as a site of...
The bones form the framework of our body. We know that bones protect our vital organs, regulate calcium and phosphorous homeostasis, and function as a site of erythropoiesis. More recently, however, the identification of bone hormones has allowed us to envision bones as endocrine organs too. Within the last few years, the bone hormones osteocalcin and lipocalin 2 have been implicated with glucose and energy metabolism. We systematically reviewed articles surrounding this subject and found a clear relationship between the osteocalcin levels and glucose tolerance and insulin sensitivity. We also found that many journals have shown the detrimental effects of an absences of lipocalin 2 from adipocytes. As osteocalcin administration to mice showed decreased blood glucose levels and promoted glucose tolerance and insulin sensitivity. Future studies could perhaps explore the use of osteocalcin as a supplement for type 2 diabetes.
Topics: Animals; Bone Remodeling; Bone and Bones; Carbohydrate Metabolism; Energy Metabolism; Glucose; Homeostasis; Hormones; Humans
PubMed: 31734651
DOI: 10.2478/enr-2019-0027 -
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 -
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 -
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 -
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 -
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 -
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 -
Endocrine Apr 2024Runx2 and osteocalcin have pivotal roles in bone homeostasis. Polymorphism of these two genes could alter the function of osteoblasts and consequently bone mineral... (Meta-Analysis)
Meta-Analysis
PURPOSE
Runx2 and osteocalcin have pivotal roles in bone homeostasis. Polymorphism of these two genes could alter the function of osteoblasts and consequently bone mineral density (BMD). Attempts to understand the relationship between these polymorphisms and BMD in postmenopausal women across a variety of populations have yielded inconsistent results. This meta-analysis seeks to define the relationship between these polymorphisms with BMD in postmenopausal women.
METHODS
Eligible studies were identified from three electronic databases. Data were extracted from the eligible studies (4 studies on Runx2 and 6 studies on osteocalcin), and associations of Runx2 T > C and osteocalcin HindIII polymorphisms with BMD in postmenopausal women were assessed using standard difference in means (SDM) and 95% confidence intervals (CI) as statistical measures.
RESULTS
A significant difference in the lumbar spine (LS) BMD in postmenopausal women was observed between the TT and CC homozygotes for the Runx2 T > C (SDM = -0.445, p-value = 0.034). The mutant genotypes (CC) showed significantly lower LS BMD in comparison to wild type genotypes under recessive model of genetic analysis (TC + TT vs. CC: SDM = -0.451, p-value = 0.032). For osteocalcin, HindIII polymorphism, the mutant genotypes (HH) was associated with significantly higher BMD for both LS and femoral neck (FN) than the wild type (hh) homozygotes (SDM = 0.152, p-value = 0.008 and SDM = 0.139, p-value = 0.016 for LS and FN, respectively). There was no association between total hip (TH) BMD and the osteocalcin HindIII polymorphism.
CONCLUSIONS
Runx2 T > C and osteocalcin HindIII polymorphisms influence the level of BMD in postmenopausal women and may be used as predictive markers of osteoporosis.
Topics: Female; Humans; Bone Density; Osteocalcin; Postmenopause; Polymorphism, Genetic; Osteoporosis; Genotype; Osteoporosis, Postmenopausal
PubMed: 38055125
DOI: 10.1007/s12020-023-03621-2 -
Bone Feb 2021Bone turnover is the cellular machinery responsible for bone integrity and strength and, in the clinical setting, it is assessed using bone turnover markers (BTMs).... (Review)
Review
BACKGROUND
Bone turnover is the cellular machinery responsible for bone integrity and strength and, in the clinical setting, it is assessed using bone turnover markers (BTMs). Acute exercise can induce mechanical stress on bone which is needed for bone remodelling, but to date, there are conflicting results in regards to the effects of varying mechanical stimuli on BTMs.
OBJECTIVES
This systematic review examines the effects of acute aerobic, resistance and impact exercises on BTMs in middle and older-aged adults and examines whether the responses are determined by the exercise mode, intensity, age and sex.
METHODS
We searched PubMed, SCOPUS, Web of Science and EMBASE up to 22nd April 2020. Eligibility criteria included randomised controlled trials (RCTs) and single-arm studies that included middle-aged (50 to 65 years) and older adults (>65 years) and, a single-bout, acute-exercise (aerobic, resistance, impact) intervention with measurement of BTMs. PROSPERO registration number CRD42020145359.
RESULTS
Thirteen studies were included; 8 in middle-aged (n = 275, 212 women/63 men, mean age = 57.9 ± 1.5 years) and 5 in older adults (n = 93, 50 women/43 men, mean age = 68.2 ± 2.2 years). Eleven studies included aerobic exercise (AE, 7 middle-aged/4 older adults), and two included resistance exercise (RE, both middle-aged). AE significantly increased C-terminal telopeptide (CTX), alkaline phosphatase (ALP) and bone-ALP in middle-aged and older adults. AE also significantly increased total osteocalcin (tOC) in middle-aged men and Procollagen I Carboxyterminal Propeptide and Cross-Linked Carboxyterminal Telopeptide of Type I Collagen in older women. RE alone decreased ALP in older adults. In middle-aged adults, RE with impact had no effect on tOC or BALP, but significantly decreased CTX. Impact (jumping) exercise alone increased Procollagen Type 1 N Propeptide and tOC in middle-aged women.
CONCLUSION
Acute exercise is an effective tool to modify BTMs, however, the response appears to be exercise modality-, intensity-, age- and sex-specific. There is further need for higher quality and larger RCTs in this area.
Topics: Aged; Alkaline Phosphatase; Biomarkers; Bone Density; Bone Remodeling; Collagen Type I; Exercise; Female; Humans; Male; Middle Aged; Peptide Fragments; Procollagen
PubMed: 33227507
DOI: 10.1016/j.bone.2020.115766 -
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