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Frontiers in Public Health 2022Vitamin K (VK) as a nutrient, is a cofactor in the carboxylation of osteocalcin (OC), which can bind with hydroxyapatite to promote bone mineralization and increase bone... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Vitamin K (VK) as a nutrient, is a cofactor in the carboxylation of osteocalcin (OC), which can bind with hydroxyapatite to promote bone mineralization and increase bone strength. However, some studies have been inconsistent on whether vitamin K2 (VK2) can maintain or improve bone mineral density (BMD) and reduce the incidence of fractures in postmenopausal women. Therefore, the main objective of this meta-analysis was to determine the effect of VK2 as a nutritional supplement on BMD and fracture incidence in postmenopausal women.
METHODS
We searched PubMed, EMBASE, and Cochrane Library databases (published before March 17, 2022) and then extracted and pooled data from all randomized controlled trials (RCTs) that met the inclusion criteria.
RESULTS
Sixteen RCTs with a total of 6,425 subjects were included in this meta-analysis. The overall effect test of 10 studies showed a significant improvement in lumbar spine BMD (BMD LS) ( = 0.006) with VK2. The subgroup analysis of VK2 combination therapy showed that BMD LS was significantly maintained and improved with the administration of VK2 ( = 0.03). The overall effect test of the six RCTs showed no significant difference in fracture incidence between the two groups (RR=0.96, P=0.65). However, after excluding one heterogeneous study, the overall effect test showed a significant reduction in fracture incidence with VK2 (RR = 0.43, = 0.01). In addition, this meta-analysis showed that VK2 reduced serum undercarboxylated osteocalcin (uc-OC) levels and the ratio of uc-OC to cOC in both subgroups of VK2 combined intervention and alone. However, for carboxylated osteocalcin (cOC), both subgroup analysis and overall effect test showed no significant effect of VK2 on it. And the pooled analysis of adverse reactions showed no significant difference between the VK2 and control groups (RR = 1.03, 95%CI 0.87 to 1.21, = 0.76).
CONCLUSIONS
The results of this meta-analysis seem to indicate that VK2 supplementation has a positive effect on the maintenance and improvement of BMD LS in postmenopausal women, and it can also reduce the fracture incidence, serum uc-OC levels and the ratio of uc-OC to cOC. In conclusion, VK2 can indirectly promote bone mineralization and increase bone strength.
Topics: Bone Density Conservation Agents; Female; Humans; Osteocalcin; Osteoporosis, Postmenopausal; Randomized Controlled Trials as Topic; Vitamin K 2
PubMed: 36033779
DOI: 10.3389/fpubh.2022.979649 -
Frontiers in Nutrition 2023Resveratrol is a natural polyphenol compound that is widely present in herbal medicines such as , , and Catsiatora Linn and is used in traditional Chinese medicine to...
BACKGROUND
Resveratrol is a natural polyphenol compound that is widely present in herbal medicines such as , , and Catsiatora Linn and is used in traditional Chinese medicine to treat metabolic bone deseases. Animal experiments have shown that resveratrol may have a strong treatment effect against osteoporosis (OP). The purpose of this study was to explore the efficacy of resveratrol in treating OP animal models based on preclinical research data.
METHODS
This study was completed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched the PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure (CNKI) databases from inception to May 8, 2023, to identify animal experiments on the treatment of OP with resveratrol. The effect sizes of bone mineral density (BMD), parameters of micro-CT, serum calcium, phosphorus, alkaline phosphatase (ALP) and osteocalcin were expressed as the mean differences (MDs) and 95% confidence intervals (CIs). RevMan 5.4 software was used for data analysis.
RESULTS
This meta-analysis included a total of 15 animal experiments, including 438 OP rats. The meta-analysis results showed that compared with the control group, resveratrol (<10, 10-25, 40-50, ≥ 60 mg/kg/day) significantly increased femoral and lumbar bone mineral density (BMD) in OP rats ( < 0.05). Resveratrol (<10 mg/kg/day) significantly increased the BMD of the total body (MD = 0.01, 95% CI: 0.01 to 0.01, < 0.001). In terms of improving the parameters related to micro-CT, resveratrol (40-50 mg/kg/day) can increase trabecular thickness and trabecular number and reduce trabecular spacing ( < 0.05). Compared with the control group, resveratrol can reduce the concentration of calcium and phosphorus in serum but has no significant effect on serum ALP and osteocalcin ( > 0.05). The results of subgroup analysis showed that resveratrol increased the whole-body BMD of SD rats ( = 0.002) but did not improve the whole-body BMD of 3-month-old rats ( = 0.17).
CONCLUSION
Resveratrol can increase BMD in OP rat models, and its mechanism of action may be related to improving bone microstructure and regulating calcium and phosphorus metabolism. The clinical efficacy of resveratrol in the treatment of OP deserves further research.
PubMed: 37575330
DOI: 10.3389/fnut.2023.1234756 -
Frontiers in Pediatrics 2022Osteocalcin plays a role in glucose metabolism in mice, but its relevance in human energetic metabolism is controversial. Its relationship with markers of energetic... (Review)
Review
BACKGROUND
Osteocalcin plays a role in glucose metabolism in mice, but its relevance in human energetic metabolism is controversial. Its relationship with markers of energetic metabolism in the pediatric population has not been systematically addressed in infants and adolescents.
OBJECTIVE
This study aims to assess the mean differences between tOC, ucOC, and cOC among healthy children and children with type 1 or type 2 diabetes (T1D or T2D) and the correlation of these bone molecules with metabolic markers.
METHODS
A systematic review and metanalysis were performed following PRISMA criteria to identify relevant observational studies published in English and Spanish using PubMed, Scopus, EBSCO, and Web of Science databases. The risk of bias was assessed using New Castle-Ottawa scale. Effect size measures comprised standardized mean difference (SMD) and Pearson correlations. Heterogeneity and meta-regressions were performed.
RESULTS
The 20 studies included were of high quality and comprised 3,000 pediatric patients who underwent tOC, cOC, or ucOC measurements. Among healthy subjects, there was a positive correlation of ucOC with WC and weight, a positive correlation of tOC with FPG, HDL-c, WC, height, and weight, and a negative correlation between tOC and HbA1c. Among diabetic subjects, a negative correlation of ucOC with HbA1c and glycemia in both T1D and T2D was found and a negative correlation between tOC and HbA1c in T1D but not in T2D. The ucOC concentrations were lower in T2D, T1D, and patients with abnormal glucose status than among controls. The serum concentrations of tOC concentrations were lower among T1D than in controls. The patient's age, altitude, and HbA1c influenced the levels of serum tOC.
CONCLUSION
Osteocalcin is involved in energy metabolism in pediatric subjects because it is consistently related to metabolic and anthropometric parameters.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier: CRD42019138283.
PubMed: 36714656
DOI: 10.3389/fped.2022.1075738 -
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 -
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 -
Complementary Therapies in Clinical... Aug 2021To systematically evaluate the effectiveness of balneotherapy and/or aquatic exercise on bone metabolism. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To systematically evaluate the effectiveness of balneotherapy and/or aquatic exercise on bone metabolism.
DESIGN
A systematic literature search was conducted from inception to January 4, 2021. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated using a fixed-effect model according to study heterogeneity.
RESULTS
Seven articles involving 467 participants were selected. Three balneotherapy studies were qualitatively integrated. The results showed that bone resorption slowed down with or without stimulation of bone formation. A pooled meta-analysis of four studies on aquatic exercise showed significant evidence for a reduction in parathyroid hormone (PTH; SMD = -0.71; 95% CI, -1.04 to -0.38; P < 0.001), and a significant increase in osteocalcin (OC; SMD = 0.60; 95% CI, 0.16 to 1.03; P = 0.007) after aquatic exercise.
CONCLUSION
Balneotherapy and aquatic exercise had significant effects on bone metabolism, reducing bone resorption and/or increasing bone formation. This study highlights the importance of balneotherapy and aquatic exercise for bone health.
Topics: Balneology; Exercise; Exercise Therapy; Humans; Hydrotherapy
PubMed: 34167042
DOI: 10.1016/j.ctcp.2021.101429 -
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 -
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 -
Complementary Therapies in Medicine May 2022To determine whole body vibration influence on human bone density and bone biomarkers. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To determine whole body vibration influence on human bone density and bone biomarkers.
METHODS
We identified studies in Medline, Web of Science, Cumulative Index of Nursing and Allied Health, SPORTDiscus, Embase and Cochrane from inception to November 2021. Human randomized controlled trials involving commercially available whole body vibration platforms were included. Outcomes included bone density mean difference and serum concentrations of biomarkers (Procollagen type 1 N-terminal Propeptides, Osteocalcin, Bone specific alkaline phosphatase, and C-terminal Telopeptide of type 1 collagen). Random effects model (Hedges' g effect-size metric and 95% confidence-intervals) compared whole body vibration effect on bone density and bone biomarkers. Moderator analyses assessed health status, age, menopausal status, vibration type, vibration frequency, and study duration influence.
RESULTS
Meta-analysis of 30 studies revealed bone density improvement after whole body vibration (Hedges' g = 0.11; p = 0.05; 95% CI = 0.00, 0.22). Whole body vibration improved bone density in healthy (Hedges' g = 0.10; p = 0.01; 95% CI = 0.02, 0.17) and postmenopausal women (Hedges' g = 0.09; p = 0.02; 95% CI = 0.01, 0.18). Bone density also increased following side-alternating whole body vibration intervention (Hedges' g = 0.21; p = 0.02; 95% CI = 0.04, 0.37). Whole body vibration had no significant effect on either bone formation biomarkers (Hedges' g = 0.22; p = 0.01; 95% CI = 0.05, 0.40) or bone resorption biomarkers (Hedges' g = 0.03; p = 0.74; 95% CI = -0.17, 0.23).
CONCLUSION
Whole body vibration may be clinically useful as non-pharmacological/adjunct therapy to mitigate osteoporosis risk in healthy postmenopausal females. Additional studies are needed to determine the underlying mechanisms.
Topics: Bone Density; Female; Humans; Physical Therapy Modalities; Vibration
PubMed: 35093509
DOI: 10.1016/j.ctim.2022.102811 -
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