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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 -
Medicine Oct 2023To systematically evaluate the correlation between serum osteocalcin levels and cognitive function status in type 2 diabetes mellitus (T2D) patients. (Meta-Analysis)
Meta-Analysis
BACKGROUND
To systematically evaluate the correlation between serum osteocalcin levels and cognitive function status in type 2 diabetes mellitus (T2D) patients.
METHODS
This review was conducted according to the PRISMA guidelines, and was developed and submitted to PROSPERO (CRD42022339295). We comprehensively searched PubMed, EMBASE, Web of Science, Scopus, ProQuest, and Chinese Databases (China National Knowledge Infrastructure, Wan Fang, Chinese Science and Technology Periodical Database, and China Biology Medicine) up to 1 June 2023. 3 investigators performed independent literature screening and data extraction of the included literature, and 2 investigators performed an independent quality assessment of case-control studies using the Newcastle-Ottawa-Scale tool. Data analysis was performed using Review Manager 5.4 software. For continuous various outcomes, mean difference (MD) or standardized MD with 95% confidence intervals (CIs) was applied for assessment by fixed-effect or random-effect model analysis. The heterogeneity test was performed by the Q statistic and quantified using I2, and publication bias was evaluated using a funnel plot.
RESULTS
9 studies with T2D were included (a total of 1310 subjects). Meta-analysis results indicated that cognitive function was more impaired in patients with lower serum osteocalcin levels [MD = 9.91, 95% CI (8.93, -10.89), I2 = 0%]. Serum osteocalcin levels were also significantly different between the 2 groups of T2D patients based on the degree of cognitive impairment [MD = -0.93, 95% CI (-1.09, -0.78), I2 = 41%]. It summarized the statistical correlation between serum osteocalcin and cognitive function scores in patients with T2D at r = 0.43 [summary Fisher's Z = 0.46, 95% CI (0.39, -0.50), I2 = 41%). After sensitivity analysis, the heterogeneity I2 decreased to 0%, indicating that the results of the meta-analysis are more reliable.
CONCLUSION SUBSECTIONS
Based on a meta-analysis of included studies, we concluded that there is a moderately strong positive correlation between serum osteocalcin levels and patients' cognitive function in T2D. An intervention to increase serum osteocalcin levels can contribute to delaying and improving cognitive decline in patients with T2D.
Topics: Humans; Case-Control Studies; Cognition; Diabetes Mellitus, Type 2; Functional Status; Osteocalcin
PubMed: 37832077
DOI: 10.1097/MD.0000000000034440 -
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 -
Plants (Basel, Switzerland) May 2023Bone metabolism is a complex process which is influenced by the activity of bone cells (e.g., osteocytes, osteoblasts, osteoclasts); the effect of some specific... (Review)
Review
Bone metabolism is a complex process which is influenced by the activity of bone cells (e.g., osteocytes, osteoblasts, osteoclasts); the effect of some specific biomarkers (e.g., parathyroid hormone, vitamin D, alkaline phosphatase, osteocalcin, osteopontin, osteoprotegerin, osterix, RANKL, Runx2); and the characteristic signaling pathways (e.g., RANKL/RANK, Wnt/β, Notch, BMP, SMAD). Some phytochemical compounds-such as flavonoids, tannins, polyphenols, anthocyanins, terpenoids, polysaccharides, alkaloids and others-presented a beneficial and stimulating effect in the bone regeneration process due to the pro-estrogenic activity, the antioxidant and the anti-inflammatory effect and modulation of bone signaling pathways. Lately, nanomedicine has emerged as an innovative concept for new treatments in bone-related pathologies envisaged through the incorporation of medicinal substances in nanometric systems for oral or local administration, as well as in nanostructured scaffolds with huge potential in bone tissue engineering.
PubMed: 37653972
DOI: 10.3390/plants12102055 -
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 -
Nutrition (Burbank, Los Angeles County,... Dec 2023Menopause and vitamin D deficiency increase bone reabsorption and bone fracture risk in women in postmenopause, and vitamin D supplementation may improve bone health and... (Review)
Review
Supplementation of vitamin D isolated or calcium-associated with bone remodeling and fracture risk in postmenopausal women without osteoporosis: A systematic review of randomized clinical trials.
Menopause and vitamin D deficiency increase bone reabsorption and bone fracture risk in women in postmenopause, and vitamin D supplementation may improve bone health and decrease bone fracture risk. This study aims to discuss the effect of vitamin D supplementation, isolated or calcium-associated, on remodeling and fracture risk bone in women in postmenopause without osteoporosis. This study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO database registration: CRD42022359796). A search was conducted in four databases and gray literature using MeSH and similar terms related to supplements, vitamin D, calcium, remodeling, and fracture bone, without the restriction of language and year of publication. A total of 3460 studies were identified, and nine were selected. Vitamin D supplementation increased 25-hydroxyvitamin D levels ≥10 ng/mL and decreased parathyroid hormone secretion dependent on baseline levels. The doses of 400 IU of vitamin D improved the percentage of carboxylated osteocalcin, whereas 800 to 1000 IU combined with calcium resulted in reduced, improved, or maintained bone mineral density and reduced alkaline phosphatase levels. However, 4000 IU alone or combined with calcium for 6 mo did not improve C-telopeptide and procollagen type 1 peptide levels. Additionally, 15 000 IU/wk increased the cortical area of metacarpal bone, whereas 500 000 IU of vitamin D annually for 5 y did not contribute to reducing the fracture risk and falls. Only one study found a reduction in fracture risk (dose of 800 IU of vitamin D plus 1200 mg of calcium). Thus, the vitamin D supplementation, alone or calcium-associated, improved the status of 25-hydroxyvitamin D and bone remodeling, but it was not possible to assert that it reduced fracture bone risk in postmenopausal women.
Topics: Humans; Female; Calcium; Postmenopause; Randomized Controlled Trials as Topic; Vitamin D; Vitamins; Osteoporosis; Fractures, Bone; Calcium, Dietary; Calcifediol; Dietary Supplements; Bone Remodeling
PubMed: 37544189
DOI: 10.1016/j.nut.2023.112151 -
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 -
Journal of Orthopaedic Surgery and... Jul 2023The effect and mechanisms of the ingredients (IRAB) of Radix Achyranthis Bidentatae (RAB) on treating osteoporosis (OP) remains debated. We aimed to summary the evidence... (Meta-Analysis)
Meta-Analysis
Antiosteoporosis effect and possible mechanisms of the ingredients of Radix Achyranthis Bidentatae in animal models of osteoporosis: systematic review and meta-analysis of in vivo studies.
BACKGROUND
The effect and mechanisms of the ingredients (IRAB) of Radix Achyranthis Bidentatae (RAB) on treating osteoporosis (OP) remains debated. We aimed to summary the evidence to evaluate the efficacy of IRAB for animal model OP and elucidate the potential mechanism of IRAB in the treatment of OP.
METHODS
In this review and meta-analysis, we searched PubMed, EMBASE, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang, Chinese Biomedical Literature Database, as well as Chinese VIP databases for targeting articles published from inception to March 2023 in English or Chinese. All randomized controlled animal trials that assessed the efficacy and safety of IRAB for OP were included. We excluded trials according to exclusion criteria. The CAMARADES 10-item quality checklist was utilized to test the risk of potential bias for each including study and modifications were performed accordingly. The primary outcome measures were bone mineral density of the femoral neck (F-BMD), serum calcium (Ca), serum phosphorus (P), serum alkaline phosphatase (ALP), bone gla protein (BGP), bone maximum stress (M-STRESS). The secondary outcome measure was the antiosteoporosis mechanisms of IRAB.
RESULTS
Data from nine articles were included in the systematic review and meta-analysis, which focused on 196 animals. Egger's test revealed the presence of publication bias in various studies regarding the primary outcome. Administration of IRAB or RAB could significantly increases the F-BMD (SMD = 2.09; 95% CI = 1.29 to 2.89; P < 0.001, I = 76%), Ca (SMD = 0.86; 95% CI = 0.39to1.34; P = 0.07, I = 49%); P (SMD = 1.01; 95% CI = 0.45-4.57; P = 0.08, I = 50%), BGP (SMD = 2.13; 95% CI = 1.48 to 2.78; I = 46%, P = 0.10), while the ALP (SMD = - 0.85; 95% CI = - 1.38 to - 0.31; I = 46%, P = 0.10) was remarkably decreased in OP model animals. Moreover, the bone biomechanical indicator M-STRESS (SMD = 2.39; 95% CI = 1.74-3.04; I = 32%, P = 0.21) was significantly improved.
CONCLUSION
Collectively, the findings suggest that the RAB or IRAB could be an effective drug or an ingredient in diet for the clinical treatment of OP in future.
Topics: Humans; Osteoporosis; Bone Density; Research Design; Osteocalcin; Phosphorus
PubMed: 37496077
DOI: 10.1186/s13018-023-04031-w -
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 -
European Journal of Clinical... Oct 2023The effects of vitamin D administration on bone turnover markers (BTMs) in adults are controversial. Thus, we carried out a meta-analysis of available randomised... (Meta-Analysis)
Meta-Analysis Review
AIM
The effects of vitamin D administration on bone turnover markers (BTMs) in adults are controversial. Thus, we carried out a meta-analysis of available randomised controlled trials (RCTs) to examine the impact of vitamin D supplementation on BTMs.
METHODS
To identify relevant RCTs, we searched the PubMed/MEDLINE, Web of Science, Scopus, Cochrane Library and Embase databases for manuscripts published up to July 2022. The present study was conducted in agreement with the PRISMA guidelines. Weighed mean difference (WMD) and 95% confidence intervals (CI) were used to calculate the magnitude of the effect of the intervention.
RESULTS
A total of 42 RCTs were included in the meta-analysis. The age of the participants enrolled in the RCTs ranged from 19.4 to 84 years. The pooled results depicted a decrease in deoxypyridinoline (DPD) concentrations (WMD: -1.58 nmol/mmol, 95% CI: -2.55, -.61, p = .001) following vitamin D supplementation. In addition, subgroup analyses demonstrated that vitamin D administration notably reduced procollagen type I N-terminal propeptide (PINP) levels in individuals aged >50 years and led to a pronounced decrease in alkaline phosphatase (ALP) values when the intervention lasted >12 weeks. No significant effect was observed on other BTMs, for example, collagen type 1 cross-linked C-telopeptide (CTX) and osteocalcin (OC) levels.
CONCLUSION
Vitamin D administration decreases DPD, PINP and ALP levels, indicating a reduced bone turnover following the intervention. Other BTMs, for example, CTX or OC values, were not affected by vitamin D prescription. Vitamin D supplementation may exert a positive effect on some important BTMs.
Topics: Adult; Humans; Vitamin D; Collagen Type I; Bone Remodeling; Alkaline Phosphatase; Biomarkers; Osteocalcin; Dietary Supplements; Randomized Controlled Trials as Topic
PubMed: 37314058
DOI: 10.1111/eci.14038