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Iranian Journal of Public Health Jan 2024Leptin has a great effect on bone through direct or indirect involvement in bone remodeling. Considering the ambiguities that exist regarding the effect of leptin on... (Review)
Review
BACKGROUND
Leptin has a great effect on bone through direct or indirect involvement in bone remodeling. Considering the ambiguities that exist regarding the effect of leptin on bone and bone-related diseases including osteoporosis, in this study, we aimed to conduct a systematic review of various studies on the effect of leptin on osteoporosis, which may find an answer to the existing ambiguities.
METHODS
The search was performed to review studies on the effects of leptin on osteoporosis by using several databases including Scopus, PubMed, Web of Science, and Google Scholar. Electronic searches were conducted on 5 Jan 2023. There was no limit on the publication date of the articles. The risk of bias for the animal study was assessed with the CAMARADES checklist, and the study quality assessment was also assessed based on the guidelines for in vivo experiments (ARRIVE). In this study, the risk of bias (quality) of human studies was assessed using the quality assessment checklists by NHLBI.
RESULTS
Overall, 34 articles were included for data extraction and quality assessment. Overall, 27 human studies and seven animal studies were included in the article. The results of most of the studies conducted in this study showed that leptin has a physiological role in maintaining bone mass and better bone quality and reduces bone marrow adipogenesis and increases bone mineral density (BMD). As plasma leptin levels increased, BMD values or bone formation biomarkers increased.
CONCLUSION
Leptin has an inhibitory role against bone resorption and increasing osteoprotegerin (OPG) levels, which, as a result, maintains bone density and reduces osteoclast activity, and has a positive relationship with increasing osteocalcin.
PubMed: 38694865
DOI: 10.18502/ijph.v53i1.14686 -
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 -
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 -
Osteoporosis International : a Journal... Jan 2017Our meta-analysis assessed the efficacy of statins on the risk of fracture, bone mineral density (BMD), and the markers of bone metabolism by collecting data from 33... (Meta-Analysis)
Meta-Analysis Review
Our meta-analysis assessed the efficacy of statins on the risk of fracture, bone mineral density (BMD), and the markers of bone metabolism by collecting data from 33 clinical trials. We found that statin treatment was associated with bone metabolism. And statins seemed to be more effective on male patients with osteoporosis. The efficacy of statins for the treatment of osteoporosis has been controversial in previous studies and meta-analyses. Our meta-analysis was conducted to examine in detail the efficacy of statins on osteoporosis. We searched PubMed, Embase, and the Cochrane Library databases for clinical trials from inception to May 2016. We included studies that described the effect of statins on the risk of fracture, BMD, or bone turnover markers. Moreover, we also conducted subgroup analyses according to the skeleton site, patient gender, and length of follow-up. A total of 33 studies which included 23 observational studies (16 cohort studies and 7 case-control studies) and 10 randomized controlled trials (RCTs) were evaluated. These 33 studies included 314,473 patients in statin group and 1,349,192 patients in control group. Statins decreased the risk of overall fractures (OR = 0.81, 95% CI 0.73-0.89) and hip fractures (OR = 0.75, 95% CI 0.60-0.92). Furthermore, the use of statins was associated with increased BMD at the total hip (standardized mean difference (SMD) = 0.18, 95% CI 0.00-0.36) and lumbar spine (SMD = 0.20, 95% CI 0.07-0.32) and improved the bone formation marker, osteocalcin (OC) (SMD = 0.21, 95% CI 0.00-0.42). However, there was no positive effect on vertebral fractures, upper extremity fractures, BMD at the femoral neck, bone-specific alkaline phosphatase (BALP), and serum C-terminal peptide of type I collagen (S-CTX). Also, compared with male subgroups, the effect on female subgroups was only slightly positive or of no statistical significance. Our meta-analysis indicates that statin treatment may be associated with a decreased risk of overall fractures and hip fractures, an increased BMD at the total hip, BMD at the lumbar spine, and OC. Moreover, our results also show that statin treatment may have a greater effect on male patients than on female patients.
Topics: Bone Density; Bone Density Conservation Agents; Bone Remodeling; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Osteoporosis; Osteoporotic Fractures; Sex Factors
PubMed: 27888285
DOI: 10.1007/s00198-016-3844-8 -
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 -
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 Epidemiology Aug 2015Serum total osteocalcin, a marker of bone formation, may regulate glucose metabolism and influence the risk of developing adverse metabolic outcomes. We conducted a... (Meta-Analysis)
Meta-Analysis Review
Serum total osteocalcin, a marker of bone formation, may regulate glucose metabolism and influence the risk of developing adverse metabolic outcomes. We conducted a systematic review and meta-analysis of published observational evidence, to assess and quantify the associations of serum total osteocalcin with type 2 diabetes and intermediate metabolic phenotypes [e.g., metabolic syndrome (MetS)]. Relevant studies were identified in a literature search of MEDLINE, EMBASE, Web of Science, and reference lists of relevant studies to May 2015. Mean differences and risk estimates (odds ratios or relative risks) with 95% CIs were aggregated using random-effects models. Fifty-two observational (38 cross-sectional, eight cohort, five case-control, and one both cross-sectional and cohort) studies with data on 46,998 non-overlapping participants were included. Baseline serum total osteocalcin levels were significantly lower in type 2 diabetes compared with non-type 2 diabetes and in MetS compared with non-MetS in pooled analysis of cross-sectional evidence. Pooled risk estimates (95% CIs) for type 2 diabetes in a comparison of extreme fourths of total osteocalcin levels were 0.23 (95% CI 0.12, 0.46) and 0.89 (95% CI 0.78, 1.01) for cross-sectional and cohort studies respectively. The corresponding estimate was 0.39 (0.27, 0.56) for MetS from cross-sectional evidence. In both cross-sectional and cohort studies, a unit increase in serum total osteocalcin levels was associated with a significant mean increase in HOMA-B and mean reduction in HbA1c; with significant mean reductions in fasting plasma glucose levels, HOMA-IR, and body mass index in only cross-sectional studies. Available evidence--mainly from cross-sectional studies, supports inverse associations of serum total osteocalcin with risk of adverse metabolic outcomes. Large-scale prospective studies are needed to establish whether serum total osteocalcin may be useful in the prevention of adverse metabolic outcomes such as type 2 diabetes.
Topics: Body Mass Index; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Metabolic Syndrome; Osteocalcin; Phenotype
PubMed: 26085114
DOI: 10.1007/s10654-015-0058-x -
Nutrition Research (New York, N.Y.) Jun 2014Phytoestrogens are candidate drugs for the treatment of osteoporosis. Many experiments have been designed to investigate the preventive effects of phytoestrogens for... (Meta-Analysis)
Meta-Analysis Review
Phytoestrogens are candidate drugs for the treatment of osteoporosis. Many experiments have been designed to investigate the preventive effects of phytoestrogens for osteoporosis; however, it is easy for a single dissenting result from animal experiments to mislead clinical investigations. Herein, we use meta-analysis to assess the evidence for a protective effect of phytoestrogens on ovariectomized rat models of osteopenia. With respect to osteoporosis, PubMed and Web of Science were searched from January 2000 to March 2013 for relevant studies of phytoestrogens in ovariectomized rats. Two reviewers independently selected and assessed the studies. Data were aggregated using a random effects model. Meta-analysis revealed that the phytoestrogen treatment group demonstrated a significantly higher femur bone mineral density and trabecular bone and lower bone turnover markers (serum alkaline phosphatase and serum osteocalcin) compared with the control ovariectomized group, thus showing a bone protective effect of phytoestrogens in ovariectomized rats. Subsequent sensitivity analyses indicated that the effect of phytoestrogens on serum alkaline phosphatase and serum osteocalcin are not robust. Despite the high heterogeneity in the systematic review of animal experiments, the present results indicated that phytoestrogens may offer the most potential for the prevention of bone loss by reducing the expected loss of trabecular bone and bone mineral density. Their effects are likely due to inhibition of bone resorption, but their benefits on bone formation are still unclear. Further studies are needed to assess the effect of phytoestrogens on bone formation and the efficacy and safety of individual phytoestrogens.
Topics: Alkaline Phosphatase; Animals; Bone Density; Bone Resorption; Bone and Bones; Databases, Factual; Female; Osteocalcin; Osteogenesis; Osteoporosis; Ovariectomy; Phytoestrogens; Rats
PubMed: 25026913
DOI: 10.1016/j.nutres.2014.05.003 -
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