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Frontiers in Endocrinology 2024Liraglutide (Lrg), a novel anti-diabetic drug that mimics the endogenous glucagon-like peptide-1 to potentiate insulin secretion, is observed to be capable of partially... (Review)
Review
INTRODUCTION
Liraglutide (Lrg), a novel anti-diabetic drug that mimics the endogenous glucagon-like peptide-1 to potentiate insulin secretion, is observed to be capable of partially reversing osteopenia. The aim of the present study is to further investigate the efficacy and potential anti-osteoporosis mechanisms of Lrg for improving bone pathology, bone- related parameters under imageology, and serum bone metabolism indexes in an animal model of osteoporosis with or without diabetes.
METHODS
Eight databases were searched from their inception dates to April 27, 2024. The risk of bias and data on outcome measures were analyzed by the CAMARADES 10-item checklist and Rev-Man 5.3 software separately.
RESULTS
Seventeen eligible studies were ultimately included in this review. The number of criteria met in each study varied from 4/10 to 8/10 with an average of 5.47. The aspects of blinded induction of the model, blinding assessment of outcome and sample size calculation need to be strengthened with emphasis. The pre-clinical evidence reveals that Lrg is capable of partially improving bone related parameters under imageology, bone pathology, and bone maximum load, increasing serum osteocalcin, N-terminal propeptide of type I procollagen, and reducing serum c-terminal cross-linked telopeptide of type I collagen (P<0.05). Lrg reverses osteopenia likely by activating osteoblast proliferation through promoting the Wnt signal pathway, p-AMPK/PGC1α signal pathway, and inhibiting the activation of osteoclasts by inhibiting the OPG/RANKL/RANK signal pathway through anti-inflammatory, antioxidant and anti-autophagic pathways. Furthermore, the present study recommends that more reasonable usage methods of streptozotocin, including dosage and injection methods, as well as other types of osteoporosis models, be attempted in future studies.
DISCUSSION
Based on the results, this finding may help to improve the priority of Lrg in the treatment of diabetes patients with osteoporosis.
Topics: Liraglutide; Animals; Osteoporosis; Disease Models, Animal; Glucagon-Like Peptide-1 Receptor; Hypoglycemic Agents; Diabetes Mellitus, Experimental; Bone Density
PubMed: 38868747
DOI: 10.3389/fendo.2024.1378291 -
The Journal of Clinical Endocrinology... May 2024Controversial results have emerged regarding whether PCOS is protective or increases the risk of bone frailty.
CONTEXT
Controversial results have emerged regarding whether PCOS is protective or increases the risk of bone frailty.
OBJECTIVE
This study investigated whether the PCOS condition affects bone parameters of premenopausal women. This is an update for a previous meta-analysis published in 2019.
DATA SOURCES
We searched MEDLINE and Embase.
STUDY SELECTION
Studies were considered eligible for the update if published in English between the 1st of October 2018 and the 31st of December 2023. The diagnosis of PCOS should be based on NIH criteria, the Rotterdam Consensus, AE-PCOS society criteria, or ICD codes in women over 18 years old. Only records with the Newcastle-Ottawa Scale > 6 were selected for data extraction.
DATA EXTRACTION
Data were extracted by two independent reviewers.
DATA SYNTHESIS
We identified 31 studies that met the inclusion criteria for qualitative analysis from 3322 studies in the whole period (1990-2023). Overall, cross-sectional studies included 1822 individuals with PCOS and 1374 controls, while cohort studies incorporated 30305 women with PCOS and 101907 controls. Contrasting profiles emerged after stratification using a BMI cutoff of 27 kg/m2. Individuals with PCOS and a BMI <27 kg/m2 exhibited lower vertebral and non-vertebral bone density, reduced bone turnover marker (osteocalcin), and increased bone resorption marker (CTX) levels. Conversely, individuals with PCOS and a BMI >27 kg/m2 exhibited increased vertebral and non-vertebral BMD, with no significant changes in bone formation and resorption markers (except osteocalcin).
CONCLUSIONS
The findings of this study alert for a low bone mass, low bone formation, and increased bone resorption PCOS with a BMI <27 kg/m2.
PubMed: 38739756
DOI: 10.1210/clinem/dgae325 -
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 -
BMC Endocrine Disorders Apr 2024Sodium glucose cotransporter 2 (SGLT2) inhibitors are widely used in type 2 diabetes mellitus (T2DM) therapy. The impact of SGLT2 inhibitors on bone metabolism has been... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Sodium glucose cotransporter 2 (SGLT2) inhibitors are widely used in type 2 diabetes mellitus (T2DM) therapy. The impact of SGLT2 inhibitors on bone metabolism has been widely taken into consideration. But there are controversial results in the study on the effect of SGLT2 inhibitors on bone metabolism in patients with T2DM. Therefore, we aimed to examine whether and to what extent SGLT2 inhibitors affect bone metabolism in patients with T2DM.
METHODS
A literature search of randomized controlled trials (RCTs) was conducted through PubMed, Web of Science, Embase, Cochrane databases, and Scopus from inception until 15 April 2023. Eligible RCTs compared the effects of SGLT2 inhibitors versus placebo on bone mineral density and bone metabolism in patients with T2DM. To evaluate the differences between groups, a meta-analysis was conducted using the random effects inverse-variance model by utilizing standardized mean differences (SMD).
RESULTS
Through screening, 25 articles were finally included, covering 22,828 patients. The results showed that, compared with placebo, SGLT2 inhibitors significantly increased parathyroid hormone (PTH, SMD = 0.13; 95%CI: 0.06, 0.20), and cross-linked C-terminal telopeptides of type I collagen (CTX, SMD = 0.11; 95%CI: 0.01, 0.21) in patients with T2DM, decreased serum alkaline phosphatase levels (ALP, SMD = -0.06; 95%CI: -0.10, -0.03), and had no significant effect on bone mineral density (BMD), procollagen type 1 N-terminal propeptide (P1NP), 25-hydroxy vitamin D, tartrate resistant acid phosphatase-5b (TRACP-5b) and osteocalcin.
CONCLUSIONS
SGLT2 inhibitors may negatively affect bone metabolism by increasing serum PTH, CTX, and decreasing serum ALP. This conclusion needs to be verified by more studies due to the limited number and quality of included studies.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, identifier CRD42023410701.
Topics: Humans; Sodium-Glucose Transporter 2 Inhibitors; Diabetes Mellitus, Type 2; Bone Density; Bone and Bones; Randomized Controlled Trials as Topic
PubMed: 38658986
DOI: 10.1186/s12902-024-01575-8 -
International Endodontic Journal Jun 2024Although several studies indicate the harmful effects of bleaching on pulp tissue, the demand for this procedure using high concentrations of hydrogen peroxide (HP) is... (Review)
Review
BACKGROUND
Although several studies indicate the harmful effects of bleaching on pulp tissue, the demand for this procedure using high concentrations of hydrogen peroxide (HP) is high.
OBJECTIVES
To investigate the influence of bleaching on the pulp tissue.
METHODS
Electronic searches were conducted (PubMed/MEDLINE, Scopus, Cochrane Library and grey literature) until February 2021. Only in vivo studies that evaluated the effects of HP and/or carbamide peroxide (CP) bleaching gels on the inflammatory response in the pulp tissue compared with a non-bleached group were included. Risk of bias was performed according to a modified Methodological Index for Non-Randomized Studies scale for human studies and the Systematic Review Centre for Laboratory Animal Experimentation's RoB tool for animal studies. Meta-analysis was unfeasible.
RESULTS
Of the 1311 studies, 30 were eligible. Of these, 18 studies evaluated the inflammatory response in animal models. All these studies reported a moderate-to-strong inflammatory response in the superficial regions of pulp, characterized by cell disorganization and necrotic areas, particularly during the initial periods following exposure to 35%-38% HP, for 30-40 min. In the evaluation of human teeth across 11 studies, seven investigated inflammatory responses, with five observing significant inflammation in the pulp of bleached teeth. In terms of tertiary dentine deposition, 11 out of 12 studies noted its occurrence after bleaching with 35%-38% HP in long-term assessments. Additionally, three studies reported significant levels of osteocalcin/osteopontin at 2 or 10 days post-treatment. Other studies indicated an increase in pro-inflammatory cytokines ranging from immediately up to 10 days after bleaching. Studies using humans' teeth had a low risk of bias, whereas animal studies had a high risk of bias.
DISCUSSION
Despite the heterogeneity in bleaching protocols among studies, High-concentrations of HP shows the potential to induce significant pulp damage.
CONCLUSIONS
High-concentrations of bleaching gel increases inflammatory response and necrosis in the pulp tissue at short periods after bleaching, mainly in rat molars and in human incisors, in addition to greater hard tissue deposition over time. However, further well-described histological studies with long-term follow-up are encouraged due to the methodological limitations of these studies.
REGISTRATION
PROSPERO (CRD42021230937).
Topics: Tooth Bleaching; Dental Pulp; Humans; Animals; Tooth Bleaching Agents; Carbamide Peroxide; Hydrogen Peroxide
PubMed: 38470103
DOI: 10.1111/iej.14061 -
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 -
The British Journal of Nutrition May 2024Vitamin D is a vital indicator of musculoskeletal health, as it plays an important role through the regulation of bone and mineral metabolism. This meta-analysis was... (Meta-Analysis)
Meta-Analysis Review
Vitamin D is a vital indicator of musculoskeletal health, as it plays an important role through the regulation of bone and mineral metabolism. This meta-analysis was performed to investigate the effects of vitamin D supplementation/fortification on bone turnover markers in women. All human randomised clinical trials reported changes in bone resorption markers (serum C-terminal telopeptide of type-I collagen (sCTX) and urinary type I collagen cross-linked N-telopeptide (uNTX)) or bone formation factors (osteocalcin (OC), bone alkaline phosphatase (BALP) and procollagen type-1 intact N-terminal propeptide (P1NP)) following vitamin D administration in women (aged ≥ 18 years) were considered. Mean differences (MD) and their respective 95 % CI were calculated based on fixed or random effects models according to the heterogeneity status. Subgroup analyses, meta-regression models, sensitivity analysis, risk of bias, publication bias and the quality of the included studies were also evaluated. We found that vitamin D supplementation had considerable effect on sCTX (MD: -0·038, 22) and OC (MD: -0·610, 24) with high heterogeneity and uNTX (MD: -8·188, 6) without heterogeneity. Our results showed that age, sample size, dose, duration, baseline vitamin D level, study region and quality of studies might be sources of heterogeneity in this meta-analysis. Subgroup analysis also revealed significant reductions in P1NP level in dose less than 600 μg/d and larger study sample size (>100 participants). Moreover, no significant change was found in BALP level. Vitamin D supplementation/fortification significantly reduced bone resorption markers in women. However, results were inconsistent for bone formation markers.
Topics: Humans; Vitamin D; Female; Dietary Supplements; Biomarkers; Bone Remodeling; Randomized Controlled Trials as Topic; Bone Resorption; Collagen Type I; Bone and Bones; Osteocalcin; Alkaline Phosphatase; Peptides; Food, Fortified
PubMed: 38221822
DOI: 10.1017/S0007114524000060 -
EFORT Open Reviews Jan 2024Loosening is a major cause for failure of total hip and total knee arthroplasties (THAs/TKAs). Preemptive diagnostics of asymptomatic loosening could open strategies to...
BACKGROUND
Loosening is a major cause for failure of total hip and total knee arthroplasties (THAs/TKAs). Preemptive diagnostics of asymptomatic loosening could open strategies to prevent gross loosening. A multitude of biomarkers may discriminate between loosened and stable implants, but it is unknown which have the best performance. The present systematic review aimed to assess which biomarkers have shown the most promising results in discriminating between stable and aseptic loosened THAs and TKAs.
METHODS
PubMed, Embase, Web of Science, Cochrane Library, and Academic Search Premier were systematically searched up to January 2020 for studies including THA/TKA and biomarkers to assess loosening. Two reviewers independently screened records, extracted data, and assessed the risk of bias using the ICROMS tool to classify the quality of the studies.
RESULTS
Twenty-eight (three high-quality) studies were included, reporting on a median of 48 patients (interquartile range 28-69). Serum and urine markers were evaluated in 22 and 10 studies, respectively. Tumor necrosis factor α and osteocalcin were significantly higher in loosened compared with stable implants. Urinary N-terminal telopeptide had significantly elevated levels in loosened prostheses.
CONCLUSION
Several serum and urine markers were promising in discriminating between loosened and stable implants. We recommend future studies to evaluate these biomarkers in a longitudinal fashion to assess whether progression of loosening is associated with a change in these biomarkers. In particular, high-quality studies assessing the usability of these biomarkers are needed.
PubMed: 38193539
DOI: 10.1530/EOR-22-0046 -
Frontiers in Medicine 2023In traditional Chinese medicine, Jintiange capsules are frequently used to treat metabolic bone diseases and strengthen bones and tendons. The main component of...
Efficacy of the Chinese herbal medicine Jintiange capsules in the postoperative treatment of osteoporotic vertebral compression fractures: a systematic review and meta-analysis.
BACKGROUND
In traditional Chinese medicine, Jintiange capsules are frequently used to treat metabolic bone diseases and strengthen bones and tendons. The main component of Jintiange capsules is bionic tiger bone powder. However, the active ingredients and proteins are derived from other animal bones, with chemical profiles similar to that of natural tiger bone. This study aimed to explore the efficacy of Jintiange capsules, a Chinese herbal medicine, in the postoperative treatment of osteoporotic vertebral compression fractures (OVCFs).
METHODS
In this systematic review, literature was retrieved using PubMed, the Cochrane Library, the Chinese National Knowledge Infrastructure, the Web of Science, the Wanfang Database, the Chinese Biomedical Literature Database, and the Chinese VIP Database from inception to July 2023. The primary outcome measures were the bone mineral density (BMD) and effective rate. The secondary outcome measures were the visual analog pain score (VAS), Oswestry disability index (ODI), Cobb's angle, serum osteocalcin, serum alkaline phosphatase, and adverse events. RevMan 5.4 and STATA 17.0 software were used for data analysis.
RESULTS
We enrolled randomized controlled trials (RCTs) focusing on 1,642 patients in the meta-analysis. The meta-analysis illustrated that Jintiange capsules significantly increased the BMD of the lumbar spine ( < 0.00001), femoral neck ( = 0.0005), and whole body ( = 0.01). The subgroup analysis of Jintiange capsules combination therapy showed that the BMD of the lumbar spine and whole body was significantly improved with Jintiange capsules ( < 0.00001). The test for the overall effect showed that Jintiange capsules had a significantly higher effective rate than the control groups ( = 0.003). Additionally, the overall effect test showed that Jintiange capsules decreased the VAS and ODI ( < 0.00001) and Cobb's angle ( = 0.02), and improved serum OC and ALP ( < 0.00001) compared with the controls. Furthermore, the pooled analysis of adverse reactions showed no serious impacts on the treatment of OVCFs.
CONCLUSION
Jintiange capsules demonstrate high safety and efficacy in the treatment of OVCFs, including increasing BMD, the lift effect rate, serum OC levels, and pain relief, decreasing the ODI, serum ALP levels, and adverse events, and improving Cobb's angle. Additional research is required to validate the efficacy of Jintiange capsules for the postoperative treatment of OVCFs.: https://www.crd.york.ac.uk/PROSPERO.
PubMed: 38162884
DOI: 10.3389/fmed.2023.1289818 -
Bone Mar 2024Neurofibromatosis type 1 (NF1) is a genetic autosomal neurocutaneous syndrome correlated with skeletal dysplasia and defects in the osseous microarchitecture. The... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Neurofibromatosis type 1 (NF1) is a genetic autosomal neurocutaneous syndrome correlated with skeletal dysplasia and defects in the osseous microarchitecture. The physiological mechanism for the development of NF1-related bone abnormal turnover is still unclear.
OBJECTIVES
A meta-analysis was performed to investigate the effects of NF1 on bone mineral density (BMD) and osseous metabolic indices in order to provide clinical evidence for the pathogenesis of the associated skeletal deformities.
METHODS
A systematic literature review search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in the PubMed/Medline and Web of Science databases from the date of inception of each database through to 10 September 2023. Specific inclusion and exclusion criteria were applied for the identification of studies examining the effects of NF1 on bone strength and metabolism. The Newcastle-Ottawa and Jadad scales were applied to assess the quality of the included studies. RevMan 5.3 software was used for the analysis of the data, and MedCalc was applied to examine publication bias.
RESULTS
Overall, 13 studies met the inclusion criteria comprised of 5 cross-sectional, 6 case-control and 2 retrospective studies. 703 patients and 973 healthy subjects formed the NF1 and control group, respectively. The results of the meta-analysis displayed that lumbar (SMD = -3.85, 95%CI = -7.53 to -0.18, Z = 2.05, p = 0.04) and femoral (SMD = -4.78, 95%CI = -8.86 to -0.69, Z = 2.29, p = 0.02) BMD was reduced in the NF1 group. Both in children and adults the serum levels of 25 hydroxyvitamin D3 were also decreased in NF1 group, but without any statistical significance (SMD = -0.62, 95%CI = -1.34 to -0.11, Z = 1.66, p = 0.10). Serum Parathyroid hormone (PTH) (SMD = 0.73, 95%CI = 0.31 to 1.15, Z = 3.43, p = 0.0006) and C-telopeptide of type 1 collagen (CTX) (SMD = 0.82, 95%CI = 0.33 to 1.30, Z = 3.29, p = 0.001) were elevated in NF1 patients, while serum calcium (SMD = -0.10, 95%CI = -0.74 to 0.53, Z = 0.32, p = 0.75) phosphorous (SMD = 0.33, 95%CI = -0.38 to 1.05, Z = 0.92, p = 0.36), alkaline phosphatase (ALP) (SMD = -0.36, 95%CI = -0.77 to 0.05, Z = 1.71, p = 0.09), osteocalcin (SMD = 1.81, 95%CI = -0.37 to -3.98, Z = 1.63, p = 0.10) and bone formation markers (SMD = 0.28, 95%CI = -0.37 to -0.94, Z = 0.85, p = 0.39) were not.
CONCLUSION
NF1 is associated with decreased BMD at the lumbar spine and femur. Taking into account that the serum levels of PTH, CTX were increased whereas the concentrations of vitamin D, calcium, phosphorous, ALP, osteocalcin and bone formation markers were not altered significantly in the NF1 patients compared with the healthy subjects, a vitamin D independent dysregulated bone cellular activity could be considered.
STUDY REGISTRATION
Registered on PROSPERO (CRD42023424751).
Topics: Adult; Child; Humans; Bone Density; Vitamin D; Neurofibromatosis 1; Calcium; Retrospective Studies; Cross-Sectional Studies; Osteocalcin; Parathyroid Hormone; Vitamins
PubMed: 38141750
DOI: 10.1016/j.bone.2023.116992