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Frontiers in Endocrinology 2022To explore the genetic causal association between osteoporosis (OP) and iron status through Mendelian randomization (MR).
OBJECTIVE
To explore the genetic causal association between osteoporosis (OP) and iron status through Mendelian randomization (MR).
METHODS
Publicly available genome-wide association study (GWAS) summary data were used for MR analysis with four iron status-related indicators (ferritin, iron, total iron binding capacity, and transferrin saturation) as exposures and three different types of OP (OP, OP with pathological fracture, and postmenopausal OP with pathological fracture) as outcomes. The inverse-variance weighted (IVW) method was used to analyze the genetic causal association between the four indicators of iron status and OP. The heterogeneity of MR results was determined using IVW and MR-Egger methods. The pleiotropy of MR results was determined using MR-Egger regression. A leave-one-SNP-out test was performed to determine whether the MR results were affected by a single nucleotide polymorphism (SNP). The weighted median method was conducted to further validate our results.
RESULTS
Based on IVW, MR-Egger and weighted median models, we found no causal association between iron status (ferritin, iron, total iron binding capacity, or transferrin saturation) and OP (P > 0.05 in all models). IVW and MR-Egger analysis of OP with pathological fracture and iron status indicators showed no potential genetic causal association (P> 0.05 in the two analyses). The results of the weighted median were consistent with those of IVW (P> 0.05 in all analyses). There was no potential genetic causal association between iron status and postmenopausal OP with pathological fracture based on serum iron (P>0.05 in all models). No heterogeneity or horizontal pleiotropy was found in any of the analyses. None of the leave-one-out tests in the analyses found any SNP that could affect the results of MR.
CONCLUSION
Our results demonstrate that there is no genetic causal association between OP and iron status, but the effects of other factors were not excluded.
Topics: Humans; Ferritins; Fractures, Spontaneous; Genome-Wide Association Study; Iron; Mendelian Randomization Analysis; Osteoporosis; Transferrins; Female; Osteoporosis, Postmenopausal
PubMed: 36568116
DOI: 10.3389/fendo.2022.996244 -
Aging Sep 2023Postmenopausal osteoporosis (PMOP) is a prevalent bone disorder with significant global impact. The elevated risk of osteoporotic fracture in elderly women poses a...
BACKGROUND
Postmenopausal osteoporosis (PMOP) is a prevalent bone disorder with significant global impact. The elevated risk of osteoporotic fracture in elderly women poses a substantial burden on individuals and society. Unfortunately, the current lack of dependable diagnostic markers and precise therapeutic targets for PMOP remains a major challenge.
METHODS
PMOP-related datasets GSE7429, GSE56814, GSE56815, and GSE147287, were downloaded from the GEO database. The DEGs were identified by "limma" packages. WGCNA and Machine Learning were used to choose key module genes highly related to PMOP. GSEA, DO, GO, and KEGG enrichment analysis was performed on all DEGs and the selected key hub genes. The PPI network was constructed through the GeneMANIA database. ROC curves and AUC values validated the diagnostic values of the hub genes in both training and validation datasets. xCell immune infiltration and single-cell analysis identified the hub genes' function on immune reaction in PMOP. Pan-cancer analysis revealed the role of the hub genes in cancers.
RESULTS
A total of 1278 DEGs were identified between PMOP patients and the healthy controls. The purple module and cyan module were selected as the key modules and 112 common genes were selected after combining the DEGs and module genes. Five Machine Learning algorithms screened three hub genes (KCNJ2, HIPK1, and ROCK1), and a PPI network was constructed for the hub genes. ROC curves validate the diagnostic values of ROCK1 in both the training (AUC = 0.73) and validation datasets of PMOP (AUC = 0.81). GSEA was performed for the low-ROCK1 patients, and the top enriched field included protein binding and immune reaction. DCs and NKT cells were highly expressed in PMOP. Pan-cancer analysis showed a correlation between low ROCK1 expression and SKCM as well as renal tumors (KIRP, KICH, and KIRC).
CONCLUSIONS
ROCK1 was significantly associated with the pathogenesis and immune infiltration of PMOP, and influenced cancer development, progression, and prognosis, which provided a potential therapy target for PMOP and tumors. However, further laboratory and clinical evidence is required before the clinical application of ROCK1 as a therapeutic target.
Topics: Aged; Humans; Female; Osteoporosis, Postmenopausal; Biomarkers; Kidney Neoplasms; Bone Diseases; Algorithms; rho-Associated Kinases; Protein Serine-Threonine Kinases
PubMed: 37683138
DOI: 10.18632/aging.205004 -
Current Opinion in Rheumatology Jul 2015Although obesity was previously believed to be protective against fracture, there is now evidence that a significant proportion of fractures in postmenopausal women... (Review)
Review
PURPOSE OF REVIEW
Although obesity was previously believed to be protective against fracture, there is now evidence that a significant proportion of fractures in postmenopausal women occur in those who are obese.
RECENT FINDINGS
In this article the epidemiology, pathophysiology and clinical management of fractures in obese postmenopausal women are discussed with particular focus on the site specificity of the effect of BMI on fracture, interactions between fat and bone and risk assessment and prevention of fractures. There is similarity in many respects between risk factors for fracture in obese and nonobese women, although falls may play a particularly important role in the obese. Treatment rates in obese postmenopausal women with fracture are currently low, and further studies are required to establish effective preventive strategies.
SUMMARY
Fractures in obese postmenopausal women contribute significantly to the overall fracture burden in this population. Further work is required to establish their pathophysiology and to develop effective preventive strategies.
Topics: Bone Density; Female; Humans; Obesity; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Risk Assessment
PubMed: 26002034
DOI: 10.1097/BOR.0000000000000182 -
Climacteric : the Journal of the... 2015Breast cancer and osteoporosis are common conditions affecting women, particularly following menopause. With increasing breast cancer incidence, effects of therapies and... (Review)
Review
Breast cancer and osteoporosis are common conditions affecting women, particularly following menopause. With increasing breast cancer incidence, effects of therapies and decreasing mortality, issues relating to the preservation of bone health with breast cancer therapy have become a priority. Contributing factors to bone loss and fractures in women with breast cancer include tumor effects, estrogen deprivation secondary to breast cancer therapies (chemotherapy, ovarian ablation or aromatase inhibitors), natural menopause and secondary causes of bone loss, typically from concurrently prescribed medications. Management of osteoporosis and other survivorship care is complex, and a multi-disciplinary approach is recommended with assessment of risk factors for bone loss, optimization of bone health through lifestyle approaches and pharmacological interventions based on evidence-based algorithms. This review examines the pathophysiology of bone loss and gives guidelines for the management of bone disease in women with breast cancer.
Topics: Bone Density Conservation Agents; Breast Neoplasms; Female; Fractures, Bone; Humans; Life Style; Menopause; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Risk Assessment; Women's Health
PubMed: 26514370
DOI: 10.3109/13697137.2015.1100383 -
Post Reproductive Health Mar 2023
Topics: Female; Humans; Osteoporosis; Osteoporosis, Postmenopausal; Bone Density
PubMed: 36357006
DOI: 10.1177/20533691221139902 -
The British Journal of Nutrition Feb 2024Postmenopausal osteoporosis is a major concern for women worldwide due to increased risk of fractures and diminished bone quality. Recent research on gut microbiota has... (Meta-Analysis)
Meta-Analysis Review
Postmenopausal osteoporosis is a major concern for women worldwide due to increased risk of fractures and diminished bone quality. Recent research on gut microbiota has suggested that probiotics can combat various diseases, including postmenopausal bone loss. Although several preclinical studies have explored the potential of probiotics in improving postmenopausal bone loss, the results have been inconsistent and the mechanism of action remains unclear. To address this, a meta-analysis was conducted to determine the effect of probiotics on animal models of postmenopausal osteoporosis. The bone parameters studied were bone mineral density (BMD), bone volume fractions (BV/TV), and hallmarks of bone formation and resorption. Pooled analysis showed that probiotic treatment significantly improves BMD and BV/TV of the ovariectomised animals. Probiotics, while not statistically significant, exhibited a tendency towards enhancing bone formation and reducing bone resorption. Next, we compared the effects of sp. and sp. on osteoporotic bone. Both probiotics improved BMD and BV/TV compared with control, but sp. had a larger effect size. In conclusion, our findings suggest that probiotics have the potential to improve bone health and prevent postmenopausal osteoporosis. However, further studies are required to investigate the effect of probiotics on postmenopausal bone health in humans.
Topics: Animals; Female; Bone and Bones; Bone Density; Osteoporosis, Postmenopausal; Postmenopause; Probiotics
PubMed: 37869975
DOI: 10.1017/S0007114523002362 -
Endocrinology and Metabolism Clinics of... Mar 2017Recently discovered mechanisms have assisted in developing new therapies for osteoporosis. New classes of drugs have been developed for the treatment of postmenopausal... (Review)
Review
Recently discovered mechanisms have assisted in developing new therapies for osteoporosis. New classes of drugs have been developed for the treatment of postmenopausal osteoporosis. Although there have been numerous advances over the past 2 decades, the search for newer therapies continues.
Topics: Bone Density Conservation Agents; Female; Humans; Osteoporosis, Postmenopausal
PubMed: 28131134
DOI: 10.1016/j.ecl.2016.11.001 -
Small (Weinheim An Der Bergstrasse,... Feb 2024Insufficient bone formation and excessive bone resorption caused by estrogen deficiency are the major factors resulting in the incidence of postmenopausal osteoporosis...
Insufficient bone formation and excessive bone resorption caused by estrogen deficiency are the major factors resulting in the incidence of postmenopausal osteoporosis (PMOP). The existing drugs usually fail to re-establish the osteoblast/osteoclast balance from both sides and generate side-effects owing to the lack of bone-targeting ability. Here, engineered cell-membrane-coated nanogels PNG@mR&C capable of scavenging receptor activator of nuclear factor-κB ligand (RANKL) and responsively releasing therapeutic PTH 1-34 in the bone microenvironment are prepared from RANK and CXCR4 overexpressed bone mesenchymal stem cell (BMSC) membrane-coated chitosan biopolymers. The CXCR4 on the coated-membranes confer bone-targeting ability, and abundant RANK effectively absorb RANKL to inhibit osteoclastogenesis. Meanwhile, the release of PTH 1-34 triggered by osteoclast-mediated acid microenvironment promote osteogenesis. In addition, the dose and frequency are greatly reduced due to the smart release property, prolonged circulation time, and bone-specific accumulation. Thus, PNG@mR&C exhibits satisfactory therapeutic effects in the ovariectomized (OVX) mouse model. This study provides a new paradigm re-establishing the bone metabolic homeostasis from multitargets and shows great promise for the treatment of PMOP.
Topics: Humans; Animals; Mice; Female; Osteoclasts; Osteoporosis, Postmenopausal; Nanogels; Biomimetics; Cell Differentiation; Osteoblasts; Osteogenesis; NF-kappa B
PubMed: 37794621
DOI: 10.1002/smll.202303494 -
Cancer Journal (Sudbury, Mass.)This narrative review analyzes the customization of menopause hormone therapy (MHT) for osteoporosis prevention and treatment in the context of the patients' age and... (Review)
Review
This narrative review analyzes the customization of menopause hormone therapy (MHT) for osteoporosis prevention and treatment in the context of the patients' age and menopausal age. In short, MHT is indicated in most women suffering from menopause before the age of 45 years except for breast cancer survivors. These women should be treated with MHT until the age of 50 years. For women who have entered menopause at around the age of 50 years, risks associated with MHT are low, and MHT is a safe option, provided there is an indication for it. We suggest that pursuing MHT entails different risks than initiating it, after the age of 60 years. In both cases, advantages and risks should be evaluated. We suggest using risk calculators to assess the magnitude of these risks and choosing regimens that entail the lowest breast and thrombosis risks.
Topics: Breast Neoplasms; Female; Hormone Replacement Therapy; Humans; Menopause; Middle Aged; Osteoporosis, Postmenopausal
PubMed: 35594468
DOI: 10.1097/PPO.0000000000000592 -
Nature Oct 2017
Topics: Adult; Aged; Aged, 80 and over; Aging; Bone Density; Bone Remodeling; Cancellous Bone; DNA Damage; Denosumab; Diphosphonates; Early Diagnosis; Estrogen Replacement Therapy; Estrogens; Female; Humans; Male; Middle Aged; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Women's Health
PubMed: 28976955
DOI: 10.1038/550S15a