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Frontiers in Endocrinology 2022Postmenopausal osteoporosis (PMOP) is one of the most commonly occurring conditions worldwide and is characterized by estrogen deficiency as well as persistent calcium...
OBJECTIVE
Postmenopausal osteoporosis (PMOP) is one of the most commonly occurring conditions worldwide and is characterized by estrogen deficiency as well as persistent calcium loss with age. The aim of our study was to identify significant ferroptosis-associated biomarkers for PMOP.
METHODS AND MATERIALS
We obtained our training dataset from the Gene Expression Omnibus (GEO) database using GSE56815 expression profiling data. Meanwhile, we extracted ferroptosis-associated genes for further analysis. Differentially expressed ferroptosis-associated genes (DEFAGs) between OP patients and normal controls were selected using the "limma" package. We established a ferroptosis-associated gene signature using training models, specifically, random forest (RF) and support vector machine (SVM) models. It was further validated in another dataset (GSE56814) which also showed a high AUC: 0.98, indicating high diagnostic value. Using consensus clustering, the OP patient subtypes were identified. A ferroptosis associated gene (FAG)-Scoring scheme was developed by PCA. The important candidate genes associated with OP were also compared between different ferrclusters and geneclusters.
RESULTS
There were significant DEFAGs acquired, of which five (HMOX1, HAMP, LPIN1, MAP3K5, FLT3) were selected for establishing a ferroptosis-associated gene signature. Analyzed from the ROC curve, our established RF model had a higher AUC value than the SVM model (RF model AUC:1.00). Considering these results, the established RF model was chosen to be the most appropriate training model. Later, based on the expression levels of the five DEFAGs, a clinical application nomogram was established. The OP patients were divided into two subtypes (ferrcluster A, B and genecluster A, B, respectively) according to the consensus clustering method based on DEFAGs and differentially expressed genes (DEGs). Ferrcluster B and genecluster B had higher ferroptosis score than ferrcluster A and genecluster A, respectively. The expression of COL1A1 gene was significantly higher in ferrcluster B and gencluster B compared with ferrcluster A and gencluster A, respectively, while there is no statistical difference in term of VDR gene, COL1A2 genes, and PTH gene expressions between ferrcluster A and B, together with gencluster A and B.
CONCLUSIONS
On the basis of five explanatory variables (HMOX1, HAMP, LPIN1, MAP3K5 and FLT3), we developed a diagnostic ferroptosis-associated gene signature and identified two differently categorized OP subtypes that may potentially be applied for the early diagnosis and individualized treatment of PMOP. The ER gene, VDR gene, IL-6 gene, COL1A1 and COL1A2 genes, and PTH gene are important candidate gene of OP, however, more studies are still anticipated to further elucidate the relationship between these genes and ferroptosis in OP.
Topics: Biomarkers; Female; Ferroptosis; Humans; Osteoporosis, Postmenopausal; Phosphatidate Phosphatase; ROC Curve
PubMed: 36105394
DOI: 10.3389/fendo.2022.986384 -
Osteoporosis International : a Journal... May 2014Osteoporosis causes an elevated fracture risk. We propose the continued use of T-scores as one means for diagnosis but recommend that, alternatively, hip fracture;...
UNLABELLED
Osteoporosis causes an elevated fracture risk. We propose the continued use of T-scores as one means for diagnosis but recommend that, alternatively, hip fracture; osteopenia-associated vertebral, proximal humerus, pelvis, or some wrist fractures; or FRAX scores with ≥3% (hip) or 20% (major) 10-year fracture risk also confer an osteoporosis diagnosis.
INTRODUCTION
Osteoporosis is a common disorder of reduced bone strength that predisposes to an increased risk for fractures in older individuals. In the USA, the standard criterion for the diagnosis of osteoporosis in postmenopausal women and older men is a T-score of ≤ -2.5 at the lumbar spine, femur neck, or total hip by bone mineral density testing.
METHODS
Under the direction of the National Bone Health Alliance, 17 clinicians and clinical scientists were appointed to a working group charged to determine the appropriate expansion of the criteria by which osteoporosis can be diagnosed.
RESULTS
The group recommends that postmenopausal women and men aged 50 years should be diagnosed with osteoporosis if they have a demonstrable elevated risk for future fractures. This includes having a T-score of less than or equal to -2.5 at the spine or hip as one method for diagnosis but also permits a diagnosis for individuals in this population who have experienced a hip fracture with or without bone mineral density (BMD) testing and for those who have osteopenia by BMD who sustain a vertebral, proximal humeral, pelvic, or, in some cases, distal forearm fracture. Finally, the term osteoporosis should be used to diagnose individuals with an elevated fracture risk based on the World Health Organization Fracture Risk Algorithm, FRAX.
CONCLUSIONS
As new ICD-10 codes become available, it is our hope that this new understanding of what osteoporosis represents will allow for an appropriate diagnosis when older individuals are recognized as being at an elevated risk for fracture.
Topics: Absorptiometry, Photon; Age Factors; Aged; Algorithms; Bone Density; Female; Femur Neck; Hip Joint; Humans; Lumbar Vertebrae; Male; Middle Aged; Osteoporosis; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Risk Assessment
PubMed: 24577348
DOI: 10.1007/s00198-014-2655-z -
Journal of Orthopaedic Surgery and... Aug 2023Osteoporosis affects more than 200 million women worldwide, with postmenopausal women being particularly susceptible to this condition and its severe sequelae... (Meta-Analysis)
Meta-Analysis
Osteoporosis affects more than 200 million women worldwide, with postmenopausal women being particularly susceptible to this condition and its severe sequelae disproportionately, such as osteoporotic fractures. To date, the current focus has been more on symptomatic treatment, rather than preventive measures. To address this, we performed a meta-analysis aiming to identify potential predictors of osteoporotic fractures in postmenopausal women, with the ultimate goal of identifying high-risk patients and exploring potential therapeutic approaches. We searched Embase, MEDLINE and Cochrane with search terms (postmenopausal AND fracture) AND ("risk factor" OR "predictive factor") in May 2022 for cohort and case-control studies on the predictors of osteoporotic fracture in postmenopausal women. Ten studies with 1,287,021 postmenopausal women were found eligible for analyses, in which the sample size ranged from 311 to 1,272,115. The surveyed date spanned from 1993 to 2021. Our results suggested that age, BMI, senior high school and above, parity ≥ 3, history of hypertension, history of diabetes mellitus, history of alcohol intake, age at menarche ≥ 15, age at menopause < 40, age at menopause > 50, estrogen use and vitamin D supplements were significantly associated with osteoporotic fracture in postmenopausal women. Our findings facilitate the early prediction of osteoporotic fracture in postmenopausal women and may contribute to potential therapeutic approaches. By focusing on preventive strategies and identifying high-risk individuals, we can work toward reducing the burden of osteoporosis-related fractures in this vulnerable population.
Topics: Humans; Female; Osteoporotic Fractures; Osteoporosis, Postmenopausal; Postmenopause; Osteoporosis; Risk Factors; Bone Density
PubMed: 37543616
DOI: 10.1186/s13018-023-04051-6 -
Women's Health (London, England) 2022Heart failure (HF) is a prevalent clinical syndrome that causes significant physical limitations. Osteoporosis is also an important cause of loss of functionality, and... (Review)
Review
Heart failure (HF) is a prevalent clinical syndrome that causes significant physical limitations. Osteoporosis is also an important cause of loss of functionality, and it mainly affects women. There are several reports linking HF and osteoporosis, and both share risk factors. Most of the data available so far point to bone fragility as a consequence of HF, and several mechanisms have been identified to explain this relationship. Among the proposed pathophysiological mechanisms are the hyperactivation of the renin-angiotensin-aldosterone system and the increase in parathyroid hormone, functional limitation, production of inflammatory mediators and the use of drugs for HF. The role of osteoprotegerin has gained attention owing to its cardiovascular and skeletal effects, its observed deficiency during the postmenopausal period along with its compensatory increases in HF and severe osteoporosis. The objective of this review was to perform a literature search for the main evidence on skeletal impairment in HF, with emphasis on women. As for epidemiological studies, we selected data from 3 meta-analyses and 20 individual observational studies, which together showed the interrelationship between the two clinical conditions in terms of both decreased bone density and increased fracture risk. In conclusion, HF and osteoporosis are interrelated conditions mediated by complex pathophysiological mechanisms which may be more relevant for postmenopausal women, considered to be a vulnerable population for both cardiovascular diseases and bone fragility.
Topics: Female; Humans; Bone Density; Osteoporosis; Fractures, Bone; Heart Failure; Risk Factors; Osteoporosis, Postmenopausal
PubMed: 36321835
DOI: 10.1177/17455057221135501 -
Journal of Bone and Mineral Research :... Nov 2021The Active-Controlled Fracture Study in Postmenopausal Women With Osteoporosis at High Risk (ARCH) trial (NCT01631214; https://clinicaltrials.gov/ct2/show/NCT01631214)... (Clinical Trial)
Clinical Trial
Romosozumab improves lumbar spine bone mass and bone strength parameters relative to alendronate in postmenopausal women: results from the Active-Controlled Fracture Study in Postmenopausal Women With Osteoporosis at High Risk (ARCH) trial.
The Active-Controlled Fracture Study in Postmenopausal Women With Osteoporosis at High Risk (ARCH) trial (NCT01631214; https://clinicaltrials.gov/ct2/show/NCT01631214) showed that romosozumab for 1 year followed by alendronate led to larger areal bone mineral density (aBMD) gains and superior fracture risk reduction versus alendronate alone. aBMD correlates with bone strength but does not capture all determinants of bone strength that might be differentially affected by various osteoporosis therapeutic agents. We therefore used quantitative computed tomography (QCT) and finite element analysis (FEA) to assess changes in lumbar spine volumetric bone mineral density (vBMD), bone volume, bone mineral content (BMC), and bone strength with romosozumab versus alendronate in a subset of ARCH patients. In ARCH, 4093 postmenopausal women with severe osteoporosis received monthly romosozumab 210 mg sc or weekly oral alendronate 70 mg for 12 months, followed by open-label weekly oral alendronate 70 mg for ≥12 months. Of these, 90 (49 romosozumab, 41 alendronate) enrolled in the QCT/FEA imaging substudy. QCT scans at baseline and at months 6, 12, and 24 were assessed to determine changes in integral (total), cortical, and trabecular lumbar spine vBMD and corresponding bone strength by FEA. Additional outcomes assessed include changes in aBMD, bone volume, and BMC. Romosozumab caused greater gains in lumbar spine integral, cortical, and trabecular vBMD and BMC than alendronate at months 6 and 12, with the greater gains maintained upon transition to alendronate through month 24. These improvements were accompanied by significantly greater increases in FEA bone strength (p < 0.001 at all time points). Most newly formed bone was accrued in the cortical compartment, with romosozumab showing larger absolute BMC gains than alendronate (p < 0.001 at all time points). In conclusion, romosozumab significantly improved bone mass and bone strength parameters at the lumbar spine compared with alendronate. These results are consistent with greater vertebral fracture risk reduction observed with romosozumab versus alendronate in ARCH and provide insights into structural determinants of this differential treatment effect. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Topics: Alendronate; Antibodies, Monoclonal; Bone Density; Bone Density Conservation Agents; Female; Humans; Lumbar Vertebrae; Osteoporosis; Osteoporosis, Postmenopausal; Postmenopause
PubMed: 34190361
DOI: 10.1002/jbmr.4409 -
Journal of Orthopaedic Surgery and... Jul 2023Physical activity (PA) is generally encouraged for the treatment of osteoporosis. However, epidemiological statistics on the level of physical activity required for bone...
BACKGROUND
Physical activity (PA) is generally encouraged for the treatment of osteoporosis. However, epidemiological statistics on the level of physical activity required for bone health are scarce. The purpose of this research was to analyze the association between PA and total spine bone mineral density (BMD) in postmenopausal women.
METHODS
The research study included postmenopausal women aged ≥ 50 from the National Health and Nutrition Examination Survey. The metabolic equivalent (MET), weekly frequency, and duration of each activity were used to calculate PA. Furthermore, the correlations between BMD and PA were investigated by multivariable weighted logistic regression.
RESULTS
Eventually, 1681 postmenopausal women were included, with a weighted mean age of 62.27 ± 8.18 years. This study found that performing ≥ 38MET-h/wk was linked to a lower risk of osteoporosis after controlling for several covariates. Furthermore, the subgroup analysis revealed that the connection between total spine BMD and moderate-to-vigorous PA was more obvious among postmenopausal women aged < 65 years or individuals with normal BMI (< 25 kg/m).
CONCLUSION
Physical activity ranging from moderate to vigorous was linked to higher total spine BMD in postmenopausal women.
Topics: Humans; Female; Middle Aged; Aged; Bone Density; Nutrition Surveys; Cross-Sectional Studies; Postmenopause; Absorptiometry, Photon; Osteoporosis; Exercise; Osteoporosis, Postmenopausal
PubMed: 37454096
DOI: 10.1186/s13018-023-03976-2 -
Medicine Oct 2023To investigate the causal relationship between metformin use and osteoporosis and different subtypes of osteoporosis using a 2-sample Mendelian randomization method....
To investigate the causal relationship between metformin use and osteoporosis and different subtypes of osteoporosis using a 2-sample Mendelian randomization method. Data from genome-wide association studies were analyzed, with the exposure factor being metformin and the outcome variables being osteoporosis and different subtypes. Mendelian randomization was performed using Inverse Variance Weighted (IVW), MR-Egger, and weight median (WM) methods, and heterogeneity tests, horizontal multivariate analyses, and sensitivity analyses were performed. The IVW method analysis with metformin and osteoporosis showed P = 1.53E-04, OR (95%CI) = 1.81E-02 (2.27E-02-1.44E-01); the IVW method analysis with metformin and postmenopausal osteoporosis with pathologic fracture showed P = 2.22E-01, OR (95%CI) = 4.89E-02 (3. 83E-04-6.23E + 00); the IVW method using metformin with osteoporosis with pathological fracture showed that P = 2.14E-01, OR (95%CI) = 1.64E + 00(5.78E-02-6.44E-04); the IVW method using metformin with pharmacological osteoporosis with pathological fracture showed that P = 9. 83E- 01, OR (95%CI) = 1.11E + 00 (3.99E-05-3.11E + 04); IVW method of metformin use and pharmacological osteoporosis showed that P = 5.99E-01, OR (95%CI) = 2.27E + 01 (2.00E-04-2.57E + 06); there is a causal relationship between metformin use and osteoporosis, but there is no causal relationship between metformin use and postmenopausal osteoporosis with pathological fracture, osteoporosis with pathological fracture, pharmacological osteoporosis, and pharmacological osteoporosis with pathological fracture, and metformin use is a protective factor for osteoporosis.
Topics: Humans; Female; Osteoporosis, Postmenopausal; Fractures, Spontaneous; Genome-Wide Association Study; Mendelian Randomization Analysis; Osteoporosis; Metformin
PubMed: 37904346
DOI: 10.1097/MD.0000000000035191 -
Obstetrics and Gynecology Clinics of... Sep 2011Loss of ovarian function has a profound impact on female skeletal health. Bone mineral density findings from the Study of Women's Health Across the Nation demonstrate an... (Review)
Review
Loss of ovarian function has a profound impact on female skeletal health. Bone mineral density findings from the Study of Women's Health Across the Nation demonstrate an accelerated rate of bone loss during the menopausal transition. The greatest reduction occurs in the year before the final menstrual period and the first 2 years thereafter. Clinical management includes maintenance of adequate dietary calcium and vitamin D intake, attention to modifiable risk factors, and osteoporosis screening. Indications, benefits, and risks of pharmacologic osteoporosis therapy should be assessed individually; there are currently no established guidelines addressing the treatment and prevention of osteoporosis in perimenopausal women.
Topics: Absorptiometry, Photon; Bone Density; Female; Fractures, Bone; Hormones; Humans; Osteoporosis, Postmenopausal; Perimenopause
PubMed: 21961717
DOI: 10.1016/j.ogc.2011.07.001 -
Sao Paulo Medical Journal = Revista... 2023Osteoporosis compromises bone strength and increases the risk of fractures. Zoledronate prevents loss of bone mass and reduces the risk of fractures. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Osteoporosis compromises bone strength and increases the risk of fractures. Zoledronate prevents loss of bone mass and reduces the risk of fractures.
OBJECTIVES
To determine the efficacy and safety of zoledronate in postmenopausal women with osteopenia and osteoporosis.
DESIGN AND SETTINGS
A systematic review and meta-analysis was conducted within the evidence-based health program at the Universidade Federal de São Paulo.
METHODS
An electronic search of the CENTRAL, MEDLINE, Embase, and LILACS databases was performed until February 2022. Randomized controlled trials comparing zoledronate with placebo or other bisphosphonates were included. Standard methodological procedures were performed according to the Cochrane Handbook and the certainty of evidence for the Grading of Recommendations Assessment, Development, and Evaluation Working Group. Two authors assessed the risk of bias and extracted data on fractures, adverse events, bone turnover markers (BTM), and bone mineral density (BMD).
RESULTS
Twelve trials from 6,652 records were included: nine compared zoledronate with placebo, two trials compared zoledronate with alendronate, and one trial compared zoledronate with ibandronate. Zoledronate reduced the incidence of fractures in osteoporotic [three years: morphometric vertebral fractures (relative risk, RR = 0.30 (95% confidence interval, CI: 0.24-0.38))] and osteopenic women [six years: morphometric vertebral fractures (RR = 0.39 (95%CI: 0.25-0.61))], increased incidence of post-dose symptoms [RR = 2.56 (95%CI: 1.80-3.65)], but not serious adverse events [RR = 0.97 (95%CI: 0.91-1.04)]. Zoledronate reduced BTM and increased BMD in osteoporotic and osteopenic women.
CONCLUSION
This review supports the efficacy and safety of zoledronate in postmenopausal women with osteopenia for six years and osteoporosis for three years.
PROSPERO REGISTRATION NUMBER
CRD42022309708, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=309708.
Topics: Female; Humans; Zoledronic Acid; Bone Density Conservation Agents; Postmenopause; Brazil; Osteoporosis; Fractures, Bone; Bone Density; Osteoporosis, Postmenopausal
PubMed: 37255065
DOI: 10.1590/1516-3180.2022.0480.R1.27032023 -
British Journal of Sports Medicine Sep 1996
Topics: Aged; Bone Density; Bone and Bones; Exercise; Female; Fractures, Bone; Humans; Male; Middle Aged; Muscle, Skeletal; Osteoporosis; Osteoporosis, Postmenopausal; Risk Factors
PubMed: 8889107
DOI: 10.1136/bjsm.30.3.191