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Cytokine & Growth Factor Reviews Apr 2020Postmenopausal osteoporosis (PMOP) is a prevalent skeletal disorder associated with menopause-related estrogen withdrawal. PMOP is characterized by low bone mass,... (Review)
Review
Postmenopausal osteoporosis (PMOP) is a prevalent skeletal disorder associated with menopause-related estrogen withdrawal. PMOP is characterized by low bone mass, deterioration of the skeletal microarchitecture, and subsequent increased susceptibility to fragility fractures, thus contributing to disability and mortality. Accumulating evidence indicates that abnormal expansion of marrow adipose tissue (MAT) plays a crucial role in the onset and progression of PMOP, in part because both bone marrow adipocytes and osteoblasts share a common ancestor lineage. The cohabitation of MAT adipocytes, mesenchymal stromal cells, hematopoietic cells, osteoblasts and osteoclasts in the bone marrow creates a microenvironment that permits adipocytes to act directly on other cell types in the marrow. Furthermore, MAT, which is recognized as an endocrine organ, regulates bone remodeling through the secretion of adipokines and cytokines. Although an enhanced MAT volume is linked to low bone mass and fractures in PMOP, the detailed interactions between MAT and bone metabolism remain largely unknown. In this review, we examine the possible mechanisms of MAT expansion under estrogen withdrawal and further summarize emerging findings regarding the pathological roles of MAT in bone remodeling. We also discuss the current therapies targeting MAT in osteoporosis. A comprehensive understanding of the relationship between MAT expansion and bone metabolism in estrogen deficiency conditions will provide new insights into potential therapeutic targets for PMOP.
Topics: Adipocytes; Adipose Tissue; Aging; Animals; Bone Marrow; Bone Marrow Cells; Bone Remodeling; Female; Humans; Mice; Osteoporosis, Postmenopausal
PubMed: 32081538
DOI: 10.1016/j.cytogfr.2020.02.003 -
Women's Health (London, England) 2022Increased understanding of the Wnt signaling pathway has led to the development of romosozumab, one of the most potent osteoanabolic agents to date for osteoporosis... (Review)
Review
Increased understanding of the Wnt signaling pathway has led to the development of romosozumab, one of the most potent osteoanabolic agents to date for osteoporosis treatment. Romosozumab is a monoclonal antibody that inhibits sclerostin, a natural inhibitor of the Wnt signaling pathway. Romosozumab, by inhibiting sclerostin activates the Wnt signaling pathway, leading to increased bone formation and decreased bone resorption. The pivotal ARCH and FRAME studies established romosozumab's fracture reduction efficacy. Romosozumab was superior to alendronate in fracture reduction and bone mineral density gain in the ARCH study. Romosozumab treatment should be followed sequentially with a potent antiresorptive agent. The antifracture efficacy gained from romosozumab is maintained or improved after transitioning to an antiresorptive agent. As one of the most potent osteoanabolic agents, the introduction of romosozumab has significantly increased our ability to treat osteoporosis. Studies have provided important information on using romosozumab with other osteoporosis medications to optimize osteoporosis treatment. Romosozumab used before antiresorptive medications is associated with more significant bone mineral density increases than when an antiresorptive agent is used before romosozumab. Romosozumab is recommended for osteoporosis treatment in patients at very high risk for fracture with low cardiovascular risk. Romosozumab is generally well tolerated, with 4%-5% of patients having injection site reactions. The ARCH trial showed a higher risk of cardiovascular events in patients receiving romosozumab. Romosozumab carries a black box warning that romosozumab should not be initiated in patients with myocardial infarction or stroke in the preceding year. However, the information on romosozumab and increased cardiovascular risk is conflicting. The risk of cardiovascular disease with romosozumab is unclear. While romosozumab has demonstrated significant osteoanabolic effect and antifracture efficacy and will benefit high fracture risk patients, further studies are needed to investigate the cardiovascular safety of romosozumab.
Topics: Alendronate; Antibodies, Monoclonal; Bone Density; Bone Density Conservation Agents; Cardiovascular Diseases; Female; Heart Disease Risk Factors; Humans; Osteoporosis; Osteoporosis, Postmenopausal; Risk Factors
PubMed: 36154750
DOI: 10.1177/17455057221125577 -
Phytomedicine : International Journal... Jul 2022Postmenopausal osteoporosis (PMOP) is a serious problem for the women over 50 years old. Natural product puerarin (PUE) has been proven to improve PMOP with high safety....
BACKGROUND
Postmenopausal osteoporosis (PMOP) is a serious problem for the women over 50 years old. Natural product puerarin (PUE) has been proven to improve PMOP with high safety. PMOP is a metabolic disorder affecting bone metabolism, indicating that endogenous metabolites amelioration may be a novel strategy for PMOP therapy. However, what the metabolic profile of POMP will be after PUE treatment is still obscure.
PURPOSE
We purpose to figure out the metabolic characteristics of PMOP and to explore the intrinsic mechanism on the anti-osteoporosis efficacy after PUE treatment based on the serum metabolomics.
METHODS
We established OVX rats as osteoporosis model, and the animals were distributed into Sham, OVX, and OVX+PUE (100 mg/kg/d) group. The femurs were analyzed by μ-CT and three-point bending test. Serum metabolomics was performed by UPLC/Q-TOF-MS. We also determined the body weight, liver weight, and the levels of serum TC, TG, LDL-C, and HDL-C. The key proteins of the PPARγ pathway and Wnt pathway were analyzed by Western blot and qPCR experiments.
RESULTS
PUE treatment for 14 weeks both improved the bone structure and ameliorated lipid metabolism in ovariectomized rats. By determination and further analysis of serum metabolomics, we revealed that the endogenous metabolites was significantly changed in ovariectomized rats, and PUE treatment adjusted 23 differential metabolites, which were involved in phospholipid metabolism metabolism and PUFAs metabolic pathways. Close correlationships were futher found between the indexes of bone metabolism, lipid metabolism and the differential metabolites, particularly LysoPA, S1P and n-3/n-6 PUFAs. Further, we discovered that PUE regulated differentiation of BMSCs to elicit anti-osteoporosis efficacy, attributing to Wnt/β-catenin signaling activation and PPARγ pathway inhibition initiated by metabolomics.
CONCLUSION
PUE improves OVX-induced osteoporosis and lipid metabolism by regulating phospholipid metabolism and biosynthesis of PUFAs, resulting in reducing the adipogenic differentiation and promoting osteogenic differentiation of BMSCs via Wnt pathway activation and PPARγ pathway inhibition in ovariectomized rats. The study provides us a novel mechanism to explain the improvement of osteoporosis by PUE, depicts a metabolic profile of PMOP, and gives us another point cut for further exploring the pathogenesis of PMOP and looking for biomarkers of osteoporosis.
Topics: Animals; Fatty Acids, Unsaturated; Female; Humans; Isoflavones; Lipid Metabolism; Metabolomics; Osteogenesis; Osteoporosis, Postmenopausal; Ovariectomy; PPAR gamma; Phospholipids; Rats
PubMed: 35636175
DOI: 10.1016/j.phymed.2022.154198 -
Neuro Endocrinology Letters 2015Today's knowledge and studies show a firm correlation between osteoporosis and periodontitis, particularly in postmenopausal women. This review study deals with... (Review)
Review
Today's knowledge and studies show a firm correlation between osteoporosis and periodontitis, particularly in postmenopausal women. This review study deals with epidemiological and etiopathogenetic association between chronic periodontitis and an osteoporosis. A special emphasis is put on explanation of possible relations between a premature tooth loss and decrease of length and density of jaw bones, particularly their alveolar prolongations. The second part of the paper deals with principles of treatment in patients suffering of osteoporosis. Osteoporosis reduces density of jaw bones and decreases a number of teeth in jaws, but it does not affect other clinical signs and markers of periodontitis such as inflammation, bleeding and the depth of periodontal pockets and microbial plaque.
Topics: Bone Density Conservation Agents; Estrogen Replacement Therapy; Female; Humans; Jaw; Male; Osteoporosis; Osteoporosis, Postmenopausal; Periodontitis
PubMed: 26707036
DOI: No ID Found -
The New England Journal of Medicine Feb 2024
Topics: Female; Humans; Osteoporosis, Postmenopausal; Bone Density
PubMed: 38354156
DOI: 10.1056/NEJMc2314624 -
Aging May 2020Reduced bone mineral density (BMD) is associated with an altered microbiota in senile osteoporosis. However, the relationship among gut microbiota, BMD and bone...
Reduced bone mineral density (BMD) is associated with an altered microbiota in senile osteoporosis. However, the relationship among gut microbiota, BMD and bone metabolic indexes remains unknown in postmenopausal osteoporosis. In this study, fecal microbiota profiles for 106 postmenopausal individuals with osteopenia (n=33) or osteoporosis (n=42) or with normal BMD (n=31) were determined. An integrated 16S rRNA gene sequencing and LC-MS-based metabolomics approach was applied to explore the association of estrogen-reduced osteoporosis with the gut microbiota and fecal metabolic phenotype. Adjustments were made using several statistical models for potential confounding variables identified from the literature. The results demonstrated decreased bacterial richness and diversity in postmenopausal osteoporosis. Additionally, showed significant differences in abundance levels among phyla and genera in the gut microbial community were found. Moreover, postmenopausal osteopenia-enriched N-acetylmannosamine correlated negatively with BMD, and distinguishing metabolites were closely associated with gut bacterial variation. Both serum procollagen type I N propeptide (P1NP) and C-terminal telopeptide of type I collagen (CTX-1) correlated positively with osteopenia-enriched , and . However, we did not find a significant correlation between bacterial diversity and estrogen. These observations will lead to a better understanding of the relationship between bone homeostasis and the microbiota in postmenopausal osteoporosis.
Topics: Absorptiometry, Photon; Bone Density; Bone Remodeling; Bone and Bones; Collagen Type I; Feces; Female; Gastrointestinal Microbiome; Humans; Mass Spectrometry; Metabolomics; Middle Aged; Osteoporosis, Postmenopausal; RNA, Ribosomal, 16S
PubMed: 32392181
DOI: 10.18632/aging.103168 -
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 -
Gynecological Endocrinology : the... Apr 2020Vitamin K (vit K) belongs to a large group of fat-soluble compounds whose formulation is MK (menaquinone) (MK-2 to MK-14), that seem to be involved in different... (Review)
Review
Vitamin K (vit K) belongs to a large group of fat-soluble compounds whose formulation is MK (menaquinone) (MK-2 to MK-14), that seem to be involved in different biological functions. In particular, vit K has been recently recognized as efficacious and safe in treatment of bone loss, as it contributes to structural integrity of osteocalcin (OC), the major non-collagenous protein typically found in bone matrix. Several studies proved low vit K intake is linked to bone loss and to increased fracture risk in both sexes. Nowadays, vit K supplementation is considered a significant manner to enhance the association of calcium and vitamin D whose role on bone health is largely recognized. On the other hand, vit K may be used alone or with other drugs to preserve bone quality/strength from skeletal degradation after menopause and/or in patients affected by secondary osteoporosis. In this paper, we review the most recent data about vit K on skeleton.
Topics: Bone Density; Bone Diseases, Metabolic; Bone and Bones; Calcium; Dietary Supplements; Female; Humans; Male; Osteoporosis; Osteoporosis, Postmenopausal; Risk Factors; Vitamin D; Vitamin K 2
PubMed: 31711322
DOI: 10.1080/09513590.2019.1689554 -
The Journal of Clinical Endocrinology... Sep 2022Abaloparatide reduced fracture risk in postmenopausal women with osteoporosis in the Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE). Its effect in... (Randomized Controlled Trial)
Randomized Controlled Trial
CONTEXT
Abaloparatide reduced fracture risk in postmenopausal women with osteoporosis in the Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE). Its effect in Japanese patients remains unexamined.
OBJECTIVE
This work aimed to determine the efficacy and safety of abaloparatide in increasing bone mineral density (BMD) in Japanese patients with osteoporosis at high fracture risk.
METHODS
This was a randomized, double-blind, placebo-controlled study conducted in Japan. Postmenopausal women and men with osteoporosis with high fracture risk were given daily subcutaneous 80 µg abaloparatide or placebo for 78 weeks (18 months). The primary end point was percentage change in lumbar spine (LS) BMD from baseline at the last visit. Secondary end points included time-course changes in LS, total hip (TH), and femoral neck (FN) BMDs and bone turnover markers, and cumulative number of fractures.
RESULTS
Abaloparatide increased LS, TH, and FN BMDs (mean [95% CI]) by 12.5% (10.3%-14.8%; P < .001), 4.3% (3.3%-5.3%), and 4.3% (2.9%-5.6%), respectively, vs placebo. Serum procollagen type I N-terminal propeptide increased rapidly to ~ 140% above baseline at 6 weeks and gradually decreased but was approximately 25% higher than baseline at 78 weeks. Serum carboxy-terminal cross-linking telopeptide of type I collagen gradually increased to 50% above baseline at 24 weeks and decreased gradually to the placebo-group level from 60 weeks. Four vertebrae of 3 participants in the placebo group, but none in the abaloparatide group, developed new vertebral fractures. The safety profile was similar to that in the ACTIVE study.
CONCLUSION
In Japanese patients with postmenopausal and male osteoporosis with high fracture risk, abaloparatide for 78 weeks robustly increased LS, TH, and FN BMDs, suggesting a similar efficacy in Japanese patients vs the ACTIVE study population.
Topics: Bone Density; Bone Density Conservation Agents; Collagen Type I; Double-Blind Method; Female; Humans; Japan; Lumbar Vertebrae; Male; Osteoporosis; Osteoporosis, Postmenopausal; Parathyroid Hormone-Related Protein
PubMed: 35977548
DOI: 10.1210/clinem/dgac486 -
Endocrine Practice : Official Journal... Apr 2021
Topics: Endocrinologists; Female; Humans; Osteoporosis, Postmenopausal; Risk Assessment
PubMed: 33577970
DOI: 10.1016/j.eprac.2021.01.019