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Proceedings of the National Academy of... Feb 2024Postmenopausal osteoporosis arises from imbalanced osteoclast and osteoblast activity, and mounting evidence suggests a role for the osteoimmune system in bone...
Postmenopausal osteoporosis arises from imbalanced osteoclast and osteoblast activity, and mounting evidence suggests a role for the osteoimmune system in bone homeostasis. Bisphosphonate (BP) is an antiresorptive agent, but its treatment failure rate can be as high as 40%. Here, we performed single-cell RNA sequencing on peripheral immune cells from carefully selected postmenopausal women: non-osteoporotic, osteoporosis improved after BP treatment, and BP-failed cases. We found an increase in myeloid cells in patients with osteoporosis (specifically, T cell receptor+ macrophages). Furthermore, lymphoid lineage cells varied significantly, notably elevated natural killer cells (NKs) in the BP-failed group. Moreover, we provide fruitful lists of biomarkers within the immune cells that exhibit condition-dependent differences. The existence of osteoporotic- and BP-failure-specific cellular information flows was revealed by cell-cell interaction analysis. These findings deepen our insight of the osteoporosis pathology enhancing comprehension of the role of immune heterogeneity in postmenopausal osteoporosis and BP treatment failure.
Topics: Humans; Female; Diphosphonates; Osteoporosis, Postmenopausal; Bone Density; Bone Density Conservation Agents; Osteoporosis; Gene Expression Profiling
PubMed: 38346184
DOI: 10.1073/pnas.2316871121 -
Scientific Reports Jan 2018Results on the relationships between vitamin D receptor (VDR) gene polymorphisms and postmenopausal osteoporosis (PMOP) susceptibility and bone mineral density (BMD) are... (Meta-Analysis)
Meta-Analysis Review
Results on the relationships between vitamin D receptor (VDR) gene polymorphisms and postmenopausal osteoporosis (PMOP) susceptibility and bone mineral density (BMD) are conflicting. The aim of the study is to identify more eligible studies that calculated pooled OR and WMD with 95% CI to assess their associations. Overall, there were significant correlations between VDR ApaI, VDR FokI and PMOP susceptibility. Subgroup analysis showed that VDR ApaI polymorphism significantly decreased the osteoporosis risk in Caucasian postmenopausal women. In Asian populations, VDR BsmI and VDR FokI were associated with an increased risk of PMOP. As to the associations between VDR polymorphisms and BMD, Caucasian PMOP women carrying the ApaI aa genotype were at risk of high BMD in femoral neck, and low femoral neck BMD was observed in Caucasian PMOP women with FokI Ff genotype. PMOP women with the Cdx2 GA genotype had a lower lumbar spine BMD in overall and Caucasian populations compared with PMOP women with GG genotype. Different VDR gene polymorphisms have different impacts on PMOP risk and BMD.
Topics: Asian People; Bone Density; Bone and Bones; Deoxyribonucleases, Type II Site-Specific; Female; Gene Expression; Genetic Predisposition to Disease; Humans; Middle Aged; Osteoporosis, Postmenopausal; Polymorphism, Restriction Fragment Length; Postmenopause; Receptors, Calcitriol; White People
PubMed: 29343720
DOI: 10.1038/s41598-017-18670-7 -
Clinical Interventions in Aging 2007In the elderly population, osteoporosis is a significant clinical problem leading to disability and even death. Many patients remain untreated, despite effective... (Review)
Review
In the elderly population, osteoporosis is a significant clinical problem leading to disability and even death. Many patients remain untreated, despite effective therapies, because of patients' unwillingness to take current therapies or inability to tolerate the therapies. For this reason, ongoing research continues to search for more effective and tolerable osteoporosis agents. Bazedoxifene is a selective estrogen receptor modulator (SERM) currently in development for osteoporosis prevention and treatment. A new drug application (NDA) for postmenopausal osteoporosis prevention was recently submitted to the FDA. Preclinical and clinical studies with bazedoxifene demonstrate more tissue selectivity than other SERMs. In particular, bazedoxifene has minimal if any agonist activity in the uterus and is able to antagonize effects of estrogen on the uterus. Animal studies and early clinical studies suggest effects in the bone similar to other SERMs with prevention of postmenopausal bone loss. Until more data on efficacy and safety are published, however, its role in osteoporosis is unknown.
Topics: Animals; Bone Density Conservation Agents; Estrogens; Female; Humans; Indoles; Osteoporosis; Osteoporosis, Postmenopausal; Selective Estrogen Receptor Modulators; Treatment Outcome; Uterus
PubMed: 18044180
DOI: No ID Found -
Nutrients Mar 2023Osteoporosis is a prevalent issue among postmenopausal women, who have a higher incidence of the condition than men. This study aimed to examine the relationship between...
Osteoporosis is a prevalent issue among postmenopausal women, who have a higher incidence of the condition than men. This study aimed to examine the relationship between phytochemical-rich food intake and osteoporosis incidence in premenopausal and postmenopausal women. The data analyzed included 4600 women aged 40-69 who were free of osteoporosis at baseline, with dietary intake evaluated through a semi-quantitative food frequency questionnaire and osteoporosis prevalence determined using interviewer-administered questionnaires and bone mineral density tests. The phytochemical index (PI) was calculated to reflect the intake levels of phytochemical-rich foods. Postmenopausal women in the highest PI quartile had a 16% lower risk of osteoporosis (95% confidence interval (CI): 0.71 to 0.99, for trend = 0.02) than those in the lowest quartile, while no significant association was observed among premenopausal women (hazard ratio: 0.98, 95% CI: 0.78 to 1.24, for trend = 0.8). These findings suggest that consuming phytochemical-rich foods may have a protective effect against osteoporosis in postmenopausal women, offering valuable scientific insights. However, additional research is needed to validate these findings using biochemical data. Overall, this study highlights the potential of dietary interventions to reduce the risk of osteoporosis in postmenopausal women.
Topics: Male; Humans; Female; Bone Density; Prospective Studies; Osteoporosis, Postmenopausal; Osteoporosis; Phytochemicals; Republic of Korea
PubMed: 37049447
DOI: 10.3390/nu15071605 -
BMC Endocrine Disorders Jul 2023Osteoporosis (OP) is one of the diseases that endanger the health of the elderly population. Klotho protein is a hormone with anti-aging effects. A few studies have...
BACKGROUND
Osteoporosis (OP) is one of the diseases that endanger the health of the elderly population. Klotho protein is a hormone with anti-aging effects. A few studies have discussed the relationship between Klotho and OP. However, there is still a lack of research on larger populations. This study aims to evaluate the association between OP and Klotho in American postmenopausal women.
METHODS
This is a retrospective study. We searched the National Health and Nutrition Examination Survey (NHANES) database and collected data of 3 survey cycles, finally involving 871 postmenopausal women over 50 years old in the present study. All participants took dual-energy X-ray absorptiometry examination and serum Klotho testing at the time of investigation. After adjusting the possible confounding variables, a multivariate regression model was employed to estimate the relationship between OP and Klotho proteins. Besides, the P for trend and restricted cubic spline (RCS) were applied to examine the threshold effect and calculate the inflection point.
RESULTS
Factors influencing the occurrence of OP included age, ethnicity, body mass index and Klotho levels. Multivariate regression analysis indicated that the serum Klotho concentration was lower in OP patients than that in participants without OP (OR[logKlotho] = 0.568, P = 0.027). The C-index of the prediction model built was 0.765, indicating good prediction performance. After adjusting the above-mentioned four variables, P values for trend showed significant differences between groups. RCSs revealed that when the Klotho concentration reached 824.09 pg/ml, the risk of OP decreased drastically.
CONCLUSION
Based on the analysis of the data collected from the NHANES database, we propose a correlation between Klotho and postmenopausal OP. A higher serum Klotho level is related to a lower incidence of OP. The findings of the present study can provide guidance for research on diagnosis and risk assessment of OP.
Topics: Humans; Female; Aged; Middle Aged; Nutrition Surveys; Cross-Sectional Studies; Bone Density; Postmenopause; Retrospective Studies; Osteoporosis; Osteoporosis, Postmenopausal
PubMed: 37452417
DOI: 10.1186/s12902-023-01380-9 -
Journal of Bone and Mineral Research :... Dec 1993The noninvasive assessment of bone turnover has received increasing attention over the past few years because of the need for sensitive markers in the clinical... (Review)
Review
The noninvasive assessment of bone turnover has received increasing attention over the past few years because of the need for sensitive markers in the clinical investigation of osteoporosis. Markers of bone formation include the serum measurement of total and bone-specific alkaline phosphatase, osteocalcin, and type I collagen extension peptides. Assessment of bone resorption can be achieved with measurement of fasting urinary calcium and hydroxyproline, urinary hydroxylysine glycosides, urinary excretion of the pyridinium cross-links (pyridinoline and deoxypyridinoline), and plasma tartrate-resistant acid phosphatase activity. Several studies performed in a variety of metabolic bone diseases have shown these markers to be of unequal sensitivity and specificity. In addition, some of them are not fully characterized. For assessment of the level of bone turnover in women with vertebral osteoporosis, serum osteocalcin and urinary pyridinoline appear to be the most sensitive markers so far. Programs combining bone mass measurement and assessment of bone turnover by several markers in women at the time of menopause are being developed in an attempt to improve the assessment of the risk for osteoporosis. Efforts are being made to develop more convenient assays and to identify other markers of bone turnover. A battery of various specific markers is likely to improve the assessment of the complex and subtle abnormalities of bone metabolism that characterize metabolic bone diseases, especially the various aspects of osteoporosis.
Topics: Biomarkers; Bone Density; Bone Diseases, Metabolic; Bone Resorption; Bone and Bones; Chromatography, High Pressure Liquid; Female; Humans; Menopause; Osteogenesis; Osteoporosis; Osteoporosis, Postmenopausal
PubMed: 8122526
DOI: 10.1002/jbmr.5650081323 -
BMC Musculoskeletal Disorders Mar 2021Osteoporosis and cardiovascular disease (CVD) are age-related diseases. It is reported that patients with CVD have a higher risk of bone loss. This retrospective study...
BACKGROUND
Osteoporosis and cardiovascular disease (CVD) are age-related diseases. It is reported that patients with CVD have a higher risk of bone loss. This retrospective study sought to reveal the association between osteoporosis and CVD in Chinese women. Although epidemiological evidence has indicated a relationship between the two, clinical data in southeast China are lacking.
METHODS
In total, 2873 participants completed the baseline survey from January 2007 to October 2019, and 2039 were included in this retrospective study. We divided all subjects into an osteoporosis group and a non-osteoporosis group based on their bone mineral density (BMD). Dual-energy X-ray absorptiometry (DXA) was used to examine BMD. The general information came from the questionnaire survey. Cardiovascular diseases were defined by asking participants at the first visit and checking relevant medical records if they had suffered from hypertension, coronary heart disease, or cerebral infarction.
RESULTS
According to the criterion, the osteoporosis group had 678 subjects, and the non-osteoporosis group had 1361 subjects. Subjects in the osteoporosis group had a significantly higher prevalence of hypertension and coronary heart disease. Besides, the proportion of subjects who drank tea and drank milk were relatively higher in the osteoporosis group. The odds ratio (OR) for suffering from osteoporosis was high if the patients had hypertension.
CONCLUSIONS
This study indicated that Chinese postmenopausal women with osteoporosis had a higher prevalence of hypertension. Hypertension was significantly associated with osteoporosis.
Topics: Absorptiometry, Photon; Bone Density; Case-Control Studies; China; Female; Humans; Hypertension; Osteoporosis; Osteoporosis, Postmenopausal; Postmenopause; Retrospective Studies
PubMed: 33678168
DOI: 10.1186/s12891-021-04124-9 -
Endokrynologia Polska 2011Strontium ranelate is one of the first-line agents with proven anti-fracture activity used in the therapy of post-menopausal osteoporosis. Its mechanism of action makes... (Review)
Review
Strontium ranelate is one of the first-line agents with proven anti-fracture activity used in the therapy of post-menopausal osteoporosis. Its mechanism of action makes it, however, different from other drugs, since it simultaneously stimulates two reverse processes: bone formation and bone resorption. The action of the agent depends on various mechanisms, including the activation of calcium receptors, localised on osteoblasts and osteoclasts, and on the influence on the OPG/RANKL system. The drug effectively prevents spinal, hip and extravertebral fractures. The agent's anti-fracture efficacy within the spine does not depend on the patient's age, or on base BMD values, or on the concentration of bone metabolism markers. As to the anti-fracture efficacy in the hip, it concerns women with an increased bone fracture risk. Strontium ranelate increases bone mineral density within the lumbar spine and the hip, decreases the concentrations of bone resorption markers, and increases the concentrations of bone formation markers. The drug is administered in a daily 2.0 g oral dose. This paper presents indications to therapy with strontium ranelate, specifying also its side effects and contraindications. We compare the anti-fracture efficacy of strontium ranelate to the efficacy of other agents of proven anti-fracture activity, based on published clinical studies.
Topics: Aged, 80 and over; Animals; Bone Density Conservation Agents; Female; Humans; Organometallic Compounds; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Thiophenes
PubMed: 21365582
DOI: No ID Found -
Annals of the New York Academy of... Mar 2010The Study of Women's Health Across the Nation (SWAN) is an NIH-funded, multidisciplinary, longitudinal observational study of middle-aged U.S. women of multiple... (Review)
Review
The Study of Women's Health Across the Nation (SWAN) is an NIH-funded, multidisciplinary, longitudinal observational study of middle-aged U.S. women of multiple ethnicities in or near Boston, Newark, Pittsburgh, Detroit, Chicago, Oakland, and Los Angeles. SWAN measures multiple variables annually, including spine and hip areal bone mineral density (aBMD), serum and urine indices of bone remodeling, and pituitary, ovarian, and adrenal hormones. This chapter outlines the findings of the SWAN study so far.
Topics: Biomarkers; Bone Remodeling; Female; Humans; Longitudinal Studies; Menopause; Multicenter Studies as Topic; Osteoporosis, Postmenopausal; Women's Health
PubMed: 20392219
DOI: 10.1111/j.1749-6632.2009.05233.x -
Clinical Therapeutics 1996Osteoporosis is a debilitating disease that results in nearly 1.3 million fractures per year in the United States. The cost of treating these fractures has been... (Comparative Study)
Comparative Study Review
Osteoporosis is a debilitating disease that results in nearly 1.3 million fractures per year in the United States. The cost of treating these fractures has been estimated to be as high as $10 billion per year. These costs are expected to more than double during the next 50 years unless comprehensive programs of prevention and treatment are initiated. Both pharmacologic and nonpharmacologic interventions (eg, diet and exercise) have been shown to have a significant impact on the incidence of osteoporosis, depending on the time of their application. Unfortunately, osteoporosis is often not diagnosed until after fractures have occurred, when it may be too late for treatment to have a major impact. To be most effective, therapy should be started early, before serious bone loss has occurred. Because of its efficacy and relatively low acquisition cost, long-term hormone replacement therapy (HRT) is considered first-line pharmacologic therapy for the prevention of osteoporosis. However, for various reasons, less than 25% of US women who might benefit from HRT are receiving it. Aside from HRT, the only other products approved by the US Food and Drug Administration for the treatment of osteoporosis are salmon calcitonin and alendronate. Several other agents are under development, including sustained-release fluoride and other products in the bisphosphonate class. The development and adoption of early detection programs and treatment guidelines are crucial to help ease the economic burden of osteoporosis. These guidelines should incorporate preventive measures such as diet and exercise, risk assessment through proper screening programs, and the appropriate use of pharmaceutical products. The purpose of this paper is to discuss relevant economic issues associated with osteoporosis and discuss the need for a management algorithm that could be used to more efficiently prevent and treat this disease. We conclude that further modeling is needed to determine which programs and treatments are most cost-effective within each at-risk subgroup. As clinicians better understand the need for preventive care and the advantages of the various pharmacologic therapies, patients with osteoporosis will receive higher-quality and more efficient medical care.
Topics: Calcitonin; Estrogen Replacement Therapy; Female; Fractures, Bone; Humans; Osteoporosis, Postmenopausal; Practice Guidelines as Topic
PubMed: 8851459
DOI: 10.1016/s0149-2918(96)80186-x