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Ferroptosis: Regulatory mechanisms and potential targets for bone metabolism: A review. Medicine Bone homeostasis is a homeostasis process constructed by osteoblast bone formation and osteoclast bone resorption. Bone homeostasis imbalance and dysfunction are the basis for the development of various orthopedic diseases such as osteoporosis, osteoarthritis, and steroid-induced avascular necrosis of femoral head. Previous studies have demonstrated that ferroptosis can induce lipid peroxidation through the generation of reactive oxygen species, activate a number of signaling pathways, and participate in the regulation of osteoblast bone formation and osteoclast bone resorption, resulting in bone homeostasis imbalance, which is an important factor in the pathogenesis of many orthopedic diseases, but the mechanism of ferroptosis is still unknown. In recent years, it has been found that, in addition to iron metabolism and intracellular antioxidant system imbalance, organelle dysfunction is also a key factor affecting ferroptosis. This paper takes this as the starting point, reviews the latest literature reports at home and abroad, elaborates the pathogenesis and regulatory pathways of ferroptosis and the relationship between ferroptosis and various organelles, and summarizes the mechanism by which ferroptosis mediates bone homeostasis imbalance, with the aim of providing new directions for the research related to ferroptosis and new ideas for the prevention and treatment of bone and joint diseases. 10.1097/MD.0000000000039158
Senile Osteoporosis: The Involvement of Differentiation and Senescence of Bone Marrow Stromal Cells. Qadir Abdul,Liang Shujing,Wu Zixiang,Chen Zhihao,Hu Lifang,Qian Airong International journal of molecular sciences Senile osteoporosis has become a worldwide bone disease with the aging of the world population. It increases the risk of bone fracture and seriously affects human health. Unlike postmenopausal osteoporosis which is linked to menopause in women, senile osteoporosis is due to aging, hence, affecting both men and women. It is commonly found in people with more than their 70s. Evidence has shown that with age increase, bone marrow stromal cells (BMSCs) differentiate into more adipocytes rather than osteoblasts and undergo senescence, which leads to decreased bone formation and contributes to senile osteoporosis. Therefore, it is necessary to uncover the molecular mechanisms underlying the functional changes of BMSCs. It will benefit not only for understanding the senile osteoporosis development, but also for finding new therapies to treat senile osteoporosis. Here, we review the recent advances of the functional alterations of BMSCs and the related mechanisms during senile osteoporosis development. Moreover, the treatment of senile osteoporosis by aiming at BMSCs is introduced. 10.3390/ijms21010349
Inhibiting Cellular Senescence: A New Therapeutic Paradigm for Age-Related Osteoporosis. The Journal of clinical endocrinology and metabolism Context:With the aging of the population and projected increase in osteoporotic fractures coupled with the declining use of osteoporosis medications, there is a compelling need for new approaches to treat osteoporosis. Given that age-related osteoporosis generally coexists with multiple other comorbidities (e.g., atherosclerosis, diabetes, frailty) that share aging as the leading risk factor, there is growing interest in the "Geroscience Hypothesis," which posits that manipulation of fundamental aging mechanisms will delay the appearance or severity of multiple chronic diseases because these diseases share aging as the underlying risk factor. In this context, one fundamental aging mechanism that has received considerable attention recently as contributing to multiple age-related morbidities is cellular senescence. This mini-review provides an overview on cellular senescence with a focus on its role in mediating age-related bone loss. Methods:This summary is based on the authors' knowledge of the field supplemented by a PubMed search using the terms "senescence," "aging," and "bone." Results:There is compelling evidence from preclinical models and supportive human data demonstrating an increase in senescent cells in the bone microenvironment with aging. These cells produce a proinflammatory secretome that leads to increased bone resorption and decreased bone formation, and approaches that either eliminate senescent cells or impair the production of their proinflammatory secretome have been shown to prevent age-related bone loss in mice. Conclusions:Targeting cellular senescence represents a novel therapeutic strategy to prevent not only bone loss but potentially multiple age-related diseases simultaneously. 10.1210/jc.2017-02694
Current Status of Bone-Forming Therapies for the Management of Osteoporosis. Sølling Anne Sophie Koldkjær,Harsløf Torben,Langdahl Bente Drugs & aging In patients with osteoporosis and severely reduced bone mass and/or recurring fractures, antiresorptive therapy may not be the optimal first-line treatment. Two recent clinical trials comparing bone-forming treatment with antiresorptive therapy have demonstrated that bone-forming treatment is superior in reducing the fracture risk in patients with severe osteoporosis. All of the currently available bone-forming agents-teriparatide, abaloparatide, and romosozumab-increase bone mineral density (BMD) and reduce the fracture risk; however, the effect wears off with time and treatment is therefore only transient. Thus, a bone-forming therapy should be followed by antiresorptive treatment with a bisphosphonate or denosumab. The BMD response to bone-forming treatment is reduced in patients previously treated with antiresorptive drugs; however, based on the findings of the VERO trial, the anti-fracture efficacy of bone-forming treatment in comparison with antiresorptives seems to be preserved. This review provides an overview of the existing bone-forming therapies for osteoporosis including considerations of sequential and combination therapy. 10.1007/s40266-019-00675-8
Advances in mesenchymal stem cell transplantation for the treatment of osteoporosis. Cell proliferation Osteoporosis is a systemic metabolic bone disease with characteristics of bone loss and microstructural degeneration. The personal and societal costs of osteoporosis are increasing year by year as the ageing of population, posing challenges to public health care. Homing disorders, impaired capability of osteogenic differentiation, senescence of mesenchymal stem cells (MSCs), an imbalanced microenvironment, and disordered immunoregulation play important roles during the pathogenesis of osteoporosis. The MSC transplantation promises to increase osteoblast differentiation and block osteoclast activation, and to rebalance bone formation and resorption. Preclinical investigations on MSC transplantation in the osteoporosis treatment provide evidences of enhancing osteogenic differentiation, increasing bone mineral density, and halting the deterioration of osteoporosis. Meanwhile, the latest techniques, such as gene modification, targeted modification and co-transplantation, are promising approaches to enhance the therapeutic effect and efficacy of MSCs. In addition, clinical trials of MSC therapy to treat osteoporosis are underway, which will fill the gap of clinical data. Although MSCs tend to be effective to treat osteoporosis, the urgent issues of safety, transplant efficiency and standardization of the manufacturing process have to be settled. Moreover, a comprehensive evaluation of clinical trials, including safety and efficacy, is still needed as an important basis for clinical translation. 10.1111/cpr.12956
The Role of Osteoclast Energy Metabolism in the Occurrence and Development of Osteoporosis. Frontiers in endocrinology In recent decades, the mechanism underlying bone metabolic disorders based on energy metabolism has been heavily researched. Bone resorption by osteoclasts plays an important role in the occurrence and development of osteoporosis. However, the mechanism underlying the osteoclast energy metabolism disorder that interferes with bone homeostasis has not been determined. Bone resorption by osteoclasts is a process that consumes large amounts of adenosine triphosphate (ATP) produced by glycolysis and oxidative phosphorylation. In addition to glucose, fatty acids and amino acids can also be used as substrates to produce energy through oxidative phosphorylation. In this review, we summarize and analyze the energy-based phenotypic changes, epigenetic regulation, and coupling with systemic energy metabolism of osteoclasts during the development and progression of osteoporosis. At the same time, we propose a hypothesis, the compensatory recovery mechanism (involving the balance between osteoclast survival and functional activation), which may provide a new approach for the treatment of osteoporosis. 10.3389/fendo.2021.675385
Oxidative Stress and Inflammation in Osteoporosis: Molecular Mechanisms Involved and the Relationship with microRNAs. International journal of molecular sciences Osteoporosis is characterized by the alteration of bone homeostasis due to an imbalance between osteoclastic bone resorption and osteoblastic bone formation. Estrogen deficiency causes bone loss and postmenopausal osteoporosis, the pathogenesis of which also involves oxidative stress, inflammatory processes, and the dysregulation of the expression of microRNAs (miRNAs) that control gene expression at post-transcriptional levels. Oxidative stress, due to an increase in reactive oxygen species (ROS), proinflammatory mediators and altered levels of miRNAs enhance osteoclastogenesis and reduce osteoblastogenesis through mechanisms involving the activation of MAPK and transcription factors. The present review summarizes the principal molecular mechanisms involved in the role of ROS and proinflammatory cytokines on osteoporosis. Moreover, it highlights the interplay among altered miRNA levels, oxidative stress, and an inflammatory state. In fact, ROS, by activating the transcriptional factors, can affect miRNA expression, and miRNAs can regulate ROS production and inflammatory processes. Therefore, the present review should help in identifying targets for the development of new therapeutic approaches to osteoporotic treatment and improve the quality of life of patients. 10.3390/ijms24043772
Mesenchymal stem/stromal cells-derived exosomes for osteoporosis treatment. World journal of stem cells Osteoporosis is a systemic bone disease, which leads to decreased bone mass and an increased risk of fragility fractures. Currently, there are many anti-resorption drugs and osteosynthesis drugs, which are effective in the treatment of osteoporosis, but their usage is limited due to their contraindications and side effects. In regenerative medicine, the unique repair ability of mesenchymal stem cells (MSCs) has been favored by researchers. The exosomes secreted by MSCs have signal transduction and molecular delivery mechanisms, which may have therapeutic effects. In this review, we describe the regulatory effects of MSCs-derived exosomes on osteoclasts, osteoblasts, and bone immunity. We aim to summarize the preclinical studies of exosome therapy in osteoporosis. Furthermore, we speculate that exosome therapy can be a future direction to improve bone health. 10.4252/wjsc.v15.i3.83
Prospect of Stem Cell Therapy and Regenerative Medicine in Osteoporosis. Frontiers in endocrinology The field of cell therapy and regenerative medicine can hold the promise of restoring normal tissues structure and function. Additionally, the main targets of stem cell-based therapies are chronic diseases and lifelong disabilities without definite cures such as osteoporosis. Osteoporosis as one of the important causes of morbidity in older men and post-menopausal women is characterized by reduced bone quantity or skeletal tissue atrophy that leads to an increased risk of osteoporotic fractures. The common therapeutic methods for osteoporosis only can prevent the loss of bone mass and recover the bone partially. Nevertheless, stem cell-based therapy is considered as a new approach to regenerate the bone tissue. Herein, mesenchymal stem cells as pivotal candidates for regenerative medicine purposes especially bone regeneration are the most common type of cells with anti-inflammatory, immune-privileged potential, and less ethical concerns than other types of stem cells which are investigated in osteoporosis. Based on several findings, the mesenchymal stem cells effectiveness near to a great extent depends on their secretory function. Indeed, they can be involved in the establishment of normal bone remodeling via initiation of specific molecular signaling pathways. Accordingly, the aim herein was to review the effects of stem cell-based therapies in osteoporosis. 10.3389/fendo.2020.00430
Diagnosis and Management of Osteoporosis: A Comprehensive Review of Guidelines. Obstetrical & gynecological survey Importance:Osteoporosis causes increased morbidity and mortality, and thus poses a significant economic burden to the health systems worldwide. Objective:The aim of this study was to review and compare the most recently published major guidelines on diagnosis and management of this common medical entity. Evidence Acquisition:A thorough comparative review of the most influential guidelines from the RACGP (Royal Australian College of General Practitioners), the ESCEO-IOF (European Society for Clinical and Economic Aspects of Osteoporosis-International Osteoporosis Foundation), the NOGG (National Osteoporosis Guideline Group), the NAMS (North American Menopause Society), the ES (Endocrine Society), and the ACOG (American College of Obstetricians and Gynecologists) was conducted. Results:The reviewed guidelines generally agree on the definition, the criteria, and investigations used to diagnose osteoporosis. They also concur regarding the risk factors for osteoporosis and the suggested lifestyle modifications (calcium and vitamin D intake, normal body weight, reduction of alcohol consumption, and smoking cessation). However, there is lack of consensus on indications for fracture risk assessment in the general population and the exact indications for bone mineral density assessment. Referral to a bone specialist is reserved for complex cases of osteoporosis (NOGG, NAMS, and ACOG) or in case of inadequate access to care (RACGP). The use of hip protectors to reduce the risk of fractures is supported by RACGP, NOGG, and NAMS, solely for high-risk elderly patients in residential care settings. All guidelines reviewed recognize the efficacy of the pharmacologic agents (ie, bisphosphonates, denosumab, hormone therapy, and parathyroid hormone analogs). Nonetheless, recommendations regarding monitoring of pharmacotherapy differ, primarily in the case of bisphosphonates. The proposed intervals of repeat bone mineral density testing after initiation of drug therapy are set at 2 years (RACGP), 1-3 years (NAMS, ES, and ACOG), or 3-5 years (ESCEO-IOF and NOGG). All guidelines agree upon the restricted use of bone turnover markers only in bone specialist centers for treatment monitoring purposes. Finally, the definition of treatment failure varies among the reviewed guidelines. Conclusions:Osteoporosis is a distressing condition for women, mainly those of postmenopausal age. Thus, it seems of paramount importance to develop consistent international practice protocols for more cost-effective diagnostic and management techniques, in order to improve women's quality of life. 10.1097/OGX.0000000000001181
Osteoporosis and Fragility Fractures: currently available pharmacological options and future directions. Best practice & research. Clinical rheumatology Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. The average lifetime risk of a 50-year-old woman to suffer a fracture of the spine, hip, proximal humerus, or distal forearm has been estimated at close to 50%. In general, pharmacological treatment is recommended in patients who suffered a fragility fracture because their risk of suffering a subsequent fracture is increased dramatically. Therefore, many guidelines recommend pharmacological treatment in patients without a prevalent fracture if their fracture probability is comparable to or higher than that of a person of the same age with a prevalent fracture. The present review aims to highlight currently available pharmacological treatment options and their antifracture efficacy including safety aspects. Drug classes discussed comprise bisphosphonates, selective estrogen receptor modulators, parathyroid hormone peptides and derivatives, humanized monoclonal antibodies, and estrogens and gestagens and their combinations. Furthermore, a brief glimpse is provided into a potentially promising treatment option that involves mesenchymal stem cells. 10.1016/j.berh.2022.101780
A Mini Review on Osteoporosis: From Biology to Pharmacological Management of Bone Loss. Journal of clinical medicine Osteoporosis refers to excessive bone loss as reflected by the deterioration of bone mass and microarchitecture, which compromises bone strength. It is a complex multifactorial endocrine disease. Its pathogenesis relies on the presence of several endogenous and exogenous risk factors, which skew the physiological bone remodelling to a more catabolic process that results in net bone loss. This review aims to provide an overview of osteoporosis from its biology, epidemiology and clinical aspects (detection and pharmacological management). The review will serve as an updated reference for readers to understand the basics of osteoporosis and take action to prevent and manage this disease. 10.3390/jcm11216434
The effect of cytokines on osteoblasts and osteoclasts in bone remodeling in osteoporosis: a review. Frontiers in immunology The complicated connections and cross talk between the skeletal system and the immune system are attracting more attention, which is developing into the field of Osteoimmunology. In this field, cytokines that are among osteoblasts and osteoclasts play a critical role in bone remodeling, which is a pathological process in the pathogenesis and development of osteoporosis. Those cytokines include the tumor necrosis factor (TNF) family, the interleukin (IL) family, interferon (IFN), chemokines, and so on, most of which influence the bone microenvironment, osteoblasts, and osteoclasts. This review summarizes the effect of cytokines on osteoblasts and osteoclasts in bone remodeling in osteoporosis, aiming to providing the latest reference to the role of immunology in osteoporosis. 10.3389/fimmu.2023.1222129
Epigenetic Regulation in Mesenchymal Stem Cell Aging and Differentiation and Osteoporosis. Wang Ruoxi,Wang Yu,Zhu Lisha,Liu Yan,Li Weiran Stem cells international Mesenchymal stem cells (MSCs) are a reliable source for cell-based regenerative medicine owing to their multipotency and biological functions. However, aging-induced systemic homeostasis disorders and cell culture passaging induce a functional decline of MSCs, switching MSCs to a senescent status with impaired self-renewal capacity and biased differentiation tendency. MSC functional decline accounts for the pathogenesis of many diseases and, more importantly, limits the large-scale applications of MSCs in regenerative medicine. Growing evidence implies that epigenetic mechanisms are a critical regulator of the differentiation programs for cell fate and are subject to changes during aging. Thus, we here review epigenetic dysregulations that contribute to MSC aging and osteoporosis. Comprehending detailed epigenetic mechanisms could provide us with a novel horizon for dissecting MSC-related pathogenesis and further optimizing MSC-mediated regenerative therapies. 10.1155/2020/8836258
Sirt1: An Increasingly Interesting Molecule with a Potential Role in Bone Metabolism and Osteoporosis. Biomolecules Osteoporosis (OP) is a common metabolic bone disease characterized by low bone mass, decreased bone mineral density, and degradation of bone tissue microarchitecture. However, our understanding of the mechanisms of bone remodeling and factors affecting bone mass remains incomplete. Sirtuin1 (SIRT1) is a nicotinamide adenine dinucleotide-dependent deacetylase that regulates a variety of cellular metabolisms, including inflammation, tumorigenesis, and bone metabolism. Recent studies have emphasized the important role of SIRT1 in bone homeostasis. This article reviews the role of SIRT1 in bone metabolism and OP and also discusses therapeutic strategies and future research directions for targeting SIRT1. 10.3390/biom14080970
An updated overview of the search for biomarkers of osteoporosis based on human proteomics. Journal of orthopaedic translation Osteoporosis is a chronic metabolic disease that increases bone fragility and, leads to severe osteoporotic fractures. In recent years, the use of high-throughput omics to explore physiological and pathological biomarkers related to bone metabolism has gained popularity. In this review, we first briefly review the technical approaches of proteomics. Additionally, we summarize the relevant literature in the last decade to provide a comprehensive overview of advances in human proteomics related to osteoporosis. We describe the specific roles of various proteins related to human bone metabolism, highlighting their potential as biomarkers for risk assessment, early diagnosis and disease course monitoring in osteoporosis. Finally, we outline the main challenges currently faced by human proteomics in the field of osteoporosis and offer suggestions to address these challenges, to inspire the search for novel osteoporosis biomarkers and a foundation for their clinical translation. In conclusion, proteomics is a powerful tool for discovering osteoporosis-related biomarkers, which can not only provide risk assessment, early diagnosis and disease course monitoring, but also reveal the underlying mechanisms of disease and provide key information for personalized treatment. The translational potential of this article:This review provides an insightful summary of recent human-based studies on osteoporosis-associated proteomics, which can aid the search for novel osteoporosis biomarkers based on human proteomics and the clinical translation of research results. 10.1016/j.jot.2024.08.015
Insights into the Role of Macrophage Polarization in the Pathogenesis of Osteoporosis. Oxidative medicine and cellular longevity Millions of people worldwide suffer from osteoporosis, which causes bone fragility and increases the risk of fractures. Osteoporosis is closely related to the inhibition of osteogenesis and the enhancement of osteoclastogenesis. In addition, chronic inflammation and macrophage polarization may contribute to osteoporosis as well. Macrophages, crucial to inflammatory responses, display different phenotypes under the control of microenvironment. There are two major phenotypes, classically activated macrophages (M1) and alternatively activated macrophages (M2). Generally, M1 macrophages mainly lead to bone resorption, while M2 macrophages result in osteogenesis. M1/M2 ratio reflects the "fluid" state of macrophage polarization, and the imbalance of M1/M2 ratio may cause disease such as osteoporosis. Additionally, antioxidant drugs, such as melatonin, are applied to change the state of macrophage polarization and to treat osteoporosis. In this review, we introduce the mechanisms of macrophage polarization-mediated bone resorption and bone formation and the contribution to the clinical strategies of osteoporosis treatment. 10.1155/2022/2485959
NLRP3 Inflammasome: A New Target for Prevention and Control of Osteoporosis? Jiang Na,An Jinyang,Yang Kuan,Liu Jinjin,Guan Conghui,Ma Chengxu,Tang Xulei Frontiers in endocrinology Osteoporosis is a systemic bone metabolism disease that often causes complications, such as fractures, and increases the risk of death. The nucleotide-binding oligomerization domain-like-receptor family pyrin domain-containing 3 (NLRP3) inflammasome is an intracellular multiprotein complex that regulates the maturation and secretion of Caspase-1 dependent proinflammatory cytokines interleukin (IL)-1β and IL-18, mediates inflammation, and induces pyroptosis. The chronic inflammatory microenvironment induced by aging or estrogen deficiency activates the NLRP3 inflammasome, promotes inflammatory factor production, and enhances the inflammatory response. We summarize the related research and demonstrate that the NLRP3 inflammasome plays a vital role in the pathogenesis of osteoporosis by affecting the differentiation of osteoblasts and osteoclasts. IL-1β and IL-18 can accelerate osteoclast differentiation by expanding inflammatory response, and can also inhibit the expression of osteogenic related proteins or transcription factors. and experiments showed that the overexpression of NLRP3 protein was closely related to aggravated bone resorption and osteogenesis deficiency. In addition, abnormal activation of NLRP3 inflammasome can not only produce inflammation, but also lead to pyroptosis and dysfunction of osteoblasts by upregulating the expression of Caspase-1 and gasdermin D (GSDMD). In conclusion, NLRP3 inflammasome overall not only accelerates bone resorption, but also inhibits bone formation, thus increasing the risk of osteoporosis. Thus, this review highlights the recent studies on the function of NLRP3 inflammasome in osteoporosis, provides information on new strategies for managing osteoporosis, and investigates the ideal therapeutic target to treat osteoporosis. 10.3389/fendo.2021.752546
The emerging role of microRNAs in bone remodeling and its therapeutic implications for osteoporosis. Feng Qianyun,Zheng Sheng,Zheng Jia Bioscience reports Osteoporosis, a common and multifactorial disease, is influenced by genetic factors and environments. However, the pathogenesis of osteoporosis has not been fully elucidated yet. Recently, emerging evidence suggests that epigenetic modifications may be the underlying mechanisms that link genetic and environmental factors with increased risks of osteoporosis and bone fracture. MicroRNA (miRNA), a major category of small noncoding RNA with 20-22 bases in length, is recognized as one important epigenetic modification. It can mediate post-transcriptional regulation of target genes with cell differentiation and apoptosis. In this review, we aimed to profile the role of miRNA in bone remodeling and its therapeutic implications for osteoporosis. A deeper insight into the role of miRNA in bone remodeling and osteoporosis can provide unique opportunities to develop a novel diagnostic and therapeutic approach of osteoporosis. 10.1042/BSR20180453
Cell life-or-death events in osteoporosis: All roads lead to mitochondrial dynamics. Pharmacological research Mitochondria exhibit heterogeneous shapes and networks within and among cell types and tissues, also in normal or osteoporotic bone tissues with complex cell types. This dynamic characteristic is determined by the high plasticity provided by mitochondrial dynamics and is stemmed from responding to the survival and functional requirements of various bone cells in a specific microenvironments. In contrast, mitochondrial dysfunction, induced by dysregulation of mitochondrial dynamics, may act as a trigger of cell death signals, including common apoptosis and other forms of programmed cell death (PCD). These PCD processes consisting of tightly structured cascade gene expression events, can further influence the bone remodeling by facilitating the death of various bone cells. Mitochondrial dynamics, therefore, drive the bone cells to stand at the crossroads of life and death by integrating external signals and altering metabolism, shape, and signal-response properties of mitochondria. This implies that targeting mitochondrial dynamics displays significant potential in treatment of osteoporosis. Considerable effort has been made in osteoporosis to emphasize the parallel roles of mitochondria in regulating energy metabolism, calcium signal transduction, oxidative stress, inflammation, and cell death. However, the emerging field of mitochondrial dynamics-related PCD is not well understood. Herein, to bridge the gap, we outline the latest knowledge on mitochondrial dynamics regulating bone cell life or death during normal bone remodeling and osteoporosis. 10.1016/j.phrs.2024.107383
Osteoporosis and the Potential of Cell-Based Therapeutic Strategies. Macías Iratxe,Alcorta-Sevillano Natividad,Rodríguez Clara I,Infante Arantza International journal of molecular sciences Osteoporosis, the most common chronic metabolic bone disease, is characterized by low bone mass and increased bone fragility. Nowadays more than 200 million individuals are suffering from osteoporosis and still the number of affected people is dramatically increasing due to an aging population and longer life, representing a major public health problem. Current osteoporosis treatments are mainly designed to decrease bone resorption, presenting serious adverse effects that limit their safety for long-term use. Numerous studies with mesenchymal stem cells (MSCs) have helped to increase the knowledge regarding the mechanisms that underlie the progression of osteoporosis. Emerging clinical and molecular evidence suggests that inflammation exerts a significant influence on bone turnover, thereby on osteoporosis. In this regard, MSCs have proven to possess broad immunoregulatory capabilities, modulating both adaptive and innate immunity. Here, we will discuss the role that MSCs play in the etiopathology of osteoporosis and their potential use for the treatment of this disease. 10.3390/ijms21051653
Role of bone-forming agents in the management of osteoporosis. McClung Michael R Aging clinical and experimental research Recent evidence confirms the superiority of osteoanabolic therapy compared to anti-remodeling drugs for rapid improvement in bone density and fracture risk reduction, providing strong justification for the use of these anabolic agents as the initial therapy in high-risk patients, to be followed by anti-remodeling therapy. This review will highlight the results of recent studies and define the current status of osteoanabolic therapy for osteoporosis. 10.1007/s40520-020-01708-8
The role of lipid metabolism in osteoporosis: Clinical implication and cellular mechanism. Genes & diseases In recent years, researchers have become focused on the relationship between lipids and bone metabolism balance. Moreover, many diseases related to lipid metabolism disorders, such as nonalcoholic fatty liver disease, atherosclerosis, obesity, and menopause, are associated with osteoporotic phenotypes. It has been clinically observed in humans that these lipid metabolism disorders promote changes in osteoporosis-related indicators bone mineral density and bone mass. Furthermore, similar osteoporotic phenotype changes were observed in high-fat and high-cholesterol-induced animal models. Abnormal lipid metabolism (such as increased oxidized lipids and elevated plasma cholesterol) affects bone microenvironment homeostasis via cross-organ communication, promoting differentiation of mesenchymal stem cells to adipocytes, and inhibiting commitment towards osteoblasts. Moreover, disturbances in lipid metabolism affect the bone metabolism balance by promoting the secretion of cytokines such as receptor activator of nuclear factor-kappa B ligand by osteoblasts and stimulating the differentiation of osteoclasts. Conclusively, this review addresses the possible link between lipid metabolism disorders and osteoporosis and elucidates the potential modulatory mechanisms and signaling pathways by which lipid metabolism affects bone metabolism balance. We also summarize the possible approaches and prospects of intervening lipid metabolism for osteoporosis treatment. 10.1016/j.gendis.2023.101122
From gut to bone: deciphering the impact of gut microbiota on osteoporosis pathogenesis and management. Frontiers in cellular and infection microbiology Osteoporosis (OP) is characterized by decreased bone mineral density (BMD) and increased fracture risk, poses a significant global health burden. Recent research has shed light on the bidirectional relationship between gut microbiota (GM) and bone health, presenting a novel avenue for understanding OP pathogenesis and developing targeted therapeutic interventions. This review provides a comprehensive overview of the GM-bone axis, exploring the impact of GM on OP development and management. We elucidate established risk factors and pathogenesis of OP, delve into the diversity and functional changes of GM in OP. Furthermore, we examine experimental evidence and clinical observations linking alterations in GM composition or function with variations in BMD and fracture risk. Mechanistic insights into microbial mediators of bone health, such as microbial metabolites and products, are discussed. Therapeutic implications, including GM-targeted interventions and dietary strategies, are also explored. Finally, we identify future research directions and challenges in translating these findings into clinical practice. 10.3389/fcimb.2024.1416739
V-ATPases and osteoclasts: ambiguous future of V-ATPases inhibitors in osteoporosis. Theranostics Vacuolar ATPases (V-ATPases) play a critical role in regulating extracellular acidification of osteoclasts and bone resorption. The deficiencies of subunit a3 and d2 of V-ATPases result in increased bone density in humans and mice. One of the traditional drug design strategies in treating osteoporosis is the use of subunit a3 inhibitor. Recent findings connect subunits H and G1 with decreased bone density. Given the controversial effects of ATPase subunits on bone density, there is a critical need to review the subunits of V-ATPase in osteoclasts and their functions in regulating osteoclasts and bone remodeling. In this review, we comprehensively address the following areas: information about all V-ATPase subunits and their isoforms; summary of V-ATPase subunits associated with human genetic diseases; V-ATPase subunits and osteopetrosis/osteoporosis; screening of all V-ATPase subunits variants in GEFOS data and in-house data; spectrum of V-ATPase subunits during osteoclastogenesis; direct and indirect roles of subunits of V-ATPases in osteoclasts; V-ATPase-associated signaling pathways in osteoclasts; interactions among V-ATPase subunits in osteoclasts; osteoclast-specific V-ATPase inhibitors; perspective of future inhibitors or activators targeting V-ATPase subunits in the treatment of osteoporosis. 10.7150/thno.28391
Insights into the Mechanism of Osteoporosis and the Available Treatment Options. Current pharmaceutical biotechnology Osteoporosis, one of the most prevalent bone illnesses, majorly affects postmenopausal women and men over 50 years of age. Osteoporosis is associated with an increased susceptibility to fragility fractures and can result in persistent pain and significant impairment in affected individuals. The primary method for diagnosing osteoporosis involves the assessment of bone mineral density (BMD) through the utilisation of dual energy x-ray absorptiometry (DEXA). The integration of a fracture risk assessment algorithm with bone mineral density (BMD) has led to significant progress in the diagnosis of osteoporosis. Given that osteoporosis is a chronic condition and multiple factors play an important role in maintaining bone mass, comprehending its underlying mechanism is crucial for developing more effective pharmaceutical interventions for the disease. The effective management of osteoporosis involves the utilisation of appropriate pharmacological agents in conjunction with suitable dietary interventions and lifestyle modifications. This review provides a comprehensive understanding of the types of osteoporosis and elucidates the currently available pharmacological treatment options and their related mechanism of action and usage. 10.2174/0113892010273783231027073117
Recent advances in senescence-associated secretory phenotype and osteoporosis. Heliyon The worldwide elderly population is on the rise, and aging is a major osteoporosis risk factor. Senescent cells accumulation can have a detrimental effect the body as we age. The senescence-associated secretory phenotype (SASP), an essential cellular senescence hallmark, is an important mechanism connecting cellular senescence to osteoporosis. This review describes in detail the characteristics of SASPs and their regulatory agencies, and shed fresh light on how SASPs from different senescent cells contribute to osteoporosis development. Furthermore, we summarized various innovative therapy techniques that target SASPs to lower the burden of osteoporosis in the elderly and discussed the potential challenges of SASPs-based therapy for osteoporosis as a new clinical trial. 10.1016/j.heliyon.2024.e25538
Noncoding RNAs: the crucial role of programmed cell death in osteoporosis. Frontiers in cell and developmental biology Osteoporosis is the most common skeletal disease characterized by an imbalance between bone resorption and bone remodeling. Osteoporosis can lead to bone loss and bone microstructural deterioration. This increases the risk of bone fragility and fracture, severely reducing patients' mobility and quality of life. However, the specific molecular mechanisms involved in the development of osteoporosis remain unclear. Increasing evidence suggests that multiple noncoding RNAs show differential expression in the osteoporosis state. Meanwhile, noncoding RNAs have been associated with an increased risk of osteoporosis and fracture. Noncoding RNAs are an important class of factors at the level of gene regulation and are mainly involved in cell proliferation, cell differentiation, and cell death. Programmed cell death is a genetically-regulated form of cell death involved in regulating the homeostasis of the internal environment. Noncoding RNA plays an important role in the programmed cell death process. The exploration of the noncoding RNA-programmed cell death axis has become an interesting area of research and has been shown to play a role in many diseases such as osteoporosis. In this review, we summarize the latest findings on the mechanism of noncoding RNA-mediated programmed cell death on bone homeostasis imbalance leading to osteoporosis. And we provide a deeper understanding of the role played by the noncoding RNA-programmed cell death axis at the gene regulatory level of osteoporosis. We hope to provide a unique opportunity to develop novel diagnostic and therapeutic approaches for osteoporosis. 10.3389/fcell.2024.1409662
Current status and dilemmas of osteoporosis screening tools: A narrative review. Clinical nutrition ESPEN OBJECTIVE:This review aims to explore the strengths and dilemmas of existing osteoporosis screening tools and suggest possible ways of optimization, in addition to exploring the potential of AI-integrated X-ray imaging in osteoporosis screening, especially its ability to improve accuracy and applicability to different populations. To break through the dilemma of low accessibility, poor clinical translation, complexity of use, and apparent limitations of screening results of existing osteoporosis screening tools. DATA SOURCES:A comprehensive literature search was performed using PubMed, Web of Science, and CNKI databases. The search included articles published between 2000 and 2023, focusing on studies evaluating osteoporosis screening tools, Artificial intelligence applications in medical imaging, and implementing AI technologies in clinical settings. STUDY SELECTION:The Osteoporosis Risk Assessment Tool for Asians (OSTA), the Simple Calculated Osteoporosis Risk Estimator (SCORE), age, body size, one or no estrogen ever (ABONE), and the Osteoporosis Risk Index (OSIRIS) are the six commonly used screening tools for osteoporosis that are discussed in this review. In addition, the performance of AI-integrated imaging systems is explored in light of relevant research advances in Artificial intelligence in osteoporosis screening. Studies of the use of these tools in different populations and their advantages and disadvantages were included in the selection criteria. RESULTS:The results highlight that AI-integrated X-ray imaging technologies offer significant improvements over traditional osteoporosis screening tools. Artificial intelligence systems demonstrated higher accuracy by incorporating complex clinical data and providing personalized assessments for diverse populations. The studies showed that AI-driven imaging could enhance sensitivity and specificity, particularly in detecting early-stage bone density loss in patients with complex clinical profiles. The findings also suggest that Artificial intelligence technologies have the potential to be effectively applied in resource-limited settings through the use of mobile devices and remote diagnostics. CONCLUSIONS:AI-integrated X-ray imaging technology significantly advances osteoporosis screening, offering more accurate and adaptable solutions than traditional tools. Its ability to incorporate complex clinical data and apply it across various demographic groups makes it particularly promising in diverse and resource-limited environments. Further research is needed to explore the full potential of AI in enhancing screening accessibility and effectiveness, particularly in underserved populations. 10.1016/j.clnesp.2024.10.001
Use of bone turnover markers in the management of osteoporosis. Jain Sumeet,Camacho Pauline Current opinion in endocrinology, diabetes, and obesity PURPOSE OF REVIEW:Osteoporosis is a common public health problem that is often undertreated and underdiagnosed. The clinical management of osteoporosis is often reactionary to devastating fracture events. Bone turnover markers may improve the ease and rapidity at which osteoporosis is monitored and treated. Bone turnover markers are biochemical byproducts of bone formation or bone resorption. The clinical use of bone turnover markers is limited by significant preanalytical variability. Effective interpretation of bone turnover markers requires a detailed understanding of the variables that can affect their responses to osteoporosis treatment and monitoring. RECENT FINDINGS:Progress is continuously being made on the standardization of bone turnover markers. The literature on the response of bone turnover markers to unique clinical situations is expanding. Data for evidence-based reference intervals for bone turnover markers has increased. Variables that affect the appropriate timing of lab draws like diurnal variation, postprandial status, exercise and alcohol use have been described. Studies examining the expected response of bone turnover markers to treatments of osteoporosis and other medications that affect bone health continue to increase. SUMMARY:Bone turnover markers have clinical utility in the comprehensive evaluation of osteoporosis. When interpreted with caution and with a good understanding of their natural variability, bone turnover markers provide information that supplements osteoporosis management and provides useful clinical information about conditions that alter bone turnover. 10.1097/MED.0000000000000446
New Developments in Fracture Risk Assessment for Current Osteoporosis Reports. Leslie William D,Morin Suzanne N Current osteoporosis reports PURPOSE OF REVIEW:Identifying individuals at high fracture risk can be used to target those likely to derive the greatest benefit from treatment. This narrative review examines recent developments in using specific risk factors used to assess fracture risk, with a focus on publications in the last 3 years. RECENT FINDINGS:There is expanding evidence for the recognition of individual clinical risk factors and clinical use of composite scores in the general population. Unfortunately, enthusiasm is dampened by three pragmatic randomized trials that raise questions about the effectiveness of widespread population screening using clinical fracture prediction tools given suboptimal participation and adherence. There have been refinements in risk assessment in special populations: men, patients with diabetes, and secondary causes of osteoporosis. New evidence supports the value of vertebral fracture assessment (VFA), high resolution peripheral quantitative CT (HR-pQCT), opportunistic screening using CT, skeletal strength assessment with finite element analysis (FEA), and trabecular bone score (TBS). The last 3 years have seen important developments in the area of fracture risk assessment, both in the research setting and translation to clinical practice. The next challenge will be incorporating these advances into routine work flows that can improve the identification of high risk individuals at the population level and meaningfully impact the ongoing crisis in osteoporosis management. 10.1007/s11914-020-00590-7
The therapeutic potential of mesenchymal stem cells in treating osteoporosis. Biological research Osteoporosis (OP), a common systemic metabolic bone disease, is characterized by low bone mass, increasing bone fragility and a high risk of fracture. At present, the clinical treatment of OP mainly involves anti-bone resorption drugs and anabolic agents for bone, but their long-term use can cause serious side effects. The development of stem cell therapy and regenerative medicine has provided a new approach to the clinical treatment of various diseases, even with a hope for cure. Recently, the therapeutic advantages of the therapy have been shown for a variety of orthopedic diseases. However, these stem cell-based researches are currently limited to animal models; the uncertainty regarding the post-transplantation fate of stem cells and their safety in recipients has largely restricted the development of human clinical trials. Nevertheless, the feasibility of mesenchymal stem cells to treat osteoporotic mice has drawn a growing amount of intriguing attention from clinicians to its potential of applying the stem cell-based therapy as a new therapeutic approach to OP in the future clinic. In the current review, therefore, we explored the potential use of mesenchymal stem cells in human OP treatment. 10.1186/s40659-021-00366-y
An update on the role of ferroptosis in the pathogenesis of osteoporosis. EFORT open reviews Ferroptosis is a novel form of programmed cell death, distinguished from apoptosis, autophagy, and programmed necrosis and has received much attention since it was defined in 2012. Ferroptotic cells physiologically exhibit iron metabolism dysregulation, oxidative stress, and lipid peroxidation. Morphologically, they show plasma membrane disruption, cytoplasmic swelling, and mitochondrial condensation. Osteoporosis is taken more and more seriously as the proportion of the aging population continues to increase globally. Interestingly, ferroptosis has been demonstrated to be involved in the development and progression of osteoporosis in many extant studies. The review summarizes iron metabolism, lipid peroxidation, and the different regulatory signals in ferroptosis. Changes in signaling mechanisms within osteoblasts, osteoclasts, and osteocytes after ferroptosis occur are explained here. Studies showed ferroptosis play an important role in different osteoporosis models (diabetes osteoporosis, postmenopausal osteoporosis, glucocorticoid-induced osteoporosis). Inhibitors and EC (Exos) targeting ferroptosis could ameliorate bone loss in osteoporotic mice by protecting cells against lipid peroxidation. Shortly, we hope that more effective and appropriate clinical therapy means will be utilized in the treatment of osteoporosis. 10.1530/EOR-23-0148
Wnt Antagonists in Hematopoietic and Immune Cell Fate: Implications for Osteoporosis Therapies. Chicana Betsabel,Donham Cristine,Millan Alberto J,Manilay Jennifer O Current osteoporosis reports PURPOSE OF REVIEW:We reviewed the current literature on the roles of the Wnt antagonists sclerostin (Sost) and sclerostin-containing domain protein 1 (Sostdc1) on bone homeostasis, the relationship of the hypoxia-inducible factor (Hif) and von Hippel-Lindau (Vhl) pathways on Sost expression, and how changes in bone induced by depletion of Sost, Sostdc1, and Vhl affect hematopoietic cells. RECENT FINDINGS:B cell development is adversely affected in Sost-knockout mice and is more severely affected in Vhl-knockout mice. Inflammation in the Sost bone microenvironment could alter hematopoietic stem cell behavior. Sostdc1 mice display defects in natural killer cell development and cytotoxicity. Depletion of Sost and Sostdc1 have effects on immune cell function that warrant investigation in patients receiving Wnt antagonist-depleting therapies for treatment of bone diseases. Additional clinical applications for manipulation of Wnt antagonists include cancer immunotherapies, stem cell transplantation, and directed differentiation to immune lineages. 10.1007/s11914-019-00503-3
Wnt/β-catenin signaling pathway: proteins' roles in osteoporosis and cancer diseases and the regulatory effects of natural compounds on osteoporosis. Molecular medicine (Cambridge, Mass.) Osteoblasts are mainly derived from mesenchymal stem cells in the bone marrow. These stem cells can differentiate into osteoblasts, which have the functions of secreting bone matrix, promoting bone formation, and participating in bone remodeling. The abnormality of osteoblasts can cause a variety of bone-related diseases, including osteoporosis, delayed fracture healing, and skeletal deformities. In recent years, with the side effects caused by the application of PTH drugs, biphosphonate drugs, and calmodulin drugs, people have carried out more in-depth research on the mechanism of osteoblast differentiation, and are actively looking for natural compounds for the treatment of osteoporosis. The Wnt/β-catenin signaling pathway is considered to be one of the important pathways of osteoblast differentiation, and has become an important target for the treatment of osteoporosis. The Wnt/β-catenin signaling pathway, whether its activation is enhanced or its expression is weakened, will cause a variety of diseases including tumors. This review will summarize the effect of Wnt/β-catenin signaling pathway on osteoblast differentiation and the correlation between the related proteins in the pathway and human diseases. At the same time, the latest research progress of natural compounds targeting Wnt/β-catenin signaling pathway against osteoporosis is summarized. 10.1186/s10020-024-00957-x
Effects of miRNAs, lncRNAs and circRNAs on osteoporosis as regulatory factors of bone homeostasis (Review). Li Zhichao,Xue Haipeng,Tan Guoqing,Xu Zhanwang Molecular medicine reports Osteoporosis is a common metabolic bone disorder typically characterized by decreased bone mass and an increased risk of fracture. At present, the detailed molecular mechanism underlying the development of osteoporosis remains to be elucidated. Accumulating evidence shows that non‑coding (nc)RNAs, such as microRNAs (miRNAs), long ncRNAs (lncRNAs) and circular RNAs (circRNAs), play significant roles in osteoporosis through the post‑transcriptional regulation of gene expression as regulatory factors. Previous studies have demonstrated that ncRNAs participate in maintaining bone homeostasis by regulating physiological and developmental processes in osteoblasts, osteoclasts and bone marrow stromal cells. In the present review, the latest research investigating the involvement of miRNAs, lncRNAs and circRNAs in regulating the differentiation, proliferation, apoptosis and autophagy of cells that maintain the bone microenvironment in osteoporosis is summarized. Deeper insight into the aspects of osteoporosis pathogenesis involving the deregulation of ncRNAs could facilitate the development of therapeutic approaches for osteoporosis. 10.3892/mmr.2021.12428
Exploring the regulatory mechanism of osteoporosis based on intestinal flora: A review. Medicine Osteoporosis is 1 of the common diseases of bone metabolism in clinic. With the aging of the population in China, osteoporosis is becoming more and more serious, and it has become 1 of the major public health problems. However, traditional therapies, such as calcium therapy and estrogen therapy, can cause serious adverse effects and damage to the body when ingested over a long period of time. Therefore, there is an urgent need to explore alternative therapies with less side effects in clinical practice. Intestinal flora is a hot topic of research in recent years. It has been studied in inflammatory bowel disease, diabetes, depression and so on. Recently, intestinal flora has received increasing attention in the pathways regulating bone metabolism. This paper contains a review of recent studies related to osteoporosis and gut flora in terms of its metabolites, immune, endocrine, and brain-gut axis pathways. The strong association between intestinal flora and bone metabolism suggests, to some extent, that intestinal flora can be a potential target for osteoporosis prevention and treatment, providing new ideas and therapies for the prevention and treatment of osteoporosis. 10.1097/MD.0000000000032499
Sirtuins: exploring next-gen therapeutics in the pathogenesis osteoporosis and associated diseases. Immunopharmacology and immunotoxicology OBJECTIVE:Osteoporosis poses a substantial public health challenge due to an ageing population and the lack of adequate treatment options. The condition is marked by a reduction in bone mineral density, resulting in an elevated risk of fractures. The reduction in bone density and strength, as well as musculoskeletal issues that come with aging, present a significant challenge for individuals impacted by these conditions, as well as the healthcare system worldwide. METHODS:Literature survey was conducted until May 2023 using databases such as Web of Science, PubMed, Scopus, and Google Scholar. RESULT:Sirtuins 1-7 (SIRT1-SIRT7), which are a group of Nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases, possess remarkable capabilities to increase lifespan and combat diseases related to aging. Research has demonstrated that these proteins play an important role in regular skeletal development and maintenance by directly impacting bone cells. Their dysfunction could be a factor in various bone conditions. Studies conducted on animals before clinical trials have shown that administering Sirtuins agonists to mice provides a safeguard against osteoporosis resulting from aging, menopause, and immobilization. These findings imply that Sirtuins may be a viable target for addressing the irregularity in bone remodeling and treating osteoporosis and other skeletal ailments. CONCLUSION:The purpose of this review was to present a thorough and current evaluation of the existing knowledge on Sirtuins biology, with a particular emphasis on their involvement in maintaining bone homeostasis and contributing to osteoporosis. Additionally, the review examines potential pharmacological interventions targeting Sirtuins for the treatment of osteoporosis. 10.1080/08923973.2024.2315418
From Genomics to Metabolomics: Molecular Insights into Osteoporosis for Enhanced Diagnostic and Therapeutic Approaches. Biomedicines Osteoporosis (OP) is a prevalent skeletal disorder characterized by decreased bone mineral density (BMD) and increased fracture risk. The advancements in omics technologies-genomics, transcriptomics, proteomics, and metabolomics-have provided significant insights into the molecular mechanisms driving OP. These technologies offer critical perspectives on genetic predispositions, gene expression regulation, protein signatures, and metabolic alterations, enabling the identification of novel biomarkers for diagnosis and therapeutic targets. This review underscores the potential of these multi-omics approaches to bridge the gap between basic research and clinical applications, paving the way for precision medicine in OP management. By integrating these technologies, researchers can contribute to improved diagnostics, preventative strategies, and treatments for patients suffering from OP and related conditions. 10.3390/biomedicines12102389
Current Status of the Diagnosis and Management of Osteoporosis. International journal of molecular sciences Osteoporosis has been defined as the silent disease of the 21st century, becoming a public health risk due to its severity, chronicity and progression and affecting mainly postmenopausal women and older adults. Osteoporosis is characterized by an imbalance between bone resorption and bone production. It is diagnosed through different methods such as bone densitometry and dual X-rays. The treatment of this pathology focuses on different aspects. On the one hand, pharmacological treatments are characterized by the use of anti-resorptive drugs, as well as emerging regenerative medicine treatments such as cell therapies and the use of bioactive hydrogels. On the other hand, non-pharmacological treatments are associated with lifestyle habits that should be incorporated, such as physical activity, diet and the cessation of harmful habits such as a high consumption of alcohol or smoking. This review seeks to provide an overview of the theoretical basis in relation to bone biology, the existing methods for diagnosis and the treatments of osteoporosis, including the development of new strategies. 10.3390/ijms23169465
Osteoporosis: Emerging targets on the classical signaling pathways of bone formation. European journal of pharmacology Osteoporosis is a multifaceted skeletal disorder characterized by reduced bone mass and structural deterioration, posing a significant public health challenge, particularly in the elderly population. Treatment strategies for osteoporosis primarily focus on inhibiting bone resorption and promoting bone formation. However, the effectiveness and limitations of current therapeutic approaches underscore the need for innovative methods. This review explores emerging molecular targets within crucial signaling pathways, including wingless/integrated (WNT), bone morphogenetic protein (BMP), hedgehog (HH), and Notch signaling pathway, to understand their roles in osteogenesis regulation. The identification of crosstalk targets between these pathways further enhances our comprehension of the intricate bone metabolism cycle. In summary, unraveling the molecular complexity of osteoporosis provides insights into potential therapeutic targets beyond conventional methods, offering a promising avenue for the development of new anabolic drugs. 10.1016/j.ejphar.2024.176574
Advances in the interaction between endoplasmic reticulum stress and osteoporosis. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie The endoplasmic reticulum (ER) is the main site for protein synthesis, folding, and secretion, and accumulation of the unfolded/misfolded proteins in the ER may induce ER stress. ER stress is an important participant in various intracellular signaling pathways. Prolonged- or high-intensity ER stress may induce cell apoptosis. Osteoporosis, characterized by imbalanced bone remodeling, is a global disease caused by many factors, such as ER stress. ER stress stimulates osteoblast apoptosis, increases bone loss, and promotes osteoporosis development. Many factors, such as the drug's adverse effects, metabolic disorders, calcium ion imbalance, bad habits, and aging, have been reported to activate ER stress, resulting in the pathological development of osteoporosis. Increasing evidence shows that ER stress regulates osteogenic differentiation, osteoblast activity, and osteoclast formation and function. Various therapeutic agents have been developed to counteract ER stress and thereby suppress osteoporosis development. Thus, inhibition of ER stress has become a potential target for the therapeutic management of osteoporosis. However, the in-depth understanding of ER stress in the pathogenesis of osteoporosis still needs more effort. 10.1016/j.biopha.2023.115134
Knowledge Mapping of Macrophages in Osteoporosis: A Bibliometric Analysis (1999-2023). Orthopaedic surgery BACKGROUND:Osteoporosis is a common metabolic disorder that significantly impacts quality of life in the elderly population. Macrophages play a crucial role in the development of osteoporosis by regulating bone metabolism through cytokine secretion. However, there is a lack of scholarly literature in the field of bibliometrics on this topic. OBJECTIVE:This study provides a detailed analysis of the research focus and knowledge structure of macrophage studies in osteoporosis using bibliometrics. METHODS:The scientific literature on macrophage research in the context of osteoporosis, retrieved from the Web of Science Core Collection (WoSCC) database spanning from January 1999 to December 2023, has been incorporated for bibliometric examination. The data is methodically analyzed and visually represented using analytical and visualization tools including VOSviewer, CiteSpace, Scimago Graphica, the Bibliometrix R package, and Pajek. RESULTS AND CONCLUSIONS:In the last quarter-century, there has been a consistent rise in the quantity of scholarly publications focusing on the relationship between macrophages and osteoporosis, resulting in a total of 1499 research documents. These studies have originated from 45 different countries, with China, South Korea, and the United States being the most prominent contributors, and the United States having the highest frequency of citations. Noteworthy research institutions involved in this field include Shanghai Jiao Tong University, Wonkwang University, Huazhong University of Science and Technology, and Seoul National University. The Journal of Bone and Mineral Research is widely regarded as the premier and most frequently referenced publication in the field. These publications involve the collaboration of 8744 authors, with Lee Myeung Su contributing the most articles, and Takayanagi being the most co-cited author. Key emerging research focal points are encapsulated in keywords such as "mTOR," "BMSCs," "bone regeneration," and "exosome." The relationships between exosome from macrophage sources and those from BMSCs, along with the regulatory role of the mTOR signaling pathway on macrophages, represent crucial directions for future development in this field. This study represents the inaugural comprehensive bibliometric analysis detailing trends and advancements in macrophage research within the osteoporosis domain. It delineates recent frontiers and hotspots, providing valuable insights for researchers in this particular area of study. 10.1111/os.14159
Exploring the Role of Hormones and Cytokines in Osteoporosis Development. Biomedicines The disease of osteoporosis is characterized by impaired bone structure and an increased risk of fractures. There is a significant impact of cytokines and hormones on bone homeostasis and the diagnosis of osteoporosis. As defined by the World Health Organization (WHO), osteoporosis is defined as having a bone mineral density (BMD) that is 2.5 standard deviations (SD) or more below the average for young and healthy women (T score < -2.5 SD). Cytokines and hormones, particularly in the remodeling of bone between osteoclasts and osteoblasts, control the differentiation and activation of bone cells through cytokine networks and signaling pathways like the nuclear factor kappa-B ligand (RANKL)/the receptor of RANKL (RANK)/osteoprotegerin (OPG) axis, while estrogen, parathyroid hormones, testosterone, and calcitonin influence bone density and play significant roles in the treatment of osteoporosis. This review aims to examine the roles of cytokines and hormones in the pathophysiology of osteoporosis, evaluating current diagnostic methods, and highlighting new technologies that could help for early detection and treatment of osteoporosis. 10.3390/biomedicines12081830
Recent advances in models for screening potential osteoporosis drugs. Merlotti D,Materozzi M,Picchioni T,Bianciardi S,Alessandri M,Nuti R,Gennari L Expert opinion on drug discovery INTRODUCTION:Osteoporosis is a growing health and health-economic problem due to the increased proportion of elderly people in the population. Basic and clinical advances in research over the past two decades have led to the development of different compounds with antiresorptive or anabolic activity on bone that improved substantially the management of patients with osteoporosis over calcitonin or estrogen replacement. New compounds are in preclinical and clinical development. Areas covered: In this review, the authors review the approaches for the preclinical and clinical development of antiresorptive and anabolic agents for osteoporosis, particularly focusing on the recent advances in technology and in the understanding of skeletal biology, together with their implications on novel osteoporosis drug discovery. Expert opinion: Based on the available evidence from the approved drugs for the treatment osteoporosis as well as from the different compounds under clinical development, it has become clear that long term nonclinical pharmacological studies with either bone quality and off-target effects as the main outcomes should be required for new drugs intended to treat osteoporosis. At the same time, basic and clinical advances in research have underlined the necessity to develop new technologies and new models for a thorough screening of the effects of new drugs on the different components of skeletal aging and bone fragility that cannot be assessed by bone mass measurement. 10.1080/17460441.2018.1480609
Osteoporosis treatment and pain relief: A scoping review. European journal of pain (London, England) BACKGROUND AND OBJECTIVE:Anti-osteoporosis (OP) drugs have been suggested to contribute to pain reduction during OP management. This scoping review aimed at mapping the literature on pain relief with anti-OP drugs in OP treatment. DATABASES AND DATA TREATMENT:Medline, Pubmed and Cochrane databases were searched by two reviewers with keywords combinations. Randomized controlled and real-life English studies, pain as an endpoint, antiosteoporosis drugs were inclusion criteria. Case reports, surveys, comment letters, conference abstracts, animal studies and grey literature were excluded. Predetermined data were extracted by two reviewers and disagreement solved through discussion. RESULTS:A total of 130 articles were identified, 31 publications were included, 12 randomized clinical trials and 19 observational studies. Pain reduction was assessed by different tools: Visual Analogue Scale, Verbal Rating Scale, Facial Scale or as a domain of quality of life questionnaires including Short form 8, 36, mini-OP, Japanese OP, Qualeffo, Roland Morris Disability questionnaires. Collective data show that anti-OP drugs may display an analgesic effect that may be linked to the local mode of action of drugs on bone and consecutive modulation of pain sensitization. The methodology of the studies showed a heterogeneity of endpoints, comparators, statistical approaches and follow-up duration. CONCLUSION:Considering the limitations of the literature, there is a need for more rigorous trials and larger real-life studies taking into account the recommendations published for research in rheumatology and in pain medicine. The identification of responders, patient subtypes, and of analgesic-effect doses would allow optimization and individualization for pain relief in patients with OP. SIGNIFICANCE STATEMENT:This scoping review shows that anti-OP drugs may improve pain and quality of life of patients with OP. The heterogeneity in design, choice of endpoints, methodology, comparators and follow-up duration of included randomized clinical trials and real-life studies does not allow so far to identify a predominant antiosteoporosis drug or an optimal dosage for pain relief. These gaps need to be addressed and warrant further research in the future for optimizing pain improvement in the course of OP drug treatment. 10.1002/ejp.2156
Stem Cell Interventions for Bone Healing: Fractures and Osteoporosis. Sanghani-Kerai Anita,McCreary Dara,Lancashire Henry,Osagie Liza,Coathup Melanie,Blunn Gordon Current stem cell research & therapy With the ageing population, musculoskeletal conditions are becoming more inherent. Delayed union is defined as a slower than normal fracture healing response, with no healing after 4 to 6 months; however, the union is anticipated given sufficient time. In the context of delayed/non-union, fragility fractures in osteoporotic populations carry significant patient morbidity and socioeconomic costs. Multiple mechanisms hinder fracture healing in osteoporotic patients, imbalanced bone remodelling leads to impaired bone microarchitecture due to reduced osteoblast number and activity and as such, callus formation is diminished. Since stem cells can self-renew and differentiate into various tissue lineages, they are becoming very popular in tissue regeneration in musculoskeletal conditions. In this review, we discuss the role of stem cells in physiological fracture healing and their potential therapeutic use following a fracture. We explore the potential of stem cells, the release of chemokines and cytokines to reduce fracture risk in osteoporosis. 10.2174/1574888X13666180410160511
The treatment gap: The missed opportunities for osteoporosis therapy. Fuggle Nicholas R,Curtis Beth,Clynes Michael,Zhang Jean,Ward Kate,Javaid Muhammad Kassim,Harvey Nicholas C,Dennison Elaine,Cooper Cyrus Bone Despite substantial advances in delineation of the epidemiology, pathophysiology, risk assessment and treatment of osteoporosis over the last three decades, a substantial proportion of men and women at high risk of fracture remain untreated - the so-called "treatment gap". This review summarises the important patient-, physician- and policyrelated causes of this treatment gap, before discussing in greater detail: (a) the evidence base for the efficacy of bisphosphonates in osteoporosis; (b) recent evidence relating to the adverse effects of this widely used therapeutic class, most notably atypical femoral fracture and osteonecrosis of the jaw; (c) available strategies to improve both secondary and primary prevention pathways for the management of this disorder. 10.1016/j.bone.2020.115833
Pyroptosis mediates osteoporosis via the inflammation immune microenvironment. Frontiers in immunology Osteoporosis represents a systemic imbalance in bone metabolism, augmenting the susceptibility to fractures among patients and emerging as a notable mortality determinant in the elderly population. It has evolved into a worldwide concern impacting the physical well-being of the elderly, imposing a substantial burden on both human society and the economy. Presently, the precise pathogenesis of osteoporosis remains inadequately characterized and necessitates further exploration. The advancement of osteoporosis is typically linked to the initiation of an inflammatory response. Cells in an inflammatory environment can cause inflammatory death including pyroptosis. Pyroptosis is a recently identified form of programmed cell death with inflammatory properties, mediated by the caspase and gasdermin families. It is regarded as the most inflammatory form of cell death in contemporary medical research. Under the influence of diverse cytokines, macrophages, and other immune cells may undergo pyroptosis, releasing inflammatory factors, such as IL-1β and IL-18. Numerous lines of evidence highlight the pivotal role of pyroptosis in the pathogenesis of inflammatory diseases, including cancer, intestinal disorders, hepatic conditions, and cutaneous ailments. Osteoporosis progression is frequently associated with inflammation; hence, pyroptosis may also play a role in the pathogenesis of osteoporosis to a certain extent, making it a potential target for treatment. This paper has provided a comprehensive summary of pertinent research concerning pyroptosis and its impact on osteoporosis. The notion proposing that pyroptosis mediates osteoporosis via the inflammatory immune microenvironment is advanced, and we subsequently investigate potential targets for treating osteoporosis through the modulation of pyroptosis. 10.3389/fimmu.2024.1371463
Osteoporosis: what the clinician needs to know? Balzano Rosario Francesco,Mattera Maria,Cheng Xiaoguang,Cornacchia Samantha,Guglielmi Giuseppe Quantitative imaging in medicine and surgery Osteoporosis is a common condition and an important cause of disability. For this reason, early detection of the disease and patients at higher risk of bone fractures is compulsory. In the recent years, conventional quantitative methods have been spreading for the diagnosis of osteoporosis; moreover, new improvements in computed tomography (CT) and magnetic resonance imaging (MRI) have been made in this field and imaging findings may correlate to the morphological and structural changes within the bone. 10.21037/qims.2018.02.05
Is there a role for essential fatty acids in osteoporosis? European journal of clinical nutrition Inflammatory markers are inversely associated with bone density, geometry, and strength in postmenopausal women, and elderly subjects suggesting that osteoporosis is a low-grade systemic inflammatory condition. But glucocorticoids that are potent anti-inflammatory compounds instead of arresting/preventing osteoporosis induce osteoporosis. These results indicate that IL-6 and TNF-α, post-menopausal state, and steroids produce osteoporosis by an unidentified mechanism. Pro-inflammatory cytokines, estrogen, and steroids bring about their actions by influencing the metabolism of essential fatty acids (EFAs). I propose that EFAs and their metabolites act as second messengers of actions of corticosteroids, cytokines, and estrogen. This implies that EFAs are of benefit in the prevention and management of osteoporosis. This argument is supported by the observation that plasma phospholipid content of unsaturated fatty acids is decreased in those with osteoporosis. The reports that long-chain metabolites of EFAs including arachidonic acid, docosahexaenoic acid and eicosapentaenoic acid, and lipoxin A4 are of benefit in the prevention and management of osteoporosis lends further support to this proposal. 10.1038/s41430-024-01456-2
Targeting fundamental aging mechanisms to treat osteoporosis. Feehan Jack,Al Saedi Ahmed,Duque Gustavo Expert opinion on therapeutic targets : Osteoporotic fractures represent a growing burden of mortality, morbidity and socioeconomic cost to health-care systems worldwide. Osteoporosis is a disease uniquely associated with aging, therefore, an understanding of the physiological mechanisms underpinning its development as we age may open new avenues for therapeutic exploitation. Novel treatments, as well as refinement of the current approaches, are vital in the effort to sustain healthy, independent patients across the lifespan.: This review covers the anabolic and catabolic pathways seen in bone maintenance, highlighting how they are changed with age, leading to osteoporosis. It will also discuss how these changes may be targeted therapeutically, in the development of new therapies, and the refinement of those already in use.: New effective and safe treatments for osteoporosis are still needed. Bone anabolics seem to be the most appropriate therapeutic approach to osteoporosis in older persons. Considering that bone and muscle mass synchronically decline with aging thus predisposing older persons to falls and fractures, combined therapeutic approaches to osteosarcopenia with a dual anabolic effect on muscle and bone will be a major advance in the treatment of these devastating conditions in the future. 10.1080/14728222.2019.1702973
Controversies in Osteoporosis Treatment of Nursing Home Residents. Journal of the American Medical Directors Association Osteoporotic fractures are a common and serious health problem for older adults living in nursing homes (NHs). Risk of fracture increases with age and dementia status, yet gaps in evidence result in controversies around when to start and stop treatment for osteoporosis in NH residents, particularly those who have high fracture risk but have limited life expectancy. In this article, we discuss these areas of controversy. We provide an overview of current guidelines that explicitly address osteoporosis treatment strategies for NH residents, review the evidence for osteoporosis medications in NH residents, and use these sources to suggest practical recommendations for clinical practice and for research. Three published guidelines (from the United States, Canada, and Australia) and several studies provide the current basis for clinical decisions about osteoporosis treatment for NH residents. Practical approaches may include broad use of vitamin D and selective use of osteoporosis medication based on risks, benefits, and goals of care. Clinicians still lack strong evidence to guide treatment of NH residents with advanced dementia, multimorbidity, or severe mobility impairment. Future priorities for research include identifying optimal approaches to risk stratification and prevention strategies for NH residents and evaluating the risk-benefit profile of pharmacologic treatments for osteoporosis NH residents across key clinical strata. In the absence of such evidence, decisions for initiating and continuing treatment should reflect a patient-centered approach that incorporates life expectancy, goals of care, and the potential burden of treatment. 10.1016/j.jamda.2022.09.013
Exploring epigenetic strategies for the treatment of osteoporosis. Molecular biology reports The worldwide trend toward an aging population has resulted in a higher incidence of chronic conditions, such as osteoporosis. Osteoporosis, a prevalent skeletal disorder characterized by decreased bone mass and increased fracture risk, encompasses primary and secondary forms, each with distinct etiologies. Mechanistically, osteoporosis involves an imbalance between bone resorption by osteoclasts and bone formation by osteoblasts. Current pharmacological interventions for osteoporosis, such as bisphosphonates, denosumab, and teriparatide, aim to modulate bone turnover and preserve bone density. Hormone replacement therapy and lifestyle modifications are also recommended to manage the condition. While current medications offer therapeutic options, they are not devoid of limitations. Recent studies have highlighted the importance of epigenetic mechanisms, including DNA methylation and histone modifications, in regulating gene expression during bone remodeling. The use of epigenetic drugs, or epidrugs, to target these mechanisms offers a promising avenue for therapeutic intervention in osteoporosis. In this review, we comprehensively examine the recent advancements in the application of epidrugs for treating osteoporosis. 10.1007/s11033-024-09353-4
Advancements in Osteoporosis Imaging, Screening, and Study of Disease Etiology. Current osteoporosis reports PURPOSE OF REVIEW:The purpose of this review is to inform researchers and clinicians with the most recent imaging techniques that are employed (1) to opportunistically screen for osteoporosis and (2) to provide a better understanding into the disease etiology of osteoporosis. RECENT FINDINGS:Phantomless calibration techniques for computed tomography (CT) may pave the way for better opportunistic osteoporosis screening and the retroactive analysis of imaging data. Additionally, hardware advances are enabling new applications of dual-energy CT and cone-beam CT to the study of bone. Advances in MRI sequences are also improving imaging evaluation of bone properties. Finally, the application of image registration techniques is enabling new uses of imaging to investigate soft tissue-bone interactions as well as bone turnover. While DXA remains the most prominent imaging tool for osteoporosis diagnosis, new imaging techniques are becoming more widely available and providing additional information to inform clinical decision-making. 10.1007/s11914-021-00699-3
Potential Effects of Exosomes and their MicroRNA Carrier on Osteoporosis. Current pharmaceutical design Osteoporosis is a common localized or systemic skeletal illness in the clinic, characterized by bone production weakness and increased bone resorption, resulting in a reduction in bone mineral density (BMD), and affecting mostly postmenopausal women. The risk of osteoporosis or even osteoporotic fracture increases as age increases, putting more pressure on society and families. Although anti-osteoporosis drugs have been developed, some side effects are still observed in the treatment group. Hence the need for more reasonable therapeutic strategies. Exosomes are nanosized extracellular vesicles (EVs) secreted virtually by all types of cells in vivo, which play an important role in intercellular communication. Compared with conventional drugs and stem cells transplantation therapy, exosomes have apparent advantages of lower toxicity and immunogenicity. Exosomes contain many functional molecules, such as proteins, lipids, mRNAs, microRNAs (miRNAs), which can be transferred into recipient cells to regulate a series of signaling pathways and influence physiological and pathological behavior. In this review, we briefly summarize the current knowledge of exosomes and the therapeutic potential of exosomal miRNAs derived from mesenchymal stem cells (MSCs), osteoblasts, osteoclasts, and macrophages in osteoporosis. Finally, a prospect of new treatment strategies for osteoporosis using new biomaterial scaffolds combined with exosomes is also given. 10.2174/1381612828666220128104206
FAM19A5 in vascular aging and osteoporosis: Mechanisms and the "calcification paradox". Ageing research reviews Aging induces a progressive decline in the vasculature's structure and function. Vascular aging is a determinant factor for vascular ailments in the elderly. FAM19A5, a recently identified adipokine, has demonstrated involvement in multiple vascular aging-related pathologies, including atherosclerosis, cardio-cerebral vascular diseases and cognitive deficits. This review summarizes the current understanding of FAM19A5' role and explores its putative regulatory mechanisms in various aging-related disorders, including cardiovascular diseases (CVDs), metabolic diseases, neurodegenerative diseases and malignancies. Importantly, we provide novel insights into the underlying therapeutic value of FAM19A5 in osteoporosis. Finally, we outline future perspectives on the diagnostic and therapeutic potential of FAM19A5 in vascular aging-related diseases. 10.1016/j.arr.2024.102361
Comprehensive analysis of epigenetics mechanisms in osteoporosis. Frontiers in genetics Epigenetic modification pertains to the alteration of genetic-expression, which could be transferred to the next generations, without any alteration in the fundamental DNA sequence. Epigenetic modification could include various processes such as DNA methylation, histone alteration, non-coding RNAs (ncRNAs), and chromatin adjustment are among its primary operations. Osteoporosis is a metabolic disorder that bones become more fragile due to the decrease in mineral density, which could result in a higher risk of fracturing. Recently, as the investigation of the causal pathology of osteoporosis has been progressed, remarkable improvement has been made in epigenetic research. Recent literatures have illustrated that epigenetics is estimated to be one of the most contributing factors to the emergence and progression of osteoporosis. This dissertation primarily focuses on indicating the research progresses of epigenetic mechanisms and also the regulation of bone metabolism and the pathogenesis of osteoporosis in light of the significance of epigenetic mechanisms. In addition, it aims to provide new intelligence for the treatment of diseases related to bone metabolism. 10.3389/fgene.2023.1153585
Osteoporosis: A role for lipids. During Alexandrine Biochimie An inverse relationship between bone marrow (BM) adiposity and bone mass has been described in different physiological and pathological conditions, including osteoporosis (OP). In osteoporotic patients, lower bone mass density is indeed associated with higher BM fat content, suggesting a potential role for bone lipids in the OP pathogenesis. Nevertheless, some questions remain. Is that BM adiposity a cause or a consequence of the bone loss? What kinds of lipids are involved? Human data are somehow contradictories regarding bone lipid signature related to OP, and animal data are needed to support on one or another way the human observations. Bone lipid signature associated to OP needs to be clarified if we want to understand better their roles in OP. In that context, by using an ovariectomy-induced OP murine model and looking at lipids in two bone compartments: BM and mineralized tissue (MT), our first challenge was to identify local lipid changes in relation to OP, in view to explore later the mechanisms by which those compounds could alter bone quality, particularly during the mineralization process. As the most striking data, long-term OP resulted in an accumulation of triglycerides, reduced levels of arachidonic and docosahexaenoic acids, an increase of stearoyl-CoA desaturase indices and a reduction of sphingomyelin in the MT, and potential consequences on bone properties and cell activities are discussed. The reader will appreciate that we are at an early stage of understanding the roles of lipids in the OP development and more investigations will be necessary. 10.1016/j.biochi.2020.08.004
Biomarkers of Osteoporosis: An Update. Parveen Bushra,Parveen Abida,Vohora Divya Endocrine, metabolic & immune disorders drug targets BACKGROUND:Osteoporosis, characterized by compromised bone quality and strength is associated with bone fragility and fracture risk. Biomarkers are crucial for the diagnosis or prognosis of a disease as well as elucidating the mechanism of drug action and improve decision making. OBJECTIVE:An exhaustive description of traditional markers including bone mineral density, vitamin D, alkaline phosphatase, along with potential markers such as microarchitectural determination, trabecular bone score, osteocalcin, etc. is provided in the current piece of work. This review provides insight into novel pathways such as the Wnt signaling pathway, neuro-osseous control, adipogenic hormonal imbalance, gut-bone axis, genetic markers and the role of inflammation that has been recently implicated in osteoporosis. METHODS:We extensively reviewed articles from the following databases: PubMed, Medline and Science direct. The primary search was conducted using a combination of the following keywords: osteoporosis, bone, biomarkers, bone turnover markers, diagnosis, density, architecture, genetics, inflammation. CONCLUSION:Early diagnosis and intervention delay the development of disease and improve treatment outcome. Therefore, probing for novel biomarkers that are able to recognize people at high risk for developing osteoporosis is an effective way to improve the quality of life of patients and to understand the pathomechanism of the disease in a better way. 10.2174/1871530319666190204165207
NADPH oxidases in bone homeostasis and osteoporosis. Schröder Katrin Free radical biology & medicine Bone is a tissue with constant remodeling, where osteoblasts form and osteoclasts degrade bone. Both cell types are highly specialized in their function and both form from precursors and have to be replaced on a regular basis. This replacement represents one control level of bone homeostasis. The second important level would be the control of the function of osteoblasts and osteoclasts in order to keep the balance of bone -formation and -degradation. Both differentiation and control of cellular function are potentially redox sensitive processes. In fact, reactive oxygen species (ROS) are utilized by a wide range of cells for differentiation and control of cellular signaling and function. A major source of ROS is the family of NADPH oxidases. The sole function of those enzymes is the formation of ROS in a controlled and targeted manner. Importantly the members of the NADPH oxidase family differ in their localization and in the type and amount of ROS produced. Accordingly the impact of the members of the NADPH oxidase family on differentiation and function differs between cell types. This review will highlight the function of different NADPH oxidases in differentiation and function of bone cells and thereby will discuss the role of NADPH oxidases in bone homeostasis and osteoporosis. 10.1016/j.freeradbiomed.2018.08.036
An insight into the paradigms of osteoporosis: From genetics to biomechanics. Al Anouti Fatme,Taha Zainab,Shamim Sadia,Khalaf Kinda,Al Kaabi Leena,Alsafar Habiba Bone reports Considered as one of the major epidemics of the 21st century, osteoporosis affects approximately 200 million people globally, with significant worldwide impact on rates of morbidity and mortality and massive socioeconomic burdens. Mainly characterized by decreased bone mineral density (BMD) and increased risk of bone fragility/deterioration, this devastating silent epidemic typically has no symptoms until a fracture occurs. The multifactorial disease, osteoporosis is instigated by complex interactions between genetic, metabolic and environmental factors, with severe impact on the biomechanics of the musculoskeletal system. This article provides a review of the epidemiology, genetic and biomechanical aspects of primary osteoporosis. The review begins with a summary of the epidemiology and global prevalence of osteoporosis. Sections 1 and 2 discuss the genetic associations and molecular signaling pathways involved in normal and pathological osteogenesis while Section 3 explores the biomechanics of osteoporosis and its quantitative damaging effects on critical bone mechanical properties, and associated bone remodeling. Overall, this review summarizes the recent findings about osteoporosis and emphasizes the importance of an integrative holistic approach in investigating osteoporosis towards providing better informed, more effective preventive and treatment modalities. Importantly, this work also explores the limited available literature on the various aspects of osteoporosis in the United Arab Emirates (UAE), Gulf Cooperation Council (GCC), and Middle East despite its alarming prevalence in the region, and highlights the need for further research and studies taking into consideration the importance of the vitamin D receptor () gene influencing the development of osteoporosis. 10.1016/j.bonr.2019.100216
The Potential of Exosomes for Osteoporosis Treatment: A Review. Drug design, development and therapy As a continuous process comprising bone resorption and formation, bone remodeling, plays an essential role in maintaining the balance of bone metabolism. One type of metabolic osteopathy is osteoporosis, which is defined by low bone mass and deteriorating bone microstructure. Osteoporosis patients are more likely to experience frequent osteoporotic fractures, which makes osteoporosis prevention and treatment crucial. A growing body of research has revealed that exosomes, which are homogenous vesicles released by most cell types, play a major role in mediating a number of pathophysiological processes, including osteoporosis. Exosomes may act as a mediator in cell-to-cell communication and offer a fresh perspective on information sharing. This review discusses the characteristics of exosomes and outlines the exosomes' underlying mechanism that contributes to the onset of osteoporosis. Recent years have seen a rise in interest in the role of exosomes in osteoporosis, which has given rise to innovative therapeutic approaches for the disease prevention and management. 10.2147/DDDT.S437596
Osteoblast-n-Osteoclast: Making Headway to Osteoporosis Treatment. Kaur Malkiet,Nagpal Manju,Singh Manjinder Current drug targets BACKGROUND:Bone is a dynamic tissue that continuously undergoes the modeling and remodeling process to maintain its strength and firmness. Bone remodeling is determined by the functioning of osteoblast and osteoclast cells. The imbalance between the functioning of osteoclast and osteoblast cells leads to osteoporosis. Osteoporosis is divided into primary and secondary osteoporosis. Generally, osteoporosis is diagnosed by measuring bone mineral density (BMD) and various osteoblast and osteoclast cell markers. METHODS:Relevant literature reports have been studied and data has been collected using various search engines like google scholar, scihub, sciencedirect, pubmed, etc. A thorough understanding of the mechanism of bone targeting strategies has been discussed and related literature has been studied and compiled. RESULTS:Bone remodeling process has been described in detail including various approaches for targeting bone. Several bone targeting moieties have been stated in detail along with their mechanisms. Targeting of osteoclasts and osteoblasts using various nanocarriers has been discussed in separate sections. The toxicity issues or Biosafety related to the use of nanomaterials have been covered. CONCLUSION:The treatment of osteoporosis targets the inhibition of bone resorption and the use of agents that promote bone mineralization to slow disease progression. Current osteoporosis therapy involves the use of targeting moieties such as bisphosphonates and tetracyclines for targeting various drugs. Nanotechnology has been used for targeting various drug molecules such as RANKLinhibitors, parathyroid hormone analogues, estrogen agonists and antagonists, Wnt signaling enhancer and calcitonin specifically to bone tissue (osteoclast and osteoblasts). So, a multicomponent treatment strategy targeting both the bone cells will be more effective rather than targeting only osteoclasts and it will be a potential area of research in bone targeting used to treat osteoporosis. The first section of the review article covers various aspects of bone targeting. Another section comprises details of various targeting moieties such as bisphosphonates, tetracyclines; and various nanocarriers developed to target osteoclast and osteoblast cells and summarized data on in vivo models has been used for assessment of bone targeting, drawbacks of current strategies and future perspectives. 10.2174/1389450121666200731173522
Bone regeneration in osteoporosis: opportunities and challenges. Drug delivery and translational research Osteoporosis is a bone disorder characterised by low bone mineral density, reduced bone strength, increased bone fragility, and impaired mineralisation of bones causing an increased risk of bone fracture. Several therapies are available for treating osteoporosis which include bisphosphonates, anti-resorptive agents, oestrogen modulators, etc. These therapies primarily focus on decreasing bone resorption and do not assist in bone regeneration or offering permanent curative solutions. Additionally, these therapies are associated with severe adverse events like thromboembolism, increased risk of stroke, and hypocalcaemia. To overcome these limitations, bone regenerative pathways and approaches are now considered to manage osteoporosis. The bone regenerative pathways involved in bone regeneration include wingless-related integration site/β-catenin signalling pathway, notch signalling pathway, calcium signalling, etc. The various regenerative approaches which possess potential to heal and replace the bone defect site include scaffolds, cements, cell therapy, and other alternative medicines. The review focuses on describing the challenges and opportunities in bone regeneration for osteoporosis. 10.1007/s13346-022-01222-6
Bone Aging, Cellular Senescence, and Osteoporosis. JBMR plus Changes in aging bone that lead to osteoporosis are mediated at multiple levels, including hormonal alterations, skeletal unloading, and accumulation of senescent cells. This pathological interplay is superimposed upon medical conditions, potentially bone-wasting medications, modifiable and unmodifiable personal risk factors, and genetic predisposition that accelerate bone loss with aging. In this study, the focus is on bone hemostasis and its dysregulation with aging. The major physiological changes with aging in bone and the role of cellular senescence in contributing to age-related osteoporosis are summarized. The aspects of bone aging are reviewed including remodeling deficits, uncoupling phenomena, inducers of cellular senescence related to bone aging, roles of the senescence-associated secretory phenotype, radiation-induced bone loss as a model for bone aging, and the accumulation of senescent cells in the bone microenvironment as a predominant mechanism for age-related osteoporosis. The study also addresses the rationale and potential for therapeutic interventions based on the clearance of senescent cells or suppression of the senescence-associated secretory phenotype. © 2021 The Authors. published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. 10.1002/jbm4.10488
Melatonin: Another avenue for treating osteoporosis? Li Tian,Jiang Shuai,Lu Chenxi,Yang Wenwen,Yang Zhi,Hu Wei,Xin Zhenlong,Yang Yang Journal of pineal research Melatonin is a signal molecule that modulates the biological circadian rhythms of vertebrates. Melatonin deficiency is thought to be associated with several disorders, including insomnia, cancer, and cardiovascular and neurodegenerative diseases. Accumulating evidence has also indicated that melatonin may be involved in the homeostasis of bone metabolism. Age-related reductions in melatonin are considered to be critical factors in bone loss and osteoporosis with aging. Thus, serum melatonin levels might serve as a biomarker for the early detection and prevention of osteoporosis. Compared to conventional antiosteoporosis medicines, which primarily inhibit bone loss, melatonin both suppresses bone loss and promotes new bone formation. Mechanistically, by activating melatonin receptor 2 (MT2), melatonin upregulates the gene expression of alkaline phosphatase (ALP), bone morphogenetic protein 2 (BMP2), BMP6, osteocalcin, and osteoprotegerin to promote osteogenesis while inhibiting the receptor activator of NF-kB ligand (RANKL) pathway to suppress osteolysis. In view of the distinct actions of melatonin on bone metabolism, we hypothesize that melatonin may be a novel remedy for the prevention and clinical treatment of osteoporosis. 10.1111/jpi.12548
Anorexia Nervosa and Osteoporosis: Pathophysiology and Treatment. Steinman Jeremy,Shibli-Rahhal Amal Journal of bone metabolism Anorexia nervosa (AN) affects 2.9 million people, many of whom experience bone loss and increased fracture risk. In this article, we review data on the underlying pathophysiology of AN-related osteoporosis and possible approaches to disease management. Available research suggests that low body weight and decreased gonadal function are the strongest predictors of bone loss and fractures in patients with AN. Additionally, other metabolic disturbances have been linked to bone loss, including growth hormone resistance, low leptin concentrations, and hypercortisolemia, but those correlations are less consistent and lack evidence of causality. In terms of treatment of AN-related bone disease, weight gain has the most robust impact on bone mineral density (BMD). Restoration of gonadal function seems to augment this effect and may independently improve BMD. Bisphosphonates, insulin-like growth factor 1 supplementation, and teriparatide may also be reasonable considerations, however need long-term efficacy and safety data. 10.11005/jbm.2019.26.3.133
Epigenetic regulations of cellular senescence in osteoporosis. Ageing research reviews Osteoporosis (OP) is a prevalent age-related disease that is characterized by a decrease in bone mineral density (BMD) and systemic bone microarchitectural disorders. With age, senescent cells accumulate and exhibit the senescence-associated secretory phenotype (SASP) in bone tissue, leading to the imbalance of bone homeostasis, osteopenia, changes in trabecular bone structure, and increased bone fragility. Cellular senescence in the bone microenvironment involves osteoblasts, osteoclasts, and bone marrow mesenchymal stem cells (BMSCs), whose effects on bone homeostasis are regulated by epigenetics. Therefore, the epigenetic regulatory mechanisms of cellular senescence have received considerable attention as potential targets for preventing and treating osteoporosis. In this paper, we systematically review the mechanisms of aging-associated epigenetic regulation in osteoporosis, emphasizing the impact of epigenetics on cellular senescence, and summarize three current methods of targeting cellular senescence, which is helpful better to understand the pathogenic mechanisms of cellular senescence in osteoporosis and provides strategies for the development of epigenetic drugs for the treatment of osteoporosis. 10.1016/j.arr.2024.102235
Irisin and Its Role in Postmenopausal Osteoporosis and Sarcopenia. Biomedicines Menopause, an extremely delicate phase in a woman's life, is characterized by a drop in estrogen levels. This decrease has been associated with the onset of several diseases, including postmenopausal osteoporosis and sarcopenia, which often coexist in the same person, leading to an increased risk of fractures, morbidity, and mortality. To date, there are no approved pharmacological treatments for sarcopenia, while not all of those approved for postmenopausal osteoporosis are beneficial to muscles. In recent years, research has focused on the field of myokines, cytokines, or peptides secreted by skeletal muscle fibers following exercise. Among these, irisin has attracted great interest as it possesses myogenic properties but at the same time exerts anabolic effects on bone and could therefore represent the link between muscle and bone. Therefore, irisin could represent a new therapeutic strategy for the treatment of osteoporosis and also serve as a new biomarker of sarcopenia, thus facilitating diagnosis and pharmacological intervention. The purpose of this review is to provide an updated summary of what we know about the role of irisin in postmenopausal osteoporosis and sarcopenia. 10.3390/biomedicines12040928
Micronutrient intake to protect against osteoporosis during and after critical illness. Current opinion in clinical nutrition and metabolic care PURPOSE OF REVIEW:Improved survival from critical illness has enhanced the focus on ways to augment functional outcomes following discharge from the Intensive Care Unit. An area that is gaining increased attention is the effect of critical illness on bone health and fragility fractures following the episode. This review discusses the micronutrients that may play a role in bone metabolism and the potential benefits of their supplementation to prevent osteoporosis. These include calcium, phosphorous, magnesium, vitamin D, vitamin C, vitamin K, and certain trace elements. FINDINGS:Although there is sound physiological basis for the involvement of these micronutrients in bone health and fracture prevention, there are few clinically relevant publications in this area with calcium and vitamin D being the best studied to date. SUMMARY:In the absence of high-quality evidence in critically ill populations, attention to measurement and supplementation of these micronutrients as per current guidelines outlining micronutrient requirements in enteral and parenteral nutrition might mitigate bone loss and its sequelae in the recovery phase from critical illness. 10.1097/MCO.0000000000000979
Machine Learning Solutions for Osteoporosis-A Review. Smets Julien,Shevroja Enisa,Hügle Thomas,Leslie William D,Hans Didier Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research Osteoporosis and its clinical consequence, bone fracture, is a multifactorial disease that has been the object of extensive research. Recent advances in machine learning (ML) have enabled the field of artificial intelligence (AI) to make impressive breakthroughs in complex data environments where human capacity to identify high-dimensional relationships is limited. The field of osteoporosis is one such domain, notwithstanding technical and clinical concerns regarding the application of ML methods. This qualitative review is intended to outline some of these concerns and to inform stakeholders interested in applying AI for improved management of osteoporosis. A systemic search in PubMed and Web of Science resulted in 89 studies for inclusion in the review. These covered one or more of four main areas in osteoporosis management: bone properties assessment (n = 13), osteoporosis classification (n = 34), fracture detection (n = 32), and risk prediction (n = 14). Reporting and methodological quality was determined by means of a 12-point checklist. In general, the studies were of moderate quality with a wide range (mode score 6, range 2 to 11). Major limitations were identified in a significant number of studies. Incomplete reporting, especially over model selection, inadequate splitting of data, and the low proportion of studies with external validation were among the most frequent problems. However, the use of images for opportunistic osteoporosis diagnosis or fracture detection emerged as a promising approach and one of the main contributions that ML could bring to the osteoporosis field. Efforts to develop ML-based models for identifying novel fracture risk factors and improving fracture prediction are additional promising lines of research. Some studies also offered insights into the potential for model-based decision-making. Finally, to avoid some of the common pitfalls, the use of standardized checklists in developing and sharing the results of ML models should be encouraged. © 2021 American Society for Bone and Mineral Research (ASBMR). 10.1002/jbmr.4292
Sarcopenic obesity and osteoporosis: Research progress and hot spots. Experimental gerontology Sarcopenic obesity (SO) and osteoporosis (OP) are associated with aging and obesity. The pathogenesis of SO is complex, including glucolipid and skeletal muscle metabolic disorders caused by inflammation, insulin resistance, and other factors. Growing evidence links muscle damage to bone loss. Muscle-lipid metabolism disorders of SO disrupt the balance between bone formation and bone resorption, increasing the risk of OP. Conversely, bones also play a role in fat and muscle metabolism. In the context of aging and obesity, the comprehensive review focuses on the effects of mechanical stimulation, mesenchymal stem cells (MSCs), chronic inflammation, myokines, and adipokines on musculoskeletal, at the same time, the impact of osteokines on muscle-lipid metabolism were also analyzed. So far, exercise combined with diet therapy is the most effective strategy for increasing musculoskeletal mass. A holistic treatment of musculoskeletal diseases is still in the preliminary exploration stage. Therefore, this article aims to improve the understanding of musculoskeletal -fat interactions in SO and OP, explores targets that can provide holistic treatment for SO combined with OP, and discusses current limitations and challenges. We hope to provide relevant ideas for developing specific therapies and improving disease prognosis in the future. 10.1016/j.exger.2024.112544
Potassium: A Frontier in Osteoporosis. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme Osteoporosis is a significant public health concern, particularly in aging populations, leading to fractures, decreased mobility, and reduced quality of life. While calcium and vitamin D have long been recognized as essential for bone health, emerging research suggests that potassium may play a crucial role in maintaining bone density and preventing osteoporosis. This manuscript explores the relationship between potassium and osteoporosis, delving into the mechanisms, epidemiological evidence, and potential therapeutic implications of potassium in bone health. Furthermore, the manuscript discusses the sources of dietary potassium, its impact on bone metabolism, and the future directions in research and clinical practice regarding potassium's role in osteoporosis management. 10.1055/a-2254-8533
Ferroptosis: A Frontier in Osteoporosis. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme Reduced bone mass and degeneration of the microarchitecture of bone tissue are the hallmarks of osteoporosis, a bone metabolic disease that increases skeletal fragility and fracture susceptibility. Osteoporosis is primarily caused by unbalanced bone remodeling, in which bone synthesis is outpaced by bone resorption caused by osteoclasts. Along with the bone-building vitamins calcium and vitamin D, typical medications for treating osteoporosis include bisphosphonates and calcitonin. The present therapies effectively stop osteoclast activation that is too high, however they come with varying degrees of negative effects. Numerous factors can contribute to osteoporosis, which is characterized by a loss of bone mass and density due to the deterioration of the bone's microstructure, which makes the bone more fragile. As a result, it is a systemic bone condition that makes patients more likely to fracture. Interest in the function of ferroptosis in the pathophysiology of osteoporosis is developing. In this review, we go through the shape of the cell, the fundamental mechanisms of ferroptosis, the relationship between osteoclasts and osteoblasts, the association between ferroptosis and diabetic osteoporosis, steroid-induced osteoporosis, and the relationship between ferroptosis and postmenopausal osteoporosis. The functions of ferroptosis and osteoporosis in cellular function, signaling cascades, pharmacological inhibition, and gene silencing have been better understood thanks to recent advances in biomedical research. 10.1055/a-2230-2664
Disuse Osteoporosis: Clinical and Mechanistic Insights. Calcified tissue international Disuse osteoporosis describes a state of bone loss due to local skeletal unloading or systemic immobilization. This review will discuss advances in the field that have shed light on clinical observations, mechanistic insights and options for the treatment of disuse osteoporosis. Clinical settings of disuse osteoporosis include spinal cord injury, other neurological and neuromuscular disorders, immobilization after fractures and bed rest (real or modeled). Furthermore, spaceflight-induced bone loss represents a well-known adaptive process to microgravity. Clinical studies have outlined that immobilization leads to immediate bone loss in both the trabecular and cortical compartments accompanied by relatively increased bone resorption and decreased bone formation. The fact that the low bone formation state has been linked to high levels of the osteocyte-secreted protein sclerostin is one of the many findings that has brought matrix-embedded, mechanosensitive osteocytes into focus in the search for mechanistic principles. Previous basic research has primarily involved rodent models based on tail suspension, spaceflight and other immobilization methods, which have underlined the importance of osteocytes in the pathogenesis of disuse osteoporosis. Furthermore, molecular-based in vitro and in vivo approaches have revealed that osteocytes sense mechanical loading through mechanosensors that translate extracellular mechanical signals to intracellular biochemical signals and regulate gene expression. Osteocytic mechanosensors include the osteocyte cytoskeleton and dendritic processes within the lacuno-canalicular system (LCS), ion channels (e.g., Piezo1), extracellular matrix, primary cilia, focal adhesions (integrin-based) and hemichannels and gap junctions (connexin-based). Overall, disuse represents one of the major factors contributing to immediate bone loss and osteoporosis, and alterations in osteocytic pathways appear crucial to the bone loss associated with unloading. 10.1007/s00223-021-00836-1
Operationalizing Treat-to-Target for Osteoporosis. Endocrinology and metabolism (Seoul, Korea) Treat-to-target (TTT) for osteoporosis is a concept for individualizing patient treatment decisions that focuses on achieving an acceptable level of fracture risk rather than response to treatment alone. While a response to treatment is essential in order to achieve an acceptable level of risk, it is not necessarily sufficient. Some patients have a good response to treatment yet remain at high level of fracture risk. Since there is no way to directly measure bone strength in patients treated for osteoporosis, a surrogate measurement must be used. Bone mineral density (BMD) is commonly used to select patients for treatment and has emerged as the most useful surrogate for assessing reduction of fracture risk after treatment is started. Recent large meta-regression studies have shown a robust correlation between larger increases in BMD with treatment and greater reductions in fracture risk. Application of TTT for osteoporosis involves assessing fracture risk before starting treatment and initiating treatment with an agent that is most likely to reduce fracture risk to an acceptable level, represented by a target BMD T-score, over a reasonable period of time. This review offers suggestions for implementing TTT for osteoporosis in clinical practice and managing patients who fail or succeed in reaching the target. More study is needed to fully validate the use of TTT for osteoporosis for initiating and modifying treatments to reduce fracture risk. 10.3803/EnM.2021.970
The Sequential Therapy in Osteoporosis. Indian journal of orthopaedics Background:Osteoporosis management often involves a sequential treatment approach to optimize patient outcomes and minimize fracture risks. This strategy is tailored to individual patient characteristics, treatment responses, and fracture risk profiles. Methods:A thorough literature review was systematically executed using prominent databases, including PubMed and EMBASE. The primary aim was to identify original articles and clinical trials evaluating the effectiveness of sequential therapy with anti-osteoporosis drugs, focusing on the period from 1995 to 2023. The analysis encompassed an in-depth examination of osteoporosis drugs, delineating their mechanisms of action, side effects, and current trends as elucidated in the literature. Results and Discussion:Our study yielded noteworthy insights into the optimal sequencing of pharmacologic agents for the long-term treatment of patients necessitating multiple drugs. Notably, the achievement of optimal improvements in bone mass is observed when commencing treatment with an anabolic medication, followed by the subsequent utilization of an antiresorptive drug. This stands in contrast to initiating therapy with a bisphosphonate, which may potentially diminish outcomes in the post-anabolic intervention period. Furthermore, it has been discerned that caution should be exercised against transitioning from denosumab to PTH homologs due to the adverse effects of heightened bone turnover and sustained weakening of bone structure. Despite the absence of fracture data substantiating the implementation of integrated anabolic/antiresorptive pharmacotherapy, the incorporation of denosumab and teriparatide presents a potential avenue worthy of consideration for individuals at a heightened vulnerability to fragility fractures. Conclusions:A judiciously implemented sequential treatment strategy in osteoporosis offers a flexible and tailored approach to address diverse clinical scenarios, optimizing fracture prevention and patient outcomes. 10.1007/s43465-023-01067-2
Nutrition and Osteoporosis Prevention. Current osteoporosis reports PURPOSE OF REVIEW:Osteoporosis affects 50% of women and 20% of men after the age of 50. Fractures are associated with significant morbidity, increased mortality and altered quality of life. Lifestyle measures for fragility fracture prevention include good nutrition including adequate protein and calcium intakes, vitamin D sufficiency, and regular weight bearing physical exercise. RECENT FINDINGS:Dietary protein is one of the most important nutritional considerations as it affects bone mineral density, trabecular and cortical microstructure, and bone strength. When calcium intake is sufficient, higher dietary protein intake is associated with lower risk of fracture. Dairy products are a valuable source of calcium and high quality protein. Dairy product consumption, particularly fermented dairy products, are associated with a lower risk of hip fracture and vegan diets are associated with increased fracture risk. Other dietary factors associated with reduced fracture risk include at least 5 servings per day of fruits and vegetables, regular tea drinking, adherence to a Mediterranean diet and other dietary patterns which provide fibers, polyphenols and fermented dairy products. Such dietary patterns may confer health benefits through their effect on gut microbiota composition and/or function. A balanced diet including minerals, protein, fruits and vegetables is an important element in the prevention of osteoporosis and of fragility fracture. 10.1007/s11914-024-00892-0
Management of difficult osteoporosis. Russell Linda A Best practice & research. Clinical rheumatology Osteoporosis and associated low-impact fractures are common. There is associated morbidity and mortality with low-impact fractures. It is critical to identify which patients would benefit from therapy. General treatment considerations are reviewed. Currently available treatment options are discussed. Certain patient populations pose challenges in the treatment of osteoporosis. An in-depth review of clinically challenging scenarios is presented: Treatment of patients with severe osteoporosis, Treatment of Premenopausal women with low bone density, Treatment of osteoporosis in patients with kidney disease, Treatment of Osteoporosis in patients on glucocorticoid therapy, Treatment of osteoporosis in patients with a fracture. 10.1016/j.berh.2019.04.002
Osteoporosis: A Narrative Review. Cureus Osteoporosis is a disease of global concern, with significant implications for mortality, morbidity, strain on national health resources, and the negative impact on the quality of life associated with the condition. As we witness a primarily aging population, future predictions indicate that risk factors for osteoporosis will be more prevalent, leading to an increase in the number of individuals suffering from the condition and associated fractures. However, the future of osteoporosis in terms of diagnosis and treatment is optimistic. Understanding of bone quality and examination of it has improved with the onset of magnetic resonance imaging (MRI) and other imaging techniques such as micro-computer tomography. Innovative therapies specifically targeting osteoporotic bone metabolism on a microscopic level hold promise. This narrative review provides details on the background, prognosis, and future treatment strategies of osteoporosis. 10.7759/cureus.43031
Updates in CKD-Associated Osteoporosis. Current osteoporosis reports PURPOSE OF REVIEW:Chronic kidney disease (CKD) is associated with bone loss and fractures. The purpose of this review is to provide clinicians with an overview of the underlying pathogenesis of CKD-associated osteoporosis, and a summary of the current diagnostic and therapeutic approaches to this disease. RECENT FINDINGS:In 2017, the Kidney Disease Improving Global Outcomes Committee on Bone Quality updated their guidelines to include screening for osteoporosis and fracture risk by dual energy X-ray absorptiometry in patients with CKD. Once a diagnosis of osteoporosis and/or fracture risk is established, it is not clear how nephrologists should manage their patients. Patients with CKD should be screened for CKD-associated osteoporosis and considered for strategies that prevent bone loss and fractures. Assessment of bone turnover via imaging, biochemical testing, or bone biopsy can help guide the choice of therapy. Randomized controlled trials are needed to assess safety and efficacy of treatments to prevent bone loss and fractures. 10.1007/s11914-018-0491-3
Polypharmacy in Osteoporosis Treatment. Clinics in geriatric medicine In older adults, polypharmacy and osteoporosis frequently occur contemporaneously. Polypharmacy is increasingly recognized as a risk factor for hip and fall-related fractures. Treatments for osteoporosis include antiresorptive (alendronate, risedronate, zoledronic acid, ibandronate, denosumab) and osteoanabolic (teriparatide, abaloparatide, romosozumab) agents. Polypharmacy is associated with worse adherence to pharmacologic therapy. Thus, the selection of osteoporosis treatment should be individualized and based on a variety of factors, including underlying fracture risk (high vs very high risk), medical comorbidities, medication burden, as well as fracture risk reduction profiles, modes of administration, and side effects of treatment options. 10.1016/j.cger.2022.05.011
Gut Microbiome and Osteoporosis. Ding Kai,Hua Fei,Ding Wenge Aging and disease Gut microbiome refers to the microbes that live in human digestive tract and are symbiotic with the human body. They participate in the regulation of various physiological and pathological processes of the human body and are associated with various diseases. The pathological process of osteoporosis is affected by gut microbes. The molecular mechanisms of osteoporosis mainly include: 1) Intestinal barrier and nutrient absorption (involving SCFAs). 2) Immunoregulation (Th-17 and T-reg cells balance). 3) Regulation of intestinal-brain axis (involving 5-HT). Gut microbes can increase bone mass and improve osteoporosis by inhibiting osteoclast proliferation and differentiation, inducing apoptosis, reducing bone resorption, or promoting osteoblast proliferation and maturation. However, the therapeutic effect of gut microbes on osteoporosis remains to be further proven. At present, some of the findings on the impact of gut microbes on osteoporosis has been applied in clinical, including early diagnosis and intervention of osteoporosis and adjuvant therapy. In this article, we reviewed the molecular mechanisms underlying the regulatory effect of gut microbes on osteoporosis and the clinical practice of using gut microbes to improve bone health. 10.14336/AD.2019.0523
Psoriasis and osteoporosis: a literature review. Clinical and experimental dermatology Psoriasis is a chronic inflammatory skin disease with complex comorbidities. Recent evidence has revealed how the inflammatory nature of psoriasis affects bone mineral density and may lead to osteoporosis. This review outlines the current understanding and advances on the association between psoriasis and osteoporosis. The current literature suggests an increased risk of osteopenia and osteoporosis in patients with extensive and chronic psoriasis, compounded by other lifestyle and genetic factors. It suggests that prophylactic measures such as vitamin D supplementation and increasing weight-bearing exercises can help, but in patients with extensive psoriasis, prolonged systemic inflammation may require long-term management. Although there have been many short-term RCTs on the efficacy and safety of biologics in psoriasis, clinical studies looking at the long-term effects of biologics, such as whether they might improve bone mineral density in these patients with psoriasis are yet to be conducted. 10.1111/ced.15174
Osteoporosis: Current Concepts. Akkawi Ibrahim,Zmerly Hassan Joints Osteoporosis is a worldwide disease characterized by reduction of bone mass and alteration of bone architecture resulting in increased bone fragility and increased fracture risk. Causes of osteoporosis include increasing age, female sex, postmenopausal status, hypogonadism or premature ovarian failure, low body mass index, ethnic background, rheumatoid arthritis, low bone mineral density (BMD), vitamin D deficiency, low calcium intake, hyperkyphosis, current smoking, alcohol abuse, immobilization, and long-term use of certain medications. The diagnosis of osteoporosis is established by measurement of BMD of the hip and spine using dual energy X-ray absorptiometry. According to the World Health Organization criteria, osteoporosis is defined as a BMD that lies 2.5 standard deviation or more below the average value for young healthy women. Bone turnover biomarker detection may be useful in monitoring osteoporosis treatment and assessing fracture risk but not for diagnosis of osteoporosis. Management of osteoporosis consists of nonpharmacological interventions, which are recommended for all subjects, and pharmacological therapy in all postmenopausal women who have had an osteoporotic fracture or have BMD values consistent with osteoporosis. 10.1055/s-0038-1660790
Osteoporosis and Obesity. Indian journal of orthopaedics Introduction:This article concisely overviews the complex relationship between obesity and bone health. Obesity, characterized by excessive fat accumulation, has been traditionally associated with higher bone mineral density. Also, recent data suggest a favorable bone microarchitecture profile in these patients. However, the increase in bone mineral density does not necessarily confer protection against fractures, and the risk of fractures may vary depending on the skeletal sites. Factors affecting bone health:Various factors, including mechanical factors, hormones, cytokines, inflammation, and bone marrow adiposity, contribute to the adverse effect of obesity on bone. The article explores these factors alongside non-invasive techniques and tools like the Fracture Risk Assessment (FRAX) to evaluate fracture risk. Bone and Adipose tissue:This article also highlights the essential roles of hormones such as vitamin D, Parathormone (PTH), FGF-23 (Fibroblast Growth Factor 23), which affect bone health, and some of the hormones secreted from the adipose tissues such as adiponectin and leptin. Obesity Paradox and Sarcopenic Obesity:The article delves into the intriguing obesity paradox, where an increased BMI correlates with higher bone mineral density but not necessarily reduced fracture risk. Sarcopenic obesity, a combination of excessive fat accumulation and reduced muscle mass, further complicates the relationship between obesity and bone health. Conclusions:Physicians should keep a comprehensive approach to treating obese patients with osteoporosis, including lifestyle modifications, weight management, fall prevention strategies, and pharmacological interventions. Further research is needed to better understand the relationship between obesity and bone health. 10.1007/s43465-023-01052-9
Diabetes and Osteoporosis. Indian journal of orthopaedics Bone fragility is an emerging complication of diabetes. People with diabetes are at a significantly higher risk of fractures compared to the general population. Bone fragility occurs in diabetes as a result of complex and poorly understood mechanisms occurring at the cellular level contributed by vascular, inflammatory and mechanical derangements. Bone mineral density (BMD) as assessed by DEXA is low in type 1 diabetes. Type 2 diabetes has a high risk of fracture despite a normal to raised BMD. DEXA thus underestimates the fracture risk in diabetes. Data are scare regarding the efficacy of the available therapies in this low bone turnover state. 10.1007/s43465-023-01049-4
Treating osteoporosis to prevent fractures: current concepts and future developments. Lorentzon Mattias Journal of internal medicine Antiresorptive drugs, such as the bisphosphonates and the RANKL inhibitor denosumab, are currently the most widely used osteoporosis medications. These drugs increase bone mineral density (BMD) and reduce the risk of vertebral (by 40-70%), nonvertebral (by 25-40%) and hip fractures (by 40-53%) in postmenopausal women with osteoporosis. Due to the risk of rare side-effects, the use of bisphosphonates has been limited to up to 10 years with oral bisphosphonates and 6 years with intravenous zoledronic acid. Despite their well-proven efficacy and safety, few women at high risk of fracture are started on treatment. Case finding strategies, such as fracture risk-based screening in primary care using the fracture risk assessment tool (FRAX) and Fracture Liaison Services, have proved effective in increasing treatment rates and reducing fracture rates. Recently, anabolic therapy with teriparatide was demonstrated to be superior to the bisphosphonate risedronate in preventing vertebral and clinical fractures in postmenopausal women with vertebral fracture. Treatment with the sclerostin antibody romosozumab increases BMD more profoundly and rapidly than alendronate and is also superior to alendronate in reducing the risk of vertebral and nonvertebral fracture in postmenopausal women with osteoporosis. For patients with severe osteoporosis and high fracture risk, bisphosphonates alone are unlikely to be able to provide long-term protection against fracture and restore BMD. For those patients, sequential treatment, starting with a bone-building drug (e.g. teriparatide), followed by an antiresorptive, will likely provide better long-term fracture prevention and should be the golden standard of future osteoporosis treatment. 10.1111/joim.12873
Overview of treatment approaches to osteoporosis. Langdahl Bente L British journal of pharmacology Efficient therapies are available for the treatment of osteoporosis. Anti-resorptive therapies, including bisphosphonates and denosumab, increase bone mineral density (BMD) and reduce the risk of fractures by 20-70%. Bone-forming or dual-action treatments stimulate bone formation and increase BMD more than the anti-resorptive therapies. Two studies have demonstrated that these treatments are superior to anti-resorptives in preventing fractures in patients with severe osteoporosis. Bone-forming or dual-action treatments should be followed by anti-resorptive treatment to maintain the fracture risk reduction. The BMD gains seen with bone-forming and dual-action treatments are greater in treatment-naïve patients compared to patients pretreated with anti-resorptive treatments. However, the antifracture efficacy seems to be preserved. Treatment failure will often lead to switch of treatment from orally to parentally administrated anti-resorptives treatment or from anti-resorptive to bone-forming or dual-action treatment. Osteoporosis is a chronic condition and therefore needs a long-term management plan with a personalized approach to treatment. LINKED ARTICLES: This article is part of a themed issue on The molecular pharmacology of bone and cancer-related bone diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.9/issuetoc. 10.1111/bph.15024
Calcium supplementation in osteoporosis: useful or harmful? Chiodini Iacopo,Bolland Mark J European journal of endocrinology Osteoporosis and fragility fractures are important social and economic problems worldwide and are due to both the loss of bone mineral density and sarcopenia. Indeed, fragility fractures are associated with increased disability, morbidity and mortality. It is known that a normal calcium balance together with a normal vitamin D status is important for maintaining well-balanced bone metabolism, and for many years, calcium and vitamin D have been considered crucial in the prevention and treatment of osteoporosis. However, recently, the usefulness of calcium supplementation (alone or with concomitant vitamin D) has been questioned, since some studies reported only weak efficacy of these supplementations in reducing fragility fracture risk. On the other hand, besides the gastrointestinal side effects of calcium supplements and the risk of kidney stones related to use of co-administered calcium and vitamin D supplements, other recent data suggested potential adverse cardiovascular effects from calcium supplementation. This debate article is focused on the evidence regarding both the possible usefulness for bone health and the potential harmful effects of calcium and/or calcium with vitamin D supplementation. 10.1530/EJE-18-0113
How to manage osteoporosis before the age of 50. Rozenberg S,Bruyère O,Bergmann P,Cavalier E,Gielen E,Goemaere S,Kaufman J M,Lapauw B,Laurent M R,De Schepper J,Body J J Maturitas This narrative review discusses several aspects of the management of osteoporosis in patients under 50 years of age. Peak bone mass is genetically determined but can also be affected by lifestyle factors. Puberty constitutes a vulnerable period. Idiopathic osteoporosis is a rare, heterogeneous condition in young adults due in part to decreased osteoblast function and deficient bone acquisition. There are no evidence-based treatment recommendations. Drugs use can be proposed to elderly patients at very high risk. Diagnosis and management of osteoporosis in the young can be challenging, in particular in the absence of a manifest secondary cause. Young adults with low bone mineral density (BMD) do not necessarily have osteoporosis and it is important to avoid unnecessary treatment. A determination of BMD is recommended for premenopausal women who have had a fragility fracture or who have secondary causes of osteoporosis: secondary causes of excessive bone loss need to be excluded and treatment should be targeted. Adequate calcium, vitamin D, and a healthy lifestyle should be recommended. In the absence of fractures, conservative management is generally sufficient, but in rare cases, such as chemotherapy-induced osteoporosis, antiresorptive medication can be used. Osteoporosis in young men is most often of secondary origin and hypogonadism is a major cause; testosterone replacement therapy will improve BMD in these patients. Diabetes is characterized by major alterations in bone quality, implying that medical therapy should be started sooner than for other causes of osteoporosis. Primary hyperparathyroidism, hyperthyroidism, Cushing's syndrome and growth hormone deficiency or excess affect cortical bone more often than trabecular bone. 10.1016/j.maturitas.2020.05.004
Pathogenic mechanisms of glucocorticoid-induced osteoporosis. Cytokine & growth factor reviews Glucocorticoid (GC) is one of the most prescribed medicines to treat various inflammatory and autoimmune diseases. However, high doses and long-term use of GCs lead to multiple adverse effects, particularly glucocorticoid-induced osteoporosis (GIO). Excessive GCs exert detrimental effects on bone cells, including osteoblasts, osteoclasts, and osteocytes, leading to impaired bone formation and resorption. The actions of exogenous GCs are considered to be strongly cell-type and dose dependent. GC excess inhibits the proliferation and differentiation of osteoblasts and enhances the apoptosis of osteoblasts and osteocytes, eventually contributing to reduced bone formation. Effects of GC excess on osteoclasts mainly include enhanced osteoclastogenesis, increased lifespan and number of mature osteoclasts, and diminished osteoclast apoptosis, which result in increased bone resorption. Furthermore, GCs have an impact on the secretion of bone cells, subsequently disturbing the process of osteoblastogenesis and osteoclastogenesis. This review provides timely update and summary of recent discoveries in the field of GIO, with a particular focus on the effects of exogenous GCs on bone cells and the crosstalk among them under GC excess. 10.1016/j.cytogfr.2023.03.002
Male osteoporosis. Archives of endocrinology and metabolism Osteoporosis, a disease classically attributed to postmenopausal women, is underappreciated, underdiagnosed, and undertreated in men. However, it is not uncommon for osteoporotic fractures to occur in men. About 40% of fractures occur in men with an incidence that has increased over the years. After a first fracture, the risk of a subsequent episode, as well as the risk of death, is higher in the male than in the female population. Despite these facts, only 10% of men with osteoporosis receive adequate treatment. Up to half of the cases of male osteoporosis have a secondary cause, the most common being hypogonadism, excessive alcohol consumption, and chronic use of glucocorticoids. The International Society for Clinical Densitometry (ISCD) recommends using the female database for the diagnosis of osteoporosis by DXA (T-score ≤ -2.5 in men over 50 years old). In addition, osteoporosis can also be diagnosed independently of the BMD if a fragility fracture is present, or if there is a high risk of fractures by FRAX. Treatment is similar to postmenopausal osteoporosis, because the data regarding changes in bone density track closely to those in women. Data concerning fracture risk reduction are not as certain because the clinical trials have included fewer subjects for shorter period of time. In men with symptomatic hypogonadism, testosterone replacement, if indicated, can improve BMD. 10.20945/2359-3997000000563
Treatment Sequence for Osteoporosis. Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists BACKGROUND:Osteoporosis is a chronic progressive disease that requires lifelong monitoring and treatment. Sequencing from one treatment to another at different ages and stages of disease is an approach that can maximize benefits and avoid potential risks from long-term treatment with a single agent. OBJECTIVE:This article reviews clinical trial data in postmenopausal women that evaluate the effects of antiresorptive agents followed by other antiresorptives, osteoanabolic agents followed by antiresorptives, and antiresorptives followed by osteoanabolic medications. METHODS:Literature review and discussion. RESULTS:When medications are discontinued, in the absence of sequential therapy, bone turnover rates return to baseline or above baseline, and bone loss occurs. The rate of bone loss differs for different treatments, with a very slow decline after stopping bisphosphonates and a particularly rapid decline after stopping denosumab. Careful attention to osteoporosis medication transitions can mitigate bone density loss and its consequences. For women who remain at high risk, switching from bisphosphonates to the more potent antiresorptive, denosumab, will result in further improvement in bone mineral density (BMD). When indicated, stopping denosumab can be accomplished safely by transition to an adequate bisphosphonate regimen. For high- and very-high-risk patients, treating with osteoanabolic agents first, followed by antiresorptive agents, produces substantially larger BMD gains than the reverse treatment sequence, with the biggest differences seen for BMD of the hip. CONCLUSION:Awareness of the importance of treatment sequences can help improve osteoporosis care across the postmenopausal lifespan. 10.1016/j.eprac.2024.01.014
Osteoporosis and diabetes: The dual pandemics. JPMA. The Journal of the Pakistan Medical Association Bone health is an important, but neglected aspect of diabetes care. People with type 1 diabetes are known to have a lower bone mineral density (BMD), which put them at a greater risk of osteoporosis and fractures. While BMD in those with type 2 diabetes is often misleading, multiple factors operate to increase the risk of falls and fractures in them. This article provides an overview of osteoporosis in diabetes. It proposes a LEMON mnemonic to understand the multifaceted aspects of bone care. 10.47391/JPMA.22-86
Postmenopausal Osteoporosis. The New England journal of medicine 10.1056/NEJMcp2307353
Molecular and Cellular Mechanisms of Osteoporosis. International journal of molecular sciences Osteoporosis is a widespread systemic disease characterized by a decrease in bone mass and an imbalance of the microarchitecture of bone tissue. Experimental and clinical studies devoted to investigating the main pathogenetic mechanisms of osteoporosis revealed the important role of estrogen deficiency, inflammation, oxidative stress, cellular senescence, and epigenetic factors in the development of bone resorption due to osteoclastogenesis, and decreased mineralization of bone tissue and bone formation due to reduced function of osteoblasts caused by apoptosis and age-depended differentiation of osteoblast precursors into adipocytes. The current review was conducted to describe the basic mechanisms of the development of osteoporosis at molecular and cellular levels and to elucidate the most promising therapeutic strategies of pathogenetic therapy of osteoporosis based on articles cited in PubMed up to September 2023. 10.3390/ijms242115772
Osteoporosis. Annals of internal medicine Osteoporosis is a common systemic skeletal disorder resulting in bone fragility and increased fracture risk. Evidence-based screening strategies improve identification of patients who are most likely to benefit from drug treatment to prevent fracture. In addition, careful consideration of when pharmacotherapy should be started, choice of medication, and duration of treatment maximizes the benefits of fracture prevention while minimizing potential harms of long-term drug exposure. 10.7326/AITC202401160
Update on Osteoporosis Screening and Management. Anam Anika K,Insogna Karl The Medical clinics of North America Osteoporosis is a metabolic bone disease characterized by low bone mass and microarchitectural deterioration of bone tissue leading to an increased risk of fragility fractures. Central dual-energy X-ray absorptiometry measurements are the gold standard for determining bone mineral density. A well-balanced diet containing adequate amounts of calcium and vitamin D, exercise, smoking cessation, and limited alcohol intake are important to maintain bone health. Pharmacologic agents should be recommended in postmenopausal women who are at high risk for fractures. Newer anabolic therapies including teriparatide, abaloparatide, and romosozumab have emerged for use in severe osteoporosis. 10.1016/j.mcna.2021.05.016
Osteoporosis: An Update on Screening, Diagnosis, Evaluation, and Treatment. Orthopedics Osteoporosis screening, diagnosis, and treatment have gained much attention in the health care community over the past 2 decades. During this time, creation of multispecialty awareness programs (eg, "Own the Bone," American Orthopedic Association; "Capture the Fracture," International Osteoporosis Foundation) and improvements in diagnostic protocols have been evident. Significant advances in technology have elucidated elements of genetic predisposition for decreased bone mineral density in the aging population. Additionally, several novel drug therapies have entered the market and provide more options for primary care and osteoporosis specialists to medically manage patients at risk for fragility fractures. Despite this, adherence to osteoporosis screening and treatment protocols has been surprisingly low by health care practitioners, including orthopedic surgeons. Continued awareness and education of this skeletal disorder is crucial to effectively care for our aging population. [. 2023;46(1):e20-e26.]. 10.3928/01477447-20220719-03
Osteoporosis in Men: A Review of an Underestimated Bone Condition. International journal of molecular sciences Osteoporosis is called the 'silent disease' because, although it does not give significant symptoms when it is not complicated, can cause fragility fractures, with serious consequences and death. Furthermore, the consequences of osteoporosis have been calculated to weigh heavily on the costs of health systems in all the countries. Osteoporosis is considered a female disease. Actually, the hormonal changes that occur after menopause certainly determine a significant increase in osteoporosis and the risk of fractures in women. However, while there is no doubt that women are more exposed to osteoporosis and fragility fractures, the literature clearly indicates that physicians tend to underestimate the osteoporosis in men. The review of the literature done by the authors shows that osteoporosis and fragility fractures have a high incidence also in men; and, furthermore, the risk of fatal complications in hip fractured men is higher than that for women. The authors report the evidence of the literature on male osteoporosis, dwelling on epidemiology, causes of osteoporosis in men, diagnosis, and treatment. The analysis of the literature shows that male osteoporosis is underscreened, underdiagnosed, and undertreated, both in primary and secondary prevention of fragility fractures. 10.3390/ijms22042105
Molecular Mechanisms and Emerging Therapeutics for Osteoporosis. Noh Ji-Yoon,Yang Young,Jung Haiyoung International journal of molecular sciences Osteoporosis is the most common chronic metabolic bone disease. It has been estimated that more than 10 million people in the United States and 200 million men and women worldwide have osteoporosis. Given that the aging population is rapidly increasing in many countries, osteoporosis could become a global challenge with an impact on the quality of life of the affected individuals. Osteoporosis can be defined as a condition characterized by low bone density and increased risk of fractures due to the deterioration of the bone architecture. Thus, the major goal of treatment is to reduce the risk for fractures. There are several treatment options, mostly medications that can control disease progression in risk groups, such as postmenopausal women and elderly men. Recent studies on the basic molecular mechanisms and clinical implications of osteoporosis have identified novel therapeutic targets. Emerging therapies targeting novel disease mechanisms could provide powerful approaches for osteoporosis management in the future. Here, we review the etiology of osteoporosis and the molecular mechanism of bone remodeling, present current pharmacological options, and discuss emerging therapies targeting novel mechanisms, investigational treatments, and new promising therapeutic approaches. 10.3390/ijms21207623
Osteoporosis: Pathophysiology and therapeutic options. EXCLI journal Osteoporosis is a metabolic bone disease that, on a cellular level, results from osteoclastic bone resorption not compensated by osteoblastic bone formation. This causes bones to become weak and fragile, thus increasing the risk of fractures. Traditional pathophysiological concepts of osteoporosis focused on endocrine mechanisms such as estrogen or vitamin D deficiency as well as secondary hyperparathyroidism. However, research over the last decades provided exiting new insights into mechanisms contributing to the onset of osteoporosis, which go far beyond this. Selected mechanisms such as interactions between bone and the immune system, the gut microbiome, and cellular senescence are reviewed in this article. Furthermore, an overview on currently available osteoporosis medications including antiresorptive and bone forming drugs is provided and an outlook on potential future treatment options is given. 10.17179/excli2020-2591
Ferroptosis: A New Regulatory Mechanism in Osteoporosis. Liu Pan,Wang Wenzhao,Li Zheng,Li Yao,Yu Xiaoping,Tu Ji,Zhang Zhengdong Oxidative medicine and cellular longevity Osteoporosis can be caused by a multitude of factors and is defined by a decrease in bone density and mass caused by the destruction of bone microstructure, resulting in increased bone brittleness. Thus, it is a systemic bone disease in which patients are prone to fracture. The role of ferroptosis in the pathogenesis of osteoporosis has become a topic of growing interest. In this review, we discuss the cell morphology, basic mechanisms of ferroptosis, the relationship between ferroptosis and osteoclasts and osteoblasts, as well as the relationship between ferroptosis and diabetic osteoporosis, steroid-induced osteoporosis, and postmenopausal osteoporosis. Emerging biomedical research has provided new insights into the roles of ferroptosis and osteoporosis, such as in cellular function, signaling pathways, drug inhibition, and gene silencing. The pathophysiology and mechanism of ferroptosis and osteoporosis need to be further studied and elucidated to broaden our understanding of iron metabolism and immune regulation. Studies using animal models of osteoporosis in vivo and cell models in vitro will help clarify the relationship between ferroptosis and osteoporosis and provide research ideas for the elucidation of new mechanisms and development of new technologies and new drugs for the treatment of osteoporosis in the future. 10.1155/2022/2634431
Mitochondrial quality control and its role in osteoporosis. Frontiers in endocrinology Mitochondria are important organelles that provide cellular energy and play a vital role in cell differentiation and apoptosis. Osteoporosis is a chronic metabolic bone disease mainly caused by an imbalance in osteoblast and osteoclast activity. Under physiological conditions, mitochondria regulate the balance between osteogenesis and osteoclast activity and maintain bone homeostasis. Under pathological conditions, mitochondrial dysfunction alters this balance; this disruption is important in the pathogenesis of osteoporosis. Because of the role of mitochondrial dysfunction in osteoporosis, mitochondrial function can be targeted therapeutically in osteoporosis-related diseases. This article reviews different aspects of the pathological mechanism of mitochondrial dysfunction in osteoporosis, including mitochondrial fusion and fission, mitochondrial biogenesis, and mitophagy, and highlights targeted therapy of mitochondria in osteoporosis (diabetes induced osteoporosis and postmenopausal osteoporosis) to provide novel targets and prevention strategies for the prevention and treatment of osteoporosis and other chronic bone diseases. 10.3389/fendo.2023.1077058
T-Cell Mediated Inflammation in Postmenopausal Osteoporosis. Frontiers in immunology Osteoporosis is the most prevalent metabolic bone disease that affects half the women in the sixth and seventh decade of life. Osteoporosis is characterized by uncoupled bone resorption that leads to low bone mass, compromised microarchitecture and structural deterioration that increases the likelihood of fracture with minimal trauma, known as fragility fractures. Several factors contribute to osteoporosis in men and women. In women, menopause - the cessation of ovarian function, is one of the leading causes of primary osteoporosis. Over the past three decades there has been growing appreciation that the adaptive immune system plays a fundamental role in the development of postmenopausal osteoporosis, both in humans and in mouse models. In this review, we highlight recent data on the interactions between T cells and the skeletal system in the context of postmenopausal osteoporosis. Finally, we review recent studies on the interventions to ameliorate osteoporosis. 10.3389/fimmu.2021.687551
Postmenopausal Osteoporosis: Latest Guidelines. Arceo-Mendoza Rod Marianne,Camacho Pauline M Endocrinology and metabolism clinics of North America Significant development has occurred in the treatment of postmenopausal osteoporosis. We review the most recent guidelines from the American Association of Clinical Endocrinologists/American College of Endocrinology, Endocrine Society, and the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis/International Osteoporosis Foundation Guidelines. 10.1016/j.ecl.2021.03.009
Osteoporosis in Older Adults. Johnston Catherine Bree,Dagar Meenakshi The Medical clinics of North America Osteoporosis and osteoporosis-related fractures are common causes of morbidity and mortality in older adults. Healthy adults should be counseled about measures to prevent osteoporosis. Women should be screened for osteoporosis beginning at age 65. Screening for osteoporosis in men should be considered when risk factors are present. Appropriate screening intervals are controversial. Women and men with osteoporosis should be offered pharmacologic therapy. Choice of therapy should be based on safety, cost, convenience, and other patient-related factors. Bisphosphonates are a first-line therapy for many patients with osteoporosis. Other treatments for osteoporosis include denosumab, teriparatide, abaloparatide, romosozumab, and selective estrogen receptor modulators. 10.1016/j.mcna.2020.06.004
Advances in pathogenesis and therapeutic strategies for osteoporosis. Pharmacology & therapeutics Osteoporosis, is the most common bone disorder worldwide characterized by low bone mineral density, leaving affected bones vulnerable to fracture. Bone homeostasis depends on the precise balance between bone resorption by osteoclasts and bone matrix formation by mesenchymal lineage osteoblasts, and involves a series of complex and highly regulated steps. Bone homeostasis will be disrupted when the speed of bone resorption is faster than bone formation. Based on various regulatory mechanisms of bone homeostasis, a series of drugs targeting osteoporosis have emerged in clinical practice, including bisphosphonates, selective estrogen receptor modulators, calcitonin, molecular-targeted drugs and so on. However, many drugs have major adverse effects or are unsuitable for long-term use. Therefore, it is very urgent to find more effective therapeutic drugs based on the new pathogenesis of osteoporosis. In this review, we summarize novel mechanisms involved in the pathological process of osteoporosis, including the roles of gut microbiome, autophagy, iron balance and cellular senescence. Based on the above pathological mechanism, we found promising drugs for osteoporosis treatment, such as: probiotics, alpha-ketoglutarate, senolytics and hydrogen sulfide. This new finding may provide an important basis for elucidating the complex pathological mechanisms of osteoporosis and provide promising drugs for clinical osteoporosis treatment. 10.1016/j.pharmthera.2022.108168