Bone Remodeling Process Research Articles

The Potential Mechanism of Soy Isoflavones in Treating Osteoporosis: Focusing on Bone Metabolism and Oxidative Stress.

Osteoporosis is divided into primary and secondary types. Primary osteoporosis may result from estrogen deficiency in postmenopausal women, imbalanced bone remodeling in the elderly, or imbalanced adolescent-type bone development. Secondary osteoporosis can be caused by factors like long-term glucocorticoid treatment, chronic kidney disease (CKD), estrogen deprivation, oxidative stress, diabetes, and obesity. This review focuses on the therapeutic potential of soy isoflavones for osteoporosis. At the cellular level, soy isoflavones, as natural plant extracts and phytoestrogens, are crucial for osteoblastogenesis and differentiation, osteoclastogenesis, osteoclast mineralization, and bone marrow mesenchymal stromal cell differentiation. They also maintain calcium homeostasis by regulating extracellular calcium and vitamin D levels. In terms of oxidative stress, soy isoflavones mitigate it in the endoplasmic reticulum and mitochondria, thus regulating cellular senescence, autophagy, and bone remodeling processes. Moreover, soy isoflavones can relieve symptoms related to CKD and inhibit glucocorticoid secretion, which directly or indirectly benefits the treatment of osteoporosis. Overall, soy isoflavones have the potential to treat osteoporosis by enhancing bone health, regulating metabolism, and alleviating oxidative stress. Future research should explore the potential of soy isoflavones as phytoestrogens for treating osteoporosis. This exploration should focus on clarifying the safety, identifying potential side effects, determining the optimal dosage regimen, and developing strategies to mitigate any adverse reactions. In addition, further large-scale, multicenter human clinical trials are necessary to accurately evaluate the actual therapeutic effect of soy isoflavones on osteoporosis.

Enhanced healing of critical-sized bone defects using degradable scaffolds with tailored composition through immunomodulation and angiogenesis

The impact of orthopedic scaffolds on bone defect healing, particularly the late-stage bone remodeling process, is pivotal for the therapeutic outcome. This study applies fadditively manufactured scaffolds composed of hydroxyapatite-doped poly(lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(lactide-co-glycolide) (HA-PELGA) with varying properties to treat rat calvarial defects, elucidating their significant role in bone remodeling by modulating physiological responses. We engineered two scaffolds with different polylactic acid (PLA) to polyglycolic acid (PGA) ratio (9/1 and 18/1) to vary in hydrophobicity, degradation rate, mechanical properties, and structural stability. These variations influenced physiological responses, including osteogenesis, angiogenesis, and immune reactions, thereby guiding bone remodeling. Our findings show that the HA-PELGA(18/1) scaffold, with a slower degradation rate, supported bulk bone formation due to a stable microenvironment. Conversely, the HA-PELGA(9/1) scaffold, with a faster degradation rate and more active interfaces, facilitated the formation of a thin bone layer and higher bone infiltration. This study demonstrates these degradable scaffolds help to promote bone healing and reveals how scaffold properties influence the bone remodeling process, offering a potential strategy to optimize scaffold design aiming at late-stage bone defect healing.

Non-Canonical Wnt16 and microRNA-145 Mediate the Response of Human Bone Marrow Stromal Cells to Additively Manufactured Porous 3-Dimensional Biomimetic Titanium–Aluminum–Vanadium Constructs

Metal 3D printing is increasingly being used to manufacture titanium–aluminum–vanadium (Ti6Al4V) implants. In vitro studies using 2D substrates demonstrate that the osteoblastic differentiation of bone marrow stromal cells (MSCs) on Ti6Al4V surfaces, with a microscale/nanoscale surface topography that mimics an osteoclast resorption pit, involves non-canonical Wnt signaling; Wnt3a is downregulated and Wnt5a is upregulated, leading to the local production of BMP2 and semaphorin 3A (sema3A). In this study, it was examined whether the regulation of MSCs in a 3D environment occurs by a similar mechanism. Human MSCs from two different donors were cultured for 7, 14, or 21 days on porous (3D) or solid (2D) constructs fabricated by powder-bed laser fusion. mRNA and secretion of osteoblast markers, as well as factors that enhance peri-implant osteogenesis, were analyzed, with a primary focus on the Wnt family, sema3A, and microRNA-145 (miR-145) signaling pathways. MSCs exhibited greater production of osteocalcin, latent and active TGFβ1, sema3A, and Wnt16 on the 3D constructs compared to 2D, both of which had similar microscale/nanoscale surface modifications. Wnt3a was reduced on 2D constructs as a function of time; Wnt11 and Wnt5a remained elevated in the 3D and 2D cultures. To better understand the role of Wnt16, cultures were treated with rhWnt16; endogenous Wnt16 was blocked using an antibody. Wnt16 promoted proliferation and inhibited osteoblast differentiation, potentially by reducing production of BMP2 and BMP4. Wnt16 expression was reduced by exogenous Wnt16 in 3D cells. Addition of the anti-Wnt16 antibody to the cultures reversed the effects of exogenous Wnt16, indicating an autocrine mechanism. Wnt16 increased miR-145-5p, suggesting a potential feedback mechanism. The miR-145-5p mimic increased Wnt16 production and inhibited sema3A in a 3D porous substrate-specific manner. Wnt16 did not affect sema3A production, but it was reduced by miR-145-5p mimic on the 3D constructs and stimulated by miR-145-5p inhibitor. Media from 7-, 14-, and 21-day cultures of MSCs grown on 3D constructs inhibited osteoclast activity to a greater extent than media from the 2D cultures. The findings present a significant step towards understanding the complex molecular interplay that occurs in 3D Ti6Al4V constructs fabricated by additive manufacturing. In addition to enhancing osteogenesis, the 3D porous biomimetic structure inhibits osteoclast activities, indicating its role in modulating bone remodeling processes. Our data suggest that the pathway mediated by sema3A/Wnt16/miR145-5p was enhanced by the 3D surface and contributes to bone regeneration in the 3D implants. This comprehensive exploration contributes valuable insights to guide future strategies in implant design, customization, and ultimately aims at improving clinical outcomes and successful osseointegration.

The Impact of Traditional Chinese Medicines on Osteoclastogenesis through NF-κB Signaling Pathway: A Review

Osteoclasts are specialized cells responsible for bone resorption, which plays a crucial role in the dynamic processes of bone remodeling and maintenance. Osteolytic skeletal disorders, such as osteoporosis, arise from an imbalance between the activities of osteoclasts and osteoblasts. The regulatory mechanisms underlying osteoclast differentiation, known as osteoclastogenesis, are governed by the receptor activator of nuclear factor kappa-B ligand (RANKL)/receptor activator of NF-κB (RANK)/osteoprotegerin (OPG) signaling system. In this system, the RANK, a type 1 transmembrane protein, acts as a central regulator of osteoclastogenesis through various signaling pathways. This review seeks to explore the influence of Traditional Chinese Medicines (TCM) on osteoclastogenesis, focusing on the NF-κB signaling pathway. This study aims to offer valuable insights into potential therapeutic strategies for managing osteolytic skeletal disorders by investigating the interaction between TCM and the regulatory mechanisms that control osteoclast function. A comprehensive literature review was conducted, concentrating on studies that examine the effects of TCM on osteoclastogenesis and the NF-κB signaling pathway. Databases such as PubMed, Web of Science, and Google Scholar were searched for peer-reviewed articles, reviews, and clinical studies. The inclusion criteria focused on studies addressing the impact of TCM on osteoclast function and the associated molecular mechanisms, especially those involving the RANKL/RANK/OPG system and the NF-κB pathway. The review identified several TCM compounds with regulatory effects on osteoclastogenesis. These compounds were found to modulate the NF-κB pathway, influencing osteoclast differentiation and activity. Key findings highlighted the discovery of specific TCM herbs and their active ingredients that can inhibit osteoclast formation and function, promoting bone health. The mechanisms of action often involved suppressing RANKL-induced NF-κB activation, a crucial process for osteoclast differentiation and bone resorption. This review underscores the potential of TCMs as therapeutic agents for osteolytic skeletal disorders through their modulation of the NF-κB signaling pathway. The findings suggest that TCM may significantly regulate osteoclastogenesis, offering new avenues for developing treatments for conditions like osteoporosis. However, further research and clinical trials are necessary to fully elucidate the therapeutic potential of TCM and translate these findings into clinical practice.

Effect of initial bone morphology on alveolar bone remodeling following molar extraction: A retrospective study.

The clinical evidence about alveolar ridge changes following molar extraction and how the alveolar bone morphology influences the ridge dimensional changes remains limited. A total of 192 patients with 199 molar extractions were included in this retrospective study. Cone-beam computed tomography (CBCT) images of patients were obtained 0-3 months pre extraction and 6-12 months post extraction. Outcome variables included the change rate in ridge height and width. The effect of morphology on the outcomes was explored by single-factor analysis, correlation analysis, and a multiple linear regression model. Significant resorption of alveolar bone occurred vertically and horizontally after molar extraction. Jaw, furcation involvement, number of roots, number of bone wall defects, extraction reasons, overall relative bone loss (RBL), bone height of the furcation region, thickness of the lingual/palatal wall, and height difference between buccal and lingual/palatal walls (|HB-HL|) were significantly correlated with the change in the height of the central alveolar bone (HC). The number of bone wall defects, overall RBL, and |HB-HL| were significantly correlated with horizontal width change. HC resorption was higher in sockets with |HB-HL|>2.5mm and overall RBL>50%. The alveolar bone presented significant resorption after extraction. Anatomical characteristics affected the dimensions of the alveolar bone after molar extraction. When the initial overall RBL was severe or |HB-HL| was larger, the loss of alveolar bone dimensions was even more. In recent years, it has been demonstrated that the local anatomical morphology of extraction sites may influence the process of alveolar bone remodeling. However, most studies have focused on the anterior teeth, with fewer investigations addressing molar extraction sites. Therefore, we aimed to describe ridge changes following molar extraction and investigate how alveolar bone morphology influences ridge dimensional changes. In this retrospective study, we included a total of 199 alveolar sockets from 192 patients with molar extractions and obtained the corresponding cone-beam computed tomography (CBCT) images 0-3 months pre extraction and 6-12 months post extraction. The results showed significant resorption of the alveolar bone following molar extraction. We found that anatomical characteristics significantly affect the dimensions of the alveolar bone after molar extraction. Specifically, the loss of alveolar bone dimensions was greater when the initial overall relative bone loss (RBL) was severe or when the difference between buccal and lingual/palatal walls was greater.

The Differential Impact of Clear Aligners and Fixed Orthodontic Appliances on Periodontal Health: A Systematic Review

Background/objective: In orthodontic therapy, the periodontal ligament plays a critical role in the bone remodeling process by stimulating osteoblasts in tension zones and promoting bone resorption through osteoclasts in compression zones in response to mechanical stress. These processes are regulated by key cytokines, such as RANKL and IL-1, which are influenced by factors such as patient age and force application. This work evaluates the effectiveness of clear aligners versus traditional braces on periodontal health in patients with periodontitis, following PRISMA guidelines and utilizing specific inclusion and exclusion criteria. Methods: A systematic review of 1664 records was conducted, leading to the inclusion of eight studies that focus on the impact of orthodontic treatments on periodontal health. The review identifies various biases present in the literature. Results: The findings reveal that clear aligners, in contrast to fixed appliances, improve oral hygiene and reduce inflammation, leading to better periodontal outcomes. Fixed appliances, on the other hand, may exacerbate plaque accumulation and inflammation, which can worsen periodontal health. Conclusions: Clear aligners offer advantages over fixed appliances in terms of enhancing periodontal health, improving patient compliance, and providing long-term benefits, particularly in patients with severe periodontitis. The effectiveness of clear aligners is linked to better management of periodontal complications and overall oral hygiene. Treatment decisions should be based on patient-specific criteria to optimize outcomes.

Regulation of Bone Remodeling by Metal-Phenolic Networks for the Treatment of Systemic Osteoporosis.

Osteoporosis is a systemic metabolic disease that impairs bone remodeling by favoring osteoclastic resorption over osteoblastic formation. Nanotechnology-based therapeutic strategies focus on the delivery of drug molecules to either decrease bone resorption or increase bone formation rather than regulating the entire bone remodeling process, and osteoporosis interventions suffer from this limitation. Here, we present a multifunctional nanoparticle based on metal-phenolic networks (MPNs) for the treatment of systemic osteoporosis by regulating both osteoclasts and osteoblasts. In the osteoporotic microenvironment, the MPN nanoparticles degrade and trigger the release of bioactive metals (strontium ions, SrII) to promote osteogenesis and functionalized phenols (epigallocatechin gallate, EGCG) to suppress osteoclastogenesis. Injecting these nanoparticles into the tail vein of an ovariectomized mouse model, trabecular bone loss has been significantly prevented in the femoral head and vertebrae, along with increased trabecular bone volume and decreased trabecular bone separation. Overall, this work represents a versatile approach to explore MPN nanomaterials for the treatment of systemic osteoporosis and related orthopedic diseases.

The comparison of serum bone-turnover markers in different stage of chronic kidney disease and the associated impact of intradialytic cycling in patients with end-stage renal disease.

Bone turnover markers reflected the bone remodeling process and bone health in clinical studies. Studies on variation of bone remodeling markers in different stage CKD were scant, and this study investigated the role of bedside intradialytic cycling in altering concentrations of bone-remodeling markers in patients with end-stage renal disease (ESRD). Participants were segmented into four groups: a group with eGFR >60 ml/min/1.73 m2, a chronic kidney disease group with eGFR 15-60 mL/min/1.73 m2), an ESRD group with an exercise intervention, and an ESRD group with standard care. Comparison of bone turnover markers was performed among groups. The intervention consisting of 12 weeks of intradialytic cycling was performed during dialysis. The variation of bone-remodeling markers was compared between the ESRD with exercise along with the ESRD with standard care after 12-week monitoring. Bone-formative marker levels (bone-specific alkaline phosphatase and procollagen type 1 amino-terminal propeptide, P1NP) were higher in ESRD patients than in non-ESRD patients and were correlated with indoxyl sulfate and intact parathyroid hormone concentrations (p < 0.05). Postexercise concentrations of tartrate-resistant acid phosphatase-5b (p = 0.003) and N-terminal telopeptide-1 (p = 0.001) had increased in the ESRD patients after 12 weeks of bedside cycling. Bone-formative marker concentration was not altered in the exercise group after cycling. Bone-formative marker concentrations increased with the severity of chronic kidney disease. Bone formative markers concentration increased along with CKD severity. We demonstrated the bone resorptive markers tartrate-resistant acid phosphatase-5b and N-terminal telopeptide-1 increased after intradialytic cycling in ESRD patients.

Bioactive Compounds from Propolis on Bone Homeostasis: A Narrative Review.

This narrative review explores the potential effects of Propolis and its bioactive compounds on bone health. Propolis, a resinous product collected by bees, is renowned for its antimicrobial, anti-inflammatory, and antioxidant properties. Recent research emphasizes its positive role in osteogenesis, primarily through the modulation of osteoclast and osteoblast activity via molecular pathways. Key mechanisms include reducing inflammatory cytokines, protecting against oxidative stress, and upregulating growth factor essential for bone formation. While compounds such as Caffeic Acid Phenethyl Ester, Apigenin, Quercetin, and Ferulic Acid have been well-documented, emerging evidence points to the significant roles of less-studied compounds like Pinocembrin, Kaempferol, p-Coumaric acid, and Galangin. This review synthesizes the current literature, focusing on the mechanisms by which these bioactive compounds influence osteogenesis. Firstly, it explores the techniques for characterizing bioactive compounds presented in propolis, the chemogeographic variations in its composition, and the effects of both crude extracts and isolated compounds on bone tissue, offering a comprehensive analysis of recent findings across different experimental models. Further, it discusses the effects of Propolis compounds on bone health. In summary, these compounds modulate signaling pathways, including nuclear factor kappa beta, wingless-related integration site, mitogen-activated protein kinase, vascular endothelial growth factor, and reactive oxygen species. These pathways influence the receptor activator of nuclear factor kappa-β/receptor activator of nuclear factor kappa-β ligand/osteoprotegerin system, fostering bone cell differentiation. This regulation mitigates excessive osteoclast formation, stimulates osteoblast activity, and ultimately contributes to the restoration of bone homeostasis by maintaining a balanced bone remodeling process.

Alternating electrical fields to stimulate osteogenic cells and biomimetic calcium phosphate-coated titanium substrates-A combinatorial approach to bone regeneration.

Biophysical stimuli such as alternating electrical fields can mimic endogenous electrical potentials and currents in natural bone. This can help to improve the healing and reconstruction of bone tissue. However, little is known about the combined influence of biomaterials and alternating electric fields on bone cells. Therefore, this study aimed to investigate the impact of both, biomaterials and alternating electric fields, on osteoblast as well as osteoclast differentiation. Initially, either RAW 264.7 or MC3T3-E1 cells were seeded on Ti6Al4V substrates as a load-bearing implant material, modified with biomimetic calcium phosphate (BCP), or uncoated as a reference. The cells were stimulated towards osteoclastic and osteoblastic differentiation via respective growth factors. The effects of BCP substrate modification on cell differentiation were examined after 7days for RAW 264.7 and after 14days for MC3T3-E1 cells. In a further series of tests, either RAW 264.7 or MC3T3-E1 cells were seeded on BCP-modified Ti6Al4V substrates, stimulated towards differentiation using growth factors, and further electrically stimulated via alternating electric fields of different voltages and frequencies. In parallel to the first test series RAW 264.7 and MC3T3-E1 cells were stimulated for 7 and 14days, respectively. Cell morphology was examined via scanning electron microscopy. Cell viabilities were assessed via WST-8 assay. Electrically stimulated MC3T3-E1 cell orientation was evaluated based on fluorescence microscopy images. Marker genes were examined via qPCR. While BCP increased osteoclast-specific gene expression, it had the opposite effect on osteoblast-related genes compared to respective cells seeded on uncoated Ti6Al4V substrates. ES with different parameters showed a broad cellular response due to electrocoupling. While cell viability assessments and gene expression analyses showed clear differences between ES samples and unstimulated controls, only minor cell morphology and orientation differences were observed. Furthermore, there was no clear trend towards a dominant influence of either voltage or frequency as control parameters. Further studies were initiated to investigate the underlying intracellular mechanisms targeted by ES. This work provides an introduction to the targeted control of cellular processes using defined electric fields. The optimization of voltage and frequency could provide therapeutic windows to control specific cellular functions and potentially improve bone regeneration and remodeling processes.

The Role of the Periosteum in Bone Formation From Adolescence to Old Age.

Bone formation is a complex process involving the coordinated activity of many different cell types, including osteoblasts and osteocytes. The periosteum is a dense membrane of connective tissue that covers the outer surface of bones and is essential for the growth, repair, and maintenance of osseous tissue. The present study aims to summarize the contribution of the periosteum in bone formation from adolescence to adulthood and old age. This is a narrative literature review using the PubMed electronic internet database. The search was based on the keyword "periosteal bone formation". Inclusion criteria were preclinical or clinical studies evaluating the role of the periosteum in bone formation. Non-English studies were excluded. The original search provided 126 published papers. After inclusion and exclusion criteria, we finally accepted 20 articles for our current review. After checking the references list of the included studies, 14 more studies were added, leaving 34 studies for the present review. Across the lifespan, periosteal bone formation undergoes dynamic changes. During adolescence, the periosteum is highly osteogenic and actively contributes to rapid bone growth. In adulthood, it plays a role in maintaining bone strength and adapting to mechanical loading. In adulthood, the periosteum continues to provide a source of osteoprogenitor cells, which contribute to the ongoing process of bone remodeling and repair. At more advanced ages, the response of the periosteum to hormones and cytokines in terms of bone formation decreases; however, the power of osteogenetic differentiation of periosteal cells may be preserved.

Transcriptional regulation of Rankl by Txnip-Ecd in aging and diabetic related osteoporosis.

Bone homeostasis between osteoclast bone resorption and osteoblastic bone formation is tightly regulated by a series of factors such as the receptor activator of nuclear factor-κB ligand (RANKL). Denosumab that neutralizes RANKL is effective and widely applied in the treatment of postmenopausal osteoporosis. However, factors that participated in the RANKL-related bone remodeling process in primary and secondary osteoporosis are less known. Revealing the novel transcriptional regulatory mechanism of RANKL is of great significance for the treatment of osteoporosis. After differential expression genes (DEGs) intersection and screening, we generated Thioredoxin-interacting protein (Txnip) bone marrow-derived mesenchymal stromal cells (BMSCs) genetic knockout mice and performed bone histomorphometry and histological analysis. RNA-Sequencing, Western blotting and immunofluorescence staining verified Rankl downregulation. Co-immunoprecipitation and immunofluorescence staining were used for Rankl regulation mechanism exploration. A specific inhibitor was selected for treatment effect verification. Txnip knockout in BMSCs impaired its osteogenic differentiation, suppressed Rankl expression and subsequent osteoclast formation and thus led to increased bone mass. The regulatory function of Txnip on Rankl expression was revealed for the first time through the novel transcription-related Ecdysoneless (Ecd)-P300 axis. Pharmacological inhibition of Txnip can effectively prevent bilateral ovariectomy (OVX)-induced osteoporosis. Inhibition of Txnip is an alternative way to suppress Rankl-mediated osteoblast and osteoclast crosstalk. This interesting finding rendered Txnip an ideal therapeutic target for the treatment of both ovariectomy-induced and diabetes-induced osteoporosis.

Metabolism-Related Adipokines and Metabolic Diseases: Their Role in Osteoarthritis.

Osteoarthritis (OA) affects several joints but tends to be more prevalent in those that are weight-bearing, such as the knees, which are the most heavily loaded joints in the body. The incidence and disability rates of OA have continued to increase and seriously jeopardise the quality of life of middle-aged and older adults. However, OA is more than just a wear and tear disease; its aetiology is complex, and its pathogenesis is poorly understood. Metabolic syndrome (MetS) has emerged as a critical driver of OA development. This condition contributes to the formation of a distinct phenotype, termed metabolic syndrome-associated osteoarthritis (MetS-OA),which differs from other metabolically related diseases by its unique pathophysiological mechanisms and clinical presentation. As key mediators of MetS, metabolic adipokines such as leptin, lipocalin, and resistin regulate inflammation and bone metabolism through distinct or synergistic signaling pathways. Their modulation of inflammatory responses and bone remodeling processes plays a critical role in the pathogenesis and progression of OA. Due to their central role in regulating inflammation and bone remodeling, metabolic adipokines not only deepen our understanding of MetS-OA pathogenesis but also represent promising targets for novel therapeutic strategies that could slow disease progression and improve clinical outcomes in affected patients.

Is Tumor Growth Influenced by the Bone Remodeling Process?

In this study, we develop a comprehensive model to investigate the intricate relationship between the bone remodeling process, tumor growth, and bone diseases such as multiple myeloma. By analyzing different scenarios within the Basic Multicellular Unit, we uncover the dynamic interplay between remodeling and tumor progression. The model developed developed in the paper are based on the well accepted Komarova's and Ayati's models for the bone remodeling process, then these models were modified to include the effects of the tumor growth. Our in silico experiments yield results consistent with existing literature, providing valuable insights into the complex dynamics at play. This research aims to improve the clinical management of bone diseases and metastasis, paving the way for targeted interventions and personalized treatment strategies to enhance the quality of life for affected individuals.

Inhibitory Effects of Oil Palm Leaf Extract on Osteoclastogenesis in RAW 264.7 Macrophages

Osteoporosis is a bone disorder caused by an imbalance in the bone remodelling process, specifically between osteoblastogenesis and osteoclastogenesis, and is associated with increased oxidative stress. This study aims to investigate the antioxidant activity of oil palm leaf extracts (OPLEs) and their effects on osteoclastogenesis in murine macrophages (RAW 264.7), comparing the results with those of vitamin C (VC). Methanol extract of oil palm leaves (MEOPL) demonstrated the highest total phenolic content (TPC) at 284.26 mg GAE/g dry weight. The antioxidant activity, assessed via DPPH scavenging and FRAP assays, showed that MEOPL had a DPPH inhibition rate of 89.41% and a FRAP value of 105.67%. In cytotoxicity assays, MEOPL-treated cells exhibited significantly higher viability compared to VC-treated cells, with viability percentages exceeding 60% at concentrations up to 0.625 mg/mL. MEOPL also significantly reduced osteoclastogenesis, as indicated by a dose-dependent decrease in TRAP-positive multinucleated cells and a notable reduction in RANKL gene expression. These findings suggest that MEOPL possesses superior anti-osteoclastogenic properties compared to VC and holds promise as a potential therapeutic agent for the prevention and treatment of osteoporosis. However, as this study utilised an in vitro model, the direct translation of these results to clinical scenarios is limited, and further in vivo studies are necessary to confirm the clinical relevance of MEOPL.

Primary Osteoporosis Induced by Androgen and Estrogen Deficiency: The Molecular and Cellular Perspective on Pathophysiological Mechanisms and Treatments.

Primary osteoporosis is closely linked to hormone deficiency, which disrupts the balance of bone remodeling. It affects postmenopausal women but also significantly impacts older men. Estrogen can promote the production of osteoprotegerin, a decoy receptor for RANKL, thereby preventing RANKL from activating osteoclasts. Furthermore, estrogen promotes osteoblast survival and function via activation of the Wnt signaling pathway. Likewise, androgens play a critical role in bone metabolism, primarily through their conversion to estrogen in men. Estrogen deficiency accelerates bone resorption through a rise in pro-inflammatory cytokines (IL-1, IL-6, TNF-α) and RANKL, which promote osteoclastogenesis. In the classic genomic pathway, estrogen binds to estrogen receptors in the cytoplasm, forming a complex that migrates to the nucleus and binds to estrogen response elements on DNA, regulating gene transcription. Androgens can be defined as high-affinity ligands for the androgen receptor; their combination can serve as a ligand-inducible transcription factor. Hormone replacement therapy has shown promise but comes with associated risks and side effects. In contrast, the non-genomic pathway involves rapid signaling cascades initiated at the cell membrane, influencing cellular functions without directly altering gene expression. Therefore, the ligand-independent actions and rapid signaling pathways of estrogen and androgen receptors can be harnessed to develop new drugs that provide bone protection without the side effects of traditional hormone therapies. To manage primary osteoporosis, other pharmacological treatments (bisphosphonates, teriparatide, RANKL inhibitors, sclerostin inhibitors, SERMs, and calcitonin salmon) can ameliorate osteoporosis and improve BMD via actions on different pathways. Non-pharmacological treatments include nutritional support and exercise, as well as the dietary intake of antioxidants and natural products. The current study reviews the processes of bone remodeling, hormone actions, hormone receptor status, and therapeutic targets of primary osteoporosis. However, many detailed cellular and molecular mechanisms underlying primary osteoporosis seem complicated and unexplored and warrant further investigation.

Unlocking the Epigenetic Symphony: Histone Acetylation Orchestration in Bone Remodeling and Diseases.

Histone acetylation orchestrates a complex symphony of gene expression that controls cellular fate and activities, including the intricate processes of bone remodeling. Despite its proven significance, a systematic illustration of this process has been lacking due to its complexity, impeding clinical application. In this review, we delve into the central regulators of histone acetylation, unveiling their multifaceted roles in modulating bone physiology. We explore both contradictory and overlapping roles among these regulators and assess their potential as therapeutic targets for various bone disorders. Furthermore, we highlight current applications and discuss looming questions for a more effective use of epigenetic therapy in bone diseases, aiming to address gaps in knowledge and clinical practice. By providing a panoramic view of histone acetylation's impact on bone health and disease, this review unveils promising avenues for therapeutic intervention and enhances our understanding of skeletal physiology, crucial for improving therapeutical outcomes and quality of patients' life.

Sex-specific association between platelet content and bone mineral density in adults: a cross-sectional study

BackgroundOsteoporosis (OP) is a complex skeletal disorder characterized by reduced bone mass, microarchitectural deterioration of bone tissue, and increased susceptibility to fractures. Bone mineral density (BMD), as the best indicator of bone mineral content per unit area of bone, is one of the key diagnostic factors for OP. Platelets (PLT), serving as important immune cells and components of the coagulation system, have been demonstrated to be associated with bone formation, resorption, and remodeling processes. However, no research has established the relationship between BMD and platelet count (PC) in the American population thus far. This study aims to investigate the correlation between BMD and PC among the American population, and to appraise the effects of additional risk factors on this association.MethodsThis investigation examined the relationship between BMD and PC by analyzing data from the National Health and Nutrition Examination Survey (NHANES) between 2011 and 2018. A weighted multivariate logistic regression analysis was employed to assess this correlation. Additionally, subgroup and smooth curve analyses were conducted to delve deeper into the BMD-PC relationship and to identify other potential determinants of PC.ResultsThis study reveals a significant negative correlation between BMD and PC in the American adult population (β=-15.05, 95% CI: -22.07 to -8.03, p < 0.0001). Subgroup analysis highlights notable differences in this correlation between genders and various racial groups. Smooth curve fitting and generalized additive models were applied to further explore the relationship between BMD and PC, considering the influence of multiple factors.ConclusionThe present study investigated the correlation between BMD and PC in adults, with a particular focus on the potential risk factors for thrombocytopenia. This negative correlation was found to be markedly pronounced in males, an association not observed in females. Additionally, a potential inverse relationship between BMD and hemoglobin (HGB) levels was identified. Consequently, for individuals with elevated bone mass or osteoporosis (OP), we advocate for routine complete blood count monitoring to identify hematological irregularities. Considering the significant variations by sex, age, and race, special vigilance is advised for changes in PC among non-Hispanic white males under the age of 55.

Evaluating Biomarkers of Bone Health After an 8-Week Walking Program in Non-Ambulatory Stroke Survivors: A Pilot Study.

Background/Objectives: Stroke survivors have a significantly increased likelihood of developing osteoporosis, a condition characterized by weak and brittle bones as well as an elevated risk of bone fractures. However, previous studies on exercise intervention have mostly been on stroke survivors who are able to walk. The objective of this study was to examine the effect of walking exercise on bone health in non-ambulatory stroke survivors. Methods: This pre- and post-test study enrolled a group of chronic non-ambulatory stroke survivors. They were instructed to complete an 8-week aerobic walking exercise program, three sessions per week. Serum concentrations of osteocalcin (OC) and carboxy-terminal telopeptides of type I collagen (ICTP) were evaluated at baseline and after completing the walking exercise program. In addition, we assessed the ambulation capacity and balance control using the functional ambulation category (FAC) and Berg Balance Scale (BBS), respectively. Results: A total of 9 out of 10 non-ambulatory stroke survivors who were recruited completed the intervention. The serum concentration of OC significantly increased from 8.51 ± 2.28 ng/mL to 9.39 ± 2.97 ng/mL (p < 0.10). The serum concentration of ICTP significantly increased from 4.45 ± 2.58 ng/mL to 5.31 ± 2.92 ng/mL (p < 0.10). Both FAC and BBS scores significantly improved from 1.0 ± 0 to 1.33 ± 0.5 (p < 0.1) and from 7.22 ± 10.02 to 15.78 ± 14.81 (p < 0.01), respectively. Conclusions: The findings of this pilot study suggest that walking exercise may improve bone health by initiating a bone remodeling process in chronic non-ambulatory stroke survivors.

Changes of bone turnover markers and bone mineral density among postmenopausal Thai women with osteoporosis receiving generic risedronate

BackgroundOsteoporosis has been recognized as a significant health issue in Thailand. Pharmacological interventions are important way to prevent fracture. However, one of the main challenges in selecting a medication is high cost, particularly for brand-name drugs. Data on generic bisphosphonate use in Thai are still lacking. Therefore, our study aimed to assess the efficacy and safety of generic risedronate in postmenopausal Thai women with osteoporosis.MethodsThis prospective study was conducted at King Chulalongkorn Memorial Hospital, Bangkok, Thailand, from December 2022 to January 2024. Serum C-terminal cross-linking telopeptide of type I collagen (CTX) and procollagen type I N-propeptide (P1NP) were measured at baseline. All participants subsequently received 35 milligrams of oral risedronate once weekly for 52 weeks. Serum CTX and P1NP were remeasured at different time points. BMD was reevaluated at 52 weeks after risedronate treatment initiation.ResultsA total of 80 participants were included. The mean age was 65.2 ± 6.6 years. The mean body mass index (BMI) was 23.45 ± 3.49 kg/m2. The median (IQR) serum CTX level at 12 weeks was significantly lower than that at baseline (0.28 (0.16–0.46) ng/mL versus 0.44 (0.26–0.64) ng/mL, respectively; p value < 0.01). The suppression of serum CTX was confirmed at 52 weeks after treatment initiation. Compared with those at baseline, the serum P1NP levels were significantly lower at 24 weeks after treatment initiation (30.33 (19.19–39.58) ng/mL versus 41.90 (30.33–68.67) ng/mL, respectively; p value < 0.01). In terms of the BMD assessment at 52 weeks, significant improvements were observed in both areal BMD (g/cm2) and T scores at all measured sites compared with baseline. The lumbar spine, femoral neck, and total hip BMD increased from baseline by 4.76%, 3.84% and 4.54%, respectively.ConclusionPostmenopausal women with osteoporosis who were treated with generic risedronate demonstrated significant suppression of the bone remodelling process at 3, 6, and 12 months after treatment initiation. Additionally, significant improvements in the lumbar spine, femoral neck, and total hip BMD were observed at 12 months of therapy. These findings suggest that generic risedronate could be considered a reasonable and interesting option for treating postmenopausal women with osteoporosis in Thailand.