Reduced Bone Density Research Articles

Investigation of the History of Distal Radius Fractures in Patients Over 55 Years Old Suffering from Hip Fractures.

This study aimed to examine the incidence of distal radius fractures in patients aged 55 and above who had also experienced hip fractures. Osteoporosis-associated fractures, particularly hip fractures, are common and serious in older individuals with reduced bone density. Previous research has suggested a relationship between hip fractures and distal radius fractures. The study included patients over 55 years old who had presented with hip fractures at Akhtar Hospital in the past five years. Patients with a history of hip fractures more than five years before experiencing the distal radius fracture were excluded. Personal information was extracted from medical records, and the collected data were analyzed in SPSS software using statistical methods, such as t-tests and paired t-tests. This study involved 1,745 patients with hip fractures and 183 individuals without fractures. The average age of the patients was 75.8±10.4 years old, with the majority being female (59.6%). Among the hip fractures, 59.6%, 34.5%, and 5.9% were intertrochanteric fractures, neck of femur fractures, and subtrochanteric fractures, respectively. Overall, 15.8% of individuals with hip fractures also had distal radius fractures. The average age and gender distribution of the patients were similar in both groups, with no significant difference. However, the prevalence of distal radius fractures was significantly higher in the hip fracture group, compared to the control group. It was found that individuals over the age of 55 with distal radius fractures, especially females, are more susceptible to hip fractures. Distal radius fractures have a significant impact on the occurrence of hip fractures in patients. Therefore, older individuals with osteoporosis should be cautious and avoid high-risk activities that could lead to falls and fractures.

Testosterone and Glucose Homeostasis in Adult Males: Current Insights and Future Prospects.

Insulin plays a central role in blood glucose regulation, with insulin resistance contributing to the progression of prediabetes to diabetes, underscoring the importance of early intervention. Androgens, primarily synthesized in the testis under pituitary gland influence, impact male reproductive function. Testosterone, crucial for sexual development and secondary male characteristics, declines with age, leading to issues like anemia, sexual dysfunction, and reduced bone density. Sex-specific differences in glucose metabolism highlight males' lower insulin sensitivity and less effective glucose utilization compared to females due to androgenic effects. Testosterone's intricate role extends to potential benefits in glycemic control, fat mass reduction, and muscle strength increase in men with diabetes. However, cautious consideration of testosterone therapy is crucial, especially in the presence of underlying health conditions, warranting further research for clear guidelines in managing hyperglycemia.

Macrophage Polarization and Its Impact on Osteoporosis.

Owing to its reduced bone density and higher risk for fractures, osteoporosis remains an international public health crisis. Research highlights the essential role played by macrophage polarization in osteoporosis and indicates that the balance between pro-inflammatory M1 macrophages and anti-inflammatory M2 macrophages influences bone metabolism. This review examines how M1 and M2 macrophages contribute to the development of osteoporosis and evaluates existing therapeutic approaches aimed at controlling macrophage polarization. It also describes future study areas that will allow improved management and treatment of osteoporosis.

Comparison of Cytokine RANTES/CCL5 Inflammation in Apical Periodontitis and in Jawbone Cavitations - Retrospective Clinical Study.

Apical periodontitis (AP) is one of the most common endodontic diseases associated with osteo destructive cytokine production. The literature also reports cytokine studies in fatty degenerative osteonecrotic bone marrow defects (BMDJ/FDOJ) independent of AP. We compare the RANTES/CCL5 (R/C) chemokine production between AP and BMDJ/FDOJ. For both pathologies, the R/C expression was also compared to radiographic diagnosis in 2D-OPG, 3D-CBCT/DVT. Postoperative samples were collected and divided in three different groups: HB (healthy jawbone) (n=19), APs (n=19), and BMDJ/FDOJ (n=7). The R/C expression was evaluated using multiplex analysis. In addition, two clinical cases from AP and BMDJ/FDOJ groups were randomly selected and radiographic diagnosis in 2D-OPG and 3D-CBCT/DVT was compared to TAU measurements and R/C expression in AP and in BMDJ/FDOJ. BMDJ/FDOJ showed the highest R/C expression (2498.71 pg/mL), followed by AP (841.85 pg/mL) and HB (149.85 pg/mL) (AP vs BMDJ/FDOJ = p=0.01; AP vs HB = p=<0.01; BMDJ/FDOJ vs HB = p=<0.01). In both clinical cases, the radiographic findings depict the AP areas in OPG and CBCT/DVT, in contrast to the BMDJ/FDOJ areas. Conversely, the systemic immunological R/C expressions are threefold and fivefold excessive in both cases. AP is recognized as a pathology requiring treatment, while the pathogenesis of BMDJ/FDOJ is controversially discussed in the literature, despite stronger potential systemic immunological effects (breast cancer (case 1) and multiple sclerosis (case 2)). The inadequate radiographic representation of reduced bone density in BMDJ/FDOJ areas could be a reason for this contradiction. The data presented provide the first quantitative analysis of R/C expression in AP and BMDJ/FDOJ. BMDJ/FDOJ showed high R/C expression than AP, besides the diagnostic through radiographs being extremely poor. To cover this imprecision, a radiation-free TAU device is available.

Covariations between scapular shape and bone density in B-glenoids: A statistical shape and density modeling-approach.

B-type glenoids arecharacterized by posterior humeral head migration and/or bony-erosion-induced glenoid retroversion. Patients with this type of osteoarthritic glenoids are known to be at increased risk of glenoid component loosening after anatomic total shoulder arthroplasty (aTSA). One of the main challenges in B glenoid surgical planning is to find a balance between correcting the bony shape and maintaining the quality of the bone support. This study aims to systematically quantify variabilities in terms of scapular morphology and bone mineral density in patients with B glenoids and to identify patterns of covariation between these two features. Using computed tomography scan images of 62 patients, three-dimensionalscapular surface models were constructed. Rigid and nonrigid surface registration of the scapular surfaces, followed by volumetric registration and material mapping, enabled us to develop statistical shapemodel(SSM) and statistical density model(SDM). Partial least square correlation (PLSC) was used to identify patterns of covariation. The developed SSM and SDM represented 85.9% and 56.6% of variabilities in terms of scapular morphology and bone density, respectively. PLSC identified four modes of covariation, explaining 66.0% of the correlation between these two variations. Covariation of posterior-inferior glenoid erosion with posterior sclerotic bone formation in association with reduction of bone density in the anterior and central part of the glenoid was detected as the primary mode of covariation. Identification of these asymmetrical distribution of bone density can inform us about possible reasons behind glenoid component loosening in B glenoids and surgical guidelines in terms of the compromise between bony shape correction and bone support quality.

Exploring In Vivo Models of Musculoskeletal Frailty: A Comprehensive Systematic Review

Musculoskeletal frailty—a common and debilitating condition linked to aging and chronic diseases—presents a major public health issue. In vivo models have become a key tool for researchers as they investigate the condition’s underlying mechanisms and develop effective interventions. This systematic review examines the current body of research on in vivo models of musculoskeletal frailty, without any time constraints. To achieve this aim, we utilized three electronic databases and incorporated a total of 11 studies. Our investigation delves into varied animal models that simulate specific features of musculoskeletal frailty, including muscle loss, bone density reduction, and functional decline. Furthermore, we examine the translational prospects of these models in augmenting our comprehension of musculoskeletal frailty and streamlining the production of groundbreaking therapeutic approaches. This review provides significant insights and guidance for healthcare researchers and practitioners who aim to combat musculoskeletal frailty, ultimately enhancing the quality of life for older adults and individuals affected by this condition.

Unraveling the Relationship Between Osteoporosis, Treatment Modalities, and Oral Health: A Comprehensive Review.

This review delves into the intricate interplay between osteoporosis, its treatment approaches, and oral health. The examination underscores the substantial impact of osteoporosis, characterized by reduced bone density, on various oral health parameters such as periodontal health, tooth loss, and jawbone density. While pharmacological interventions, including bisphosphonates and hormone replacement therapy, play a crucial role in managing osteoporosis, they necessitate careful consideration, particularly about the risk of osteonecrosis of the jaw. A comprehensive approach involving collaboration between dentists and healthcare providers is imperative for holistic patient care. Implementing screening protocols for osteoporosis in dental settings and meticulously planning dental procedures for patients undergoing osteoporosis treatments are vital aspects of clinical practice. This review also sheds light on emerging trends in osteoporosis research, such as the influence of genetic factors and the microbiome, emphasizing the necessity for innovative treatment modalities. In conclusion, the review provides valuable insights into the nuanced connections between osteoporosis and oral health, thereby laying a foundation for informed clinical practices and guiding future research initiatives. Furthermore, it highlights the importance of optimizing dental procedures and assessing long-term oral health outcomes as critical avenues for future research endeavors.

Sarcopenia and Osteoporosis.

Osteoporosis and sarcopenia are major health issues which are going to have a significant impact in an aging global population. Osteoporosis, which reduces bone density and increases fracture risk, and sarcopenia, which causes muscle loss and strength loss, have a complicated risk profile with consequences that go beyond bone and muscle health. This chapter illuminates the complex link between osteoporosis and sarcopenia, including overlapping causes, clinical consequences, and new treatments. This chapter covers bone and muscle biology, age-related changes that cause osteoporosis and sarcopenia, and the importance of physical exercise and diet in their prevention and management. It also discusses clinical evaluation methods, risk assessment and diagnostic criteria for early diagnosis and intervention. Novel therapies and continuing research in the management of osteoporosis and sarcopenia are also discussed. Medications, exercise, and nutrition can promote bone and muscle health. This chapter aims to explore the recent concepts by elucidating the complex relationship between osteoporosis and sarcopenia and advocating for integrated care paradigms.

Influence of bone density on stability in TBW

Osteoporosis is a common disease that leads to a reduction in bone density and increases the risk of fractures. Stable surgical treatment is particularly important for these fractures. The aim of this study was to examine the influence of bone density in the area of ​​the proximal ulna on the failure of the fixation technique of K-wires in tension band wiring (TBW). We provided 10 ulna specimens with TBW and biomechanically examined the pull-out strength of bi- and tricortical K-wires. Bone density measurement was performed using qCT. In the paired t-test, the tricortical group showed a significantly higher pull-out strength in relation to bone density than the bicortical group (p = 0.001). Furthermore, the Pearson correlation showed a high influence of bone density on pull-out strength in the tricortical group (r = 0.544), but without significance (p = 0.100).Our work shows that bone density has a direct effect on the pull-out strength of K-wires in TBW. TBW should therefore be used as osteosynthesis technique, especially in young patients with non-osteoporotic bones. In the case of osteoporotic fractures, alternative procedures should be preferred.

Emphatic information on bone mineral loss using quantitative ultrasound sonometer for expeditious prediction of osteoporosis

Osteoporosis (OP) and osteoarthritis (OA) are skeletal disorders characterized by a reduction in bone density and quality, resulting in increased fragility and susceptibility to fractures. These illnesses are exhibiting a higher prevalence among both males and females. Fracture risk is determined by using the BMD score (Bone Mineral Density). Looking at the bone loss that comes with osteoarthritis (OA) and osteoporosis (OP), this study also looks at the technological methods used to test for these conditions in order to improve therapies and treatment plans for older people. As a matter of consideration, the prevalence of osteoporosis is higher among postmenopausal women (20%) compared to premenopausal women (14.28%) and males (6.77%). The utilization of a preliminary calcaneal Quantitative Ultrasound (QUS) examination is warranted in order to effectively handle the matter of osteoporosis. The prompt assessment of a patient can provide valuable insights into potential fractures and aid in the prevention of bone injury. In a nutshell, it is imperative to comprehend the impact of OA (osteoarthritis) and OP (osteoporosis) on bone health in order to effectively manage the escalating apprehensions surrounding these conditions. Sophisticated diagnostic techniques, such as the calcaneal quantitative ultrasound (QUS) test, have the potential to enhance the well-being of older individuals by enabling early detection and treatment of many ailments.

Urolithin A attenuates osteoclast differentiation and compensates for ovariectomy-induced bone loss in mice by inhibiting PI3K/AKT/mTOR signaling pathway

Backgrounds and purposesOsteoporosis (OP) is a debilitating illness distinguished by a reduction in bone density and microstructure, which leads to fragility, fracture risk, and increased mortality, particularly in the elderly and postmenopausal women. Growing evidence suggests that various plant derivatives could be a potential therapy for osteoporosis. Ellagic acid is a phenolic found naturally in extracts from plants such as pomegranate, blackberry and berry. In earlier research, ellagic acid (EA) was reported to have certain benefits on osteoporosis, however, EA was limited by its weak bioactivity. Urolithin A (UA), an ellagic acid metabolite present in the intestinal bacteria, which had a greater bioavailability. However, its therapeutic effects and mechanisms in osteoporosis remain to be explored. Study designIn this work, we explored about how UA affected the molecular processes of osteoclasts differentiation in vitro. We also performed the ovariectomy-induced osteoporotic mice model in order to evaluate how UA impacted the bone loss of osteoporosis. Methods1. TRAP staining analysis to examine the impact of UA on osteoclast differentiation. 2. RT-PCR for evaluating UA's impact on the expression of genes relevant to osteoclasts. Bone resorption experiment and scan by electron microscope in order to determine the impact of UA on osteoclast function. 3.Using western blotting, investigate the impact of UA on the osteoclast differentiation-related signaling pathway. 4. Developed an osteoporosis mouse model for evaluating the preventative impact of UA on bone loss after an ovariectomy. Results1. UA reduced osteoclast development in a dosage manner without cytotoxicity. 2. UA suppresses osteoclast-related gene expression as well as the function of osteoclast bone resorption. 3. UA regulates osteoclast development by decreasing PI3K/AKT/mTOR signaling pathway phosphorylation as well as Nfatc1 transcription and translation. 4. Animal study demonstrated that UA reduced bone loss in ovariectomy-induced osteoporotic mice. ConclusionUA reduced the development and bone resorption function of osteoclast, was shown as inhibiting expression of osteoclast-associated specific genes as well as the PI3K/AKT/mTOR signaling pathway and decreasing Nfatc1 expression. In vivo, UA prevented bone loss in ovariectomy-induced osteoporotic mice. Finally, UA shown tremendous promise in the prevention and treatment of osteoporosis.

Gamma-aminobutyric acid (GABA)-mediated bone formation and its implications for anti-osteoporosis strategies: Exploring the relation between GABA and GABA receptors

Osteoporosis is a significant global health concern, linked to reduced bone density and an increased fracture risk, with effective treatments still lacking. This study explored the potential of gamma-aminobutyric acid (GABA) and its receptors as a novel approach to promote osteogenesis and address osteoporosis. GABA concentrations up to 10 mM were well-tolerated by MC3T3-E1 preosteoblast, stimulating osteoblast differentiation and mineralization in a concentration- and time-dependent manner. In vivo experiments with zebrafish larvae demonstrated the ability of GABA to improve vertebral formation and enhanced bone density, indicating the potential therapeutic value for osteoporosis. Notably, GABA countered the adverse effects of prednisolone on vertebral formation, bone density, and osteogenic gene expression in zebrafish larvae, suggesting a promising therapeutic solution to counteract corticosteroid-induced osteoporosis. Moreover, our study highlighted the involvement of GABA receptors in mediating the observed osteogenic effects. By using GABAA, GABAB, and GABAC receptor antagonists, we demonstrated that blocking these receptors attenuated GABA-induced osteoblast differentiation and vertebral formation in both MC3T3-E1 cells and zebrafish larvae, underscoring the importance of GABA receptor interactions in promoting bone formation. In conclusion, these findings underscore the osteogenic potential of GABA and its ability to mitigate the detrimental effects of corticosteroids on bone health. Targeting GABA and its receptors could be a promising strategy for the development of novel therapeutic interventions to address osteoporosis. However, further investigations are warranted to fully elucidate the underlying molecular mechanism of GABA and its clinical applications in treating osteoporosis.

Patient perspectives on digital health and physical activity in Parkinson’ disease: a brief research report

Background People living with Parkinson’s disease (PwP) typically have lower levels of physical activity (PA) which predisposes them to heart disease, reduced bone density and low exercise tolerance. Digital health has been shown to be effective at promoting PA in several clinical cohorts and monitoring PA in PwP. In addition, PwP have reported positive experiences with using digital health modalities such as smartwatches and telehealth. However, the perspectives of PwP on how best to use digital health to promote PA has yet to be investigated. The aim of this study was to investigate current levels of digital skills in PwP and the perspectives and opinions of PwP on the use of digital health for PA interventions. Methods Eighty-nine PwP living in Ireland completed a cross-sectional questionnaire looking at current levels of PA and self-reported levels of digital skills. Results The majority of participants believed that PA was beneficial for PwP and had a moderate to high level of digital skills. Important factors to consider when constructing a digital health PA intervention included ease of access, low cost, variety of exercises and physical activity options and a feedback function. Conclusion PwP have a moderate to high level of self-reported digital skills. This study provides useful information on factors that should be considered when constructing a digital PA intervention for PwP

Bio-orthogonal engineered peptide: A multi-functional strategy for the gene therapy of osteoporotic bone loss

Osteoporosis is a degenerative disease affecting millions of elderly people globally and increases the risk of bone fractures due to the reduced bone density. Drugs are normally prescribed to treat osteoporosis, especially after surgical treatment of osteoporotic fractures. However, many anti-osteoporotic drugs produce deleterious side effects. The recent development of gene therapy utilizing oligonucleotides (ONs) has spurred the development of new therapies for osteoporosis. Nevertheless, most ONs lack the capability of cell penetration and lysosome escape and hence, intracellular delivery of ON remains a challenge. Herein, a novel strategy is demonstrated to efficiently deliver ON to cells by combining ON with the cell-penetrating peptide (CPP) via the bio-orthogonal click reaction. Several dopamine (DOPA) groups are also introduced into the fabricated peptide to scavenge intracellular reactive oxygen species (ROS). Owing to favorable properties such as good cytocompatibility, cell penetration, lysosome escape, ROS scavenging, and osteoclastogenesis suppression, the hybrid CPP-DOPA-ON peptide improves the osteoporotic conditions significantly in vivo even when bone implants are involved. This strategy has great potential in the treatment of osteoporosis and potentially broadens the scope of gene therapy.

Clinical Features, Incidence and Treatment Outcome in Pregnancy-Associated Osteoporosis: A Single-Centre Experience over Two Decades

Pregnancy-associated osteoporosis (PAO) is a rare syndrome which typically presents with vertebral fractures during pregnancy or lactation. The medical records of sixteen patients with PAO who presented to a specialist clinic at the Western General Hospital in Edinburgh over a 20-year period were reviewed to evaluate the mode of presentation, potential risk factors and response to treatment. The most common presentation was back pain occurring in 13/16 (81.2%) individuals due to multiple vertebral fractures. The diagnosis was usually made postpartum and in 12/16 individuals (75.0%), PAO presented during the woman’s first pregnancy. Medicines which could have contributed to the development of PAO included thromboprophylaxis therapies in 8 subjects (50.0%), inhaled or injected corticosteroids in 5 (31.3%), anticonvulsants in 2 (12.5%) and a LHRH agonist in 1 (6.3%). Five individuals reported a family history of osteoporosis, and two pregnancies were complicated by hyperemesis gravidarum. Treatments administered included calcium and vitamin D supplements, bisphosphonates and teriparatide. Bone mineral density increased following the diagnosis in all cases, regardless of treatment given. One patient had further fracture during follow-up, but four patients had subsequent pregnancies without fractures. We estimated that in this locality, the incidence of PAO was 6.8/100,000 pregnancies with a point prevalence of 4.1 per 100,000 women. This case series indicates the importance of family history of osteoporosis and thromboprophylaxis drugs as risk factors for PAO while also demonstrating that the reductions in bone density tend to reverse with time, irrespective of the treatment given.

Efficacy evaluation and metabolomics analysis of raw and salt-processed Achyranthes bidentata Radix in zebrafish larvae for osteoporosis treatment

Osteoporosis, characterized by reduced bone density and the deterioration of bone tissue, poses a significant health challenge. The mechanisms underlying the protective effects of both raw and salt-processed Achyranthes bidentata Radix in osteoporosis remains unclear. This study endeavors to unravel and analyze the therapeutic mechanisms of these two forms of Achyranthes bidentata Radix in osteoporotic zebrafish larvae, utilizing GC/MS-based metabolomics. Zebrafish larvae were categorized into five groups: blank control, model, positive control, and groups treated with raw and salt-processed Achyranthes bidentata Radix. Following drug administration, notable enhancements were observed in both mineralized bone area and cumulative optical density. Various data mining techniques were employed, encompassing principal component analysis, orthogonal projections to latent structures discriminant analysis, and metabolic pathway analysis. These analyses unveiled 26 differential endogenous metabolites with significant biological implications in the zebrafish osteoporosis model. Among these metabolites, 12 (including acetamide, L-lactic acid, threonine, glycerol, rhamnose, azelaic acid, palmitic acid, inositol, stearic acid, hexadecane, sucrose, and glyceryl monostearate) were validated using standard compounds, exhibiting strong linear correlation coefficients (R2) ranging from 0.9917 to 0.9999. Furthermore, the method demonstrated excellent repeatability, as evidenced by relative standard deviation (RSD) values below 7.37%. The average spiked recoveries of the standard compounds fell within the range of ± 15%, ranging from 85.45% to 114.28%. Additionally, the stability of the standard compounds was confirmed after three freeze-thaw cycles, with RSD values remaining below 14.40%. Collectively, the metabolomic analysis unearthed potential biomarkers that could serve as indicators of the therapeutic effects of raw and salt-processed Achyranthes bidentata Radix on osteoporosis. This research offers valuable insights into the potential utilization of these herbal remedies as natural interventions for osteoporosis.

THU413 Does Continuous Positive Airway Pressure Affect Bone Loss Process In The Population Of Sleep Apnea?

Abstract Disclosure: Y. Chen: None. A. Suresh: None. S. Haile: None. Z. Perciuleac: None. B. Soni: None. A. Cuevas Velazquez: None. A. Amirian: None. C. Udeh: None. L. Sangha: None. B. Ravichander: None. K. Aljassani: None. R. Joshi: None. A. Atrash: None. N. Ramesh: None. J. Sta. Cruz: None. S. Al-saadi: None. Introduction: Patients with obstructive sleep apnea (OSA) were reported to have higher risk of developing osteoporosis or increased bone loss. One of the theories suggested nocturnal hypoxia led to imbalanced osteoclastic activity and contributed to bone loss. Continuous Positive Airway Pressure (CPAP) is the first-line treatment for OSA, which improves airway obstruction and limits hypoxia. This study attempts to evaluate if compliant with CPAP therapy reduces bone loss. Methods: This retrospective study included patients who visited UPMC Central Pa. sleep medicine clinic from January 2010 to October 2022 with diagnosis of OSA and have at least two dual-energy X-ray absorptiometry (DEXA) after the OSA diagnosis. Patients’ records of CPAP usage on two databases, Respironics and Resmed, were used to assess the compliance of the therapy. The definition of compliance is average usage of 4hrs/night; frequency of use being 70% or above. Patient demographics, CPAP compliance, bone mineral density (BMD) and T-scores of two DEXAs were obtained. All data after diagnosis of active malignancy, hyperparathyroidism, end stage renal disease, or after patient received osteoporosis pharmacological treatment are excluded. Annual change of BMD was calculated with the difference of BMD between the two DEXA scans divided by the study interval. Two-sample t-test and chi-square test were used for analysis. Results: 265 patients were included for analysis, with 254 female (95.8%), 92.1% Caucasian, mean age 68.3 years old, mean BMI 36.7kg/m2. 165 patients were compliant and 100 were non-compliant. The two groups were identical on demographic data including age, sex, ethnicities. The median of annual BMD changes at L-spine, left femur neck, left femur total, and left radius were 0.003, −0.003, −0.002, −0.002 g/cm2 respectively in compliant group and 0.003, 0, −0.006, −0.002 g/ cm2 in non-compliant group. The annual changes of T-scores were 0, −0.043, 0, −0.036 for the compliant group and 0, 0, −0.051, −0.034 for non-compliant group. No significant within-group or between-group difference in annual bone density reduction on BMD or T-score was noted in our analysis. Discussions: Our study did not reveal the benefit of treating OSA on bone loss. Small sample size could be the leading factor for the limited effect size. Retrospective study design also restricted our study population to predominantly postmenopausal Caucasian female. Further adjustments for possible confounding factors including BMI and age might be beneficial. Future study with prospective design, larger sample size, and diverse population is encouraged to discover the effect of CPAP therapy on BMD preservation. Presentation: Thursday, June 15, 2023

Unraveling the potential mechanisms of the anti-osteoporotic effects of the Achyranthes bidentata-Dipsacus asper herb pair: a network pharmacology and experimental study.

Background: Osteoporosis is a prevalent bone metabolism disease characterized by a reduction in bone density, leading to several complications that significantly affect patients' quality of life. The Achyranthes bidentata-Dipsacus asper (AB-DA) herb pair is commonly used in Traditional Chinese Medicine (TCM) to treat osteoporosis. This study aimed to investigate the therapeutic compounds and potential mechanisms of AB-DA using network pharmacology, molecular docking, molecular dynamics simulation, and experimental verification. Methods: Identified compounds of AB-DA were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Traditional Chinese Medicine Information Database (TCM-ID), TCM@Taiwan Database, BATMAN-TCM, and relevant literature. The main bioactive ingredients were screened based on the criteria of "OB (oral bioavailability) ≥ 30, DL (drug-likeness) ≥ 0.18." Potential targets were predicted using the PharmMapper and SwissTargetPrediction websites, while disease (osteoporosis)-related targets were obtained from the GeneCards, DisGeNET, and OMIM databases. The PPI network and KEGG/GO enrichment analysis were utilized for core targets and pathway screening in the STRING and Metascape databases, respectively. A drug-compound-target-pathway-disease network was constructed using Cytoscape software to display core regulatory mechanisms. Molecular docking and dynamics simulation techniques explored the binding reliability and stability between core compounds and targets. In vitro and in vivo validation experiments were utilized to explore the anti-osteoporosis efficiency and mechanism of sitogluside. Results: A total of 31 compounds with 83 potential targets for AB-DA against osteoporosis were obtained. The PPI analysis revealed several hub targets, including AKT1, CASP3, EGFR, IGF1, MAPK1, MAPK8, and MAPK14. GO/KEGG analysis indicated that the MAPK cascade (ERK/JNK/p38) is the main pathway involved in treating osteoporosis. The D-C-T-P-T network demonstrated therapeutic compounds that mainly consisted of iridoids, steroids, and flavonoids, such as sitogluside, loganic acid, and β-ecdysterone. Molecular docking and dynamics simulation analyses confirmed strong binding affinity and stability between core compounds and targets. Additionally, the validation experiments showed preliminary evidence of antiosteoporosis effects. Conclusion: This study identified iridoids, steroids, and flavonoids as the main therapeutic compounds of AB-DA in treating osteoporosis. The underlying mechanisms may involve targeting core MAPK cascade (ERK/JNK/p38) targets, such as MAPK1, MAPK8, and MAPK14. In vivo experiments preliminarily validated the anti-osteoporosis effect of sitogluside. Further in-depth experimental studies are required to validate the therapeutic value of AB-DA for treating osteoporosis in clinical practice.

The Capacity of Magnesium to Induce Osteoclast Differentiation Is Greatly Enhanced by the Presence of Zoledronate.

Bisphosphonates (BPs) are successfully used to cure a number of diseases characterized by a metabolic reduction in bone density, such as Osteoporosis, or a neoplastic destruction of bone tissue, such as multiple myeloma and bone metastases. These drugs exert their therapeutic effect by causing a systemic osteoclast depletion that, in turn, is responsible for reduced bone resorption. Unfortunately, in addition to their beneficial activity, BPs can also determine a frightening side effect known as osteonecrosis of the jaw (ONJ). It is generally believed that the inability of osteoclasts to dispose of inflamed/necrotic bone represents the main physiopathological aspect of ONJ. In principle, a therapeutic strategy able to elicit a local re-activation of osteoclast production could counteract ONJ and promote the healing of its lesions. Using an experimental model of Vitamin D3-dependent osteoclastogenesis, we have previously demonstrated that Magnesium is a powerful inducer of osteoclast differentiation. Here we show that, surprisingly, this effect is greatly enhanced by the presence of Zoledronate, chosen for our study because it is the most effective and dangerous of the BPs. This finding allows us to hypothesize that Magnesium might play an important role in the topical therapy of ONJ.

Clinical Studies On Romosozumab: An Alternative For Individuals With A High Risk Of Osteoporotic Fractures: A Current Concepts Review (Part I)

Osteoporosis, a widespread skeletal disorder with a substantial economic burden, is characterized by reduced bone density, resulting in increased fracture risk. Sclerotin inhibition with romosozumab (ROMO) represents a new therapeutic paradigm for the treatment of postmenopausal osteoporosis. We conducted a narrative review of the literature on ROMO’s role in osteoporosis treatment. ROMO has a unique dual effect of increasing bone formation (anabolic action) and decreasing bone resorption. It is a humanized monoclonal antibody injected monthly (210 mg subcutaneously once every four weeks for 12 months) that significantly increases lumbar spine, total hip, and femoral neck bone mineral density (BMD) compared with placebo, alendronate, and teriparatide at 6 and 12 months.