Bone Remodeling Process Research Articles

Initial bone tissue reactions of hydroxyapatite/collagen-(3-glycidoxypropyl)trimethoxysilane injectable bone paste.

We have previously reported that a novel bioresorbable self-setting injectable bone paste composed of hydroxyapatite/collagen bone-like nanocomposite (HAp/Col) and (3-glycidoxypropyl)trimethoxysilane (GPTMS) was successfully prepared and was replaced with new bone within 3 months of implantation in defects created in porcine tibia. In this study, the HAp/Col-GPTMS paste was implanted into bone defects in rat tibiae to investigate the initial kinetics and bone tissue response. Even though more than 35% of GPTMS molecules should be eluted rapidly from directly injected pastes according to previously reported cell culture tests, in this study, energy-dispersive X-ray spectrometry did not detect Si (GPTMS) deposition in tissues surrounding the paste at 1 day postimplantation. Further, no abnormal inflammatory responses were observed in the surrounding tissues over the test period for both directly injected and prehardened pastes. Companying these observations with the results of the previous animal test (in which the paste was fully resorbed and was substituted with new bone), the eluted GPTMS resolved in no harm in vivo from the initial to final (completely resorbed) stages. Material resorption rates calculated from X-ray microcomputed tomography (μ-CT) images decreased with increasing in GPTMS concentration. Histological observations indicated that tartrate-resistant acid phosphatase (TRAP) active cells, (assumed to be osteoclasts), exist on the periphery of pastes. This result suggested that the paste was resorbed by osteoclasts in the same way as the HAp/Col. Since a good correlation was observed between TRAP active areas in histological sections and material resorption rate calculated from μ-CT, the TRAP activity coverage ratio offers the possibility to estimate the osteoclastic resorption ratio of materials, which are replaced with bone via bone remodeling process.

Finite element simulations on delamination-induced local stress shielding effects on aseptic loosening behavior by bone remodeling

Interfacial damages (wear, delamination) and bone damage (remodeling, micro-cracks) can significantly affect the local bone deterioration and loosening of the acetabular cup. However, limited research has been conducted on both delamination and bone remodeling. This study aims to analyze the loosening behavior of an acetabular cup caused by the interaction of both interfacial damages and bone remodeling under different boundary conditions. A three-dimensional model of the acetabular cup was developed, and mechanically-induced remodeling behavior was implemented for the surrounding bone while the interfacial delamination between the cup and bone was modeled using the fracture mechanics approach. The delamination in the low initial bone mineral density (BMDs) cases encompasses almost the entire cup surface, which significantly affects the local bone remodeling process. The bone density near the top edge could be reduced to 20% in the lowest BMDs case which exaggerates the local strain accumulation and causes it to approach the micro-breaking limit. The loosening risk of the 45∘ fixation was reported in the low BMDs case which is a major limitation in conventional operation procedures for elderly patients. The interactive effect of the low BDMs, inclination angle, and loading amplitude can reduce the aseptic loosening life by half. This can be attributed to the amplified embedding of the acetabular cup caused by the delamination-induced reduction of the bone density. In future works, we aim to further consider anisotropic bone remodeling, microstructure of the bone, and delamination initiation behavior of surface coating.

Bisphosphonate-Related Osteonecrosis of the Jaw and Oral Microbiome: Clinical Risk Factors, Pathophysiology and Treatment Options.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) represents a serious health condition, impacting the lives of many patients worldwide. The condition challenges clinical care due to its complex etiology and limited therapeutic options. A thorough understanding of the pathophysiological and patient-related factors that promote disease development is essential. Recently, the oral microbiome has been implicated as a potential driver and modulating factor of BRONJ by several studies. Modern genomic sequencing methods have provided a wealth of data on the microbial composition of BRONJ lesions; however, the role of individual species in the process of disease development remains elusive. A comprehensive PubMed search was conducted to identify relevant studies on the microbiome of BRONJ patients using the terms "microbiome", "osteonecrosis of the jaws", and "bisphosphonates". Studies focusing on symptoms, epidemiology, pathophysiology, risk factors, and treatment options were included. The principal risk factors for BRONJ are tooth extraction, surgical procedures, and the administration of high doses of bisphosphonates. Importantly, the oral microbiome plays a significant role in the progression of the disease. Several studies have identified alterations of microbial composition in BRONJ lesions. However, there is no consensus regarding bacterial species that are associated with BRONJ across studies. The bacterial genera typically found include Actinomyces, Fusobacterium, and Streptococcus. It is postulated that these microbes contribute to the pathogenesis of BRONJ by promoting inflammation and disrupting normal bone remodeling processes. Current therapeutic approaches are disease-stage-specific and the necessity for more effective treatment strategies remains. This review examines the potential causes of and therapeutic approaches to BRONJ, highlighting the link between microbial colonization and BRONJ development. Future research should seek to more thoroughly investigate the interactions between bisphosphonates, the oral microbiome, and the immune system in order to develop targeted therapies.

The effect of different types of swimming intensity on increasing serum bone specific-alkaline phosphatase levels of obese male mice (Mus Musculus)

Obesity can interfere with the bone remodeling process, training is one solution to protect bone density. However, training and its intensity on bone remodeling through the biomarker Bone Specific-Alkaline Phosphatase (BALP) with obesity is still not widely studied so it is still unclear its effectiveness. The experimental study involved 24 mice (Mus musculus) that were induced with 30% fructose once a day for 60 days. Mice were grouped into 4 groups according to the intensity of training, namely the control group without training (K1), low intensity with a load of 3% body weight (K2), moderate intensity with a load of 5% body weight (K3), while high intensity was carried out with a load of 7% body weight for 70% (K4) of the maximum duration. All training sessions with a frequency of 3 times/week, and then a post-test comparison examination of BALP levels was carried out. The average number of BALP levels (ng/mL) in each group post-test, the control group had a result of 15.77±3.10, for the provision of low-intensity training with a value of 13.92±2.23, while for the moderate intensity training group of 13.11±1.67, for the highest increase was in high-intensity training with a value of 21.10±3.70. Based on the Tukey honestly significant difference (HSD) test, the post hoc high-intensity training group was significantly different from other groups (p ≤ 0.05). All types of training intensity analyzed in this study increased BALP levels, especially in the high-intensity training group which had a very significant increase in BALP levels. Therefore, training and its intensity affect bone metabolism increase. Keywords: Aerobic Training, BALP, Obesity, Swimming, Training intensity.

Part II: A new perspective for modeling the bone remodeling process: Biology, mechanics, and pathologies

In this paper, we explore the effects of biological (pathological) and mechanical damage on bone tissue within a benchmark model. Using the Finite Element Methodology, we analyze and numerically test the model’s components, capabilities, and performance under physiologically and pathologically relevant conditions. Our findings demonstrate the model’s effectiveness in simulating bone remodeling processes and self-repair mechanisms for micro-damage induced by biological internal conditions and mechanical external ones within bone tissue. This article is the second part of a series, where the first part presented the mathematical model and the biological and physical significance of the terms used in a simplified benchmark model. It explored the bone remodeling model’s application, implementation, and results under physiological conditions.

Analysis of the causal relationship between gut microbiota and bone remodeling growth factor from the gene association

BackgroundA growing body of evidence indicates a close association between the gut microbiota (GM) and the bone remodeling (BR) process, raising suspicions that the GM may actively participate in BR by modulating the levels of growth factors. However, the precise causal relationship between them remains unclear. Due to many confounding factors, many microorganisms related to BR growth factors have not been identified. We aimed to elucidate the causal relationship between the GM and BR growth factors. MethodsWe evaluated the genome-wide association study (GWAS) summary statistics for GM and five common growth factors associated with BR: namely, bone morphogenetic proteins (BMP), transforming growth factors(TGF), insulin growth factors (IGFs), epidermal growth factors (EGFs), and fibroblast growth factors (FGF). The causal relationship between the GM and BR growth factors was studied by double-sample Mendelian randomized analysis. We used five Mendelian randomization (MR) methods, including inverse variance-weighted (IVW), MR-Egger, simple mode, weighted median, and weighted model methods. ResultsThrough MR analysis, a total of 56 bacterial genera were co-identified as associated with BMP, TGF, IGF, EGF, and FGF. Among them, eight genera were found to have a causal relationship with multiple growth factors: Marvinbryantia was causally associated with BMP-6 (P = 0.018, OR = 1.355) and TGF-β2 (P = 0.002, OR = 1.475); Lachnoclostridium, BMP-7 (P = 0.021, OR = 0.73) and IGF-1 (P = 0.046, OR = 0.804); Terrisporobacter, TGF-β (P = 0.02, OR = 1.726) and FGF-23 levels (P = 0.016, OR = 1.76); Ruminiclostridium5, TGF-β levels (P = 0.024, OR = 0.525) and FGFR-2 (P = 0.003, OR = 0.681); Erysipelatoclostridium, TGF-β2 (P = 0.001, OR = 0.739) and EGF and its receptor (EGFR) (P = 0.012, OR = 0.795); Eubacterium_brachy_group, FGFR-2 (P = 0.045, OR = 1.153) and EGF (P = 0.013, OR = 0.7); Prevotella9 with EGFR (P = 0.022, OR = 0.818) and FGFR-2 (P = 0.011, OR = 1.233) and Faecalibacterium with FGF-23 (P = 0.02, OR = 2.053) and IGF-1 (P = 0.005, OR = 0.843). ConclusionWe confirmed the causal relationship between the GM and growth factors related to BR, which provides a new perspective for the study of BR, through targeted regulation of specific bacteria to prevent and treat diseases and growth factor-mediated BR disorders.

The Study to Assess the Effectiveness of Cissus Quadrangularis among Postmenopausal Women with Osteopenia

ABSTRACT Background: Osteopenia refers to bone density that is not only normal but also not as low as that noted in osteoporosis. Osteopenia leads to osteoporosis and increases the risk of fractures. Current research is focused on agents that will prevent or slow the progression of bone loss. The Objectives of the Study: To assess the pretest and posttest levels of osteopenia among postmenopausal women, and to assess the effectiveness of Cissus quadrangularis (CQ) on postmenopausal women with osteopenia. Methodology: A true experimental study design using targeted sampling techniques was used to conduct 60 patients with osteopenia. The data were collected with the help of structured questionnaires. Confidentiality was maintained throughout the process. The data collected were analyzed using descriptive and inference statistics. Result: A total of 60 participants completed this study. The percent BMD changes in the CQ-treated groups did not differ at any site after 24 weeks compared to the placebo. Reduced bone remodeling activity was detected in both CQ-treated groups. These results correlated with the within-group comparison, which showed a continuously significant increase in both BTMs in the placebo group. Conclusion: This is the first clinical report that showed a promising effect on delaying bone loss of oral administration of CQ for 24 weeks, as indicated by a slower bone remodeling process via a reduction in BTMs. However, no change in BMD was observed.

The specificities, influencing factors, and medical implications of bone circadian rhythms.

Physiological processes within the human body are regulated in approximately 24-h cycles known as circadian rhythms, serving to adapt to environmental changes. Bone rhythms play pivotal roles in bone development, metabolism, mineralization, and remodeling processes. Bone rhythms exhibit cell specificity, and different cells in bone display various expressions of clock genes. Multiple environmental factors, including light, feeding, exercise, and temperature, affect bone diurnal rhythms through the sympathetic nervous system and various hormones. Disruptions in bone diurnal rhythms contribute to the onset of skeletal disorders such as osteoporosis, osteoarthritis and skeletal hypoplasia. Conversely, these bone diseases can be effectively treated when aimed at the circadian clock in bone cells, including the rhythmic expressions of clock genes and drug targets. In this review, we describe the unique circadian rhythms in physiological activities of various bone cells. Then we summarize the factors synchronizing the diurnal rhythms of bone with the underlying mechanisms. Based on the review, we aim to build an overall understanding of the diurnal rhythms in bone and summarize the new preventive and therapeutic strategies for bone disorders.

Entheseal surface (Sharpey's fiber insertion) alterations identify past trauma; bone base robusticity, level of routine activity.

Sharpey's fiber alterations, referred to as entheseal reaction or enthesopathy, have long been considered an indicator of daily activities. Such semantic transformation seems to conflate processes which alter the characteristics of tendonous and ligamentous attachments to bone with the rugosity and extent of their base/footprint. Rather than reflecting normal activities, it is suggested that surface reactions are actually the response to the application of sudden or unconditioned repetitive stresses-analogous to stress fractures. Thus, they are distinct from enlargement of the base/footprint, the bone remodeling process responsible for the robusticity of the area to which the enthesis attaches, which is actually a measure of actual muscle activity. Surface reactions in attachment areas represent injury, be it mechanical stress fracture-equivalents or inflammation-derived. Bone base/footprint is the reaction of the enthesis to stresses of routine physical activities. The character of underlying bone supporting Sharpey's fibers may be augmented by applied stress, but there is neither a physiologic mechanism nor is there evidence for significant addition of Sharpey's fibers beyond ontogeny. Behavior is responsible for the physiologic response of robusticity; spiculation, pathology.

Oncostatin M suppresses bone morphogenetic protein-4-induced osteoprotegerin synthesis in MC3T3-E1 osteoblast-like cells: p70 S6 kinase attenuation.

Evidence is accumulating that osteal macrophages, in addition to bone-resorbing osteoclasts and bone-forming osteoblasts, participate vitally in bone remodeling process. Oncostatin M (OSM), an inflammatory cytokine belonging to interleukin-6 superfamily, is recognized as an essential factor secreted by osteal macrophages to orchestrate bone remodeling. Osteoprotegerin (OPG) produced by osteoblasts regulates osteoclastogenesis. We have reported that bone morphogenetic protein-4 (BMP-4) stimulates OPG synthesis in MC3T3-E1 osteoblast-like cells, and that SMAD1/5/8(9), p38 mitogen-activated protein kinase (MAPK), and p70 S6 kinase are involved in the OPG synthesis. The present study aims to investigate the effect of OSM on the synthesis of OPG stimulated by BMP-4 in osteoblasts. OSM suppressed the release and the mRNA expression of OPG upregulated by BMP-4 in MC3T3-E1 cells. Neither the BMP-4-induced phosphorylation of SMAD1/5/9 nor that of p38 MAPK was affected by OSM. On the other hand, the phosphorylation of p70 S6 kinase stimulated by BMP-4 was considerably suppressed by OSM. These results strongly suggest that OSM suppresses the BMP-4-stimulated OPG synthesis via inhibition of the p70 S6 kinase-mediated pathway in osteoblast-like cells.

Role of joint adipose tissues in osteoarthritis

Osteoarthritis (OA) is the most common musculoskeletal disease, without any curative treatment. Obesity being the main modifiable risk factor for OA, much attention focused on the role of adipose tissues (AT). In addition to the involvement of visceral and subcutaneous AT via systemic ways, many arguments also highlight the involvement of local AT, present in joint tissues. Local AT include intra-articular AT (IAAT), which border the synovium, and bone marrow AT (BMAT) localized within marrow cavities in the bones. This review describes the known features and involvement of IAAT and BMAT in joint homeostasis and OA. Recent findings evidence that alteration in magnetic resonance imaging signal intensity of infrapatellar fat pad can be predictive of the development and progression of knee OA. IAAT and synovium are partners of the same functional unit; IAAT playing an early and pivotal role in synovial inflammation and fibrosis and OA pain. BMAT, whose functions have only recently begun to be studied, is in close functional interaction with its microenvironment. The volume and molecular profile of BMAT change according to the pathophysiological context, enabling fine regulation of haematopoiesis and bone metabolism. Although its role in OA has not yet been studied, the localization of BMAT, its functions and the importance of the bone remodelling processes that occur in OA argue in favour of a role for BMAT in OA.

A bone remodeling approach encoding the effect of damage and a diffusive bio-mechanical stimulus

The paper focuses on the effect of damage on the bone remodeling process. This is a crucial, although complex, aspect. A one-dimensional continuous deformable body is employed to model living bone tissue. The model incorporates the bone functional adaptation through an evolution law for an effective elastic modulus driven by mechanical feedback via a mechano-transduction diffusive signal. This type of information transduction, i.e., diffusion, is essential for the model to take into account remodeling in the case of minor injury or pathology-affected regions where there is no signal production. In addition, the model is able to also take into account potential tissue damage that may evolve over time according to a suitable evolution law. To illustrate the capability of the model to describe the mentioned complex coupled phenomena, numerical tests have been performed encompassing high external loads causing the onset of damage and cyclic loading for healing. The numerical simulations carried out via finite-element analyses yield insights into the mechanisms of bone remodeling, with the final goal of aiding clinical decisions and implant designs for bone health and repair. Overall, a key aspect of the paper is to highlight the feasibility of modeling the evolution in bone elasticity arising from the combined effect of damage and remodeling.

Osteoporosis: interferon-gamma-mediated bone remodeling in osteoimmunology.

As the world population ages, osteoporosis, the most common disease of bone metabolism, affects more than 200 million people worldwide. The etiology is an imbalance in bone remodeling process resulting in more significant bone resorption than bone remodeling. With the advent of the osteoimmunology field, the immune system's role in skeletal pathologies is gradually being discovered. The cytokine interferon-gamma (IFN-γ), a member of the interferon family, is an important factor in the etiology and treatment of osteoporosis because it mediates bone remodeling. This review starts with bone remodeling process and includes the cellular and key signaling pathways of bone remodeling. The effects of IFN-γ on osteoblasts, osteoclasts, and bone mass are discussed separately, while the overall effects of IFN-γ on primary and secondary osteoporosis are summarized. The net effect of IFN-γ on bone appears to be highly dependent on the environment, dose, concentration, and stage of cellular differentiation. This review focuses on the mechanisms of bone remodeling and bone immunology, with a comprehensive discussion of the relationship between IFN-γ and osteoporosis. Finding the paradoxical balance of IFN-γ in bone immunology and exploring the potential of its clinical application provide new ideas for the clinical treatment of osteoporosis and drug development.

Evaluation of new bone formation in critical-sized rat calvarial defect using 3D printed polycaprolactone/tragacanth gum-bioactive glass composite scaffolds

Critical-sized bone defects are a major challenge in reconstructive bone surgery and usually fail to be treated due to limited remaining bone quality and extensive healing time. The combination of 3D-printed scaffolds and bioactive materials is a promising approach for bone tissue regeneration. In this study, 3D-printed alkaline-treated polycaprolactone scaffolds (M-PCL) were fabricated and integrated with tragacanth gum- 45S5 bioactive glass (TG-BG) to treat critical-sized calvarial bone defects in female adult Wistar rats. After a healing period of four and eight weeks, the new bone of blank, M-PCL, and M-PCL/TG-BG groups were harvested and assessed. Micro-computed tomography, histological, biochemical, and biomechanical analyses, gene expression, and bone matrix formation were used to assess bone regeneration. The micro-computed tomography results showed that the M-PCL/TG-BG scaffolds not only induced bone tissue formation within the bone defect but also increased BMD and BV/TV compared to blank and M-PCL groups. According to the histological analysis, there was no evidence of bony union in the calvarial defect regions of blank groups, while in M-PCL/TG-BG groups bony integration and repair were observed. The M-PCL/TG-BG scaffolds promoted the Runx2 and collagen type I expression as compared with blank and M-PCL groups. Besides, the bone regeneration in M-PCL/TG-BG groups correlated with TG-BG incorporation. Moreover, the use of M-PCL/TG-BG scaffolds promoted the biomechanical properties in the bone remodeling process. These data demonstrated that the M-PCL/TG-BG scaffolds serve as a highly promising platform for the development of bone grafts, supporting bone regeneration with bone matrix formation, and osteogenic features. Our results exhibited that the 3D-printed M-PCL/TG-BG scaffolds are a promising strategy for successful bone regeneration.

Increased TGF-β1 level after cocoa administration during orthodontics tooth movement in Cavia cobaya

Background: Orthodontic tooth movement (OTM) is a process of tooth movement in the alveolar socket through a bone remodeling process. Cocoa contains caffeine as a bioactive component. The number of studies on the effects of caffeine on orthodontic tooth movement is rising. Purpose: This study aimed to determine the effect of caffeine in cocoa administration on TGF-β1 levels in the pressure side during orthodontic tooth movement. Methods: Twelve Cavia cobaya were divided into 4 groups: control group (ONC), treatment group with 2.3 mg caffeine in cocoa (OWC1), 3.45 mg dose (OWC2) and 4.6 mg dose (OWC3) (n=3). A NiTi open coil spring with light force was applied to two lower incisors tooth of Cavia cobaya. TGF-β1 level in GCF of the pressure side was analyzed using ELISA on days 0, 1, 7, and 14. Data were analyzed using the Two-way ANOVA test (p<0.05) and the LSD Post-Hoc test. Results: Research indicated improvement of TGF-β1 level from the control group with the least average followed group caffeine in cocoa 2.3 mg (OWC1), 3.45 mg (OWC2), and 4.6 mg (OWC3) (p<0.05). Conclusion: This study confirmed that caffeine in cocoa administration increase TGF-β1 level during orthodontics tooth movement on Cavia cobaya in the pressure side.

Effect of oxytocin receptor antagonist (GSK-221-149-A) on mandibular bone porosity in peri-menopausal rats

The period of peri-menopause (PMP) is characterized by hormonal fluctuations that impact the strength and health of bones. Oxytocin (OX), a small peptide known to be present in bone tissue, is the focus of this study. The objective of this research is to gain a better understanding of how OX precisely functions in the remodeling process of the mandibular bone. This understanding is seen as a crucial step in preventing the loss of both cortical and trabecular bone during the PMP. The current findings indicate that OX plays a role in preserving both compact and trabecular bone tissues, enhancing the mineral-to-matrix ratio, and regulating bone markers. Furthermore, it reduces porosity in both cortical and trabecular bone levels. Interestingly, these effects are reversed when an oxytocin receptor antagonist (GSK-221,149-A) is introduced, suggesting that OX’s bone-preserving action is primarily mediated through the oxytocin receptor, rather than other mechanisms.

Static magnetic field-induced IL-6 secretion in periodontal ligament stem cells accelerates orthodontic tooth movement

Static magnetic field (SMF) promoting bone tissue remodeling is a potential non-invasive therapy technique to accelerate orthodontic tooth movement (OTM). The periodontal ligament stem cells (PDLSCs), which are mechanosensitive cells, are essential for force-induced bone remodeling and OTM. However, whether and how the PDLSCs influence the process of inflammatory bone remodeling under mechanical force stimuli in the presence of SMFs remains unclear. In this study, we found that local SMF stimulation significantly enhanced the OTM distance and induced osteoclastogenesis on the compression side of a rat model of OTM. Further experiments with macrophages cultured with supernatants from force-loaded PDLSCs exposed to an SMF showed enhanced osteoclast formation. RNA-seq analysis showed that interleukin-6 (IL-6) was elevated in force-loaded PDLSCs exposed to SMFs. IL-6 expression was also elevated on the pressure side of a rat OTM model with an SMF. The OTM distance induced by an SMF was significantly decreased after injection of the IL-6 inhibitor tocilizumab. These results imply that SMF promotes osteoclastogenesis by inducing force-loaded PDLSCs to secrete the inflammatory cytokine IL-6, which accelerates OTM. This will help to reveal the mechanism of SMF accelerates tooth movement and should be evaluated for application in periodontitis patients.

In vivo validation of highly customized cranial Ti-6AL-4V ELI prostheses fabricated through incremental forming and superplastic forming: an ovine model study

Cranial reconstructions are essential for restoring both function and aesthetics in patients with craniofacial deformities or traumatic injuries. Titanium prostheses have gained popularity due to their biocompatibility, strength, and corrosion resistance. The use of Superplastic Forming (SPF) and Single Point Incremental Forming (SPIF) techniques to create titanium prostheses, specifically designed for cranial reconstructions was investigated in an ovine model through microtomographic and histomorphometric analyses. The results obtained from the explanted specimens revealed significant variations in bone volume, trabecular thickness, spacing, and number across different regions of interest (VOIs or ROIs). Those regions next to the center of the cranial defect exhibited the most immature bone, characterized by higher porosity, decreased trabecular thickness, and wider trabecular spacing. Dynamic histomorphometry demonstrated differences in the mineralizing surface to bone surface ratio (MS/BS) and mineral apposition rate (MAR) depending on the timing of fluorochrome administration. A layer of connective tissue separated the prosthesis and the bone tissue. Overall, the study provided validation for the use of cranial prostheses made using SPF and SPIF techniques, offering insights into the processes of bone formation and remodeling in the implanted ovine model.

The Biomechanical Analysis of Tibial Implants Using Meshless Methods: Stress and Bone Tissue Remodeling Analysis

Total knee arthroplasty (TKA) stands out as one of the most widely employed surgical procedures, establishing itself as the preferred method for addressing advanced osteoarthritis of the knee. However, current knee prostheses require refined design solutions. This research work focuses on a computational analysis of both the mechanical behavior of a knee joint implant and the bone remodeling process in the tibia following implantation. This research study delves into how specific design parameters, particularly the stem geometry, impact the prosthesis’s performance. Utilizing a computed tomography scan of a tibia, various TKA configurations were simulated to conduct analyses employing advanced discretization techniques, such as the finite element method (FEM) and the radial point interpolation method (RPIM). The findings reveal that the introduction of the implant leads to a marginal increase in the stress values within the tibia, accompanied by a reduction in the displacement field values. The insertion of the longest tested implant increased the maximum stress from 5.0705 MPa to 6.1584 MPa, leading to a displacement reduction from 0.016 mm to 0.0142 mm. Finally, by combining the FEM with a bone remodeling algorithm, the bone remodeling process of the tibia due to an implant insertion was simulated.

The interplay of rheumatoid arthritis and osteoporosis: exploring the pathogenesis and pharmacological approaches.

Rheumatoid arthritis (RA) and osteoporosis are two chronic disorders that are often seen together. RA is an autoimmune disorder that causes pain and inflammation in the joints, while osteoporosis is a disorder in which the bones become weak and fragile. Risk factors for bone loss in RA include disease activity, longer disease duration, erosive disease, autoantibody positivity, and joint damage leading to impaired physical activity. Recent research has shown that there is a complex interplay between immune cells, cytokines, and bone remodeling processes in both RA and osteoporosis. The bone remodeling process is regulated by cytokines and immune system signaling pathways, with osteoclasts activated through the RANK/RANKL/OPG pathway and the Wnt/DKK1/sclerostin pathway. Understanding these mechanisms can aid in developing targeted therapies for treatment of osteoporosis in RA patients. Current pharmacological approaches include anti-osteoporotic drugs such as bisphosphonates, denosumab, teriparatide, abaloparatide, raloxifene, and romosozumab. Conventional disease-modifying antirheumatic drugs such as methotrexate and biologicals including TNF inhibitors, IL-6 inhibitors, rituximab, and abatacept lower disease activity in RA and can improve bone metabolism by reducing inflammation but have limited impact on bone mineral density. This review will shed light on the relationship between osteoporosis and rheumatoid arthritis as well as the various factors that influence the onset of osteoporosis in RA patients. We also explore several treatment approaches to effectively managing osteoporosis in RA patients.