Bone Remodeling Process Research Articles

Clinical Evaluation of a Defined Zeolite-Clinoptilolite Supplementation Effect on the Selected Blood Parameters of Patients.

The natural clinoptilolite material is an inorganic crystal mineral called zeolite. It has been extensively studied and used in industrial applications and veterinary and human medicine due to positive effects on health. Limited data is available in the scientific literature about its effects on the levels of physiologically relevant minerals in the human organism. Accordingly, we performed a comprehensive and controlled monitoring of the relevant mineral and contaminants levels in human subjects supplemented with a certified clinoptilolite material within three clinical trials with different supplementation regimens. Effects of a registered and certified clinoptilolite material PMA-zeolite on selected mineral and metal levels were determined by standard biochemical methods and inductively coupled plasma mass spectrometry (ICP-MS) in the blood of subjects enrolled in three clinical trials: short-term (28 days, Mineral Metabolism and selected Blood Parameters study MMBP), medium-term (12 weeks, Morbus Crohn study), and long-term (4 years, Osteoporosis TOP study) supplementation. Lower concentrations were observed for copper (Cu) in patients with osteoporosis, which normalized again in the long-term supplementation trial, whereas sodium (Na) and calcium (Ca) levels diminished below the reference values in patients with osteoporosis. In the short- and long-term supplementation trials, increased levels of lead (Pb) were observed in PMA-zeolite-supplemented subjects, which decreased in the continued long-term supplementation trial. Increased levels of aluminum (Al) or Pb attributable to eventual leakage from the material into the bloodstream were not detected 1 h after intake in the short-term supplementation trial. Nickel (Ni) and Al were statistically significantly decreased upon long-term 4-year supplementation within the long-term supplementation trial, and arsenic (As) was statistically significantly decreased upon 12-weeks supplementation in the medium-term trial. Alterations in the measured levels for Na and Ca, as well as for Pb, in the long-term trial are probably attributable to the bone remodeling process. Checking the balance of the minerals Cu, Ca, and Na after 1 year of supplementation might be prescribed for PMA-supplemented patients with osteoporosis.Clinical Trial Registration[https://clinicaltrials.gov], identifiers [NCT03901989, NCT05178719, NCT04370535, NCT04607018].

Menopausal Transition: Prospective Study of Estrogen Status, Circulating MicroRNAs, and Biomarkers of Bone Metabolism.

ObjectiveOsteoporosis is associated with an impaired balance between bone resorption and formation, which in turn leads to bone loss and fractures. Many recent studies have underlined the regulatory role of microRNAs (miRNAs) in bone remodeling processes and their potential as biomarkers of osteoporosis. The purpose of this study was to prospectively examine the association of circulating miRNAs and bone biomarkers with estrogen status in women before and after oophorectomy, as well as in oophorectomized women on estrogen therapy.MethodsIn this prospective study, we included 11 women before oophorectomy and hysterectomy and at 201 ± 24 days after the surgery. Another 11 women were evaluated 508 ± 127 days after oophorectomy and hysterectomy and after an additional 203 ± 71 days of estradiol treatment. Serum miRNAs were profiled by sequencing. Estrogen status and biomarkers of bone metabolism were quantified. Bone mineral density was assessed in the lumbar spine.ResultsOur analysis revealed 17 miRNAs associated with estrogen levels. Of those miRNAs that were upregulated with estrogen deficiency and downregulated after estrogen therapy, miR-422a correlated with serum beta-carboxy-terminal type I collagen crosslinks (β-CTX) and procollagen 1 N-terminal propeptide (P1NP); and miR-1278 correlated with serum β-CTX, P1NP, osteocalcin, sclerostin, and Dickkopf-1(Dkk1). In contrast, we found an inverse association of miR-24-1-5p with estrogen status and a negative correlation with serum β-CTX, P1NP, osteoprotegerin, and sclerostin levels.ConclusionThe reported miRNAs associated with estrogen status and bone metabolism could be potential biomarkers of bone pathophysiology and would facilitate studies on the prevention of postmenopausal osteoporosis. Our findings require validation in an extended cohort.

Open system peridynamics

We propose, for the first time, a thermodynamically consistent formulation for open system (continuum-kinematics-inspired) peridynamics. In contrast to closed system mechanics, in open system mechanics mass can no longer be considered a conservative property. In this contribution, we enhance the balance of mass by a (nonlocal) mass source. To elaborate a thermodynamically consistent formulation, the balances of momentum, energy and entropy need to be reconsidered as they are influenced by the additional mass source. Due to the nonlocal continuum formulation, we distinguish between local and nonlocal balance equations. We obtain the dissipation inequality via a Legendre transformation and derive the structure and constraints of the constitutive expressions based on the Coleman–Noll procedure. For the sake of demonstration, we present an example for a nonlocal mass source that can model the complex process of bone remodelling in peridynamics. In addition, we provide a numerical example to highlight the influence of nonlocality on the material density evolution.

Effects of assessing the bone remodeling process in biomechanical finite element stability evaluations of dental implants

Background and objectiveWhile an accurate assessment of the biomechanical stability of implants is essential in dental prosthesis planning and associated treatment assurance, the bone remodeling process is often ignored in biomechanical studies using finite element (FE) analysis. In this study, we aimed to analyze the significance of assessing the bone remodeling process in FE analysis for evaluating the biomechanical stability of dental implants. We compared the FE results considering the bone remodeling process with FE results simulated using commonly used conditions, with no considerations of the bone remodeling process. MethodsThe mathematical model proposed by Komarova et al. was used to calculate cell population dynamics and changes in bone density at a discrete site. The model was implemented in the FE software ABAQUS, using the UMAT subroutine. Three-dimensional FE models were constructed for two types of bone (III and IV) and three values of implant diameter (4.0, 4.5, and 5.0 mm). An average biting force of 50 N in the vertical direction was applied during the bone remodeling process for 150 days. Afterwards, the maximum biting force of 200 N in the 30° oblique direction was applied to evaluate the stability of the implant systems. ResultsTo understand the impact of bone remodeling on the resultant mechanical responses, we focused on peri-implant cancellous bone based on two parameters: apparent density change and microstrain distribution. The bone density decreased by an average of 5.3 % after implantation, and it was the lowest on the 6th day. The average density increases of the peri-implant cancellous bone were 264.4 kgm3 (bone type III) and 220.0 kgm3 (bone type IV) over 150 days. For the bone stability analysis, the maximum principal strain in the peri-implant bone was used to evaluate the bone stability. If the bone remodeling process is ignored, then the bone volume within the fatigue failure range of the microstrain differs significantly from that if the bone remodeling process is considered, i.e., 60 % higher for bone type III and 33.4 % lower for bone type IV than when the bone remodeling process is considered. ConclusionsThe FE result without considering the bone remodeling process could be considered a conservative criterion for bone type III. However, in bone type IV, the FE result without considering the bone remodeling process tends to underestimate the risks. The bone remodeling process is more affected by the initial bone quality than the implant diameter.

Bone Remodeling Process Based on Hydrostatic and Deviatoric Strain Mechano-Sensing.

A macroscopic continuum model intended to provide predictions for the remodeling process occurring in bone tissue is proposed. Specifically, we consider a formulation in which two characteristic stiffnesses, namely the bulk and shear moduli, evolve independently to adapt the hydrostatic and deviatoric response of the bone tissue to environmental changes. The formulation is deliberately simplified, aiming at constituting a preliminary step toward a more comprehensive modeling approach. The evolutive process for describing the functional adaptation of the two stiffnesses is proposed based on an energetic argument. Numerical experiments reveal that it is possible to model the bone remodeling process with a different evolution for more than one material parameter, as usually done. Moreover, the results motivate further investigations into the subject.

The Role of Geranylgeraniol in Managing Bisphosphonate-Related Osteonecrosis of the Jaw.

Medication-related osteonecrosis of the jaw (ONJ) is a rare but significant adverse side effect of antiresorptive drugs. Bisphosphonate-related ONJ (BRONJ) is the most prevalent condition due to the extensive use of the drug in cancer and osteoporosis treatment. Nitrogen-containing bisphosphonates suppress osteoclastic resorption by inhibiting farnesyl pyrophosphate synthase in the mevalonate pathway, leading to deficiency of the substrate for GTPase prenylation. The bone remodelling process is uncoupled, subsequently impairing bone healing and causing ONJ. Targeted administration of geranylgeraniol (GGOH) represents a promising approach to mitigate BRONJ because GGOH is a substrate for GTPase prenylation. In the current review, the in vitro effects of GGOH on osteoclasts, osteoblasts and other related cells of the jaw are summarised. We also present and appraise the current in vivo evidence of GGOH in managing BRONJ in animal models. Lastly, several considerations of using GGOH in the clinical management of BRONJ are highlighted. As a conclusion, GGOH is a promising topical agent to manage BRONJ, pending more research on an effective delivery system and validation from a clinical trial.

Triphenyl hexene, an active substance of Betaone barley water extract, inhibits RANKL-induced osteoclast differentiation and LPS-induced osteoporosis

• Triphenyl hexene from Betaone barley water extract inhibits osteoclastogenesis. • Tirphenyl hexene reduces the transcriptional and translational expression of markers associated with osteoclastogenesis. • Triphenyl hexene decreases bone loss in an LPS-induced osteoporosis mouse model. Osteoporosis is an aging-associated disease that causes fragile bone in postmenopausal women and elderly, resulting in increased social expenses. Bone health is maintained through the bone remodeling process. In this study, we investigated the anti-osteoporotic activity of 2,3,5-triphenyl-1-hexene (TH), an active substance of water extract of Betaone barley. To analyze the effect of TH on osteoclasts, the transcriptional and translational expression levels of several osteoclastogenesis-related genes were investigated. To investigate the in vivo activity of TH, an experiment with LPS-induced osteoporosis model mice was performed, and data were analyzed using micro-CT imaging, H&E and TRAP staining. The results showed that TH reduced the transcriptional and translational expression of NFATc1, a modulator of osteoclast formation, and decreased the mRNA expression levels of various osteoclast differentiation marker genes. Moreover, TH inhibited bone resorption in the LPS-induced osteoporosis model in proportion to a concentration similar to the positive control, alendronate, and bisphosphonates.

ESEM-EDX Microanalysis at Bone-Implant Region on Immediately Loaded Implants Retrieved Postmortem.

The aim of the study was to analyze the microchemistry of human bone in different regions of interest (ROIs) on histologic samples of implants retrieved postmortem by the innovative use of an environmental scanning electronic microscope (ESEM) connected to energy-dispersive x-ray spectroscopy (EDX). Maxillary and mandibular bone blocks with inserted implants (n = 12) were obtained postmortem from a patient. The histologic samples were observed uncoated using ESEM in quadrant backscattered condition. Two ROIs (approximately 750 × 500 μm) for each implant were analyzed corresponding to the cortical thread (cortical ROI) and the middle part of each implant (approximately 3.0 mm below; middle ROI). Different electron-dense bone tissue areas were detected through grayscale intensity quantification of ESEM images. Calcium (Ca), phosphorous (P), and titanium (Ti; atomic %) were evaluated by EDX, and Ca/P ratios were calculated and used as the index to identify areas with different mineralization. The presence of Ti contaminants was investigated by EDX microanalysis. Additional ROIs approximately 2.0 mm from the implant interface and not in connection with the implant surface were analyzed as the control. Four bone areas (BAs) with different degrees of mineralization (from 1 as the lowest mineralized to 4 as the highest mineralized) were identified by Ca and P content and by tissue electron density. BA1 (bone marrow areas) and BA2 (areas with active bone remodeling) proved to have low levels of Ca and P, while BA3 (mineralized new bone areas) and BA4 (control cortical bone) had higher content of Ca and P and higher electron density. Mandibular ROIs displayed higher percentages of BA3 and BA4, while maxillary ROIs revealed a greater presence of BA2 and moderate presence of BA1. Control bone showed a high percentage of BA4. Cortical and middle ROIs showed similar BA distribution within mandibular bone, whereas in maxillary bone, a slightly higher presence of BA1 was observed. Ti ions were detected in ROIs of all specimens; the atomic % significantly decreased in the most distant areas. Ti particles were observed close to the implant interface. Analyses 2.0 mm distant from the implant thread revealed low traces of Ti in healthy bone tissue. The high percentage of BA3 and BA4 in mandibular blocks associated with low presence of BA2 suggested the fast formation of compact bone tissue after 7 months from the implant placement. The presence of BA2 in maxilla blocks suggested active bone remodeling still present after 7 months. Ti particles were observed throughout the ROIs with and without bone remodeling activity. ESEMEDX resulted as a suitable technique to obtain more complete information on microchemistry composition and density/mineralization of bone around implants. For clinical significance, maxillary and mandibular peri-implant bone revealed different mineralization patterns, which means different healing times. The presence of Ti particles at the bone-implant interface and ion translocation, likely due to wear forces in the times following the implant insertion, do not affect the bone remodeling process.

The role of Piezo1 mechanosensor in osteoclastogenesis from monocytes

Abstract Objectives Interrelations between bone and the immune system are involved in both homeostatic and pathogenic bone remodeling processes. Although emerging evidence supports that mechanosensitive Ca2+-channel Piezo1 plays a pivotal role in osteoblast-mediated bone regeneration, possible engagement of Piezo1 in the differentiation of osteoclasts from monocytes and resulting bone resorption is largely unknown. In the present study, we sought to establish the role of Piezo1 in RANKL-stimulated monocytes for their differentiation to osteoclasts in vitro. Methods Mouse RAW 264.7 monocyte cell line or bone marrow derived mononuclear cells (BMMCs) were stimulated with M-CSF and/or RANKL, in the presence or absence of Yoda1 (Piezo1 activator) or with or without hydrostatic pressure (HP). Ca2+ influx assay was employed to confirm Piezo1 channel activity. To evaluate the level of osteoclastogenesis and bone-resorptive function by mature osteoclasts, TRAP staining and pit formation assays were performed. To monitor the expressions of mRNAs for Piezo1 as well as OC-STAMP, TRAP (ACP5) and MMP9, qPCR were employed. Results Yoda1-mediated Ca2+ influx was significantly elevated in RANKL BMMCs and RAW264.7 cells, while significantly suppressing the expressions of osteoclastogenesis-related genes, OC-STAMP, MMP9 and ACP5. Moreover, the number and size of multi-nucleated TRAP-positive cells as well as formation of resorption pits were significantly down-regulated by the treatment with Yoda1 as well as HP. Conclusions The present study suggests that mechanosensitive Piezo1 channel expressed on monocytes may play a gatekeeper role in down-modulating over-activation of osteoclastogenesis and function to resorb bone. Supported by NIH NIDCR grants, DE-027851, DE-028715 and DE-331851

The Role Of BMPs in the Regulation of Osteoclasts Resorption and Bone Remodeling: From Experimental Models to Clinical Applications.

In response to mechanical forces and the aging process, bone in the adult skeleton is continuously remodeled by a process in which old and damaged bone is removed by bone-resorbing osteoclasts and subsequently is replaced by new bone by bone-forming cells, osteoblasts. During this essential process of bone remodeling, osteoclastic resorption is tightly coupled to osteoblastic bone formation. Bone-resorbing cells, multinuclear giant osteoclasts, derive from the monocyte/macrophage hematopoietic lineage and their differentiation is driven by distinct signaling molecules and transcription factors. Critical factors for this process are Macrophage Colony Stimulating Factor (M-CSF) and Receptor Activator Nuclear Factor-κB Ligand (RANKL). Besides their resorption activity, osteoclasts secrete coupling factors which promote recruitment of osteoblast precursors to the bone surface, regulating thus the whole process of bone remodeling. Bone morphogenetic proteins (BMPs), a family of multi-functional growth factors involved in numerous molecular and signaling pathways, have significant role in osteoblast-osteoclast communication and significantly impact bone remodeling. It is well known that BMPs help to maintain healthy bone by stimulating osteoblast mineralization, differentiation and survival. Recently, increasing evidence indicates that BMPs not only help in the anabolic part of bone remodeling process but also significantly influence bone catabolism. The deletion of the BMP receptor type 1A (BMPRIA) in osteoclasts increased osteoblastic bone formation, suggesting that BMPR1A signaling in osteoclasts regulates coupling to osteoblasts by reducing bone-formation activity during bone remodeling. The dual effect of BMPs on bone mineralization and resorption highlights the essential role of BMP signaling in bone homeostasis and they also appear to be involved in pathological processes in inflammatory disorders affecting bones and joints. Certain BMPs (BMP2 and -7) were approved for clinical use; however, increased bone resorption rather than formation were observed in clinical applications, suggesting the role BMPs have in osteoclast activation and subsequent osteolysis. Here, we summarize the current knowledge of BMP signaling in osteoclasts, its role in osteoclast resorption, bone remodeling, and osteoblast–osteoclast coupling. Furthermore, discussion of clinical application of recombinant BMP therapy is based on recent preclinical and clinical studies.

PHYSICAL THERAPY OF PATIENTS WITH POST-TRAUMATIC GONARTHROSIS WITH IMBALANCE OF OSTEO-ASSOCIATED MACRONUTRIENTS

According to modern concepts, bone remodeling disorders that are directly dependent on the imbalanceof osteo-associated trace elements play a key role in the pathogenesis of OA. Therefore, the purpose of ourstudy is to develop the program of physical rehabilitation of patients with post-traumatic gonarthrosisand to investigate its effect on the composition of osteoassociated macronutrients.To determine the metabolic function of bone tissue there were the results of the study of mineralhomeostasis by the level in the peripheral blood of phosphorus and magnesium, total calcium and itsionized form, as well as the amount of urinary calcium excretion. The processes of bone formation wereevaluated by the content of bone isoenzyme of alkaline phosphatase, bone resorption was evaluated bythe level of tartrate-resistant acid phosphatase. 42 patients with post-traumatic osteoarthritis of the kneejoints of I–II stages according to Kellgren-Lowrence were observed.The complex of physical therapy included the educational program, medical gymnastics and massage.The theoretical part of the program included 6 topics covering the main issues related to the risk factorsand prognosis for the disease, the main mechanisms of its progression, as well as the basics of differentphysical therapy use. The practical part of the program was carried out in a small-group way and includedthe gradual application of static, dynamic, active and proprioceptive neuromuscular stretching usingthe exercises with elastic bands and metered loading. As for the massage technology a combinationof segmental massage with Swedish technique was used in the program. The total duration of the complexprogram was 9 months, after which patients were advised to perform independent classes. The applicationof the developed program of physical rehabilitation had a positive effect on the processes of boneremodeling, and allowed to reduce the number of exacerbations during the year.

The Roles of Insulin Growth Factors-1 (IGF-1) in Bone Graft to increase Osteogenesis

Background: Bone graft material is used with periodontal flap procedure that is expected to help the growth of new bone through the process of osteogenesis, osteoinduction, and osteoconduction. Some work must be done to support the regeneration of periodontal tissue, including the three key elements of principal, such as scaffolds (collagen and bone material), signal molecules (growth factors) and cells. IGF-1 is a growth factor that has been studied to stimulate the replication of osteoblasts and bone matrix synthesis of bone remodeling process. Osteocalcin is a specific product of osteoblasts, in a previous study that the increase of osteocalcin indicates an increase in bone formation markers. Osteopontin expression by kondrosit showed the role of these cell in sintesizing matrix that have a main role for osteoclast resorpsion dan bone remodeling. Objective: To know the effect of IGF-1 on bone healing process that has been applied xenograft with attention to osteoblast, osteoclast, osteopontin and osteocalcin expression in animal model. Methods: This study was an experimental study in the rabbit. Comparing two groups, xenograft + IGF-1 and others just xenograft, was applied to the tibia’s defect for 21 days. Results: There are significant differences between the groups. The expression of osteoblast, osteopontin and osteocalcin looks more numerous after 21 days on the xenograft + IGF-1 group than the group that only uses xenograft alone. Whereas expression of osteoclast was seen to be less in the xenograft + IGF-1 group. Conclusion: the use of IGF-1 as a fisiologic mediator in regenerate periodontal tissues proved to be effective with the increased expression of osteoblast, osteopontin, osteocalcin and decreased osteoclasts.

The effect of Cissus quadrangularis L. on delaying bone loss in postmenopausal women with osteopenia: A randomized placebo-controlled trial

BackgroundOsteopenia refers to bone density that is not 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. On the basis of published evidence, Cissus quadrangularis (CQ) might potentially provide a novel natural treatment for osteopenia. PurposeTo determine the effect of 24 weeks of consecutive treatment with CQ on delaying bone loss and safety in postmenopausal women (PMW) with osteopenia. MethodsThis study is a randomized, placebo-controlled trial. Here, 134 enrolled PMW with osteopenia (> 40 years and having no period for 1–10 years) received CQ at 1.2 (CQ1.2) or 1.6 g/day (CQ1.6) or placebo. The %change in bone mineral density (BMD) at the lumbar spine (L1–L4), femoral neck, and total hip served as the primary outcome. The %change in bone turnover markers (BTMs), including C-terminal telopeptide of type 1 collagen (CTX) and procollagen type 1 amino-terminal propeptide (P1NP), was the secondary outcome. These outcomes were compared between the CQ vs. placebo group at weeks 12 and 24. The least significant change (LSC) was used to monitor clinical changes. The adverse events (AE) were monitored. ResultsA total of 108 participants completed this study. The %BMD changes in the CQ-treated groups did not differ at any site after 24 weeks compared to the placebo. Statistically significant differences were detected in CQ1.6 at the lumbar spine (0.011 ± 0.025 g/cm2, p = 0.008) and CQ1.2 at the femoral neck (–0.015 ± 0.036 g/cm2, p = 0.024) compared to baseline, but these changes did not exceed the LSC. Reduced bone remodeling activity was detected in both CQ-treated groups. Compared to the placebo, the %P1NP change was significantly reduced in CQ1.6 (–2.46 ± 26.05%; p < 0.01) at week 12 and in CQ1.2 (–3.36 ± 29.47%; p < 0.01) and CQ1.6 (–9.95 ± 22.22%; p < 0.01) at week 24. These results correlated with the within-group comparison, which showed a continuously significant increase in both BTMs in the placebo group. However, a stable CTX and a significant reduction in P1NP (p < 0.05) were detected in both CQ-treated groups. This reduction exceeded the LSC of P1NP. The incidence of adverse events did not differ among the three groups. ConclusionThis is the first clinical report that showed a promising effect on delaying bone loss of orally 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.

Network Pharmacology Deciphers the Action of Bioactive Polypeptide in Attenuating Inflammatory Osteolysis via the Suppression of Oxidative Stress and Restoration of Bone Remodeling Balance.

Oxidative stress involves enormously in the development of chronic inflammatory bone disease, wherein the overproduction of reactive oxygen species (ROS) negatively impacts the bone remodeling via promoting osteoclastogenesis and inhibiting osteogenesis. Lacking effective therapies highlights the importance of finding novel treatments. Our previous study screened a novel bioactive peptide D7 and demonstrated it could enhance the cell behaviors and protect bone marrow mesenchymal stem cells (BMSCs). Since BMSCs are progenitor cells of osteoblast (OB), we therefore ask whether D7 could also protect against the progress of inflammatory osteolysis. To validate our hypothesis and elucidate the underlying mechanisms, we first performed network pharmacology-based analysis according to the molecule structure of D7, and then followed by pharmacological evaluation on D7 by in vitro lipopolysaccharide(LPS)-induced models. The result from network pharmacology identified 20 candidate targets of D7 for inflammatory osteolysis intervention. The further analysis of Gene Ontology (GO)/KEGG pathway enrichment suggested the therapeutic effect of D7 may primarily affect osteoclast (OC) differentiation and function during the inflammatory osteolysis. Through validating the real effects of D7 on OC and OB as postulated, results demonstrated suppressive effects of D7 on LPS-stimulated OC differentiation and resorption, via the inhibition on OC marker genes. Contrarily, by improving the expression of OB marker genes, D7 displayed promotive effects on OB differentiation and alleviated LPS-induced osteogenic damage. Further mechanism study revealed that D7 could reduce LPS-induced ROS formation and strengthen antioxidants expressions in both OC and OB precursors, ameliorating LPS-triggered redox imbalance in bone remodeling. Taken together, our findings unveiled therapeutic effects of D7 against LPS-induced inflammatory osteolysis through the suppression of oxidative stress and the restoration of the bone remodeling process, providing a new therapeutic candidate for chronic inflammatory bone diseases.

Computational prediction of the long-term behavior of the femoral density after THR using the Silent Hip stem

Aseptic loosening due to the progressive periprosthetic bone resorption following total hip replacement is a crucial concern, that causes complications and failure of the arthroplasty surgery. The mismatch in stiffness between the hip implant and the surrounding femoral bone is one of the key factors leading to bone density resorption. This paper aimed to investigate the long-term response of the femoral bone after THR using the Silent Hip stem. For this purpose, a validated thermodynamic-based computational model was used to compute the change in bone density before and after THR. This model incorporated essential factors involved in bone remodeling process, such as mechanical loading, and biochemical affinities. The results of the numerical simulations using 3D finite element analysis were analyzed in five zones of interest qualitatively and quantitatively. Bone density predictions showed notable bone resorption in cervical areas, specifically in zone 1 and zone 5 of −18.7% and −14%, respectively. Conversely, bone formation was observed in the greater trochanter area (zone 2) of +25%. Stress shielding seemed to occur at cervical area due to the reduction in the mechanical loading in this region. Based on the quantitative analysis of the bone density distribution throughout the femoral bone, it appears that the Silent Hip stem achieved less bone resorption compared to conventional hip stem designs reported in the literature, which could be used for active patients.

EFFECT OF FIBROIN SPONGE ON ALVEOLAR BONE REMODELING PROCESS POST TOOTH EXTRACTION

Background: There are still quite a lot of cases of tooth extraction in Indonesia because of the cavities are not treated or because of other cases. Extraction is the main cause of 90% of bone destruction and a risk of infection and bleeding. Fibroin sponge is a natural polymer material derived from Bombyx mori silk cocoon which contains of 18 amino acids and have a good mechanically, biodegradable and biocompatible. This study aimed to determine the effect of fibroin sponge on the remodeling of post tooth extraction sockets. Method: This study was a laboratory experiment with quasy experimental design using 30 Sprague dawley rats divided into 2 groups. Each group had the mandibular left incisor extracted. The first group as a control was given 15 ug of Curaspon and the second group was given 15 ug of fibroin sponge intra alveolar. Result: The results were observed after the 3rd, 7th, 14th, 21st, 28th days under a light microscope and identified by scoring bone remodeling based on predetermined criteria. Data were analyzed using the Mann-Whitney Test followed by the Kruskall-Wallis Test. The results showed that there was no difference in the process of bone remodeling post tooth extraction in the fibroin sponge group compared to Curaspon (p&gt;0.05). Conclusion: Fibroin sponge has the same effect on the bone remodeling process as Curaspon.

Simulation on bone remodeling with stochastic nature of adult and elderly using topology optimization algorithm

Reliable and accurate predictions of bone remodeling provide essential assistance for personalized implant design and orthopedic diagnosis. However, the bone remodeling simulations fail to accurately mimic the sophisticated architecture of trabecular bone so far, due to the neglection of the stochastic behaviors of bone remodeling. In this study, we coupled the Physiological Stochasticity in Bone Remodeling into the conventional Topology Optimization algorithm (named PSBR-TO method) to predict the cancellous structure of human femur. The sensitivity function of topology optimization was amended according to the bone remodeling rules from in vivo study (Razi et al., 2015) to reflect the stochastic process of bone remodeling in various physiological conditions. To demonstrate the algorithm, the bone structures of adults and the elderly were simulated by adopting the corresponding remodeling rules. The results showed that PSBR-TO gives rise to highly similar morphological features with the natural femur bone, in terms of the trabecular orientations and bone content distribution. The predicted femurs for adults and the elderly showed that the region-dependent variations in trabecular structural parameters during aging, including BV/TV, Tb.Th, and Tb.Sp, were consistent with the natural bone. Additionally, a loading collection of thirteen activities was employed in the algorithm and succeeded in driving the femur model to reproduce cancellous structure without extra constraint of structure perimeter or local density. By means of PSBR-TO, the trabecular structure in diverse physiological conditions can be accurately predicted, showing the valuable contribution on the clinical diagnosis and patient-specific design of bone implants.

Species-independent stimulation of osteogenic differentiation induced by osteoclasts

The coupling of bone resorption and bone formation is well-recognized in the bone remodeling process, in which osteoblasts and osteoclasts are key players. However, the anabolic effect of human primary osteoclasts has rarely been reported as mouse and cell line derived osteoclasts were mostly used in previous reports. Therefore, a comprehensive comparison of mouse and human osteoclasts and their corresponding functions is needed to study cell-cell interactions between osteoclasts and osteoblasts. Osteoclasts from mouse and human origin were generated, characterized and compared, after which their anabolic effects on the osteogenic differentiation of mouse and human MSCs were assessed. Both murine RAW264.7 derived osteoclasts (mOCs) and primary human osteoclasts (hOCs) derived from buffy coats characteristically displayed multinuclearity, marked integrin β3 expression and enhanced TRAP activity. Despite comparable cell size, mOCs showed higher osteoclast density (number of osteoclasts per cm2 culture dish) and osteoclast nuclearity (average number of nuclei per osteoclast), but lower TRAP activity compared to hOCs. Culturing primary rat and human bone marrow MSCs with the conditioned medium of mOCs or hOCs showed anabolic effects regarding the osteogenic differentiation of MSCs with superiority of hOCs over mOCs. We conclude that despite morphological and functional differences between mouse and human osteoclasts, their secretory factors evoke similar anabolic effects on MSC osteogenic differentiation.

Nonlinear dynamics of membrane skeleton in osteocyte

Osteocytes play an important role in mechanosensation and conduction in bone tissue, and the change of mechanical environment can affect the sensitivity of osteocytes to external stimulation. The structure of osteocytes will be changed when they are subjected to vibrations, which influence the mechanosensitivity of osteocytes and alter the regulation of bone remodeling process. As an important mechanotransduction structure in osteocytes, the membrane skeleton greatly affects the mechanosensation and conduction of osteocytes. However, the dynamic responses of membrane skeleton to the vibration and the structural changes of membrane skeleton are unclear. Therefore, we applied a nonlinear dynamics method to explain the time-dependent changes of membrane skeleton. The semi-ellipsoidal reticulate shell structure of membrane skeleton is built based on the experimental observation in our previous work. Then, the nonlinear dynamic equations of membrane skeleton are established according to the theory of plate and shell dynamics, and the displacement–time curves, phase portraits, and Poincaré maps of membrane skeleton structure were obtained. The numeration results show that under the vibration stimulation of 15 Hz, 30 Hz, 60 Hz, and 90 Hz, the membrane skeleton is destroyed after a transient equilibrium position vibration. The vibration of 15 Hz has the most destructive effect on the membrane skeleton, the natural frequency of membrane skeleton may be less than 15 Hz. In addition, the chaos phenomenon occurs to the membrane skeleton during vibration. As a damping factor, the existence of viscosity alleviates the damage of structure. This study can help us to understand the oscillation characteristic of membrane skeleton in osteocyte.

Impact of the Endocannabinoid System on Bone Formation and Remodeling in p62 KO Mice.

Several studies have shown that the G-protein coupled cannabinoid receptor CB2 and its interaction partner p62 are molecularly involved in bone remodeling processes. Pharmacological activation of the CB2 receptor enhanced bone volume in postmenopausal osteoporosis and arthritis models in rodents, whereas knockout or mutation of the p62 protein in aged mice led to Paget’s disease of bone-like conditions. Studies of pharmacological CB2 agonist effects on bone metabolism in p62 KO mice have not been performed to date. Here, we assessed the effect of the CB2-specific agonist JWH133 after a short-term (5 days in 3-month-old mice) or long-term (4 weeks in 6-month-old mice) treatment on structural, dynamic, and cellular bone morphometry obtained by μCT of the femur and histomorphometry of the vertebral bodies in p62 KO mice and their WT littermates in vivo. A genotype-independent stimulatory effect of CB2 on bone formation, trabecular number, and trabecular thickness after short-term treatment and on tissue mineral density after long-term treatment was detected, indicating a weak osteoanabolic function of this CB2 agonist. Moreover, after short-term systemic CB2 receptor activation, we found significant differences at the cellular level in the number of osteoblasts and osteoclasts only in p62 KO mice, together with a weak increase in trabecular number and a decrease in trabecular separation. Long-term treatment showed an opposite JWH133 effect on osteoclasts in WT versus p62 KO animals and decreased cortical thickness only in treated p62 KO mice. Our results provide new insights into CB2 receptor signaling in vivo and suggest that CB2 agonist activity may be regulated by the presence of its macromolecular binding partner p62.