Prevent Bone Resorption Research Articles

Denosumab-Induced Osteonecrosis of the Jaw with FDG PET/CT imaging features.

Denosumab is a monoclonal antibody that inhibits receptor activator of nuclear factor-kappa B ligand (RANKL), which plays a crucial role in osteoclast formation, function, and survival. By blocking RANKL, denosumab helps prevent bone resorption, making it an effective therapeutic option for managing conditions associated with bone metastases and osteopenia, such as in patients with lung cancer. Lung cancer, particularly non-small cell lung cancer (NSCLC), often metastasizes to bones, and denosumab is commonly used to reduce the incidence of skeletal-related events (SREs) in these patients. However, denosumab therapy is not without its risks, and one of the most significant side effects is osteonecrosis of the jaw (ONJ), a potentially debilitating condition characterized by bone exposure and necrosis, typically following dental extractions or trauma [1][2]. This case report explores the role of FDG PET/CT in diagnosing and managing Denosumab-induced ONJ in a patient with lung cancer, underscoring the value of this imaging modality in clinical practice.

Local Application of a New Chalconic Derivative (Chalcone T4) Reduces Inflammation and Oxidative Stress in a Periodontitis Model in Rats.

Chalcones are phenolic compounds with biological properties. This study had the aim to evaluate the effects of topical administration of a new synthetic chalcone, Chalcone T4, in an animal model of periodontitis induced by ligature. Forty rats were distributed in the following experimental groups: negative control (without periodontitis and topical application of distilled water), positive control (periodontitis and topical application of distilled water), chalcone I and II (periodontitis and topical application of 0.6 mg/mL and 1.8 mg/mL, respectively). Chalcone or distilled water was administered into the gingival sulcus of the first molars daily for 10 days, starting with the ligature installation. The following outcomes were evaluated: alveolar bone loss (µCT and methylene blue dye staining), quantification of osteoclasts (histomorphometry), cell infiltrate and collagen content (stereometry), gene expression of mediators (Nfact11, Tnf-α, Mmp-13, iNos, Sod and Nrf2) by (RT-qPCR); expression of BCL-2 and Caspase-1 (immunohistochemistry). Chalcone T4 inhibited bone resorption and prevented collagen matrix degradation. Reduction in the expression of inflammatory markers (Nfact11, Tnf-α, Mmp-13, and Caspase-1), attenuation of oxidative stress (iNOS reduction, and increase in Sod), and pro-apoptotic effect of the compound (BCL-2 reduction), were associated its effects on periodontal tissues. Topical application of Chalcone T4 prevented bone resorption and inflammation, demonstrating potential in the adjunctive treatment of periodontitis.

Effects of total flavonoids of Rhizoma Drynariae on biochemical indicators of bone metabolism: a systematic review and meta-analysis.

Evidence shows that the total flavonoids of Rhizoma Drynariae (TFRD) can improve bone mineral density (BMD). However, there is no evidence to summarize the improvement of biochemical indicators of bone metabolism (BIBM). The PubMed, Web of Science, Cochrane Library, Embase, Chinese National Knowledge Infrastructure (CNKI), Wanfang Database, Chongqing VIP Information Database (VIP) and SinoMed were searched from inception to 6 May 2024. The final included studies performed meta-analyses using RevMan 5.3. Nine randomized controlled trials (RCTs) were ultimately included. The TFRD group had higher bone gla protein (BGP) and type I procollagen-N-propeptide (PINP) compared to the Other therapies (WMD: 5.11; 95% CI: 3.37, 6.84; p < 0.00001; WMD: 13.89; 95% CI: 11.81, 15.97; p < 0.00001). The tartrate-resistant acid phosphatase (TRACP) decreased significantly (WMD: -1.34; 95% CI: -1.62, -1.06; p < 0.00001). The alkaline phosphatase (ALP) increased significantly (WMD: 7.47; 95% CI: 6.29, 8.66; p < 0.00001). There were no significant differences in serum calcium (SC) or serum phosphorus (SP) levels between the TFRD and control groups (WMD: 0.08; 95% CI: -0.04, 0.20; p = 0.17; WMD: 0.02; 95% CI: -0.02, 0.05; p = 0.36). TFRD can stimulate bone formation and prevent bone resorption in osteoporosis (OP) patients, but it has no effect on SC and SP. https://www.crd.york.ac.uk/PROSPERO/.

Does Varying Platelet-Rich Fibrin Centri̇fugati̇on Protocols Enhance New Bone Formati̇on in Extracti̇on Site?

Finding a protocol that could prevent bone resorption and be implemented in clinical practice would be crucial in providing sufficient bone to replace missing teeth with implants. The study aimed to determine the effectiveness of different centrifugation platelet-rich fibrin (PRF) protocols in new bone formation and bone regenerative markers. This randomized clinical trial was conducted at Izmir Katip Çelebi Research Hospital, a population-based facility in Izmir. Study subjects were composed of patients who required extraction of anterior teeth. Exclusion criteria included periodontal disease, resorption of alveolar bone, defects, smoking, alcoholism, and systemic diseases. The independent variable was the PRF protocol. The subjects were randomly assigned to one of three groups: leukocyte platelet-rich fibrin (L-PRF), advanced platelet-rich fibrin (A-PRF) and control groups (healing naturally). The primary outcome of interest was the percentage of new bone formation, determined by analyzing the staining intensity in histomorphometric assessments of bone samples collected 8weeks after extraction. The secondary outcomes were regenerative effects measured by the immunohistochemical expression of markers such as osteocalcin, alkaline phosphatase, and proliferating cell nuclear antigen. Potential benefits were evaluated by clinical observations of pain, swelling, membrane visibility and healing. The covariates were age, sex and health conditions. Histologic comparative staining intensities and biomarkers expression between groups were evaluated by one way analysis of variance. A difference of P<.05 was considered statistically significant. The study included 57 subjects, with a mean age of 45years (±5.6); 30 were male (53%) and 27 female (47%). The control group had a mean new bone formation of 32.68% (±2.5), the A-PRF group 61.37% (±3.0), and the L-PRF group 70.74% (±3.5) (P<.001). The A-PRF group showed significantly higher osteocalcin expression than the control group (P=.013). Alkaline phosphatase and proliferating cell nuclear antigen expression scores for PRF groups were significantly higher than the control group's (P=.001). Both groups demonstrated significantly lower pain scores, reduced gingival swelling, better membrane visibility, and healing compared to the control group. PRF enhanced bone formation rates, with L-PRF showing the most significant effect.

Aesthetic surgical crown lengthening on teeth 11 and 21

Background: In dental treatment planning, aesthetic considerations are crucial due to the relationship between a smile and facial beauty. Crown lengthening is a procedure used to achieve aesthetic smiles, particularly in cases of subgingival caries, fractures, and short clinical crowns. Purpose: The purpose of this case report is to achieve aesthetic improvement of the central incisors through crown lengthening procedures. Case: A 31-year-old female patient presented with a complaint of a broken upper left front tooth and easily bleeding gums. Clinical examination revealed Ellis class 1 fracture at the incisal-distal of tooth 21. The patient exhibited poor oral hygiene with visible calculus on upper and lower jaw teeth. There was gingival hyperplasia, redness, bleeding tendency, and the gingival margin height of teeth 11 and 21 appeared lower than teeth 12 and 22. Radiographically, the alveolar crest was distant from the CEJ. Case Management: Treatment plan included crown lengthening on teeth 11 and 21 with composite restoration on tooth 21. Crown lengthening, a surgical procedure designed to increase the extent of supragingival tooth structure for restorative or aesthetic purposes by repositioning the gingival margin apically was performed. This procedure is indicated for teeth with subgingival caries, extensive caries shortening the tooth, fractures, and short clinical crowns. Conclusion: Crown lengthening should consider the biological width to prevent bone resorption, gingival recession, inflammation, or hypertrophy. When performed under ideal clinical conditions, crown lengthening provides satisfactory outcomes both functionally and aesthetically.

In vitro effects and mechanisms of Humulus lupulus extract on bone marrow progenitor cells and endothelial cells

Osteoporosis is the most common metabolic bone disorder and is associated with a high incidence of fractures. Angiogenesis and adequate blood flow are important during bone repair and maintenance. Estrogens play a key role in bone formation, in the prevention of bone resorption and vasculature maintenance. Hormone replacement therapy (HRT) has been used with great benefits for bone fracture prevention but has been linked to the development of serious important side effects, including cancer and stroke. Phytoestrogens are an attractive alternative to HRT because their chemical structure is similar to estradiol but, they could behave as selective modulators: acting as antagonists of estrogen receptors in the breast and endometrium and as agonists in the vascular endothelium and bone. Hops contain a wide variety of phytoestrogens that have individually been shown to possess estrogenic activity by either blocking or mimicking. In this study we have to evaluate the in vitro effects and mechanisms of action of hops extracts on the osteogenic and adipogenic capacity of bone marrow progenitor cells (BMPCs), and the angiogenic potential of EA.hy926 endothelial cells. We show that hops extracts increase the proliferative capacity of BMPCs and promote their osteogenic differentiation while decreasing their pro-osteoclastogenic capacity; and that these effects are mediated by the MAPK pathway. Additionally, hops extracts prevent the adipogenic differentiation of BMPCs and promote endothelial cell activity, by mechanisms also partially mediated by MAPK.

Calcium sulphate pellets (Osteoset®) improve bone graft incorporation, but not femoral head sphericity after shelf acetabuloplasty for Perthes’ disease

Introduction: Outcome of shelf acetabuloplasty in management of late onset Perthes’ disease can be affected by shelf resorption and inadequate femoral head containment. Various agents have been tried to enhance bone graft incorporation and reduce its resorption. The aim of this study was to assess whether Osteoset® (calcium sulphate pellets) can stimulate autogenous bone graft incorporation and prevent bone resorption after shelf acetabuloplasty for Perthes’ disease and whether its use can improve femoral head remodelling. Methods: Thirty-two children with Perthes’ disease who underwent shelf acetabuloplasty were divided into two groups. In 15 patients (study group) Osteoset (10 ml) mixed with autogenous bone grafts to create extra ‘shelf’ over deficient acetabulum was used. Seventeen patients who served as a control group were managed by shelf acetabuloplasty using autogenous bone graft without Osteoset. Both groups were similar with regards to age and severity of the condition. The mean age at operation was 9 years and 4 months. The mean follow-up was 53.3 and 61.5 months for Osteoset and control groups, respectively, when all patients reached skeletal maturity. On serial radiographs shelf area, extra-osseous shelf length, acetabular coverage and graft incorporation and femoral head sphericity were assessed. Results: Immediately post-operatively the shelf area and shelf length were similar in both groups. From 6 weeks post-operatively and thereafter shelf area and shelf length were significantly better in patients from the study (Osteoset) group. Patients from the control group showed a steady decline in graft area throughout the follow-up period. Graft incorporation was also faster in the Osteoset group. However, femoral head sphericity assessed by Stulberg classification was similar in both groups. Conclusion: Osteoset pellets improve graft volume, encourage earlier graft incorporation and inhibit later shelf resorption. Adding Osteoset does not improve femoral head remodelling following shelf acetabuloplasty for Perthes’ disease.

Unraveling ferroptosis in osteogenic lineages: implications for dysregulated bone remodeling during periodontitis progression

Periodontitis is a highly prevalent disease characterized by inflammation and destruction of tooth-supporting tissues that leads to tooth loss in extreme situations. Elucidating the underlying mechanisms of periodontitis pathogenesis and progression will establish the groundwork for developing effective treatment strategies. Recently, evidence concerning the role of ferroptosis in periodontitis progression has emerged. Osteogenic lineage cells are key regulators of bone remodeling. Osteogenic cell death, as observed in experimental periodontitis models, disrupts the balance between bone resorption and bone formation. However, whether the osteogenic lineage undergoes ferroptosis during periodontitis and the corresponding effect on periodontitis progression remain elusive. Here, we investigated cell-specific ferroptosis within the alveolar bone in a murine periodontitis model. Through immunofluorescence double staining and immunohistochemistry, we identified ferroptotic osteocytes and osteoblasts in inflammatory alveolar bone. Next, in vivo administration of erastin or liproxstatin-1 was conducted to either induce or inhibit ferroptosis, respectively. Severe bone resorption and inflammation, accompanied by increased osteoclast formation and impaired osteogenic potential were detected following ferroptosis activation. Subsequently, we carried out in vitro experiments on osteocytes and further verified that ferroptosis enhanced the osteocytic expression of RANKL and IL-6. These findings suggest that ferroptosis occurring within the osteogenic lineage acts as a catalyst in the progression of periodontitis by stimulating osteoclastogenesis through the secretion of inflammatory cytokines and inhibiting osteoblastic function, providing insights into ferroptosis-induced alterations in microenvironment-based intercellular communication. Ferroptosis is a promising target for controlling inflammation and preventing bone resorption in periodontitis.

Effect of α-mangostin from Garcinia mangostana on Osteoblast cells in the Wound Healing Process: A Review

Preservation of the socket after a tooth extraction is necessary to maintain the dimensions of the alveolar bone. In addition, it can speed up the healing process while preventing bone resorption. Previous research has shown that α-mangostin contained in mangosteen (Garcinia mangostana) rind can reduce alveolar bone resorption, while accelerating the bone healing process. The purpose of this study is to describe the relationship between the inflammatory process and osteoblastic differentiation after administration of α-mangostinto osteoblast cells.The inflammatory process decreased and osteoblast differentiation increased after the application of alpha-mangostin to osteoblast cells.

Loop-Neurorrhaphy Technique for Preventing Bone Resorption and Preserving Sensation in Mandibular Reconstruction.

The aim of this study was to investigate whether using an innervated vascularized iliac bone flap could effectively prevent bone resorption and maintain sensory function in the lower lip. In the innervated group, the deep circumflex iliac artery and recipient vessels were anastomosed, with simultaneous microanastomosis of ilioinguinal nerve, mental nerve, and inferior alveolar nerve. Conversely, the control group underwent solely vascular anastomosis. Computed tomography was used to assess bone quality. Sensory recovery of the lower lip was recorded using 2-point discrimination and current perception threshold testing. The study comprised a total of 40 subjects, with each group accounting for 20 participants, equally distributed in terms of gender. Hounsfield unit loss was significantly lower in the innervated group (13.26% ± 8.65%) as compared with the control group (37.98% ± 8.60%) ( P < 0.001). Moreover, 2-point discrimination values were lower in the innervated group (15.11 ± 8.39 mm) when compared with the control group (21.44 ± 7.24 mm) ( P = 0.02). The current perception threshold values for the innervated group were 176.19 ± 31.89, 64.21 ± 19.23, and 42.29 ± 18.96 at 2 kHz, 250 Hz, and 5 Hz, respectively, whereas in the control group, the current perception threshold values were 204.47 ± 36.99, 82.26 ± 27.29, and 58.89 ± 25.38 at 2 kHz, 250 Hz, and 5 Hz ( P = 0.02, P = 0.02, and P = 0.03, respectively). The innervated vascularized iliac bone flap represents a safe and effective novel approach to preserving lower lip sensation and preventing bone resorption through functional mandibular reconstruction. Therapeutic, I.

Management and maintenance of oral health: Personalized primary prevention strategies and protocols in patients at risk of developing medication-related osteonecrosis of the jaw

Skeletal complications arising from osteoporosis or bone metastases are associated with considerable pain, increased mortality, and diminished quality of life. Agents that prevent bone resorption, such as bisphosphonates, denosumab, and antiangiogenic agents, prove effective in reducing fracture risk and find extensive use in patients with osteoporosis or bone cancer metastases. Medication-related osteonecrosis of the jaw (MRONJ) is a potentially serious adverse event associated with high cumulative doses of antiresorptive drugs. Other risk factors for osteonecrosis of the jaw include glucocorticoid use, maxillary or mandibular bone surgery, poor oral hygiene, chronic inflammation, diabetes mellitus, inappropriate dentures, and other MRONJ-related medications. Preventive strategies encompass completing necessary oral surgery before initiating antiresorptive drug therapy, administering antibiotics before and/or after the procedure, rinsing the mouth with chlorhexidine, ensuring adequate wound healing post-tooth extraction, and maintaining good oral hygiene. The primary goal of treatment is to improve the patient&amp;rsquo;s quality of life by managing pain and infection, preventing the development of new lesions, and decelerating disease progression. Dentists and dental hygienists, operating within a multi-professional team, play a key role in the primary prevention of MRONJ. However, a standardized multidisciplinary approach, fostering sustained dialog between specialists involved in the management of patients at risk for MRONJ, remains essential. This review describes the preventive and individualized oral hygiene management in patients at risk for this condition.

Restoring implant fixation strength in osteoporotic bone with a hydrogel locally delivering zoledronic acid and bone morphogenetic protein 2. A longitudinal in vivo microCT study in rats

Osteoporosis poses a major public health challenge, and it is characterized by low bone mass, deterioration of the microarchitecture of bone tissue, causing a consequent increase in bone fragility and susceptibility to fractures and complicating bone fixation, particularly screw implantation. In the present study, our aim was to improve implant stability in osteoporotic bone using a thermoresponsive hyaluronan hydrogel (HA-pNIPAM) to locally deliver the bisphosphonate zoledronic acid (ZOL) to prevent bone resorption and bone morphogenetic protein 2 (BMP2) to induce bone formation.Adult female Wistar rats (n = 36) were divided into 2 treatment groups: one group of SHAM-operated animals and another group that received an ovariectomy (OVX) to induce an osteoporotic state. All animals received a polyetheretherketone (PEEK) screw in the proximal tibia. In addition, subgroups of SHAM or OVX animals received either the HA-pNIPAM hydrogel without or with ZOL/BMP2, placed into the defect site prior to screw implantation. Periprosthetic bone and implant fixation were monitored using longitudinal in vivo microCT scanning post-operatively and at 3, 6, 9, 14, 20 and 28 days. Histological assessment was performed post-mortem.Our data showed that pure hydrogel has no impact of implant fixation The ZOL/BMP2-hydrogel significantly increased bone-implant contact and peri-implant bone fraction, primarily through reduced resorption. Statement of clinical significanceLocal delivery of ZOL and BMP2 using a biocompatible hydrogel improved implant stability in osteoporotic bone. This approach could constitute a potent alternative to systemic drug administration and may be useful in avoiding implant loosening in clinical settings.

Оптимизация восстановления костной ткани у больных ревматоидным артритом и остеопорозом, осложненным переломами

The article provides a brief summary of bone remodeling, including its stages, disorders, and correction. Osteoporosis (OP) is a systemic skeletal disease in which bone resorption predominates over bone formation. OP is characterized by a decrease in bone mass and density, as well as a disturbance of bone microarchitecture. This leads to a decrease in bone strength and an increased risk of fractures. This paper describes a case of a woman with rheumatoid arthritis (RA) and OP complicated by low-trauma fractures. The authors emphasize that OP is a multifactorial disease and one of the most common bone diseases, particularly among the elderly. OP in RA is an immune- mediated secondary osteopathy and is considered both a comorbidity and complication of the underlying disease. Patients with RA have a higher bone mineral density (BMD) and a higher rate of fractures than the general population. Fractures can occur in individuals with osteopenia or normal BMD values. Therefore, it is important to carefully analyze the risk factors for OP and fractures when planning RA therapy. The ‘treat to target' strategy aims to achieve RA remission or reduce disease activity while also preventing complications, such as osteoporotic fractures. To manage bone metabolism disorders in patients with RA who also have osteoporosis and fractures, it is necessary to control RA activity and prescribe basic therapy for osteoporosis, such as ossein-hydroxyapatite complex and alfacalcidol, as well as pathogenic drugs that prevent bone resorption. Additionally, patients with osteoporosis and fractures require pain-reducing measures, restorative treatment, and rehabilitation. Effective management requires a multidisciplinary approach involving physicians from various specialties. KEYWORDS: bone tissue structure, resorption, rheumatoid arthritis, osteoporosis, fractures, pharmacotherapy of bone metabolism disorders, ossein-hydroxyapatite complex. FOR CITATION: Dydykina I.S., Kovalenko P.S., Kudinskiy D.M., Kovalenko A.A., Ivanova M.E. Optimizing bone repair in patients with rheumatoid arthritis and osteoporosis complicated by fractures. Russian Medical Inquiry. 2024;8(2):94–101 (in Russ.). DOI: 10.32364/2587- 6821-2024-8-2-7.

Mediating role of host metabolites in strontium's effect on osteoporosis among older individuals: Findings from Wuhan, China.

Strontium is receiving widespread attention due to its remarkable biological qualities in preventing bone resorption and fostering osteogenesis. However, the chemical processes behind strontium's dual activities on bone cells are not yet fully understood. This study used the metabolomic technique to identify and examine potential biomarkers between strontium exposure and osteoporosis (OP) risk. A total of 806 participants were recruited for the detection of plasma strontium content via inductively coupled plasma-mass spectrometry. Plasma metabolites were profiled in 254 participants through an untargeted metabolomics technique. Generalized linear models were primarily used to analyze associations among plasma strontium, metabolites, and OP. The mediating effects of metabolites on the strontium-OP association were further investigated. A total of 31 differential metabolites were observed, 10 of which were upregulated and 21 were downregulated in the OP group compared with the non-OP group. Five metabolites (3-phenoxybenzoic acid, Cer (t18:0/16:1), HexCer(t16:1/12:1(2OH)), HexCer(t14:2/18:1(2OH)), and TG(16:0-18:1-24:4)) were selected as potential mediators based on their significant association with OP risk and with femoral neck and lumbar spine bone mineral density (BMD). Moreover, all except TG(16:0-18:1-24:4) were involved in the OP discrimination model with excellent power combined with several traditional variables. 3-Phenoxybenzoic acid and Cer(t18:0/16:1) had significant indirect effects on the strontium-OP association. The five candidate metabolites mediated 83.79% of the strontium-OP association. Plasma strontium level was associated with reduced OP risk in the Han population in Wuhan. Thus, plasma metabolite profiling revealed five BMD/OP-associated metabolites that acted as mediators in the strontium-OP association. Our findings provided evidence of the mediating role of host plasma metabolites in strontium's effect on OP pathology.

Radially and axially graded cellular tibial stems for total knee replacement

In spite of the high success rate of existing total knee replacement implants, the aseptic loosening of components, particularly the tibial one, is a matter of concern. To control the short- and long-term loosening mechanisms, the tibial stem material shall have diverse stiffness properties in different regions and directions, such that it encourages osseointegration and prevents bone resorption. The previous studies in the literature have failed to provide designs which could satisfy these two requirements concurrently. The purpose of this study was to design heterogeneous and anisotropic porous titanium tibial stems, based on radial and axial functionally graded cellular (FGC) structures, with precisely tailored stiffness properties. A 3D voxel-based finite element model of the bone-implant construct was developed to predict the nodal micromotion at the interface, assuming a frictional contact, and the stress-shielding effect in the periprosthetic bone, assuming a perfectly bonded connection. An exponential FGC material model was assigned to the implant along each of the radial and axial directions, with the gradient parameters considered as design variables. A design of experiment (DOE) -based multi-objective optimization procedure was then employed to maximize the osseointegration potential and minimize the bone resorption index. Equivalent FGC lattices, composed of Cartesian and cylindrical arrangements of gyroid unit cells, were produced for the optimal designs and fabricated by selective laser melting (SLM) technique. In comparison with the solid stem, the radial graded design resulted in a substantial improvement in the bone resorption behavior (19.4%), but a moderate reduction in the osseointegration potential (9.4%). The axial graded design, on the other hand, was associated with a moderate improvement in the bone resorption characteristics (12.0%) and slight improvement in the osseointegration index (2.2%). The dimensional accuracy of the SLM-fabricated specimens was reasonably high (strut thickness: 0.032 to 0.076 mm RMSE, pore size: 0.029 to 0.057 mm RMSE). The radial and axial graded specimens behaved as brittle and ductile materials, respectively, in axial compression tests and failed due to buckling and excessive plastic deformation. The cylindrical lattice arrangement demonstrated a lower elastic modulus (radial graded: 1945 vs. 3053 MPa, axial graded: 779 vs. 2324 MPa) and yield strength (radial graded: 77 vs. 114 MPa, axial graded: 17 vs. 43 MPa) than the Cartesian arrangement. It was concluded that an optimal bi-directional axial and radial gradient structure with a cylindrical lattice arrangement would provide the most favorable biomechanical performance for the tibial stem.

Interleukin-21 knockout reduces bone loss in ovariectomized mice by inhibiting osteoclastogenesis.

Estrogen deficiency accelerates osteoporosis in elderly women. However, the role of IL-21 in postmenopausal osteoporosis remains unclear. Female wild-type (WT) C57BL/6 and IL-21 knockout (KO) mice were used for ovariectomy (OVX). Here, IL-21 levels were significantly increased in the serum and bone tissues of WT-OVX mice. The trabecular bone space of the femur was significantly increased, and the bone mass was reduced in OVX mice, accompanied by a significant decrease in the maximum load, energy absorption, and elastic modulus indices. In contrast, IL-21 knockout effectively alleviated the effects of OVX on bone mass. Serum TRACP-5b and receptor activator of nuclear factor kappa B ligand (RANKL) levels and osteoclastogenesis were significantly higher in OVX mice than in sham mice, while serum TRACP-5b and RANKL levels and osteoclastogenesis were significantly decreased in IL-21 KO+OVX mice compared to WT+OVX mice. IL-21 knockdown reduces TRACP-5b, RANKL, and osteoclastogenesis, effectively preventing bone resorption and alleviating the progression of OVX-induced osteoporosis.

Zoledronic Acid Prevents Bone Resorption Caused by the Combination of Radium-223, Abiraterone Acetate, and Prednisone in an Intratibial Prostate Cancer Mouse Model.

An increased risk of non-pathological fractures in patients with prostate cancer and bone metastases has been associated with combination treatment with radium-223, abiraterone, and prednisone/prednisolone in the absence of bone-protecting agents. Here, we investigated possible mechanisms leading to this outcome using an intratibial LNCaP model mimicking prostate cancer bone metastases. Male NOD.scid mice were inoculated intratibially with LNCaP prostate cancer cells and treated with vehicle, radium-223, abiraterone, prednisone, zoledronic acid, or their combinations for 28 days. Serum TRACP 5b and PSA levels were measured. Bone structure, quality, and formation rate of non-tumor-bearing and tumor-bearing tibiae were analyzed by microCT, 3-point bending assay, and dynamic histomorphometry, respectively. Radium-223 incorporation into bone was also measured. Radium-223/abiraterone/prednisone combination treatment induced a transient increase in bone resorption indicated by elevated TRACP 5b levels, which was inhibited by concurrent treatment with zoledronic acid. Furthermore, radium-223/abiraterone/prednisone combination reduced periosteal and trabecular new bone formation and the number of osteoblasts, but bone structure or biomechanical quality were not affected. The abiraterone/prednisone treatment decreased radium-223 incorporation into tumor-bearing bone, possibly explaining the lack of additional antitumor efficacy. In conclusion, radium-223/abiraterone/prednisone combination increased bone resorption, which may have been one of the mechanisms leading to an increased fracture risk in patients with mCRPC.

Metal-polyDNA nanoparticles reconstruct osteoporotic microenvironment for enhanced osteoporosis treatment.

Current clinical approaches to osteoporosis primarily target osteoclast biology, overlooking the synergistic role of bone cells, immune cells, cytokines, and inorganic components in creating an abnormal osteoporotic microenvironment. Here, metal-polyDNA nanoparticles (Ca-polyCpG MDNs) composed of Ca2+ and ultralong single-stranded CpG sequences were developed to reconstruct the osteoporotic microenvironment and suppress osteoporosis. Ca-polyCpG MDNs can neutralize osteoclast-secreted hydrogen ions, provide calcium repletion, promote remineralization, and repair bone defects. Besides, the immune-adjuvant polyCpG in MDNs could induce the secretion of osteoclastogenesis inhibitor interleukin-12 and reduce the expression of osteoclast function effector protein to inhibit osteoclast differentiation, further reducing osteoclast-mediated bone resorption. PPi4- generated during the rolling circle amplification reaction acts as bisphosphonate analog and enhances bone targeting of Ca-polyCpG MDNs. In ovariectomized mouse and rabbit models, Ca-polyCpG MDNs prevented bone resorption and promoted bone repair by restoring the osteoporotic microenvironment, providing valuable insights into osteoporosis therapy.

The Effect of Grape Seed Extract on the Alveolar, Jaw, and Skeletal Bone Remodeling: A Scoping Review.

Herbal medicine has an important part in promoting and maintaining human health. One of them was grape seed extract (GSE). Various potentials of GSE in human health have been explored, and its potential for maintaining bone health is promising. Some initial research has provided evidence that the GSE was able to affect bone remodeling (bone resorption and bone formation). This scoping review analyzed and discussed all the reports on the effect of GSE on bone healing and bone remodeling in animals in the alveolar bone, jaw bone, and skeletal bone. The further purpose is to give an opportunity to research and development of supplementation of GSE for humans.The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 guidelines were used to compose this scoping review through database on Scopus, PubMed, Science Direct, Web of Science, Embase, and manual search until December 2022. The inclusion criteria were a study that analyzed the effect of supplementation GSE on all bones.All included study was in vivo study with supplementation of GSE. The supplementation of GSE affects the alveolar bone, jaw bones, and skeletal bone by promoting bone formation and inhibiting bone resorption by suppressing inflammation, apoptosis pathways, and osteoclastogenesis. It not only supports bone remodeling in bone inflammation, osteonecrosis, osteoporosis, and arthritis but also the GSE increases bone health by increasing the density and mineral deposition in trabecula and cortical bone.The supplementation of GSE supports bone remodeling by interfering with the inflammation process and bone formation not only by preventing bone resorption but also by maintaining bone density.

SOST gene suppression stimulates osteocyte Wnt/β-catenin signaling to prevent bone resorption and attenuates particle-induced osteolysis

The most common cause for prosthetic revision surgery is wear particle-induced periprosthetic osteolysis, which leads to aseptic loosening of the prosthesis. Both SOST gene and its synthetic protein, sclerostin, are hallmarks of osteocytes. According to our previous findings, blocking SOST induces bone formation and protects against bone loss and deformation caused by titanium (Ti) particles by activating the Wnt/β-catenin cascade. Although SOST has been shown to influence osteoblasts, its ability to control wear-particle-induced osteolysis via targeting osteoclasts remains unclear. Mice were subjected to development of a cranial osteolysis model. Micro CT, HE staining, and TRAP staining were performed to evaluate bone loss in the mouse model. Bone marrow-derived monocyte-macrophages (BMMs) made from the C57BL/6 mice were exposed to the medium of MLO-Y4 (co-cultured with Ti particles) to transform them into osteoclasts. Bioinformatics methods were used to predict and validate the interaction among SOST, Wnt/β-catenin, RANKL/OPG, TNF-α, and IL-6. Local bone density and bone volume improved after SOST inhibition, both the number of lysis pores and the rate of skull erosion decreased. Histological research showed that β-catenin and OPG expression were markedly increased after SOST inhibition, whereas TRAP and RANKL levels were markedly decreased. In-vitro, Ti particle treatment elevated the expression of sclerostin, suppressed the expression of β-catenin, and increased the RANKL/OPG ratio in the MLO-Y4 cell line. TNF-α and IL-6 also elevated after treatment with Ti particles. The expression levels of NFATc1, CTSK, and TRAP in osteoclasts were significantly increased, and the number of positive cells for TRAP staining was increased. Additionally, the volume of bone resorption increased at the same time. In contrast, when SOST expression was inhibited in the MLO-Y4 cell line, these effects produced by Ti particles were reversed. All the results strongly show that SOST inhibition triggered the osteocyte Wnt/β-catenin signaling cascade and prevented wear particle-induced osteoclastogenesis, which might reduce periprosthetic osteolysis.Key messagesSOST is a molecular regulator in maintaining bone homeostasis.SOST plays in regulating bone homeostasis through the Wnt/β-catenin signaling pathway.SOST gene suppression stimulates osteocyte Wnt/β-catenin signaling to prevent bone resorption and attenuates particle-induced osteolysis.