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Bioactive Materials Jul 2024Zinc (Zn) alloys have demonstrated significant potential in healing critical-sized bone defects. However, the clinical application of Zn alloys implants is still...
Imidazole functionalized photo-crosslinked aliphatic polycarbonate drug-eluting coatings on zinc alloys for osteogenesis, angiogenesis, and bacteriostasis in bone regeneration.
Zinc (Zn) alloys have demonstrated significant potential in healing critical-sized bone defects. However, the clinical application of Zn alloys implants is still hindered by challenges including excessive release of zinc ions (Zn), particularly in the early stage of implantation, and absence of bio-functions related to complex bone repair processes. Herein, a biodegradable aliphatic polycarbonate drug-eluting coating was fabricated on zinc-lithium (Zn-Li) alloys to inhibit Zn release and enhance the osteogenesis, angiogenesis, and bacteriostasis of Zn alloys. Specifically, the photo-curable aliphatic polycarbonates were co-assembled with simvastatin and deposited onto Zn alloys to produce a drug-loaded coating, which was crosslinked by subsequent UV light irradiation. During the 60 days long-term immersion test, the coating showed distinguished stable drug release and Zn release inhibition properties. Benefiting from the regulated release of Zn and simvastatin, the coating facilitated the adhesion, proliferation, and differentiation of MC3T3-E1 cells, as well as the migration and tube formation of EA.hy926 cells. Astonishingly, the coating also showed remarkable antibacterial properties against both and . The rabbit critical-size femur bone defects model demonstrated that the drug-eluting coating could efficiently promote new bone formation and the expression of platelet endothelial cell adhesion molecule-1 (CD31) and osteocalcin (OCN). The enhancement of osteogenesis, angiogenesis, and bacteriostasis is achieved by precisely controlling of the released Zn at an appropriate level, as well as the stable release profile of simvastatin. This tailored aliphatic polycarbonate drug-eluting coating provides significant potential for clinical applications of Zn alloys implants.
PubMed: 38756420
DOI: 10.1016/j.bioactmat.2024.03.037 -
Journal of Applied Oral Science :... 2024Studies have highlighted numerous benefits of ozone therapy in the field of medicine and dentistry, including its antimicrobial efficacy against various pathogenic...
OBJECTIVE
Studies have highlighted numerous benefits of ozone therapy in the field of medicine and dentistry, including its antimicrobial efficacy against various pathogenic microorganisms, its ability to modulate the immune system effectively, reduce inflammation, prevent hypoxia, and support tissue regeneration. However, its effects on dental extraction healing remain to be elucidated. .Therefore, this study aimed to evaluate the effects of systemically administered ozone (O3) at different doses in the healing of dental extraction sockets in rats.
METHODOLOGY
To this end, 72 Wistar rats were randomly divided into four groups after extraction of the right upper central incisor: Group C - control, no systemic treatment; Group OZ0.3 - animals received a single dose of 0.3 mg/kg O3; Group OZ0.7 - a single dose of 0.7 mg/kg O3; and Group OZ1.0 - a single dose of 1.0 mg/kg O3, intraperitoneally. In total, six animals from each group were euthanized at 7, 14, and 21 days after the commencement of treatment. Bone samples were harvested and further analyzed by descriptive histology, histomorphometry, and immunohistochemistry for osteocalcin (OCN) and tartrate-resistant acid phosphatase (TRAP) protein expression.
RESULTS
All applied doses of O3 were shown to increase the percentage of bone tissue (PBT) after 21 days compared to group C. After 14 days, the OZ0.7 and OZ1.0 groups showed significantly higher PBT when compared to group C. The OZ1.0 group presented the most beneficial results regarding PBT among groups, which denotes a dose-dependent response. OCN immunostaining was higher in all groups at 21 days. However, after seven and 14 days, the OZ1.0 group showed a significant increase in OCN immunostaining compared to C group. No differences in TRAP+ osteoclasts were found between groups and time points.
CONCLUSION
Therefore, O3 therapy at higher doses might be beneficial for bone repair of the alveolar socket following tooth extraction.
Topics: Animals; Ozone; Rats, Wistar; Tooth Extraction; Tooth Socket; Wound Healing; Tartrate-Resistant Acid Phosphatase; Immunohistochemistry; Osteocalcin; Time Factors; Male; Random Allocation; Reproducibility of Results; Treatment Outcome; Reference Values
PubMed: 38747807
DOI: 10.1590/1678-7757-2023-0412 -
Journal of Periodontal Research May 2024The present study aimed to investigate the histomorphometric and immunohistochemical impacts of vitamin K2 on guided bone regeneration (GBR) in calvarial critical-size...
AIM
The present study aimed to investigate the histomorphometric and immunohistochemical impacts of vitamin K2 on guided bone regeneration (GBR) in calvarial critical-size defects (CSDs) in diabetic rats.
METHODS
A total of 30 rats were used in this study, comprising 12 non-diabetic (control) rats and 18 with streptozotocin-nicotinamide-induced experimental Diabetes mellitus (DM). In all rats, two calvarial CSDs were created: one defect was left empty (E), the other was treated with bovine-derived bone graft and collagen-based resorbable membrane (GM). Study groups were as follows: control rats administered saline (n = 6, C-E and C-GM groups) or vitamin K2 (n = 6, CK-E and CK-GM groups) and diabetic rats administered saline (n = 6, DM-E and DM-GM groups) or vitamin K2 (n = 6, DMK-E and DMK-GM groups). After 4 weeks of saline or vitamin K2 administration, the rats were euthanized. Bone defect healing and new bone formation were assessed histomorphometrically, and osteocalcin and osteopontin levels were examined immunohistochemically.
RESULTS
Percentage of new bone formation was greater in CK-GM vs. CK-E and in DMK-GM vs. DMK-E [d = 3.86 (95% CI = 16.38-28.61), d = 1.86, (95% CI = 10.74-38.58), respectively, p < .05]. Bone defect healing scores were higher in CK-GM vs. CK-E and in DMK-GM vs. DMK-E [d = 2.69 (95% CI = -2.12 to -0.87), d = 3.28 (95% CI = 0.98-1.91), respectively, p < .05]. Osteocalcin expression levels were elevated in CK-GM vs. CK-E, in DMK-GM vs. DMK-E [d = 1.19 (95% CI = 0.08-1.41), d = 1.10 (95% CI = 0.02-1.22), respectively p < .05]. Vitamin K2 enhanced osteocalcin expression levels in DMK-E vs. DM-E [d = 2.78, (95% CI = 0.56-1.53), p < .05] and in DMK-GM vs. DM-GM [d = 2.43, (95% CI = 0.65-2.10), p < .05]. Osteopontin expression was enhanced in defects treated with GM vs. E defects [C-GM vs. C-E, d = 1.56 (95% CI = 0.38-2.01); CK-GM vs. CK-E, d = 1.91 (95% CI = 0.49-1.72); DM-GM vs. DM-E, d = 2.34 (95% CI = -1.12 to -0.50); DMK-GM vs. DMK-E, d = 2.00 (95% CI = 0.58-1.91), p < .05].
CONCLUSION
The research findings suggest that administering vitamin K2 in GBR for rats with DM favorably impacts bone healing in CSDs, presenting an adjunctive strategy for bone regeneration.
PubMed: 38742688
DOI: 10.1111/jre.13287 -
Frontiers in Endocrinology 2024To investigate the relationship between bone turnover markers (BTMs) and thyroid indicators in Graves' disease (GD) and to further assess predictive value of changes in...
PURPOSE
To investigate the relationship between bone turnover markers (BTMs) and thyroid indicators in Graves' disease (GD) and to further assess predictive value of changes in early stage retrospectively.
METHODS
We studied 435 patients with GD and 113 healthy physical examiners retrospectively and followed up these two groups of patients after 6 months. We investigated the correlations between BTMs and other 15 observed factors, and analyzed the predictive value of FT and FT before and after treatment (FT-P/FT-A, FT-P/FT-A) on whether BTMs recovered.
RESULTS
The levels of thyroid hormones and BTMs in GD group were significantly higher than those in control group (P < 0.05) and decreased after 6 months of treatment. FT3, W, Ca and ALP were independent factors in predicting the elevation of OST. Duration of disease, FT3, TSH and ALP were independent factors in predicting the elevation of P1NP. Age, duration of disease, TRAb and ALP were independent factors in predicting the elevation of CTX-1. The AUC of FT-P/FT-A and FT-P/FT-A for predicting OST recovery were 0.748 and 0.705 (P < 0.05), respectively, and the cut-off values were 0.51 and 0.595. There was no predictive value for P1NP and CTX-1 recovery (P > 0.05).
CONCLUSION
BTMs were abnormally elevated in GD and were significantly correlated with serum levels of FT3, FT4, TRAb, Ca, and ALP. FT decreased more than 51% and FT dropped more than 59.5% after 6 months of treatment were independent predictors for the recovery of BTMs in GD.
Topics: Humans; Male; Female; Graves Disease; Adult; Biomarkers; Retrospective Studies; Middle Aged; Bone Remodeling; Predictive Value of Tests; Thyroid Gland; Bone and Bones; Thyroid Hormones; Case-Control Studies; Prognosis; Antithyroid Agents; Thyroxine; Triiodothyronine; Follow-Up Studies
PubMed: 38742199
DOI: 10.3389/fendo.2024.1301213 -
JBMR Plus Mar 2024Hypoparathyroidism (HypoPT) is a rare disease, often inadequately controlled by conventional treatment. PARALLAX was a mandatory post-marketing trial assessing... (Clinical Trial)
Clinical Trial
UNLABELLED
Hypoparathyroidism (HypoPT) is a rare disease, often inadequately controlled by conventional treatment. PARALLAX was a mandatory post-marketing trial assessing pharmacokinetics and pharmacodynamics of different dosing regimens of recombinant human parathyroid hormone 1-84 (rhPTH[1-84]) for treating HypoPT. The present study (NCT03364738) was a phase 4, 1-yr open-label extension of PARALLAX. Patients received only 2 doses of rhPTH(1-84) in PARALLAX and were considered treatment-naive at the start of the current study. rhPTH(1-84) was initiated at 50 μg once daily, with doses adjusted based on albumin-corrected serum calcium levels. Albumin-corrected serum calcium (primary outcome measure), health-related quality of life (HRQoL), adverse events, and healthcare resource utilization (HCRU) were assessed. The mean age of the 22 patients included was 50.0 yr; 81.8% were women, and 90.9% were White. By the end of treatment (EOT), 95.5% of patients had albumin-corrected serum calcium values in the protocol-defined range of 1.88 mmol/L to the upper limit of normal. Serum phosphorus was within the healthy range, and albumin-corrected serum calcium-phosphorus product was below the upper healthy limit throughout, while mean 24-h urine calcium excretion decreased from baseline to EOT. Mean supplemental doses of calcium and active vitamin D were reduced from baseline to EOT (2402-855 mg/d and 0.8-0.2 μg/d, respectively). Mean serum bone turnover markers, bone-specific alkaline phosphatase, osteocalcin, procollagen type I N-terminal propeptide, and type I collagen C-telopeptide increased 2-5 fold from baseline to EOT. The HCRU, disease-related symptoms and impact on HRQoL improved numerically between baseline and EOT. Nine patients (40.9%) experienced treatment-related adverse events; no deaths were reported. Treatment with rhPTH(1-84) once daily for 1 yr improved HRQoL, maintained eucalcemia in 95% of patients, normalized serum phosphorus, and decreased urine calcium excretion. The effects observed on urine calcium and the safety profile are consistent with previous findings.
CLINICAL TRIAL IDENTIFIER
NCT03364738.
PubMed: 38741607
DOI: 10.1093/jbmrpl/ziad010 -
Journal of Dentistry Jul 2024The objective of this study was to assess whether zinc-doped fluorapatite (ZnFA) could serve as an effective antimicrobial dental bone filler for bone regeneration...
OBJECTIVES
The objective of this study was to assess whether zinc-doped fluorapatite (ZnFA) could serve as an effective antimicrobial dental bone filler for bone regeneration compared to autografts.
METHODS
FA and 2 % zinc-doped FA (2ZnFA) were synthesized and characterized in-house. Compressed and sintered FA and 2ZnFA disks were incubated with bacteria to assess antimicrobial properties. Adipose-derived stem cells were cultured on these discs to evaluate the surfaces' ability to support cell growth and promote osteogenic differentiation. Surfaces exhibiting the highest expressions of the bone markers osteopontin and osteocalcin were selected for an in vivo study in a rat mandibular defect model. Twenty rats were divided into 5 groups, equally, and a 5 mm surgical defect of the jaw was left untreated or filled with 2ZnFA, FA, autograft, or demineralized bone matrix (DBM). At 12 weeks, the defects and surrounding tissues were harvested and subjected to microCT and histological evaluations.
RESULTS
Standard techniques such as FTIR, ICP-MS, fluoride probe, and XRD revealed the sintered FA and ZnFA's chemical compositions and structures. Bacterial studies revealed no significant differences in surface bacterial adhesion properties between FA and 2ZnFA, but significantly fewer bacterial loads than control titanium discs (p < 0.05). Cell culture data confirmed that both surfaces could support cell growth and promote the osteogenic differentiation of stem cells. MicroCT analysis confirmed statistical similarities in bone regeneration within FA, 2ZnFA, and autograft groups.
CONCLUSION
The data suggests that both FA and 2ZnFA could serve as alternatives to autograft materials, which are the current gold standard. Moreover, these bone fillers outperformed DBM, an allograft material commonly used as a dental bone void filler.
CLINICAL SIGNIFICANCE
The use of FA or 2ZnFA for treating mandibular defects led to bone regeneration statistically similar to autograft repair and significantly outperformed the widely used dental bone filler, DBM. Additional translational research may confirm FA-based materials as superior substitutes for existing synthetic bone fillers, ultimately enhancing patient outcomes.
Topics: Animals; Apatites; Bone Regeneration; Rats; Tissue Scaffolds; Zinc; Osteogenesis; Cell Differentiation; Bone Substitutes; Osteopontin; Stem Cells; Mandible; X-Ray Microtomography; Osteocalcin; Adipose Tissue; Anti-Infective Agents; Cell Proliferation; Male; Cells, Cultured; Bone Transplantation; Autografts; Spectroscopy, Fourier Transform Infrared
PubMed: 38740251
DOI: 10.1016/j.jdent.2024.105070 -
Biomedical Materials (Bristol, England) Jun 2024This study aimed to investigate the effects of magnesium-doped bioactive glass (Mg-BG) on the mineralization, odontogenesis, and anti-inflammatory abilities of human...
This study aimed to investigate the effects of magnesium-doped bioactive glass (Mg-BG) on the mineralization, odontogenesis, and anti-inflammatory abilities of human dental pulp stem cells (hDPSCs). Mg-BG powders with different Mg concentrations were successfully synthesized via the sol-gel method and evaluated using x-ray diffraction, Fourier-transform infrared spectroscopy, scanning electron microscopy, and transmission electron microscopy. Apatite formation was observed on the surfaces of the materials after soaking in simulated body fluid. hDPSCs were cultured with Mg-BG powder extracts in vitro, and no evident cytotoxicity was observed. Mg-BG induced alkaline phosphatase (ALP) expression and mineralization of hDPSCs and upregulated the expression of odontogenic genes, including those encoding dentin sialophosphoprotein, dentin matrix protein 1, ALP, osteocalcin, and runt-related transcription factor 2. Moreover, Mg-BG substantially suppressed the secretion of inflammatory cytokines (interleukin [IL]-4, IL-6, IL-8, and tumor necrosis factor-alpha). Collectively, the results of this study suggest that Mg-BG has excellent in vitro bioactivity and is a potential material for vital pulp therapy of inflamed pulps.
Topics: Humans; Dental Pulp; Magnesium; Anti-Inflammatory Agents; Stem Cells; Glass; Odontogenesis; Cytokines; Cells, Cultured; Biocompatible Materials; X-Ray Diffraction; Spectroscopy, Fourier Transform Infrared; Alkaline Phosphatase; Ceramics; Materials Testing; Powders; Microscopy, Electron, Scanning
PubMed: 38740053
DOI: 10.1088/1748-605X/ad4ada -
The Journal of Clinical Endocrinology... May 2024Controversial results have emerged regarding whether PCOS is protective or increases the risk of bone frailty.
CONTEXT
Controversial results have emerged regarding whether PCOS is protective or increases the risk of bone frailty.
OBJECTIVE
This study investigated whether the PCOS condition affects bone parameters of premenopausal women. This is an update for a previous meta-analysis published in 2019.
DATA SOURCES
We searched MEDLINE and Embase.
STUDY SELECTION
Studies were considered eligible for the update if published in English between the 1st of October 2018 and the 31st of December 2023. The diagnosis of PCOS should be based on NIH criteria, the Rotterdam Consensus, AE-PCOS society criteria, or ICD codes in women over 18 years old. Only records with the Newcastle-Ottawa Scale > 6 were selected for data extraction.
DATA EXTRACTION
Data were extracted by two independent reviewers.
DATA SYNTHESIS
We identified 31 studies that met the inclusion criteria for qualitative analysis from 3322 studies in the whole period (1990-2023). Overall, cross-sectional studies included 1822 individuals with PCOS and 1374 controls, while cohort studies incorporated 30305 women with PCOS and 101907 controls. Contrasting profiles emerged after stratification using a BMI cutoff of 27 kg/m2. Individuals with PCOS and a BMI <27 kg/m2 exhibited lower vertebral and non-vertebral bone density, reduced bone turnover marker (osteocalcin), and increased bone resorption marker (CTX) levels. Conversely, individuals with PCOS and a BMI >27 kg/m2 exhibited increased vertebral and non-vertebral BMD, with no significant changes in bone formation and resorption markers (except osteocalcin).
CONCLUSIONS
The findings of this study alert for a low bone mass, low bone formation, and increased bone resorption PCOS with a BMI <27 kg/m2.
PubMed: 38739756
DOI: 10.1210/clinem/dgae325 -
Bone Reports Jun 2024Dairy foods are nutritional sources of calcium, phosphorus, protein, and other nutrients that improve bone health. However, the effects of dairy consumption on bone...
Dairy consumption, bone turnover biomarkers, and osteo sono assessment index in Japanese adults: A cross-sectional analysis of data from the Iwaki Health Promotion Project.
PURPOSE
Dairy foods are nutritional sources of calcium, phosphorus, protein, and other nutrients that improve bone health. However, the effects of dairy consumption on bone biomarkers in the Japanese population remain unclear. This study explored the association between dairy consumption and bone biomarkers in Japanese adults.
METHODS
This cross-sectional study was conducted as part of the Iwaki Health Promotion Project in Aomori, Japan. In total, 1063 adults were included in the analysis. Bone turnover marker levels were measured in local citizens during their annual medical checkups. The calcaneus osteo sono assessment index (OSI) was calculated using a quantitative ultrasound technique. The dietary intake of foods and nutrients was estimated using a food frequency questionnaire. Linear regression models were established using dairy consumption and bone biomarkers with adjustments. Statistic significance was considered by < 0.05.
RESULTS
In multivariate models, the tartrate-resistant acid phosphatase 5b and parathyroid hormone concentrations were inversely associated with dietary dairy consumption after adjusting for age and sex. The undercarboxylated osteocalcin, a procollagen type I N-terminal peptide to bone alkaline phosphatase ratio, and OSI were the directly associated with dairy consumption in multivariate models with adjustment.
CONCLUSIONS
Dairy consumption is partially associated with bone turnover biomarkers and OSI in adult Japanese participants. Habitual consumption of dairy foods may contribute to the nutritional supplementation for maintaining bone health, including turnover and structure.
CLINICAL TRIAL REGISTRY NUMBER AND WEBSITE WHERE IT WAS OBTAINED
The Japanese Clinical Trials Registry (UMIN000040459), https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000046175.
PubMed: 38736771
DOI: 10.1016/j.bonr.2024.101770 -
Journal of Physiology and Pharmacology... Apr 2024Quercetin is widely distributed in plants as a flavonol compound with multiple biological activities. It has been found that quercetin can regulate bone homeostasis...
Modulation of the microRNA-6089/E2F transcription factor2 axis by querceting: implications for osteoblast viability, proliferation, migration, and osteogenic differentiation in fracture healing.
Quercetin is widely distributed in plants as a flavonol compound with multiple biological activities. It has been found that quercetin can regulate bone homeostasis through multiple pathways and targets. This study investigated the role and specific molecular mechanisms of quercetin in regulating osteoblast viability, proliferation, migration and osteogenic differentiation. A mouse model of traumatic fracture was established and then 100 mg/kg quercetin corn oil suspension was gavaged at the same time every day for 28 days. miR-6089 and E2F transcription factor 2 (E2F2) expression levels in mice were measured. Fracture healing in mice was observed. MC3T3-E1 cells were transfected with plasmids targeting miR-6089 and E2F2, and cell viability, proliferation, migration, apoptosis, and osteogenic differentiation were determined. The targeting relationship between miR-6089 and E2F2 was verified. In vivo experiments showed that quercetin significantly increased osteocalcin (OCN) expression (P<0.05) and promoted fracture healing in traumatic fracture (TF) mice. miR-6089 expression was down-regulated (P<0.05) and E2F2 expression was up-regulated (P<0.05) in TF mice. Quercetin promoted miR-6089 expression and inhibited E2F2 expression (both P<0.05). In vitro results showed that quercetin promoted miR-6089 expression and inhibited E2F2 expression in a dose-dependent manner (both P<0.05). Quercetin dose-dependently promoted MC3T3-E1 cell viability, proliferation, migration, and osteogenic differentiation, and inhibited MC3T3-E1 cell apoptosis (all P<0.05). Up-regulating miR-6089 further promoted MC3T3-E1 cell viability, proliferation, migration and osteogenic differentiation, and inhibited MC3T3-E1 cell apoptosis (all P<0.05). miR-6089 targeted and regulated E2F2 expression. Up-regulating E2F2 attenuated the promoting effect of up-regulated miR-6089 on MC3T3-E1 cell viability, proliferation, migration, osteogenic differentiation, and inhibition of apoptosis (all P<0.05). We conclude that quercetin enhances osteoblast viability, proliferation, migration, and osteogenic differentiation by modulating the miR-6089/E2F2 axis, thereby promoting fracture healing.
Topics: Animals; Male; Mice; Apoptosis; Cell Differentiation; Cell Line; Cell Movement; Cell Proliferation; Cell Survival; E2F2 Transcription Factor; Fracture Healing; MicroRNAs; Osteoblasts; Osteogenesis; Quercetin
PubMed: 38736264
DOI: 10.26402/jpp.2024.2.06