Comparison of clinical efficacy between autologous partially demineralized dentin matrix and deproteinized bovine bone mineral for bone augmentation in orthodontic patients with alveolar bone deficiency: a randomized controlled clinical trial.

BACKGROUND: It is common to see patients who need orthodontic treatment but with insufficient alveolar bone volume. However, safe and effective tooth movement requires sufficient alveolar bone width and height. The aim of this study is to compare the bone augmentation efficacy of Autologous Partially Demineralized Dentin Matrix (APDDM) and Deproteinized Bovine Bone Mineral (DBBM) in orthodontic patients with insufficient bone by using a randomized controlled clinical trial approach. MATERIALS AND METHODS: Twenty-seven orthodontic patients involving 40 posterior teeth alveolar sites (n = 40) with insufficient alveolar bone volume were randomly divided into a control group (n = 20) and an experimental group (n = 20). The patients in the experimental group were treated with APDDM, and those in the control group were treated with DBBM. After surgery, the adjacent teeth are moved toward the bone grafting sites according to the orthodontic treatment plan. Patients completed a postoperative response questionnaire by the Visual Analogue Scale (VAS) score to indicate pain and swelling in the bone grafted area at the time of suture removal; and CBCT scans were conducted before surgery, 6 months and 2 years after surgery to assess changes in buccal and central alveolar heights, as well as widths at the alveolar ridge apex and 3 mm, 5 mm below the apex, respectively. The CBCT image sequences were imported into Mimics 21.0 software in DICOM format. The data of the patients in both groups were collected and analyzed by SPSS 25.0. RESULTS: The VAS scores were significantly lower in the APDDM group than in the DBBM group (p < 0.05). Significant increases were observed in alveolar bone height and width at 6 months and 2 years postoperative (p < 0.05); At 2 years, the APDDM group exhibited a reduction in buccal crest height and in 3 mm, 5 mm width below alveolar ridge apex, relative to 6 months (p < 0.05), while the DBBM group showed a decrease only in the central height of the alveolar bone (p < 0.05). There was a significant bone augmentation increase found only 3 mm below the alveolar ridge apex in the APDDM group compared with the DBBM group among all 6 months group comparison (p < 0.05). At 2 years, the augmentation effects were similar across both groups (p > 0.05). CONCLUSION: Radiomics analysis indicates that APDDM serves as a viable bone augmentation material for orthodontic patients with insufficient alveolar bone volume, achieving comparable clinical efficacy to DBBM. Additionally, APDDM is associated with a milder postoperative response than DBBM. THE REGISTRATION NUMBER (TRN): ChiCTR2400084607.

The influence of vitamin and mineral consumption on the course of coronavirus disease (COVID-19).

OBJECTIVE: Aim: The study of the role of micronutrients in the prevention of the severe course of the coronavirus disease. PATIENTS AND METHODS: Materials and Methods: In order to fulfill the task, there was conducted an analytical review of medical and biological publications in English in the electronic databases PubMed Medline of the US National Library of Medicine (NLM), Embase, Cochrane Database of Systematic Reviews for the period from 2015 to November 2023, where included 50 published articles, 28 preprints and 109 trials. In the course of the study, the bibliographic-semantic research method was used according to the "Preferred Reporting Elements for Systematic Reviews and Meta-Analyses" (PRISMA) protocol. According to this protocol, identified literary sources were sequentially analyzed by title, keywords, abstract and full text of articles. Based on the results of 16 searches, 2650 articles from PubMed, Cochrane Database of Systematic Reviews and Embase, 3162 articles from preprint servers and 237 trials were rejected. In the final article synthesis, we included 50 published articles, 28 preprints, and 109 trials. CONCLUSION: Conclusions: The most effective in preventing complications of the coronavirus disease are vitamins A, D, E, K, C, B3, B6, B9, B12 and such mineral substances as Mg, Se and Zn. The consumption of appropriate bioactive complexes and source products can be considered a clinically and economically effective strategy for the prevention of a severe course of the coronavirus disease.

Tomographic assessment of bone changes in atrophic maxilla treated by split-crest technique and dental implants with platelet-rich fibrin and NanoBone® versus platelet-rich fibrin alone: Randomized controlled trial.

BACKGROUND: This study evaluated the clinical benefits of adding NanoBone® with split-crest technique and simultaneous implant placement covered with platelet-rich fibrin membrane in horizontally deficient maxillary ridges in terms of crestal and horizontal bone changes and patient morbidity. METHODS: Forty patients indicated for maxillary ridge splitting and simultaneous implant placement were assigned randomly to the study groups: control group (Platelet Rich Fibrin membrane) and test group (Platelet Rich Fibrin membrane + Nanobone®). The Cone Beam Computed Tomography Fusion technique was utilized to assess crestal and horizontal bone changes after five months of the surgical procedure. Patient morbidity was recorded for one week post-surgical. RESULTS: Five months post-surgical, buccal crestal bone resorption was 1.26 ± 0.58 mm for the control group and 1.14 ± 0.63 mm for the test group. Lingual crestal bone resorption was 1.40 ± 0.66 mm for the control group and 1.47 ± 0.68 mm for the test group. Horizontal bone width gain was 1.46 ± 0.44 mm for the control group and 1.29 ± 0.73 mm for the test group. There was no significant statistical difference between study groups regarding crestal and horizontal bone changes and patient morbidity. CONCLUSIONS: The tomographic assessment of NanoBone® addition in this study resulted in no statistically significant difference between study groups regarding crestal and horizontal bone changes and patient morbidity. More randomized controlled clinical trials on gap fill comparing different bone grafting materials versus no grafting should be conducted. GOV REGISTRATION NUMBER: NCT02836678, 13th January 2017.

The effect of silver diammine fluoride on In Vitro Enamel caries lesion remineralization and staining as a function of lesion baseline mineral distribution.

OBJECTIVES: to investigate whether baseline mineral distribution modulates the ability of silver diammine fluoride (SDF) to remineralize and stain enamel caries lesions. METHODS: This laboratory study followed a 3 [treatment: SDF/fluoride varnish (FV)/deionized water (DIW)] ×3 [lesion protocol: methylcellulose (MeC)/hydroxyethylcellulose (HEC)/Carbopol 907 (C907)] factorial design. Lesions were created in bovine enamel specimens (n = 20). Treatments were applied and lesions remineralized in artificial saliva. Digital transverse microradiography (TMR-D) was used to analyze lesions. Lesion color was monitored spectrophotometrically. The effects of lesion protocol and treatment on changes in lesion depth (ΔLD), mineral loss (ΔΔZ), maximum mineral density at the surface zone (ΔSZmax), and color changes related to remineralization (ΔL*remin) were analyzed using two-way ANOVA. RESULTS: The treatment×lesion protocol interaction was significant for ΔΔZ (p < 0.01) and ΔL*remin (p < 0.01), however not for ΔLD (p = 0.23) or ΔSZmax (p = 0.91). There were no differences in ΔΔZ between treatments in HEC and C907 lesions. However, DIW resulted in more remineralization than both SDF (p < 0.01) and FV (p = 0.01) in MeC lesions. Considering changes from lesion baseline after remineralization in MeC lesions, SDF treatment resulted in the highest mineral gain in the surface zone. However, DIW revealed the highest mineral gain after remineralization in the lesion body. SDF stained lesions with the intensity increasing after remineralization in C907 lesions, whereas staining decreased in MeC and HEC lesions. CONCLUSION: High fluoride treatments can interfere with continuous remineralization of caries lesions due to partial arrest. Baseline lesion mineral distribution affects SDF's ability to enhance remineralization and the staining caused by SDF. CLINICAL SIGNIFICANCE: SDF is being used to arrest active caries lesions extending into dentin and to treat dentin hypersensitivity. This study shed light on SDF's effect on an isolated process in dental caries only, remineralization. It achieved this by examining enamel caries lesions with differing mineral distributions and assessing their staining properties.

Maxillary Sinus Augmentation with Anorganic Bovine Bone Mineral of Different Particle Sizes: A Split-Mouth Study with Histomorphometric, Radiographic, and Clinical Analyses.

PURPOSE: The aim of the present study was to compare the histomorphometrically evaluated new bone formation (NB), the radiographically measured graft stability, and the clinical implant outcome for maxillary sinus augmentation grafted with deproteinized bovine bone mineral (DBBM) with either small (Bio-Oss-S, Geistlich) or large (Bio-Oss-L, Geistlich) particles. MATERIALS AND METHODS: Using a split-mouth study design, bilateral maxillary sinus augmentation was performed in 13 patients either with Bio-Oss-S particles (0.25 to 1 mm) or Bio-Oss-L particles (1 to 2 mm). After a healing period of 6 months, bone biopsies were axially retrieved in the molar region for histologic/histomorphometric analysis of NB, including subsequent staged implant placement. To determine graft stability, the maxillary sinus augmentation vertical graft heights were radiographically measured immediately after sinus augmentation, at implant placement, and at the 2- and 4-year post-augmentation follow-ups. In addition, the clinical implant-prosthodontic outcome (survival/ success/marginal bone loss) was assessed at 1 and 3 years post-loading. RESULTS: A total of 22 sinuses from 11 patients with split-mouth evaluation were ultimately available for data and statistical analysis. Histomorphometric analysis of the axially retrieved bone biopsies revealed the presence of NB (S: 25.5% ± 7.0% vs L: 23.6% ± 11.9%; P = .640), residual graft particles (S: 19.6% ± 9.2% vs L: 17.5% ± 6.3%; P = .365) as well as connective tissue (S: 54.9% ± 9.2% vs L: 58.9% ± 12.5%; P = .283), without significant differences between the use of small (Bio-Oss-S) and large (Bio-Oss-L) particles. However, there was significantly (P = .021) higher bone-to-graft contact (BGC) for the small-particle graft sites (27.9% ± 14.8%) compared to the large-particle graft sites (19.9% ± 12.9%), representing a significantly higher osteoconductivity. Both particle sizes showed significant (P < .01) vertical graft height reduction over time (4 years) of about 10%, with predominant graft reduction in the time period between sinus augmentation and implant placement compared to any follow-up periods after implant placement. At the 3-year post-loading implant evaluation, all implants and prostheses survived (100%), and the peri-implant marginal bone loss (S: 0.52 ± 0.19 mm; L: 0.48 ± 0.15 mm) as well as the peri-implant health conditions (S: 87.5%, L:81.2%) did not differ between implants inserted with the two different xenograft particles used. CONCLUSIONS: The use of small and large bovine xenograft particles for maxillary sinus augmentation provides for comparable bone formation, ensuring stable graft dimensions combined with high implant success and healthy peri-implant conditions. However, small particle size resulted in a higher BGC, providing for higher osteoconductivity than with the larger particle size.

Interplay Between Minerals in Bottled Water and Fluoride Toothpaste and Caries Lesion Remineralization.

OBJECTIVES: he aim of this in vitro study was to evaluate the effects of some bottled waters on fluoride toothpaste efficacy in enhancing caries lesion remineralization. METHODS: Early caries lesions were created in bovine enamel specimens and stratified into treatment groups based on Vickers surface microhardness (VHN). The present study followed a two (fluoride and fluoride-free toothpaste) by five (four bottled waters and tap water) factorial design. The treatment groups were bottled water with the following attributes: (a) 309.9 ppm Ca/1.20 ppm F; (b) 118.4 ppm Ca/0.16 ppm F; (c) 1.00 ppm Ca/1.01 ppm F; and (d) 0.1 ppm Ca/0.04 ppm F and tap water (48.7 ppm Ca/0.7 ppm F). The five water groups were paired either with 1100 ppm fluoride or fluoride-free toothpaste, yielding 10 groups. Specimens were pH-cycled for 10 days with the daily regimen comprised of twice daily toothpaste slurry, with four exposures to water in between. VHN was measured again and the difference was calculated (ΔVHN). Data were analyzed using two-way ANOVA at a 5% significance level. RESULTS: The two-way interaction between water and toothpaste was significant (p<0.001). All groups except fluoride-free toothpaste/bottled water with 0.1 ppm Ca/0.04 ppm F (p=0.411) had significant increases in VHN after pH cycling (p≤0.023). Fluoridated toothpaste resulted in a higher rate of remineralization compared to fluoride-free toothpaste (all p<0.001). Bottled water with 1.20 ppm F/309.9 ppm Ca exhibited the greatest extent of remineralization within fluoride toothpaste groups (p<0.001) and higher remineralization than lower fluoride water in fluoride-free toothpaste groups (p≤0.006). Within the fluoridated toothpaste group, tap water exhibited significantly less remineralization than all bottled waters (all p<0.001). CONCLUSION: Within the limitation of this study, bottled water with higher fluoride and calcium concentrations might improve fluoridated toothpaste efficacy by enhancing remineralization of early enamel caries-like lesions.

Comparison of different bone substitutes in the repair of rat calvaria critical size defects: questioning the need for alveolar ridge presentation.

OBJECTIVE: This study aimed to evaluate the effectiveness of biomaterials in bone healing of critical bone defects created by piezoelectric surgery in rat calvaria. METHOD AND MATERIALS: Histomorphologic analysis was performed to assess bone regeneration and tissue response. Fifty animals were randomized into five groups with one of the following treatments: Control group (n = 10), spontaneous blood clot formation with no bone fill; BO group (Bio-Oss, Geistlich Pharma; n = 10), defects were filled with bovine medullary bone substitute; BF group (Bonefill, Bionnovation; n = 10), defects were filled with bovine cortical bone substitute; hydroxyapatite group (n = 10), defects were filled with hydroxyapatite; calcium sulfate group (n = 10), defects were filled with calcium sulfate. Five animals from each group were euthanized at 30 and 45 days. The histomorphometry calculated the percentage of the new bone formation in the bone defect. RESULTS: All data obtained were evaluated statistically considering P < .05 as statistically significant. The results demonstrated the potential of all biomaterials for enhancing bone regeneration. The findings showed no statistical differences between all the biomaterials at 30 and 45 days including the control group without bone grafting. CONCLUSION: In conclusion, the tested biomaterials presented an estimated capacity of osteoconduction, statistically nonsignificant between them. In addition, the selection of biomaterial should consider the specific clinical aspect, resorption rates, size of the particle, and desired bone healing responses. It is important to emphasize that in some cases, using no bone filler might provide comparable results with reduced cost and possible complications questioning the very frequent use of ridge presentation procedures.

Critical-sized marginal defects around implants treated with xenografts in rabbits.

BACKGROUND: Healing of critical-size defects is a well-known problem that has been challenged in several studies. The aim of the experiment was to evaluate bone formation and osseointegration of implants installed in critical defects of the mandibular body simultaneously grafted with Bio-Oss® or Cerabone®. MATERIAL AND METHODS: Defects, 10 mm wide and 3 mm deep, were prepared at both lateral aspects of the mandible in 12 rabbits. One implant was installed in the center of the defect, and bovine xenografts produced either at low (Bio-Oss®; Low-T) or high (Cerabone®; High-T) temperatures were used to fill the defects. A collagen membrane was placed to cover the sites. Healing was evaluated 10 weeks after surgery. RESULTS: In both groups, most sites showed optimal healing with closure of the coronal entrance of the defects. However, residual defects occupied by soft tissues and biomaterial particles were observed, even though generally limited to some regions of the defect. Osseointegration of the implant surface in the region of the defect was poor in both groups. CONCLUSIONS: Circumferential marginal critical-size defects around implants filled with bovine xenografts presented regions with a complete healing in both groups. However, the healing was not complete at all regions in most defects; therefore, a complete optimal healing of critical-size marginal defects cannot be predicted.

Effect of calcium-coacervate infiltration of artificial enamel caries lesions in de- and remineralizing conditions.

OBJECTIVES: Calcium-coacervate emulsions (CC) might be considered as mineral precursors to foster remineralization of carious dental hard tissues. This study analyzed the instant effect of repeated infiltration of artificial caries lesions with a CC emulsion as well as the effects of subsequent exposure of CC-infiltrated lesions to demineralizing and remineralizing environments. METHODS: Bovine enamel specimens were partly covered with varnish to leave three exposed windows. Artificial enamel caries lesions were created (pH 4.95, 17d). Baseline controls (BL) were obtained by preparing a thin section of each specimen. Specimens were allocated to five groups. In three groups lesions were etched with 37 % phosphoric acid gel, infiltrated with dipotassium hydrogen phosphate and subsequently with a calcium coacervate emulsion, prepared by mixing CaCl2 ⋅ 2H2O with polyacrylic acid sodium salt (PAA-Na). Subsequently, the infiltration effect was either analyzed immediately (Inf.) or after exposition to either de- (Inf.+DS) or remineralizing solution (Inf.+RS) for 10 or 20 days, respectively. In two control groups specimens were exposed to either DS or RS, respectively without prior CC infiltration. Integrated mineral loss [ΔZ(vol%×µm)] was analyzed using transverse microradiography (TMR). RESULTS: Infiltration of enamel caries lesions with coacervate solution resulted in only subtle immediate mineral gain even if repeated. When exposed to demineralizing conditions, infiltrated lesions showed significantly less mineral loss compared to untreated controls (p < 0.05; Kruskal Wallis) and exhibited characteristic mineral depositions within the lesion body. CONCLUSIONS: While immediate mineral gain by infiltration was only modest, the CC-emulsion might be able to prevent demineralization in acidic conditions. CLINICAL SIGNIFICANCE: Calcium coacervates might act protective against further demineralization when infiltrated into enamel caries lesions.

Histological and radiological outcome after horizontal guided bone regeneration with bovine bone mineral alone or in combination with bone in edentulous atrophic maxilla: A randomized controlled trial.

OBJECTIVE: To assess the radiological and histological outcome after horizontal guided bone regeneration (GBR) with deproteinized bovine bone mineral (DBBM) alone or in combination with particulate autogenous bone (PAB). MATERIALS AND METHODS: Eighteen edentulous patients with an alveolar ridge of ≤4 mm were included in this split-mouth randomized controlled trial. Horizontal GBR with a graft composition of 100% DBBM (100:0) on one side and 90% DBBM and 10% PAB (90:10) on the other side were conducted in all patients. Cone beam computed tomography (CBCT) was obtained preoperatively, immediately postoperative, and after 10 months of healing. Width and volumetric changes in the alveolar process were measured on CBCT. Implants were placed after 10 months of graft healing where biopsies were obtained for histomorphometrical evaluation. RESULTS: The gained widths were 4.9 (±2.4) mm (100:0) and 4.5 (±2.0) mm (90:10) at 3 mm from the top of the crest, and 5.6 (±1.3) mm (100:0) and 4.6 (±2.1) mm (90:10) at 6 mm from the top of the crest. The mean volumetric reductions were 32.8% (±23.8) (100:0) and 38.2% (±23.2) (90:10). Histomorphometry revealed that mean percentages of bone were 50.8% (±10.7) (100:0) and 46.4% (±11.3) (90:10), DBBM were 31.6% (±12.6) (100:0) and 35.4% (±14.8) (90:10), and non-mineralized tissue were 17.6% (±11.7; 100:0) and 18.2% (±18.2) (90:10). No significant differences were evident between in any evaluated parameters. CONCLUSIONS: There were no additional effects of adding PAB to DBBM regarding bone formation, width changes, or volumetric changes after 10 months of graft healing.

Safety of cinacalcet in children and adolescents with chronic kidney disease-mineral bone disorder: systematic review and proportional meta-analysis of case series.

BACKGROUND: Mineral and bone disease in children with chronic kidney disease can cause abnormalities in calcium, phosphorus, parathyroid hormone, and vitamin D and when left untreated can result in impaired growth, bone deformities, fractures, and vascular calcification. Cinacalcet is a calcimimetic widely used as a therapy to reduce parathyroid hormone levels in the adult population, with hypocalcemia among its side effects. The analysis of safety in the pediatric population is questioned due to the scarcity of randomized clinical trials in this group. OBJECTIVE: To assess the onset of symptomatic hypocalcemia or other adverse events (serious or non-serious) with the use of cinacalcet in children and adolescents with mineral and bone disorder in chronic kidney disease. DATA SOURCES AND STUDY ELIGIBILITY CRITERIA: The bibliographic search identified 2699 references from 1927 to August/2023 (57 LILACS, 44 Web of Science, 686 PubMed, 131 Cochrane, 1246 Scopus, 535 Embase). Four references were added from the bibliography of articles found and 12 references from the gray literature (Clinical Trials). Of the 77 studies analyzed in full, 68 were excluded because they did not meet the following criteria: population, types of studies, medication, publication types and 1 article that did not present results (gray literature). PARTICIPANTS AND INTERVENTIONS: There were 149 patients aged 0-18 years old with Chronic Kidney Disease and mineral bone disorder who received cinacalcet. STUDY APPRAISAL AND SYNTHESIS METHODS: Nine eligible studies were examined for study type, size, intervention, and reported outcomes. RESULTS: There was an incidence of 0.2% of fatal adverse events and 16% of serious adverse events (p < 0.01 and I2 = 69%), in addition to 10.7% of hypocalcemia, totaling 45.7% of total adverse events. LIMITATIONS: There was a bias in demographic information and clinical characteristics of patients in about 50% of the studies and the majority of the studies were case series. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: If used in the pediatric population, the calcimimetic cinacalcet should be carefully monitored for serum calcium levels and attention to possible adverse events, especially in children under 50 months. SYSTEMATIC REVIEW REGISTRATION NUMBER (PROSPERO REGISTER): CRD42019132809.

Melatonin, vitamins and minerals supplements for the treatment of Covid-19 and Covid-like illness: A prospective, randomized, double-blind multicenter study.

BACKGROUND: Melatonin, zinc, and multivitamins are among most recommended supplements in the fight against coronavirus disease 2019 (COVID-19). We aimed to examine the efficacy and safety of this association in the treatment of COVID-19 and COVID-like illnesses. METHODS: We conducted a multicenter prospective, randomized, double-blind, controlled trial. Patients with no medical history consulting the emergency department for covid and covid-like illness and who were not hospitalized were included. Patients were assigned in a 1:1 ratio to the treatment or the placebo group. The primary outcome was studying the effectiveness of zinc multivitamin supplement and melatonin in the treatment of COVID and -like illnesses symptoms' according to the time from randomization to clinical improvement. The pre-specified secondary outcomes were date of disappearance of symptoms present on admission, appearance of an adverse effect due to the administration of the treatment, number of patients developing complications, requiring hospitalization, requiring respiratory support. RESULTS: One hundred sixty four patients were eligible for the study and were randomized to either the treatment group or the placebo group. Overall, 128 of the 164 patients had a PCR for SARS-CoV-2, yielding a positive PCR result in 49.1% of them. Regarding the disappearance of all initial presenting symptoms: on the 5th day of the follow-up, there was a significant difference between the two groups with a p value 0.04;On the 10th day, there was a significant difference too with p value of 0.038. There were no significant differences between the two groups in recovery during the 15th day of follow-up p>0.5. Finally, 100% of patients fully recovered in the treatment group vs 98.8% in the placebo group. No severe adverse events were reported throughout the trial. CONCLUSIONS: Our results showed that daily doses of Melatonin, zinc and vitamins did significantly reduce the duration of symptoms accelerating its disappearance among patients consulting with COVID-19 or COVID-19 like illness.

Evaluation of deproteinised bovine bone matrix combined with absorbable biofilm for the preservation of extraction sites of mandibular impacted wisdom teeth.

BACKGROUND: Bone defects and deep periodontal pockets often exist distal to the second molar after mandibular third molar extraction, seriously threatening the periodontal health of the second molar. OBJECTIVE: To evaluate the effect of socket preservation with bone substitute materials on alveolar bone resorption and prevention of the distal periodontal defect of the adjacent tooth after mandibular impacted third molar extraction compared with natural healing. METHODS: Ninety-nine patients with mandibular impacted teeth, treated in our hospital from January 2018 to December 2020, were randomly divided into the control and experimental groups. The experimental group underwent minimally invasive tooth extraction and socket preservation using the deproteinised bovine bone mineral, Bio-Oss and the bioabsorbable collagen membrane, Bio-Gide. The control group healed naturally after minimally invasive tooth extraction. The alveolar ridge dimension of the extraction sites, the probing depth, tooth mobility and gingival index on the distal aspect of the mandibular second molars were examined and recorded before and six months after the operations. RESULTS: There was a significant difference between the experimental group and the control group in the alveolar bone width (P< 0.05) and height (P< 0.05) before and after surgery. The probing depth of the extraction sites in both groups was reduced. CONCLUSION: Using Bio-Oss and Bio-Gide to preserve extraction sites of impacted teeth can promote recovery more effectively than natural healing on the height of the distal alveolar bone and the width of the alveolar crest of the second molar and thus improve the periodontal status of the adjacent second molar.

Vitamin and Mineral Supplementation, Weight Gain, and Poor Appetite in Patients With Cancer: Many Questions and Fewer Answers.

Patients with cancer or with a history of cancer often seek nutritional advice. In turn, cancer health care providers are often asked questions related to nutrition and cancer. Should I take high-dose vitamins or other high-dose supplements? Should I take a regular-dose vitamin or other regular-dose nutritional supplements? Will I experience weight loss during postoperative chemotherapy? What should be my weight goals during and after adjuvant therapy? In the setting of advanced cancer, what should I do to keep my appetite and weight up? This review attempts to provide data-driven answers to some of these commonly posed questions.

Comparative Osteogenesis of Three Clinical Bone Graft Materials: An In Vivo Study.

PURPOSE: To investigate bone regeneration among three different bone graft materials in a rat calvarum model. MATERIALS AND METHODS: A total of 24 rats had two 5-mm defects placed per calvarial. Rats were divided into four groups: bovine xenograft (XG), demineralized bone matrix (DBM), mineralized bone graft (MBG), and collagen membrane control (CC). Within each group, samples were collected at two time points: 4 weeks (T4) and 8 weeks (T8). Bone regeneration was assessed by microcomputed tomography (micro-CT) imaging and was analyzed using MATLAB software. Additionally, the fixed samples were subsequently demineralized for immunohistochemistry and histomorphometry. Slides were mounted and stained with hematoxylin and eosin (H&E) stain as well as bone morphogenetic protein 2 (BMP-2) and runt-related transcription factor 2 (RUNX2) markers. The numbers of positive cells/area were calculated for each group and analyzed. RESULTS: At 4 weeks, DBM showed low mineral density (7.7%) compared to the control (25.2%), but increased dramatically at 8 weeks (DBM, T8 = 27.6%; CC, T8 = 27.2%). Xenograft material showed an increase in mineral desnity between T4 and T8 (XG, T4 = 25.0%; XG, T8 = 32.3%). MBG remained consistent over the 8-week trial period (MBG, T4 = 30.4%; MBG, T8 = 30.4%). BMP-2 expression was present in cells adherent to all graft materials. RUNX2 expression was also observed in cells adherent to all graft materials, indicating that during the 4- to 8-week healing period, all materials supported osteogenesis. CONCLUSIONS: Compared to other materials, the DBM had high osteoinductive properties during the 4- to 8-week time period based on increased mineral content. All materials were associated with immunohistologic evidence of osteogenesis in the rat calvarial defect model.

Impaired Growth Plate Maturation in XLH Is due to Both Excess FGF23 and Decreased 1,25-Dihydroxyvitamin D Signaling.

X-linked hypophosphatemia (XLH) is the most common form of hereditary hypophosphatemic rickets. The genetic basis for XLH is loss of function mutations in the phosphate-regulating endopeptidase X-linked (PHEX), which leads to increased circulating fibroblast growth factor 23 (FGF23). This increase in FGF23 impairs activation of vitamin D and attenuates renal phosphate reabsorption, leading to rickets. Previous studies have demonstrated that ablating FGF23 in the Hyp mouse model of XLH leads to hyperphosphatemia, high levels of 1,25-dihydroxyvitamin D, and is not associated with the development of rickets. Studies were undertaken to define a role for the increase in 1,25-dihydroxyvitamin D levels in the prevention of rickets in Hyp mice lacking FGF23. These mice were mated to mice lacking Cyp27b1, the enzyme responsible for activating vitamin D metabolites, to generate Hyp mice lacking both FGF23 and 1,25-dihydroxyvitamin D (FCH mice). Mice were fed a special diet to maintain normal mineral ion homeostasis. Despite normal mineral ions, Hyp mice lacking both FGF23 and Cyp27b1 developed rickets, characterized by an interrupted, expanded hypertrophic chondrocyte layer and impaired hypertrophic chondrocyte apoptosis. This phenotype was prevented when mice were treated with 1,25-dihydroxyvitamin D from day 2 until sacrifice on day 30. Interestingly, mice lacking FGF23 and Cyp27b1 without the PHEX mutation did not exhibit rickets. These findings define an essential PHEX-dependent, FGF23-independent role for 1,25-dihydroxyvitamin D in XLH and have important therapeutic implications for the treatment of this genetic disorder.

A Case Report of Periodontal Regenerative Therapy Using Recombinant Human Fibroblast Growth Factor 2 and Deproteinized Bovine Bone Mineral with Non-incised Papillae Surgical Approach (NIPSA) for Angular Bone Defect in Patient with Stage III Grade C Periodontitis.

This report describes a case of Stage III Grade C periodontitis requiring periodontal regenerative therapy. The patient was a 19-year-old woman who presented with the chief complaint of gingival recession in the incisor region. An initial examination revealed that 45.3% of sites had a probing depth of ≥4 mm and 45.8% bleeding on probing. Radiographic examination showed angular bone resorption in #25, 26, 31, 36, and 46 and horizontal resorption in other regions. Initial periodontal therapy was implemented based on a clinical diagnosis of Stage III Grade C periodontitis (generalized aggressive periodontitis). Occlusal adjustment was also performed at sites showing premature contact (#26 and 36) after suppression of inflammation. Periodontal regenerative therapy using recombinant human fibroblast growth factor (rhFGF) -2 was performed on #25, 26, and 46. Combination therapy with rhFGF-2 and deproteinized bovine bone mineral (DBBM) was performed on #31 and 36. A non-incised papillae surgical approach (NIPSA) was used on #31. Periodontal conditions were then re-evaluated and the patient placed on supportive periodontal therapy. Regenerative therapy using rhFGF-2 and DBBM with NIPSA yielded an improvement in clinical parameters and bone resorption. This improvement has been adequately maintained over a 12-month period. Continued care is needed to maintain stable periodontal conditions.

Zinc deficiency impairs axonal regeneration and functional recovery after spinal cord injury by modulating macrophage polarization via NF-κB pathway.

Background: Spinal cord injury (SCI) is a devastating disease that results in permanent paralysis. Currently, there is no effective treatment for SCI, and it is important to identify factors that can provide therapeutic intervention during the course of the disease. Zinc, an essential trace element, has attracted attention as a regulator of inflammatory responses. In this study, we investigated the effect of zinc status on the SCI pathology and whether or not zinc could be a potential therapeutic target. Methods: We created experimental mouse models with three different serum zinc concentration by changing the zinc content of the diet. After inducing contusion injury to the spinal cord of three mouse models, we assessed inflammation, apoptosis, demyelination, axonal regeneration, and the number of nuclear translocations of NF-κB in macrophages by using qPCR and immunostaining. In addition, macrophages in the injured spinal cord of these mouse models were isolated by flow cytometry, and their intracellular zinc concentration level and gene expression were examined. Functional recovery was assessed using the open field motor score, a foot print analysis, and a grid walk test. Statistical analysis was performed using Wilcoxon rank-sum test and ANOVA with the Tukey-Kramer test. Results: In macrophages after SCI, zinc deficiency promoted nuclear translocation of NF-κB, polarization to pro-inflammatory like phenotype and expression of pro-inflammatory cytokines. The inflammatory response exacerbated by zinc deficiency led to worsening motor function by inducing more apoptosis of oligodendrocytes and demyelination and inhibiting axonal regeneration in the lesion site compared to the normal zinc condition. Furthermore, zinc supplementation after SCI attenuated these zinc-deficiency-induced series of responses and improved motor function. Conclusion: We demonstrated that zinc affected axonal regeneration and motor functional recovery after SCI by negatively regulating NF-κB activity and the subsequent inflammatory response in macrophages. Our findings suggest that zinc supplementation after SCI may be a novel therapeutic strategy for SCI.

Changes in bone and mineral homeostasis after short-term androgen deprivation therapy with or without androgen receptor signalling inhibitor - substudy of a single-centre, double blind, randomised, placebo-controlled phase 2 trial.

BACKGROUND: Prostate cancer (PCa) patients treated with androgen deprivation therapy (ADT) have an increased fracture risk. Exploring biomarkers for early bone loss detection is of great interest. METHODS: Pre-planned substudy of the ARNEO-trial (NCT03080116): a double blind, randomised, placebo-controlled phase 2 trial performed in high-risk PCa patients without bone metastases between March 2019 and April 2021. Patients were 1:1 randomised to treatment with gonadotropin-releasing hormone antagonist (degarelix) + androgen receptor signalling inhibitor (ARSI; apalutamide) versus degarelix + matching placebo for 12 weeks prior to prostatectomy. Before and following ADT, serum and 24-h urinary samples were collected. Primary endpoints were changes in calcium-phosphate homeostasis and bone biomarkers. FINDINGS: Of the 89 randomised patients, 43 in the degarelix + apalutamide and 44 patients in the degarelix + placebo group were included in this substudy. Serum corrected calcium levels increased similarly in both treatment arms (mean difference +0.04 mmol/L, 95% confidence interval, 0.02; 0.06), and parathyroid hormone and 1,25-dihydroxyvitamin D3 levels decreased. Bone resorption markers increased, and stable calcium isotope ratios reflecting net bone mineral balance decreased in serum and urine similarly in both groups. INTERPRETATION: This exploratory substudy suggests that 12 weeks of ADT in non-metastatic PCa patients results in early bone loss. Additional treatment with ARSI does not seem to more negatively influence bone loss in the early phase. Future studies should address if these early biomarkers are able to predict fracture risk, and can be implemented in clinical practice for follow-up of bone health in PCa patients under ADT. FUNDING: Research Foundation Flanders; KU Leuven; University-Hospitals-Leuven.

Vitamins and Minerals for Blood Pressure Reduction in the General, Normotensive Population: A Systematic Review and Meta-Analysis of Six Supplements.

Hypertension is the leading preventable risk factor for cardiovascular disease and all-cause mortality worldwide. However, studies have shown increased risk of mortality from heart disease and stroke even within the normal blood pressure (BP) range, starting at BPs above 110-115/70-75 mm Hg. Nutraceuticals, such as vitamins and minerals, have been studied extensively for their efficacy in lowering BP and may be of benefit to the general, normotensive population in achieving optimal BP. Our study investigated the effects of six nutraceuticals (Vitamins: C, D, E; Minerals: Calcium, Magnesium, Potassium) on both systolic blood pressure (SBP) and diastolic blood pressure (DBP) in this population. We performed a systematic review and pairwise meta-analysis for all six supplements versus placebo. Calcium and magnesium achieved significant reductions in both SBP and DBP of -1.37/-1.63 mm Hg and -2.79/-1.56 mm Hg, respectively. Vitamin E and potassium only yielded significant reductions in SBP with values of -1.76 mm Hg and -2.10 mm Hg, respectively. Vitamins C and D were not found to significantly lower either SBP or DBP. Future studies should determine optimal dosage and treatment length for these supplements in the general, normotensive population.