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Materials Today. Bio Apr 2023The biological functions of rare-earth elements (REEs) have become a focus of intense research. Recent studies have demonstrated that ion doping or alloying of some REEs... (Review)
Review
The biological functions of rare-earth elements (REEs) have become a focus of intense research. Recent studies have demonstrated that ion doping or alloying of some REEs can optimize the properties of traditional biomaterials. Europium (Eu), which is an REE with low toxicity and good biocompatibility, has promising applications in biomedicine. This article systematically reviews the osteogenic, angiogenic, neuritogenic, antibacterial, and anti-tumor properties of Eu-containing biomaterials, thereby paving the way for biomedical applications of Eu. Data collection for this review was completed in October 2022, and 30 relevant articles were finally included. Most articles indicated that doping of Eu ions or Eu-compound nanoparticles in biomaterials can improve their osteogenic, angiogenic, neuritogenic, antibacterial, and anti-tumor properties. The angiogenic, antibacterial, and potential neuritogenic effects of Eu(OH) nanoparticles have also been demonstrated.
PubMed: 36910271
DOI: 10.1016/j.mtbio.2023.100595 -
Journal of Clinical Medicine Feb 2023Medication-related osteonecrosis of the jaw (MRONJ) is defined by the American Association of Oral and Maxillofacial Surgeons (AAOMS) as the presence of an exposed bone... (Review)
Review
Medication-related osteonecrosis of the jaw (MRONJ) is defined by the American Association of Oral and Maxillofacial Surgeons (AAOMS) as the presence of an exposed bone area in the maxillofacial region, present for more than eight weeks in patients treated with the use of antiresorptive or antiangiogenic agents, with no history of radiation or metastatic disease. Bisphosphonates (BF) and denosumab (DS) are widely used in adults for the management of patients with cancer and osteoporosis, and recently there has been an increase in their use in child and young patients for the management of disorders such as osteogenesis imperfecta (OI), glucocorticoid-induced osteoporosis, McCune-Albright syndrome (MAS), malignant hypercalcemia, and others. There are differences between case reports in adults compared to child and young patients related to the use of antiresorptive/antiangiogenic drugs and the development of MRONJ. The aim was to analyze the presence of MRONJ in children and young patients, and the relation with oral surgery. A systematic review, following the PRISMA search matrix based on the PICO question, was conducted in PubMed, Embase, ScienceDirect, Cochrane, Google Scholar, and manual search in high-impact journals between 1960 and 2022, publications in English or Spanish, including randomized and non-randomized clinical trials, prospective and retrospective cohort studies, cases and controls studies, and series and case reports. A total of 2792 articles were identified and 29 were included; all of them published between 2007 and 2022, identifying 1192 patients, 39.68% male and 36.24% female, aged 11.56 years old on average, using these drugs mainly for OI (60.15%); 4.21 years on average was the therapy time and 10.18 drug doses administered on average; oral surgery was observed in 216 subjects, reporting 14 cases of MRONJ. We concluded that there is a low presence of MRONJ in the child and youth population treated with antiresorptive drugs. Data collection is weak, and details of therapy are not clear in some cases. Deficiencies in protocols and pharmacological characterization were observed in most of the included articles.
PubMed: 36835951
DOI: 10.3390/jcm12041416 -
Materials Today. Bio Jun 2020The ability of bone for regeneration has long been recognized. However, once beyond a critical size, spontaneous regeneration of bone is limited. Several studies have... (Review)
Review
The ability of bone for regeneration has long been recognized. However, once beyond a critical size, spontaneous regeneration of bone is limited. Several studies have focused on enhancing bone regeneration by applying mesenchymal stromal/stem cells (MSCs) in the treatment strategies. Despite the therapeutic efficacy of MSCs in bone regeneration, cell-based therapies are impeded by several challenges in maintaining the optimal cell potency and viability during expansion, storage, and final delivery to patients. Recently, there has been a paradigm shift in therapeutic mechanism of MSCs in tissue repair from one based on cellular differentiation and replacement to one based on secretion and paracrine signaling. Among the broad spectrum of trophic factors, extracellular vesicles particularly the exosomes have been reported to be therapeutically efficacious in several injury/disease indications, including bone defects and diseases. The current systematic review aims to summarize the results of the existing animal studies which were conducted to evaluate the therapeutic efficacy of MSC exosomes for bone regeneration. Following the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines, the PubMed and The Cochrane Library database were searched for relevant controlled preclinical animal studies. A total of 23 studies were identified, with the total sample size being 690 rats or mice and 38 rabbits. Generally, MSC exosomes were found to be efficacious for bone regeneration in animal models of bone defects and diseases such as osteonecrosis and osteoporosis. In these studies, MSC exosomes promoted new bone formation with supporting vasculature and displayed improved morphological, biomechanical, and histological outcomes, coupled with positive effects on cell survival, proliferation, and migration, osteogenesis, and angiogenesis. Unclear-to-low risk in bias and incomplete reporting in the primary studies highlighted the need for standardization in outcome measurements and reporting. Further studies in large animal models to establish the safety and efficacy would provide useful information on guiding the design of clinical trials.
PubMed: 32695985
DOI: 10.1016/j.mtbio.2020.100067 -
The Cochrane Database of Systematic... Jun 2020Malabsorption and deficiency of fat-soluble vitamins K may occur in cystic fibrosis, a genetic disorder affecting multiple organs. Vitamin K is known to play an...
BACKGROUND
Malabsorption and deficiency of fat-soluble vitamins K may occur in cystic fibrosis, a genetic disorder affecting multiple organs. Vitamin K is known to play an important role in both blood coagulation and bone formation, hence the role of supplementation of vitamin K in this category needs to be reviewed. This is an updated version of the review.
OBJECTIVES
To assess the effects of vitamin K supplementation in people with cystic fibrosis and to investigate the hypotheses that vitamin K will decrease deficiency-related coagulopathy, increase bone mineral density, decrease risk of fractures and improve quality of life in people with CF. Also to determine the optimal dose and route of administration of vitamin K for people with CF (for both routine and therapeutic use).
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Most recent search: 12 August 2019.
SELECTION CRITERIA
Randomised controlled trials of all preparations of vitamin K used as a supplement compared to either no supplementation (or placebo) at any dose or route and for any duration, in patients with cystic fibrosis.
DATA COLLECTION AND ANALYSIS
Two authors independently screened papers, extracted trial details and assessed their risk of bias. The quality of the evidence was assessed using the GRADE criteria.
MAIN RESULTS
Three trials (total 70 participants, aged 8 to 46 years) assessed as having a moderate risk of bias were included. One trial compared vitamin K to placebo, a second to no supplementation and the third compared two doses of vitamin K. No trial in either comparison reported our primary outcomes of coagulation and quality of life or the secondary outcomes of nutritional parameters and adverse events. Vitamin K versus control Two trials compared vitamin K to control, but data were not available for analysis. One 12-month trial (n = 38) compared 10 mg vitamin K daily or placebo in a parallel design and one trial (n = 18) was of cross-over design with no washout period and compared 5 mg vitamin K/week for four-weeks to no supplementation for four-weeks. Only the 12-month trial reported on the primary outcome of bone formation; we are very uncertain whether vitamin K supplementation has any effect on bone mineral density at the femoral hip or lumbar spine (very low-quality evidence). Both trials reported an increase in serum vitamin K levels and a decrease in undercarboxylated osteocalcin levels. The cross-over trial also reported that levels of proteins induced by vitamin K absence (PIVKA) showed a decrease and a return to normal following supplementation, but due to the very low-quality evidence we are not certain that this is due to the intervention. High-dose versus low-dose vitamin K One parallel trial (n = 14) compared 1 mg vitamin K/day to 5 mg vitamin K/day for four weeks. The trial did report that there did not appear to be any difference in serum undercarboxylated osteocalcin or vitamin K levels (very low-quality evidence). While the trial reported that serum vitamin K levels improved with supplementation, there was no difference between the high-dose and low-dose groups.
AUTHORS' CONCLUSIONS
There is very low-quality evidence of any effect of vitamin K in people with cystic fibrosis. While there is no evidence of harm, until better evidence is available the ongoing recommendations by national CF guidelines should be followed.
Topics: Adolescent; Adult; Biomarkers; Blood Coagulation; Bone Density; Child; Cystic Fibrosis; Dietary Supplements; Fractures, Bone; Humans; Middle Aged; Osteocalcin; Osteogenesis; Protein Precursors; Prothrombin; Quality of Life; Randomized Controlled Trials as Topic; Vitamin K; Vitamin K Deficiency; Vitamins
PubMed: 32497260
DOI: 10.1002/14651858.CD008482.pub6 -
Orphanet Journal of Rare Diseases Feb 2023Osteogenesis imperfecta (OI) is a rare, connective tissue disorder characterised by bone fragility, resulting in recurrent fractures and skeletal deformities....
BACKGROUND
Osteogenesis imperfecta (OI) is a rare, connective tissue disorder characterised by bone fragility, resulting in recurrent fractures and skeletal deformities. Extra-skeletal manifestations include dentinogenesis imperfecta, hearing abnormalities and lung disease. These co-morbidities combined with recurrent fractures can exert a significant impact on health-related quality of life (HR-QOL). It is important to assess HR-QOL throughout adulthood because the prevalence of some OI-specific complications increases with age.
METHODS
PubMed, EMBASE and CENTRAL databases were searched on 2nd February 2022 to identify studies reporting quantitative assessments of HR-QOL in adults with OI. The primary endpoint was to determine the impact of an OI diagnosis on adult's HR-QOL. Secondary endpoints were to (i) examine how frequently various HR-QOL assessment tools were used (ii) identify differences in HR-QOL between OI types and (iii) investigate the determinants of HR-QOL in adults with OI. Search results were exported to Endnote where two reviewers independently conducted title/abstract and full-text reviews. Data from accepted studies were extracted into Microsoft Excel. A narrative synthesis was then undertaken.
RESULTS
The review identified 17 studies with a total of 1,648 adults. The Short Form-36 (SF-36) was the most frequently reported HR-QOL assessment tool and was used in nine studies. Physical HR-QOL was reduced in adults with OI. Physical component scores (PCS) or individual physical domains of the SF-36 were lower in eight of nine studies. Mental component scores (MCS) were preserved in all six studies, however individual mental health domains of the SF-36 were reduced in some studies. The prevalence of anxiety/depression was relatively low in adults with OI. Those with type III OI had lower physical and respiratory HR-QOL but preserved mental HR-QOL compared with type I. The prevalence of fatigue and pain was higher in adults with OI compared with reference populations. Age and cardio-pulmonary co-morbidities were associated with lower HR-QOL.
CONCLUSION
OI in adulthood has a wide-ranging negative impact on HR-QOL. Physical and respiratory HR-QOL were lower, while the prevalence of pain and fatigue were higher than in reference populations. Mental HR-QOL was relatively preserved, although some deficits were identified. Age and cardio-pulmonary co-morbidities were associated with lower HR-QOL.
Topics: Adult; Humans; Osteogenesis Imperfecta; Quality of Life; Pain; Fatigue; Prevalence
PubMed: 36814291
DOI: 10.1186/s13023-023-02643-3 -
Journal of Orthopaedic Translation Mar 2020Although emerging studies have provided evidence that osteocytes are actively involved in fracture healing, there is a general lack of a detailed understanding of the... (Review)
Review
BACKGROUND
Although emerging studies have provided evidence that osteocytes are actively involved in fracture healing, there is a general lack of a detailed understanding of the mechanistic pathway, cellular events and expression of markers at different phases of healing.
METHODS
This systematic review describes the role of osteocytes in fracture healing from early to late phase. Literature search was performed in PubMed and Embase. Original animal and clinical studies with available English full-text were included. Information was retrieved from the selected studies.
RESULTS
A total of 23 articles were selected in this systematic review. Most of the studies investigated changes of various genes and proteins expression patterns related to osteocytes. Several studies have described a constant expression of osteocyte-specific marker genes throughout the fracture healing cascade followed by decline phase with the progress of healing, denoting the important physiological role of the osteocyte and the osteocyte lacuno-canalicular network in fracture healing. The reports of various markers suggested that osteocytes could trigger coordinated bone healing responses from cell death and expression of proinflammatory markers cyclooxygenase-2 and interleukin 6 at early phase of fracture healing. This is followed by the expression of growth factors bone morphogenetic protein-2 and cysteine-rich angiogenic inducer 61 that matched with the neo-angiogenesis, chondrogenesis and callus formation during the intermediate phase. Tightly controlled regulation of osteocyte-specific markers E11/Podoplanin (E11), dentin matrix protein 1 and sclerostin modulate and promote osteogenesis, mineralisation and remodelling across different phases of fracture healing. Stabilised fixation was associated with the finding of higher number of osteocytes with little detectable bone morphogenetic proteins expressions in osteocytes. Sclerostin-antibody treatment was found to result in improvement in bone mass, bone strength and mineralisation.
CONCLUSION
To further illustrate the function of osteocytes, additional longitudinal studies with appropriate clinically relevant model to study osteoporotic fractures are crucial. Future investigations on the morphological changes of osteocyte lacuno-canalicular network during healing, osteocyte-mediated signalling molecules in the transforming growth factor-beta-Smad3 pathway, perilacunar remodelling, type of fixation and putative biomarkers to monitor fracture healing are highly desirable to bridge the current gaps of knowledge.The translational potential of this article: This systematic review provides an up-to-date chronological overview and highlights the osteocyte-regulated events at gene, protein, cellular and tissue levels throughout the fracture healing cascade, with the hope of informing and developing potential new therapeutic strategies that could improve the timing and quality of fracture healing in the future.
PubMed: 32309136
DOI: 10.1016/j.jot.2019.07.005 -
Animals : An Open Access Journal From... Apr 2021The objective of this systematic review was to synthesize all the preclinical studies carried out in periosteal distraction osteogenesis (PDO) in order to evaluate the... (Review)
Review
The objective of this systematic review was to synthesize all the preclinical studies carried out in periosteal distraction osteogenesis (PDO) in order to evaluate the quality using the ARRIVE guidelines. The animal models used, and the influence of the complications, were analysed in order to establish the most appropriate models for this technique. The PRISMA statements have been followed. Bibliographic sources have been consulted manually by two reviewers. Risk of bias was evaluated using the SYRCLE tool for animal studies, and the quality of the studies with the ARRIVE 2.0 guidelines. The selection criteria established by expert researchers were applied to decide which studies should be included in the review, that resulted in twenty-four studies. Only one achieved the maximum score according to the ARRIVE 2.0 guidelines. The rabbit as an animal model has presented good results in PDO, both for calvaria and jaw. Rats have shown good results for PDO in calvaria. The minipig should not be recommended as an animal model in PDO. Despite the increase in the quality of the studies since the implementation of the ARRIVE 2.0 guidelines, it would be necessary to improve the quality of the studies to facilitate the transparency, comparison, and reproducibility of future works.
PubMed: 33923253
DOI: 10.3390/ani11051233 -
Journal of Orthopaedic Surgery and... Feb 2018This systematic review aims to summarize the clinical studies on the use of scaffolds in the repair of bony defects. (Review)
Review
BACKGROUND
This systematic review aims to summarize the clinical studies on the use of scaffolds in the repair of bony defects.
METHODS
The relevant articles were searched through PubMed database. The following keywords and search terms were used: "scaffolds," "patient," "clinic," "bone repair," "bone regeneration," "repairing bone defect," "repair of bone," "osteanagenesis," "osteanaphysis," and "osteoanagenesis." The articles were screened according to inclusion and exclusion criteria, performed by two reviewers.
RESULTS
A total of 373 articles were obtained using PubMed database. After screening, 20 articles were identified as relevant for the purpose of this systematic review. We collected the data of biological scaffolds and synthetic scaffolds. There are eight clinical studies of biological scaffolds included collagen, gelatin, and cellular scaffolds for bone healing. In addition, 12 clinical studies of synthetic scaffolds on HAp, TCP, bonelike, and their complex scaffolds for repairing bone defects were involved in this systematic review.
CONCLUSIONS
There are a lot of clinical evidences showed that application of scaffolds had a good ability to facilitate bone repair and osteogenesis. However, the ideal and reliable guidelines are insufficiently applied and the number and quality of studies in this field remain to be improved.
Topics: Animals; Bone Diseases; Bone Regeneration; Clinical Trials as Topic; Humans; Osteogenesis; Tissue Engineering; Tissue Scaffolds; Wound Healing
PubMed: 29433544
DOI: 10.1186/s13018-018-0724-2 -
International Journal of Implant... Apr 2019The review aimed at assessing the osteopromotive potential as well as soft tissue and temporomandibular joint (TMJ) cartilage healing properties of simvastatin by... (Review)
Review
The review aimed at assessing the osteopromotive potential as well as soft tissue and temporomandibular joint (TMJ) cartilage healing properties of simvastatin by summarizing its efficacy on the current dental treatment of periodontal bone and soft tissue defects, and temporomandibular joint (TMJ) arthritis from the available animals and human studies. An electronic search was performed on MEDLINE, Scopus, and Cochrane Central Register of Controlled Trials (CENTRAL) using a combination of keywords. A hand search was undertaken on seven oral surgery journals. No limitation of publication year in the English language was placed. Controlled randomized animal and human clinical trials, as well as prospective comparative studies, were included. Data on the comparison of topical/systemic simvastatin on bone healing in intrabony and furcation defects, extraction sockets, distraction osteogenesis, as well as soft tissue healing in mucogingival grafting procedures and cartilage protection in TMJ arthritis were extracted from all the eligible studies. Studies with a minimum of ten participants and follow up at least 6 months were included. Ten animal studies and six clinical studies were included in this study. All the animal studies included a minimum of eight sites per group assessed clinically, histologically, and radiographically. All human studies included clinical and radiological evaluation. The results of the review show that simvastatin administration displays positive treatment outcomes in the full range of therapies investigated in the oral regions such as periodontal infection control, periodontal and alveolar bone regeneration, soft tissue grafting, TMJ inflammation reduction, and cartilage repair. Its mechanism includes stimulating bone formation, promoting soft tissue healing, increasing articular and condylar cartilage thickness, as well as reducing inflammation at surgical sites in TMJ disorders. Simvastatin administration is beneficial to the healing of oral bone and cartilage. More studies are desired to determine its potential in soft tissue healing.
PubMed: 30963362
DOI: 10.1186/s40729-019-0168-4 -
Acta Ophthalmologica Feb 2022Osteogenesis imperfecta (OI) is a rare inherited heterogeneous connective tissue disorder characterized by bone fragility, low bone mineral density, skeletal deformity...
PURPOSE
Osteogenesis imperfecta (OI) is a rare inherited heterogeneous connective tissue disorder characterized by bone fragility, low bone mineral density, skeletal deformity and blue sclera. The dominantly inherited forms of OI are predominantly caused by mutations in either the COL1A1 or COL1A2 gene. Collagen type I is one of the major structural proteins of the eyes and therefore is the eye theoretically prone to alterations in OI. The aim of this systematic review was to provide an overview of the known ocular problems reported in OI.
METHODS
A literature search (in PubMed, Embase and Scopus), which included articles from inception to August 2020, was performed in accordance with the PRISMA guidelines.
RESULTS
The results of this current review show that almost every component of the eye could be affected in OI. Decreased thickness of the cornea and sclera is an important factor causing eye problems in patients with OI such as blue sclera. Findings that stand out are ruptures, lacerations and other eye problems that occur after minor trauma, as well as complications from standard surgical procedures.
DISCUSSION
Alterations in collagen type I affect multiple structural components of the eye. It is recommended that OI patients wear protective glasses against accidental eye trauma. Furthermore, when surgery is required, it should be approached with caution. The prevalence of eye problems in different types of OI is still unknown. Additional research is required to obtain a better understanding of the ocular defects that may occur in OI patients and the underlying pathology.
Topics: Blindness; Collagen Type I; Eye Diseases; Humans; Mutation; Osteogenesis Imperfecta; Phenotype; Risk Factors
PubMed: 34009739
DOI: 10.1111/aos.14882