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Cureus Apr 2023Fracture nonunion remains a great challenge for orthopedic surgeons. Some bone fractures don't heal promptly, resulting in delayed unions and nonunions, and there is a... (Review)
Review
Fracture nonunion remains a great challenge for orthopedic surgeons. Some bone fractures don't heal promptly, resulting in delayed unions and nonunions, and there is a need for an additional surgical procedure. Previous research has shown that teriparatide, a type of synthetic parathyroid hormone, can promote the formation of callus and lead to healing in individuals with delayed or non-healing bone fractures. Limited systematic reviews exist that examine the use of teriparatide in cases of delayed healing or non-healing bone fractures, which have their limitations. In this review, we overcome those limitations by including prospective studies, retrospective studies, case reports, and case series together. A systematic search of the literature was conducted in both PubMed and Google Scholar up to September of the year 2022. The studies included in our research included adult patients (over the age of 16) diagnosed with delayed union or nonunion of any bone in the body (flat bone, long bone, short bone, or irregular bone). The studies were limited to those written in English. The outcomes that were tracked and recorded include the healing of the fracture and any negative side effects or adverse events. The initial search yielded 504 abstracts and titles. After reviewing these, 32 articles were selected for further analysis, which included 19 case reports, five case series, two retrospective studies, and six prospective studies. Studies included daily (20 micrograms) or weekly (56.5 micrograms) subcutaneous administration of teriparatide. The duration of follow-up for these studies varied from three to 24 months. Based on the available research, it appears that administering teriparatide subcutaneously is a safe treatment option for delayed healing and non-healing bone fractures, with very few to no reported negative side effects. Using teriparatide for induction of callus formation and treating delayed and nonunions is highly safe and effective.
PubMed: 37187628
DOI: 10.7759/cureus.37478 -
Calcified Tissue International Feb 2022Objective and accurate assessment of bone union after a fracture, arthrodesis, or osteotomy is relevant for scientific and clinical purposes. Bone union is most... (Review)
Review
Objective and accurate assessment of bone union after a fracture, arthrodesis, or osteotomy is relevant for scientific and clinical purposes. Bone union is most accurately imaged with computed tomography (CT), but no consensus exists about objective assessment of bone union from CT images. It is unclear which CT-generated parameters are most suitable for bone union assessment. The aim of this review of animal studies is to find which CT-generated parameters are associated most strongly with actual bone union. Scientific databases were systematically searched. Eligible studies were studies that (1) were animal studies, (2) created a fracture, (3) assessed bone union with CT, (4) performed mechanical or histological testing as measure of actual bone union, and (5) associated CT-generated outcomes to mechanical or histological testing results. Two authors selected eligible studies and performed risk of bias assessment with QUADAS-2 tool. From 2567 studies that were screened, thirteen studies were included. Most common CT parameters that were investigated were bone mineral density, bone volume, and total callus volume. Studies showed conflicting results concerning the associations of these parameters with actual bone union. CT-assessed torsional rigidity (assessed by three studies) and callus density (assessed by two studies) showed best results. The studies investigating these two parameters reported moderate to strong associations with actual bone union. CT-assessed torsional rigidity and callus density seem the most promising parameters to represent actual bone union after a fracture, arthrodesis, or osteotomy.Prospero trial registration number: CRD42020164733.
Topics: Animals; Bone Density; Bony Callus; Fracture Healing; Fractures, Bone; Osteotomy; Tomography, X-Ray Computed
PubMed: 34417861
DOI: 10.1007/s00223-021-00904-6 -
Cell Transplantation 2022Even though reunion of bone fracture confronts clinicians, mesenchymal stromal cells (MSCs) are investigated to be curative in bone fracture. This study aimed to explore... (Meta-Analysis)
Meta-Analysis
Even though reunion of bone fracture confronts clinicians, mesenchymal stromal cells (MSCs) are investigated to be curative in bone fracture. This study aimed to explore the application potential of MSCs for healing bone fractures. By inputting search terms and retrieving studies published up to March 2021, multiple databases, including PubMed, EMBASE, Web of Science, and Cochrane Library, were searched to identify eligible studies. The mean difference (MD) and 95% confidence interval (95% CI) were calculated to analyze the main results in the meta-analysis. Data analysis was performed using Engauge Digitizer 10.8 and R Software. Of the 31 articles, 26 were preclinical studies ( = 913), and 5 were clinical trials ( = 335). Preclinically, MSCs therapy significantly augmented the progress of bone regeneration [(bone volume over tissue volume (MD7.35, 0.01)], despite some non-significant effects (on the callus index, bone strength, work to failure, and stiffness). Clinically, the MSC group had a significantly reduced incidence of poor recovery (odds ratio (OR) 0.30, 0.01); however, a significant decrease in healing time was not observed in the MSC group (MD 2.47, = 0.26). In summary, our data suggest that patients with bone fractures benefited from MSC administration and that MSCs are a potentially useful agent for bone regeneration. Despite these satisfactory outcomes, larger randomised clinical trials (RCTs) are necessary to confirm these findings.
Topics: Bone Regeneration; Bone and Bones; Fractures, Bone; Humans; Mesenchymal Stem Cells
PubMed: 35916286
DOI: 10.1177/09636897211051743 -
Journal of Clinical Medicine Apr 2024: Fracture healing is a very complex and well-orchestrated regenerative process involving many cell types and molecular pathways. Despite the high efficiency of this... (Review)
Review
: Fracture healing is a very complex and well-orchestrated regenerative process involving many cell types and molecular pathways. Despite the high efficiency of this process, unsatisfying healing outcomes, such as non-union, occur for approximately 5-10% of long bone fractures. Although there is an obvious need to identify markers to monitor the healing process and to predict a potential failure in callus formation to heal the fracture, circulating bone turnover markers' (BTMs) utility as biomarkers in association with radiographic and clinical examination still lacks evidence so far. : A systematic review on the association between BTMs changes and fracture healing in long bone non-union was performed following PRISMA guidelines. The research papers were identified via the PubMed, Cochrane, Cinahl, Web of Science, Scopus, and Embase databases. Studies in which the failure of fracture healing was associated with osteoporosis or genetic disorders were not included. : A total of 172 studies were collected and, given the inclusion criteria, 14 manuscripts were included in this review. Changes in circulating BTMs levels were detected during the healing process and across groups (healed vs. non-union patients and healthy vs. patients with non-union). However, we found high heterogeneity in patients' characteristics (fracture site, gender, and age) and in sample scheduling, which made it impossible to perform a meta-analysis. : Clinical findings and radiographic features remain the two important components of non-union diagnosis so far. We suggest improving blood sample standardization and clinical data collection in future research to lay the foundations for the effective use of BTMs as tools for diagnosing non-union.
PubMed: 38673606
DOI: 10.3390/jcm13082333 -
Bone Reports Dec 2021Osteoporosis is characterised by low bone mass and micro-architectural deterioration of bone structure. Its treatment is directed at the processes of bone formation or... (Review)
Review
INTRODUCTION
Osteoporosis is characterised by low bone mass and micro-architectural deterioration of bone structure. Its treatment is directed at the processes of bone formation or resorption, that are of utmost importance in fracture healing. We provide a comprehensive review of the literature aiming to summarize and clarify the effects of osteoporosis and its treatment on fracture healing.
MATERIAL AND METHODS
A literature search was conducted in PubMed and Embase (OVID version). In vivo animal and human studies on long bone fractures were included. A total of 93 articles were included for this review; 23 studies on the effect of osteoporosis (18 animal and 5 clinical studies) and 70 studies on the effect of osteoporosis treatment (41 animal, 26 clinical studies and 3 meta-analyses) on fracture healing.
RESULTS
In animal fracture models osteoporosis was associated with decreased callus formation and bone growth, bone mineral density, biomechanical strength and delayed cellular and differentiation processes during fracture healing. Two large databases identified osteoporosis as a risk factor for non-union whereas three other studies did not. One of those three studies however found a prolonged healing time in patients with osteoporosis. Anti-osteoporosis medication showed inconsistent effects on fracture healing in both non-osteoporotic and osteoporotic animal models. Only the parathyroid hormone and anti-resorption medication were related to improved fracture healing and delayed remodelling respectively. Clinical studies performed in predominantly hip and distal radius fracture patients showed no effect of bisphosphonates on fracture healing. Parathyroid hormone reduced time to union in several clinical trials performed in mainly hip fracture patients, but this did not result in decreased delayed or non-union rates.
CONCLUSION
Evidence that substantiates the negative influence of osteoporosis on fracture healing is predominantly from animal studies and to a lesser extent from clinical studies, since convincing clinical evidence lacks. Bisphosphonates and parathyroid hormone may be used during fracture healing, since no clear negative effect has been shown. Parathyroid hormone might even decrease time to fracture union, without decreasing union rate.
PubMed: 34458509
DOI: 10.1016/j.bonr.2021.101117 -
BMC Musculoskeletal Disorders Nov 2019Previous studies have found that bone mesenchymal stem cells (BMSCs) were capable of self-replication, multi-differentiation, and regeneration. The aim of this study was... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Previous studies have found that bone mesenchymal stem cells (BMSCs) were capable of self-replication, multi-differentiation, and regeneration. The aim of this study was to carry out a systematic review and meta-analysis of the efficacy of BMSC therapy for ovariectomized rats.
METHODS
The PubMed, Embase, Web of Science, China National Knowledge Infrastructure, VIP, and Chinese Sinomed databases were searched systematically from their initiation date to October 5, 2018. Two researchers independently screened the literatures, which used the bone mineral density (BMD), total bone volume by total tissue volume (BV/TV) (%), and trabecular thickness/spacing (Tb/Sp) as the outcome measures.
RESULTS
Five eligible studies were selected. In the BMSC treatment groups, the BMD values and normalized BV/TV values remarkably increased. In addition, in the BMSCs plus other treatment groups, the BMD and Tb/Sp values significantly increased.
CONCLUSION
This study showed that BMSCs could accelerate callus maturity, ossification and restore mechanical properties of bones in osteoporotic fractures.
Topics: Animals; Female; Humans; Mesenchymal Stem Cell Transplantation; Osteoporosis, Postmenopausal; Ovariectomy; Rats; Rats, Sprague-Dawley
PubMed: 31747888
DOI: 10.1186/s12891-019-2851-2 -
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 -
Mediators of Inflammation 2019Bone lesions are an important public health problem, with high socioeconomic costs. Bone tissue repair is coordinated by an inflammatory dynamic process mediated by...
Bone lesions are an important public health problem, with high socioeconomic costs. Bone tissue repair is coordinated by an inflammatory dynamic process mediated by osteoprogenitor cells of the periosteum and endosteum, responsible for the formation of a new bone matrix. Studies using antioxidant products from plants for bone lesion treatment have been growing worldwide. We developed a systematic review to compile the results of works with animal models investigating the anti-inflammatory activity of plant extracts in the treatment of bone lesions and analyze the methodological quality of the studies on this subject. Studies were selected in the PubMed/MEDLINE, Scopus, and Web of Science databases according to the PRISMA statement. The research filters were constructed using three parameters: animal model, bone repair, and plant extracts. 31 full-text articles were recovered from 10 countries. Phytochemical prospecting was reported in 15 studies (48.39%). The most common secondary metabolites were flavonoids, cited in 32.26% studies ( = 10). Essential criteria to animal studies were frequently underreported, suggesting publication bias. The animals treated with plant extracts presented positive results in the osteoblastic proliferation, and consequently, this treatment accelerated osteogenic differentiation and bone callus formation, as well as bone fracture repair. Possibly, these results are associated with antioxidant, regenerative, and anti-inflammatory power of the extracts. The absence or incomplete characterization of the animal models, treatment protocols, and phytochemical and toxicity analyses impairs the internal validity of the evidence, making it difficult to determine the effectiveness and safety of plant-derived products in bone repair.
Topics: Animals; Cell Differentiation; Disease Models, Animal; Female; Male; Mice; Osteogenesis; Plant Extracts; Rats
PubMed: 31885494
DOI: 10.1155/2019/1296153 -
Medicina (Kaunas, Lithuania) Dec 2023: Korean and traditional Chinese medicine state that pyrite is effective for fracture treatment, but supporting clinical data are limited. This systematic review aimed... (Meta-Analysis)
Meta-Analysis Review
: Korean and traditional Chinese medicine state that pyrite is effective for fracture treatment, but supporting clinical data are limited. This systematic review aimed to investigate the therapeutic role of Chinese patent medicine containing pyrite (CPMP) in clinical treatment for fractures. : Seven electronic databases were searched using the keywords "pyrite", "pyritum", and "zirantong" between inception and December 2022, yielding 29 published clinical studies. Randomized controlled trials that included CPMP were considered eligible regardless of the fracture type. Quality assessment and meta-analysis of the included RCTs were also performed. : Most studies showed high heterogeneity (I > 50%) and significant results ( < 0.05). Compared to the results of the control group, CPMP was more effective in terms of the primary outcome related to the efficacy rate, including the total effective rate, callus growth rate, bone union, and edema disappearance time (all < 0.00001) and in terms of secondary outcomes related to pain reduction, namely pain intensity and pain disappearance time, than the control group (both < 0.01). CPMP was more effective than the control group in terms of erythrocyte sedimentation rate ( < 0.01), hematocrit ( < 0.01), erythrocyte aggregation ( < 0.05), and plasma viscosity ( < 0.05). CPMP did not cause serious side effects, and the incidence of complications was significantly less than that in the control group. : CPMP may be a safe and effective alternative treatment for fractures and may be beneficial in preventing postoperative complications, reducing pain, relieving symptoms, and accelerating healing.
Topics: Humans; Fractures, Bone; Medicine, East Asian Traditional; Asian People; Pain; Iron; Sulfides
PubMed: 38256337
DOI: 10.3390/medicina60010076 -
Ultrasound (Leeds, England) Nov 2021This systematic review investigates which image appearances are most common when diagnosing lower limb stress fractures using ultrasound imaging, with the aim of... (Review)
Review
INTRODUCTION
This systematic review investigates which image appearances are most common when diagnosing lower limb stress fractures using ultrasound imaging, with the aim of outlining an image critique guideline for operators to support confident diagnoses.
METHOD
A comprehensive literature search of medical databases and handsearching was undertaken to identify relevant studies. All studies were critically examined for quality using the CASP critical appraisal tool. Results from eight studies were combined and interpreted using a narrative synthesis.
FINDINGS
A clear outline of common stress fracture appearances using ultrasound were identified in a combined total of 119 participants. Each finding was ranked according to its popularity. Periosteal thickening (78/119) and cortical disruption/irregularity (83/119) were noted in all eight studies. Hypervascularity of the periosteum visualised by colour Doppler imaging (66/119) was reported in six of the eight studies. Soft tissue hypervascularity (13/119), bony callus formation (5/119) and cortical break (22/119) were seen in three studies.
CONCLUSIONS
Based on the findings, we offer a guideline of the most significant preliminary image findings to be utilised by operators when examining athletes suspected of having lower limb stress fractures. The results show a gap in research for evaluating changes in appearance depending on the injury severity. Further research into distinguishing stress fractures from pathological involvement may in future reduce reliance on plain film radiography.
PubMed: 34777541
DOI: 10.1177/1742271X21995523