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Journal of Bone and Mineral Research :... May 2019The repair of a fractured bone is critical to the well-being of humans. Failure of the repair process to proceed normally can lead to complicated fractures, exemplified... (Review)
Review
The repair of a fractured bone is critical to the well-being of humans. Failure of the repair process to proceed normally can lead to complicated fractures, exemplified by either a delay in union or a complete nonunion. Both of these conditions lead to pain, the possibility of additional surgery, and impairment of life quality. Additionally, work productivity decreases, income is reduced, and treatment costs increase, resulting in financial hardship. Thus, developing effective treatments for these difficult fractures or even accelerating the normal physiological repair process is warranted. Accumulating evidence shows that microRNAs (miRNAs), small noncoding RNAs, can serve as key regulatory molecules of fracture repair. In this review, a brief description of the fracture repair process and miRNA biogenesis is presented, as well as a summary of our current knowledge of the involvement of miRNAs in physiological fracture repair, osteoporotic fractures, and bone defect healing. Further, miRNA polymorphisms associated with fractures, miRNA presence in exosomes, and miRNAs as potential therapeutic orthobiologics are also discussed. This is a timely review as several miRNA-based therapeutics have recently entered clinical trials for nonskeletal applications and thus it is incumbent upon bone researchers to explore whether miRNAs can become the next class of orthobiologics for the treatment of skeletal fractures.
Topics: Animals; Fracture Healing; Fractures, Bone; Humans; MicroRNAs
PubMed: 30866092
DOI: 10.1002/jbmr.3708 -
The emerging role of microRNAs in bone remodeling and its therapeutic implications for osteoporosis.Bioscience Reports Jun 2018Osteoporosis, a common and multifactorial disease, is influenced by genetic factors and environments. However, the pathogenesis of osteoporosis has not been fully... (Review)
Review
Osteoporosis, a common and multifactorial disease, is influenced by genetic factors and environments. However, the pathogenesis of osteoporosis has not been fully elucidated yet. Recently, emerging evidence suggests that epigenetic modifications may be the underlying mechanisms that link genetic and environmental factors with increased risks of osteoporosis and bone fracture. MicroRNA (miRNA), a major category of small noncoding RNA with 20-22 bases in length, is recognized as one important epigenetic modification. It can mediate post-transcriptional regulation of target genes with cell differentiation and apoptosis. In this review, we aimed to profile the role of miRNA in bone remodeling and its therapeutic implications for osteoporosis. A deeper insight into the role of miRNA in bone remodeling and osteoporosis can provide unique opportunities to develop a novel diagnostic and therapeutic approach of osteoporosis.
Topics: Alkaline Phosphatase; Bone Remodeling; Bone and Bones; Cell Differentiation; Core Binding Factor Alpha 1 Subunit; Epigenesis, Genetic; Fractures, Bone; Humans; MicroRNAs; Osteoblasts; Osteoclasts; Osteogenesis; Osteoporosis; Receptors, Calcitonin; Signal Transduction
PubMed: 29848766
DOI: 10.1042/BSR20180453 -
Scientific Reports May 2021Long bone fracture care in developing countries remains largely different from that of the developed world where closed reduction and internal fixation with locked...
Long bone fracture care in developing countries remains largely different from that of the developed world where closed reduction and internal fixation with locked intramedullary nail is the standard treatment. This study in a developing country presents the pattern and outcome of treatment of 370 long bone fractures using the SIGN nail over a five-year period in order to underline the wide array of patients and fractures treatable with the nail. Using a prospective descriptive approach, all the 342 patients with 370 fractures of the humerus, femur and tibia treated from July 2014 to June 2019 were studied. The fractures were reduced without image intensifier or fracture table and fixed with the SIGN nail. Post-discharge, the patients were followed up at the out-patient clinic. The mean age of the patients was 43.45 years with a range of 10-99 years. Sixty-six percent were males who were mostly injured in motorcycle accidents. Femur, tibia and humerus fractures accounted for 59.7%, 28.4% and 11.9% respectively. Eighty-six percent were diaphyseal fractures, 73% were fresh and the main previous treatment was traditional bone setting. Deep infection occurred in 4.9%, 66.0% achieved knee flexion > 90° by sixth week, the majority achieved full weight bearing and could squat and smile by 12th week. The SIGN nail is versatile, useful for treating a wide range of fractures in most age groups particularly in developing countries where orthopaedic fractures are prevalent but the more sophisticated facilities are lacking or poorly maintained.
Topics: Adolescent; Adult; Aftercare; Aged; Aged, 80 and over; Bone Nails; Child; Female; Follow-Up Studies; Fracture Fixation, Intramedullary; Fracture Healing; Fractures, Bone; Humans; Male; Middle Aged; Patient Discharge; Prospective Studies; Treatment Outcome; Young Adult
PubMed: 33980924
DOI: 10.1038/s41598-021-89544-2 -
Fertility and Sterility Nov 2019Fractures and their consequences are the clinically important manifestation of osteoporosis; preventing fractures is the primary goal of management. Effective management... (Review)
Review
Fractures and their consequences are the clinically important manifestation of osteoporosis; preventing fractures is the primary goal of management. Effective management is achievable given present knowledge and tools but is seldom prescribed. This review will cover the individual and social burden of fracture, essential information about fracture risk and its estimation, an approach to patient care emphasizing specific information to elicit and therapeutic strategies to pursue, and existing gaps in knowledge and important questions for future research.
Topics: Adult; Bone Density; Disease Management; Female; Fractures, Bone; Humans; Middle Aged; Perimenopause; Postmenopause; Risk Factors
PubMed: 31731932
DOI: 10.1016/j.fertnstert.2019.09.038 -
Orthopaedics & Traumatology, Surgery &... Feb 2017The diagnosis of pathological fracture should be considered routinely in patients with long limb-bone fractures. Investigations must be performed to establish the... (Review)
Review
The diagnosis of pathological fracture should be considered routinely in patients with long limb-bone fractures. Investigations must be performed to establish the diagnosis of pathological fracture then to determine that the bone lesion is a metastasis. In over 85% of cases, the clinical evaluation combined with a detailed analysis of the radiographs is sufficient to determine that the fracture occurred at a tumour site. Aetiological investigations establish that the tumour is a metastasis. In some patients, the diagnosis of metastatic cancer antedates the fracture. When this is not the case, a diagnostic strategy should be devised, with first- to third-line investigations. When these fail to provide the definitive diagnosis, a surgical biopsy should be performed. The primaries most often responsible for metastatic bone disease are those of the breast, lung, kidney, prostate, and thyroid gland. However, the survival gains provided by newly introduced treatments translate into an increased frequency of bone metastases from other cancers. The optimal treatment of a pathological fracture is preventive. The Mirels score is helpful for determining whether preventive measures are indicated. When selecting a treatment for a pathological fracture, important considerations are the type of tumour, availability of effective adjuvant treatments, and general health of the patient. Metastatic fractures are best managed by a multidisciplinary team. The emergent treatment should start with optimisation of the patient's general condition, in particular by identifying and treating metabolic disorders (e.g., hypercalcaemia) and haematological disorders. Treatment decisions also depend on the above-listed general factors, location of the tumour, and size of the bony defect. Prosthetic reconstruction is preferred for epiphyseal fractures and internal fixation for diaphyseal fractures.
Topics: Bone Neoplasms; Decision Support Techniques; Femoral Fractures; Fracture Fixation, Internal; Fractures, Bone; Fractures, Spontaneous; Humans
PubMed: 28089230
DOI: 10.1016/j.otsr.2016.11.001 -
Journal of Bone and Mineral Research :... Dec 2016Patients with several medical conditions, including Parkinson's disease, recent stroke, HIV, and heart failure, have a high risk of hip fracture. These patients will... (Review)
Review
Patients with several medical conditions, including Parkinson's disease, recent stroke, HIV, and heart failure, have a high risk of hip fracture. These patients will also have more severe consequences of a hip fracture, including a greater chance of dying and more prolonged disability. Together, there are nearly as many patients with medical conditions that substantially increase the risk of hip fracture as there are people with osteoporosis by femoral neck bone mineral density (BMD). The contributions of falling and decreased bone mass to the increased risks with these conditions are not certain. Although there are few data about whether and what type of treatments these patients receive to prevent fracture, it is likely that few receive pharmacologic treatments that have been shown to reduce the risk of hip fracture. There is a need to show that drug treatments that strengthen bone also reduce fracture risk in patients whose risk may be owing in greater part to traumatic falls than osteoporosis. Assuming that treatments are efficacious in these patients, there is a major opportunity to substantially reduce the incidence and consequences of hip fracture by reaching more of them with drug treatments to reduce the risk of hip fracture. This will require engagement of specialists who have little expertise and perhaps limited interest in preventing fractures, or new approaches to delivering drug treatments to prevent fracture directly to the patients at risk. © 2016 American Society for Bone and Mineral Research.
Topics: Chronic Disease; Fractures, Bone; Humans; Risk Factors
PubMed: 27813155
DOI: 10.1002/jbmr.3030 -
Polypharmacy and bone fracture risk in patients with type 2 diabetes: The Fukuoka Diabetes Registry.Diabetes Research and Clinical Practice Nov 2021To prospectively investigate the association between the number of prescribed drugs and the fracture risk in patients with type 2 diabetes.
AIMS
To prospectively investigate the association between the number of prescribed drugs and the fracture risk in patients with type 2 diabetes.
METHODS
Japanese participants with type 2 diabetes (n = 4,706; 2,755 men, 1,951 postmenopausal women; mean age, 66 years) were followed for a median of 5.3 years and grouped on the basis of the number of prescribed drugs at baseline. The main outcomes were fractures at any anatomic site and fragility fractures (fractures at hip and spine sites).
RESULTS
During follow-up, any fracture occurred in 662 participants. The overall age- and sex-adjusted fracture incidence rates per 1,000 person-years were 21.2 (0-2 drugs), 28.1 (3-5 drugs), 37.7 (6-8 drugs), and 44.0 (≥9 drugs) (p for trend < 0.001). Compared with 0-2 drugs, the multivariate-adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) for fractures were 1.34 (1.07-1.68) for 3-5 drugs, 1.76 (1.37-2.26) for 6-8 drugs, and 1.71 (1.27-2.31) in ≥ 9 drugs. The multivariate-adjusted HR (95% CI) per increment in drugs was 1.05 (1.02-1.08) (p < 0.001). Similar tendencies were observed for fragility fractures.
CONCLUSIONS
A greater number of prescribed drugs is associated with an increased bone fracture risk in patients with type 2 diabetes.
Topics: Aged; Bone Density; Diabetes Mellitus, Type 2; Female; Fractures, Bone; Hip Fractures; Humans; Male; Polypharmacy; Registries; Risk Factors
PubMed: 34678390
DOI: 10.1016/j.diabres.2021.109097 -
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 -
Developmental Cell May 2024Bone is regarded as one of few tissues that heals without fibrous scar. The outer layer of the periosteum is covered with fibrous tissue, whose function in bone...
Bone is regarded as one of few tissues that heals without fibrous scar. The outer layer of the periosteum is covered with fibrous tissue, whose function in bone formation is unknown. We herein developed a system to distinguish the fate of fibrous-layer periosteal cells (FL-PCs) from the skeletal stem/progenitor cells (SSPCs) in the cambium-layer periosteum and bone marrow in mice. We showed that FL-PCs did not participate in steady-state osteogenesis, but formed the main body of fibrocartilaginous callus during fracture healing. Moreover, FL-PCs invaded the cambium-layer periosteum and bone marrow after fracture, forming neo-SSPCs that continued to maintain the healed bones throughout adulthood. The FL-PC-derived neo-SSPCs expressed lower levels of osteogenic signature genes and displayed lower osteogenic differentiation activity than the preexisting SSPCs. Consistent with this, healed bones were thinner and formed more slowly than normal bones. Thus, the fibrous periosteum becomes the cellular origin of bones after fracture and alters bone properties permanently.
Topics: Animals; Periosteum; Mice; Osteogenesis; Fracture Healing; Cell Differentiation; Fractures, Bone; Stem Cells; Mice, Inbred C57BL; Bony Callus; Male
PubMed: 38554700
DOI: 10.1016/j.devcel.2024.03.019 -
Frontiers in Endocrinology 2020The effect of chronic intermittent hypobaric hypoxia (CIHH) on bone fracture healing is not elucidated. The present study aimed to investigate the role of CIHH on bone...
The effect of chronic intermittent hypobaric hypoxia (CIHH) on bone fracture healing is not elucidated. The present study aimed to investigate the role of CIHH on bone fracture healing and the mechanism. The Sprague-Dawley rats were randomly divided into the CIHH group and control group and monitored for 2, 4, or 8 weeks after femoral fracture surgery. Bone healing efficiency was significantly increased in the CIHH group as evidenced by higher high-density bone volume fractions, higher bone mineral density, higher maximum force, and higher stiffness. Histologically, the CIHH group exhibited superior bone formation, endochondral ossification, and angiogenic ability compared with the control group. The expression of HIF-1α and its downstream signaling proteins VEGF, SDF-1/CXCR4 axis were increased by the CIHH treatment. Moreover, the expression of RUNX2, osterix, and type I collagen in the callus tissues were also up-regulated in the CIHH group. In conclusion, our study demonstrated that CIHH treatment improves fracture healing, increases bone mineral density, and increases bone strength the activation of HIF-1α and bone production-related genes.
Topics: Animals; Arterial Pressure; Cell Differentiation; Collagen Type I; Core Binding Factor Alpha 1 Subunit; Fracture Healing; Fractures, Bone; Gene Expression Regulation; Hypoxia; Male; Neovascularization, Pathologic; Osteoblasts; Osteogenesis; Rats; Rats, Sprague-Dawley; Transcription Factors
PubMed: 33664707
DOI: 10.3389/fendo.2020.582670