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ACS Pharmacology & Translational Science Jan 2024Osteogenesis imperfecta (OI) is an uncommon genetic disorder characterized by shortness of stature, hearing loss, poor bone mass, recurrent fractures, and skeletal... (Review)
Review
Osteogenesis imperfecta (OI) is an uncommon genetic disorder characterized by shortness of stature, hearing loss, poor bone mass, recurrent fractures, and skeletal abnormalities. Pathogenic variations have been found in over 20 distinct genes that are involved in the pathophysiology of OI, contributing to the disorder's clinical and genetic variability. Although medications, surgical procedures, and other interventions can partially alleviate certain symptoms, there is still no known cure for OI. In this Review, we provide a comprehensive overview of genetic pathogenesis, existing treatment modalities, and new developments in biotechnologies such as gene editing, stem cell reprogramming, functional differentiation, and transplantation for potential future OI therapy.
PubMed: 38230285
DOI: 10.1021/acsptsci.3c00324 -
BMJ Open Nov 2023Osteogenesis imperfecta (OI) is a rare genetic disease associated with multiple fractures throughout life. It is often treated with osteoporosis medications but their...
INTRODUCTION
Osteogenesis imperfecta (OI) is a rare genetic disease associated with multiple fractures throughout life. It is often treated with osteoporosis medications but their effectiveness at preventing fractures is unknown. The Treatment of Osteogenesis Imperfecta with Parathyroid Hormone and Zoledronic Acid trial will determine if therapy with teriparatide (TPTD) followed by zoledronic acid (ZA) can reduce the risk of clinical fractures in OI.
METHODS AND ANALYSIS
Individuals aged ≥18 years with a clinical diagnosis of OI are eligible to take part. At baseline, participants will undergo a spine X-ray, and have bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) at the spine and hip. Information on previous fractures and previous bone targeted treatments will be collected. Questionnaires will be completed to assess pain and other aspects of health-related quality of life (HRQoL). Participants will be randomised to receive a 2-year course of TPTD injections 20 µg daily followed by a single intravenous infusion of 5 mg ZA, or to receive standard care, which will exclude the use of bone anabolic drugs. Participants will be followed up annually, have a repeat DXA at 2 years and at the end of study. Spine X-rays will be repeated at the end of study. The duration of follow-up will range between 2 and 8 years. The primary endpoint will be new clinical fractures confirmed by X-ray or other imaging. Secondary endpoints will include participant reported fractures, BMD and changes in pain and HRQoL.
ETHICS AND DISSEMINATION
The study received ethical approval in December 2016. Following completion of the trial, a manuscript will be submitted to a peer-reviewed journal. The results will inform clinical practice by determining if TPTD/ZA can reduce the risk of fractures in OI compared with standard care.
TRIAL REGISTRATION NUMBER
ISRCTN15313991.
Topics: Humans; Adult; Adolescent; Zoledronic Acid; Teriparatide; Osteogenesis Imperfecta; Bone Density Conservation Agents; Quality of Life; Fractures, Bone; Bone Density; Pain; Randomized Controlled Trials as Topic
PubMed: 37993151
DOI: 10.1136/bmjopen-2023-078164 -
International Journal of Surgery... Sep 2023Post-traumatic related limb osteomyelitis (PTRLO) is a complex bone infection. Currently, there are no available microbial data on a national scale that can guide...
BACKGROUND
Post-traumatic related limb osteomyelitis (PTRLO) is a complex bone infection. Currently, there are no available microbial data on a national scale that can guide appropriate antibiotic selection, and explore the dynamic changes in dominant pathogens over time. This study aimed to conduct a comprehensive epidemiological analysis of PTRLO in China.
METHODS
The study was approved by the Institutional Research Board (IRB), and 3526 PTRLO patients were identified from 212 394 traumatic limb fracture patients at 21 hospitals between 1 January 2008 and 31 December 2017. A retrospective analysis was conducted to investigate the epidemiology of PTRLO, including changes in infection rate (IR), pathogens, infection risk factors and antibiotic resistance and sensitivity.
RESULTS
The IR of PTRLO increased gradually from 0.93 to 2.16% (Z=14.392, P <0.001). Monomicrobial infection (82.6%) was significantly higher than polymicrobial infection (17.4%) ( P <0.001). The IR of Gram-positive (GP) and Gram-negative (GN) pathogens showed a significant increase from the lowest 0.41% to the highest 1.15% (GP) or 1.62% (GN), respectively. However, the longitudinal trend of GP vs. GN's composition did not show any significance (Z=±1.1918, P >0.05). The most prevalent GP strains were Methicillin-sensitive Staphylococcus aureus (MSSA) (17.03%), Methicillin-resistant Staphylococcus aureus (MRSA) (10.46%), E. faecalis (5.19%) and S. epidermidis (4.87%). In contrast, the dominant strains GN strains were Pseudomonas Aeruginosa (10.92%), E. cloacae (10.34%), E. coli (9.47%), Acinetobacter Baumannii (7.92%) and Klebsiella Pneumoniae (3.33%). In general, the high-risk factors for polymicrobial infection include opened-fracture (odds ratio, 2.223), hypoproteinemia (odds ratio, 2.328), and multiple fractures (odds ratio, 1.465). It is important to note that the antibiotics resistance and sensitivity analysis of the pathogens may be influenced by complications or comorbidities.
CONCLUSIONS
This study provides the latest data of PTRLO in China and offers trustworthy guidelines for clinical practice. (China Clinical Trials.gov number, ChiCTR1800017597).
Topics: Humans; Methicillin-Resistant Staphylococcus aureus; Retrospective Studies; Escherichia coli; Coinfection; Microbial Sensitivity Tests; Anti-Bacterial Agents; China; Fractures, Open; Osteomyelitis
PubMed: 37247014
DOI: 10.1097/JS9.0000000000000502 -
Journal of Clinical Medicine Nov 2023This study aimed to define basicervical and transcervical shear fractures using area classification and to determine the optimal osteosynthesis implants for them. The...
This study aimed to define basicervical and transcervical shear fractures using area classification and to determine the optimal osteosynthesis implants for them. The clinical outcomes of 1042 proximal femur fractures were investigated. A model of the proximal femur of a healthy adult was created from computed tomography images, and basicervical and transcervical shear fractures were established in the model. Osteosynthesis models were created using a short femoral nail with a single lag screw or two lag screws and a long femoral nail with a single lag screw or two lag screws. The minimum principal strains of the fracture surfaces were compared when the maximum loads during walking were applied to these models using finite element analysis software. Basicervical fractures accounted for 0.96% of all proximal femur fractures, 67% of which were treated with osteosynthesis; the failure rate was 0%. Transcervical shear fractures accounted for 9.6% of all proximal femur fractures, 24% of which were treated with osteosynthesis; the failure rate was 13%. Finite element analysis showed that transcervical shear fracture has high instability. To perform osteosynthesis, multiple screw insertions into the femoral head and careful postoperative management are required; joint replacement should be considered to achieve early mobility.
PubMed: 38002638
DOI: 10.3390/jcm12227024 -
Revista Espanola de Cirugia Ortopedica... Apr 2024Osteoporosis, and the consequences derived from it, such as fragility fractures, constitute a growing public health problem. Suffering from a fracture of this nature is...
Osteoporosis, and the consequences derived from it, such as fragility fractures, constitute a growing public health problem. Suffering from a fracture of this nature is the main risk factor for suffering a new fracture. It is documented that vertebral compression fractures lead to significant morbidity and mortality, in the short and long term, as well as other complications, such as sagittal imbalance and hyperkyphosis of the segment. However, we have not found documentation that analyzes the medium and long-term consequences of these injuries, assessing the type of treatment used, and the economic impact they represent. The purpose of this review is to analyze the main recent literature on the subject and make a breakdown of the consequences of these fractures in various spheres, such as economic, quality of life, sagittal balance and radiographic parameters, pain or mortality; as well as a brief analysis of epidemiology and natural history. CONCLUSION: Osteoporotic fractures constitute an emerging problem, both in the medical and economic fields. The consequences and sequelae on the patient are multiple and although surgical options offer good long-term results, it is necessary to properly select the patient, through multidisciplinary teams, to try to minimize potential complications.
PubMed: 38642735
DOI: 10.1016/j.recot.2024.03.004 -
Acta Orthopaedica Et Traumatologica... Nov 2023Orthopedic injuries, especially fractures of long bones as well as multiple fractures and comminuted fractures, are very common after destructive disasters (e.g.,...
Orthopedic injuries, especially fractures of long bones as well as multiple fractures and comminuted fractures, are very common after destructive disasters (e.g., earthquakes, wars, and hurricanes). Another frequent problem is traumatic rhabdomyolysis, which may result in crush syndrome, the second most frequent cause of death after direct traumatic impact following earthquakes. To improve outcomes, interventions should be initiated even before extrication of the victims, which include maintenance of airway patency and spine stabilization, stopping traumatic bleeding by any means, and initiating fluid resuscitation. On-site amputations have been extensively debated to liberate the victims if the release of trapped limbs is impossible. Early after the rescue, a primary survey and triage are performed, a fluid resuscitation policy is planned, complications are treated, the wounds are decontaminated, and the victim is transported to specialized hospitals. A triage and primary survey are also performed at admission to the hospitals, which are followed by a secondary survey, physical, laboratory, and imaging examinations. Washing and cleaning of the soft-tissue injuries and debridement in open, necrotic wounds are vital. Applications of fasciotomies and amputations are controversial since they are associated with both benefits and serious complications; therefore, clear indications should be defined. Crush syndrome has been described as the presence of systemic manifestations following traumatic rhabdomyolysis, the most important component of which is acute kidney injury that may contribute to fatal hyperkalemia. The overall mortality rate is around 20% in crushed patients, which underlines the importance of prevention. Treatment includes maintaining of fluid electrolyte and acid-base balance, application of dialysis, and also prevention and treatment of complications. The principles and practices in disaster medicine may differ from those applied in routine practice; therefore, organizing repeated training courses may be helpful to provide the most effective healthcare and to save as many lives as possible after mass disasters.
Topics: Humans; Crush Syndrome; Disasters; Acute Kidney Injury; Rhabdomyolysis; Fractures, Bone
PubMed: 38454211
DOI: 10.5152/j.aott.2023.23147 -
Surgical Oncology Dec 2023The skeleton is a common site for metastases. Prostate, breast, lung, renal and thyroid carcinomas account for 80 % of the original cancers, with the femur being the...
INTRODUCTION
The skeleton is a common site for metastases. Prostate, breast, lung, renal and thyroid carcinomas account for 80 % of the original cancers, with the femur being the most affected long bone. With improved oncological treatments, prolonged patient survival leads to an increased prevalence of osseous metastases. This study examines the impact of preventive surgery for impending femoral pathological fracture (IFF), versus treatment of pathological femur fracture (PFF) on patient mortality and morbidity.
METHODS
Retrospective cohort of 174 patients undergoing surgery due to femoral metastases (2004-2015). Eighty-two patients were with PFF, and 92 were with IFF based on the Mirels' score. The followed-up period was until 2016. Demographic data, oncological, pathological, radiation, surgical reports, outpatient clinical records, and imaging studies were examined. Exclusion criteria included primary tumours and Multiple Myeloma.
RESULTS
The mean age was 64.8 ± 13.3 and 60.2 ± 11.9 years (p = 0.02) in the PFF and the IFF cohorts, with 62.1 % women and 57 % men. The breast was the most common source of femoral metastases. The average Mirels' score was 10 ± 1.2. There was an association between tumour origin and survival. Carcinoma of the lung had the worst survival, while the prostate had the most prolonged survival. Survival rates differed between IFF and PFF (p = 0.03). Postoperative complications occurred in 26 % of the patient, with no difference between IFF & PFF.
CONCLUSION
Breast and lung are the most common tumours to metastasize the femur. Our study revalidates that pathological femoral fractures impede patient survival compared to impending fractures and should undergo preventive surgery. Postoperative complications do not differ between IFF and PFF but remain relatively high. Overall, patients with proximal femoral metastatic disease survive longer than previously published, probably due to improved treatment modalities.
Topics: Male; Humans; Female; Middle Aged; Aged; Fractures, Spontaneous; Retrospective Studies; Femoral Fractures; Femur; Bone Neoplasms; Postoperative Complications
PubMed: 37944334
DOI: 10.1016/j.suronc.2023.102014 -
Archives of Orthopaedic and Trauma... Jul 2023The main objective of this study is to examine chronic pain and limping in relation to lower extremity and pelvic fracture location in addition to fracture combinations...
INTRODUCTION
The main objective of this study is to examine chronic pain and limping in relation to lower extremity and pelvic fracture location in addition to fracture combinations if multiple fractures are present on the same leg that have not been previously reported. We hypothesize that fracture pattern and location of lower extremity and pelvis fractures of multiple injured patients influence their long-term pain outcome.
MATERIALS AND METHODS
Retrospective cohort study. Patients with treated multiple lower limb and pelvic fractures at a level 1 trauma center and followed up for at least 10 years postinjury were assessed. Lower leg pain subdivided into persistent, load-dependent and intermittent pain, as well as limping were recorded by using self-administered patient questionnaires and standardized physical examinations performed by a trauma surgeon. Descriptive statistics were used to present comparative measurements between groups.
RESULTS
Fifty-seven percent of patients (n = 301) showed chronic lower limb pain 10 years postinjury. Ten percent of all patients with chronic pain displayed persistent pain, and here the most common fracture combination was tibial shaft fractures in combination with femoral shaft or proximal tibial fractures (13%). One hundred fifty-one patients reported load-dependent pain, with the most common fracture combinations being fractures of the foot in combination with femoral shaft fractures or distal tibial fractures (11%). One hundred twenty patients reported intermittent pain, with the most common fracture combinations involving the shaft of the tibia with either the femoral shaft or distal tibia (9%). Two hundred fifteen patients showed a persistent limp, and here the most common fractures were fractures of the femoral shaft (19%), tibial shaft (17%), and pelvis (15%).
CONCLUSIONS
In multiple injured patients with lower extremity injuries, the combination of fractures and their location are critical factors in long-term outcome. Patients with chronic persistent or load-dependent pain often had underlying femoral shaft fractures in combination with joint fractures.
Topics: Humans; Chronic Pain; Femoral Fractures; Leg; Retrospective Studies; Tibial Fractures
PubMed: 36454306
DOI: 10.1007/s00402-022-04717-6 -
The Journal of Craniofacial Surgery Sep 2023Nasoorbitoethmoid (NOE) fractures impact growth of the craniofacial skeleton in children, which may necessitate differentiated management from adult injuries. This study...
BACKGROUND
Nasoorbitoethmoid (NOE) fractures impact growth of the craniofacial skeleton in children, which may necessitate differentiated management from adult injuries. This study describes characteristics, management, and outcomes of NOE fractures in children seen at a single institution.
METHODS
A retrospective review of patients under 18 years who presented to our institution from 2006 to 2021 with facial fractures was conducted; patients with NOE fractures were included. Data collected included demographics, mechanism of injury, fracture type, management, and outcomes.
RESULTS
Fifty-eight patients met inclusion criteria; 77.6% presented with Manson-Marcowitz Type I fractures, 17.2% with Type II, and 5.2% with Type III. The most common cause of injury was motor vehicle accidents (MVAs, 39.7%) and sports (31%). Glasgow Coma Scale and injury mechanism were not predictive of injury severity in the pediatric population ( P =0.353, P =0.493). Orbital fractures were the most common associated fractures (n=55, 94.8%); parietal bone fractures were more likely in Type III fractures ( P =0.047). LeFort III fractures were more likely in type II fractures ( P =0.011). Soft tissue and neurological injuries were the most common associated injuries regardless of NOE fracture type (81% and 58.6%, respectively). There was no significant difference in type of operative management or in the rates of adverse outcomes between types of NOE fractures.
CONCLUSIONS
These findings suggest that pediatric NOE fractures, although rare, present differently from adult NOE fractures and that revisiting predictive heuristics and treatment strategies is warranted in this population.
Topics: Child; Humans; Adolescent; Skull Fractures; Orbital Fractures; Fracture Fixation; Nasal Bone; Retrospective Studies; Maxillary Fractures; Fractures, Multiple
PubMed: 37458265
DOI: 10.1097/SCS.0000000000009514 -
Seminars in Musculoskeletal Radiology Aug 2023This article concentrates on generalized disorders causing bone fragility. The most frequent cause of brittle bone disease is osteoporosis, only diagnosed by...
This article concentrates on generalized disorders causing bone fragility. The most frequent cause of brittle bone disease is osteoporosis, only diagnosed by elimination. First, malignant osteopathy must be ruled out: fracture on metastasis or multiple myeloma, which mimics osteoporosis when presenting as diffuse demineralization. Second, patients should be screened for signs of hyperparathyroidism or osteomalacia. Much more rarely, many other pathologies can lead to brittle bone by demineralization or associated increased bone density.The radiologist needs to know the clinical context and notably the patient's age (childhood or adulthood) at discovery, and known pathologies and ongoing or previous treatments: corticotherapy, bisphosphonates, denosumab, or prior radiotherapy in the affected region. Diagnostic hypotheses are guided by the type of demineralization and the presence of lytic, mixed, or densifying areas. Lastly, the aspect and location of fractures and association with other bone abnormalities refine the diagnosis.
Topics: Humans; Adult; Child; Bone Diseases; Osteoporosis; Fractures, Bone; Diphosphonates; Radiologists
PubMed: 37748467
DOI: 10.1055/s-0043-1769776