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Medicina (Kaunas, Lithuania) May 2021Osteogenesis imperfecta (OI), or brittle bone disease, is a heterogeneous disorder characterised by bone fragility, multiple fractures, bone deformity, and short... (Review)
Review
Osteogenesis imperfecta (OI), or brittle bone disease, is a heterogeneous disorder characterised by bone fragility, multiple fractures, bone deformity, and short stature. OI is a heterogeneous disorder primarily caused by mutations in the genes involved in the production of type 1 collagen. Severe OI is perinatally lethal, while mild OI can sometimes not be recognised until adulthood. Severe or lethal OI can usually be diagnosed using antenatal ultrasound and confirmed by various imaging modalities and genetic testing. The combination of imaging parameters obtained by ultrasound, computed tomography (CT), and magnetic resource imaging (MRI) can not only detect OI accurately but also predict lethality before birth. Moreover, genetic testing, either noninvasive or invasive, can further confirm the diagnosis prenatally. Early and precise diagnoses provide parents with more time to decide on reproductive options. The currently available postnatal treatments for OI are not curative, and individuals with severe OI suffer multiple fractures and bone deformities throughout their lives. In utero mesenchymal stem cell transplantation has been drawing attention as a promising therapy for severe OI, and a clinical trial to assess the safety and efficacy of cell therapy is currently ongoing. In the future, early diagnosis followed by in utero stem cell transplantation should be adopted as a new therapeutic option for severe OI.
Topics: Adult; Collagen Type I; Female; Genetic Testing; Humans; Mesenchymal Stem Cell Transplantation; Mutation; Osteogenesis Imperfecta; Pregnancy
PubMed: 34068551
DOI: 10.3390/medicina57050464 -
The Cochrane Database of Systematic... Jul 2018Falls and fall-related injuries are common, particularly in those aged over 65, with around one-third of older people living in the community falling at least once a... (Review)
Review
BACKGROUND
Falls and fall-related injuries are common, particularly in those aged over 65, with around one-third of older people living in the community falling at least once a year. Falls prevention interventions may comprise single component interventions (e.g. exercise), or involve combinations of two or more different types of intervention (e.g. exercise and medication review). Their delivery can broadly be divided into two main groups: 1) multifactorial interventions where component interventions differ based on individual assessment of risk; or 2) multiple component interventions where the same component interventions are provided to all people.
OBJECTIVES
To assess the effects (benefits and harms) of multifactorial interventions and multiple component interventions for preventing falls in older people living in the community.
SEARCH METHODS
We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature, trial registers and reference lists. Date of search: 12 June 2017.
SELECTION CRITERIA
Randomised controlled trials, individual or cluster, that evaluated the effects of multifactorial and multiple component interventions on falls in older people living in the community, compared with control (i.e. usual care (no change in usual activities) or attention control (social visits)) or exercise as a single intervention.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies, assessed risks of bias and extracted data. We calculated the rate ratio (RaR) with 95% confidence intervals (CIs) for rate of falls. For dichotomous outcomes we used risk ratios (RRs) and 95% CIs. For continuous outcomes, we used the standardised mean difference (SMD) with 95% CIs. We pooled data using the random-effects model. We used the GRADE approach to assess the quality of the evidence.
MAIN RESULTS
We included 62 trials involving 19,935 older people living in the community. The median trial size was 248 participants. Most trials included more women than men. The mean ages in trials ranged from 62 to 85 years (median 77 years). Most trials (43 trials) reported follow-up of 12 months or over. We assessed most trials at unclear or high risk of bias in one or more domains.Forty-four trials assessed multifactorial interventions and 18 assessed multiple component interventions. (I not reported if = 0%).Multifactorial interventions versus usual care or attention controlThis comparison was made in 43 trials. Commonly-applied or recommended interventions after assessment of each participant's risk profile were exercise, environment or assistive technologies, medication review and psychological interventions. Multifactorial interventions may reduce the rate of falls compared with control: rate ratio (RaR) 0.77, 95% CI 0.67 to 0.87; 19 trials; 5853 participants; I = 88%; low-quality evidence. Thus if 1000 people were followed over one year, the number of falls may be 1784 (95% CI 1553 to 2016) after multifactorial intervention versus 2317 after usual care or attention control. There was low-quality evidence of little or no difference in the risks of: falling (i.e. people sustaining one or more fall) (RR 0.96, 95% CI 0.90 to 1.03; 29 trials; 9637 participants; I = 60%); recurrent falls (RR 0.87, 95% CI 0.74 to 1.03; 12 trials; 3368 participants; I = 53%); fall-related hospital admission (RR 1.00, 95% CI 0.92 to 1.07; 15 trials; 5227 participants); requiring medical attention (RR 0.91, 95% CI 0.75 to 1.10; 8 trials; 3078 participants). There is low-quality evidence that multifactorial interventions may reduce the risk of fall-related fractures (RR 0.73, 95% CI 0.53 to 1.01; 9 trials; 2850 participants) and may slightly improve health-related quality of life but not noticeably (SMD 0.19, 95% CI 0.03 to 0.35; 9 trials; 2373 participants; I = 70%). Of three trials reporting on adverse events, one found none, and two reported 12 participants with self-limiting musculoskeletal symptoms in total.Multifactorial interventions versus exerciseVery low-quality evidence from one small trial of 51 recently-discharged orthopaedic patients means that we are uncertain of the effects on rate of falls or risk of falling of multifactorial interventions versus exercise alone. Other fall-related outcomes were not assessed.Multiple component interventions versus usual care or attention controlThe 17 trials that make this comparison usually included exercise and another component, commonly education or home-hazard assessment. There is moderate-quality evidence that multiple interventions probably reduce the rate of falls (RaR 0.74, 95% CI 0.60 to 0.91; 6 trials; 1085 participants; I = 45%) and risk of falls (RR 0.82, 95% CI 0.74 to 0.90; 11 trials; 1980 participants). There is low-quality evidence that multiple interventions may reduce the risk of recurrent falls, although a small increase cannot be ruled out (RR 0.81, 95% CI 0.63 to 1.05; 4 trials; 662 participants). Very low-quality evidence means that we are uncertain of the effects of multiple component interventions on the risk of fall-related fractures (2 trials) or fall-related hospital admission (1 trial). There is low-quality evidence that multiple interventions may have little or no effect on the risk of requiring medical attention (RR 0.95, 95% CI 0.67 to 1.35; 1 trial; 291 participants); conversely they may slightly improve health-related quality of life (SMD 0.77, 95% CI 0.16 to 1.39; 4 trials; 391 participants; I = 88%). Of seven trials reporting on adverse events, five found none, and six minor adverse events were reported in two.Multiple component interventions versus exerciseThis comparison was tested in five trials. There is low-quality evidence of little or no difference between the two interventions in rate of falls (1 trial) and risk of falling (RR 0.93, 95% CI 0.78 to 1.10; 3 trials; 863 participants) and very low-quality evidence, meaning we are uncertain of the effects on hospital admission (1 trial). One trial reported two cases of minor joint pain. Other falls outcomes were not reported.
AUTHORS' CONCLUSIONS
Multifactorial interventions may reduce the rate of falls compared with usual care or attention control. However, there may be little or no effect on other fall-related outcomes. Multiple component interventions, usually including exercise, may reduce the rate of falls and risk of falling compared with usual care or attention control.
Topics: Accidental Falls; Accidents, Home; Aged; Aged, 80 and over; Exercise; Female; Fractures, Bone; Hospitalization; Humans; Independent Living; Male; Middle Aged; Randomized Controlled Trials as Topic; Risk Assessment
PubMed: 30035305
DOI: 10.1002/14651858.CD012221.pub2 -
Autopsy & Case Reports 2018Snyder-Robinson syndrome, also known as spermine synthase deficiency, is an X-linked intellectual disability syndrome (OMIM #390583). First described by Drs. Snyder and...
Snyder-Robinson syndrome, also known as spermine synthase deficiency, is an X-linked intellectual disability syndrome (OMIM #390583). First described by Drs. Snyder and Robinson in 1969, this syndrome is characterized by an asthenic body habitus, facial dysmorphism, broad-based gait, and osteoporosis with frequent fractures. We report here a pediatric autopsy of a 4 year old male with a history of intellectual disability, gait abnormalities, multiple fractures, and seizures previously diagnosed with Snyder-Robinson syndrome with an gene mutation (c.831G>T:p.L277F). The cause of death was hypoxic-ischemic encephalopathy secondary to prolonged seizure activity. Although Snyder-Robinson syndrome is rare, the need to recognize clinical findings in order to trigger genetic testing has likely resulted in under diagnosis.
PubMed: 30237987
DOI: 10.4322/acr.2018.031 -
Australian Prescriber Oct 2022Osteoporosis, osteopenia and minimal trauma fractures are becoming increasingly common in the ageing population. Fractures cause increases in morbidity and mortality and... (Review)
Review
Osteoporosis, osteopenia and minimal trauma fractures are becoming increasingly common in the ageing population. Fractures cause increases in morbidity and mortality and have a significant financial impact on the healthcare system and society Addressing risk factors for osteoporosis early may prevent or delay the onset of fractures and use of drugs. Calcium and vitamin D supplementation may benefit people with a high risk of deficiency (e.g. institutionalised older people) but may not be required in people without risk factors. Impact and resistance exercises and physical activity can increase bone density and prevent falls Antiresorptive drugs such as bisphosphonates and denosumab remain first-line treatment options for osteoporosis. The ongoing need for bisphosphonates should be assessed after five years and treatment may then be interrupted in some patients. Progressive bone loss will recur slowly. Denosumab therapy should not be interrupted without switching to another therapy, as post-treatment bone loss can progress rapidly. All patients will need ongoing monitoring and most will require some long-term therapy once started Raloxifene may be considered in women who do not tolerate first-line antiresorptive drugs. Romosozumab is a new anabolic treatment for osteoporosis and, together with teriparatide, is subsidised as second-line therapy for individuals with severe disease and multiple fractures. Specialist referral should be considered for patients who sustain fractures while undergoing osteoporosis therapy.
PubMed: 36382174
DOI: 10.18773/austprescr.2022.054 -
Clinical Chemistry Dec 2019
Topics: Fractures, Multiple; Humans; Infant, Newborn; Jaundice
PubMed: 31776161
DOI: 10.1373/clinchem.2019.304584 -
Emergency Medicine Journal : EMJ Feb 2007During a high-speed road traffic accident, a 26-year-old man suffered multiple fractures of his thoracic vertebrae and bilateral pneumothoraces. The day after admission...
During a high-speed road traffic accident, a 26-year-old man suffered multiple fractures of his thoracic vertebrae and bilateral pneumothoraces. The day after admission and commencement of nasogastric feeding, milky fluid was noted in his right chest drain. Feeding was stopped and a contrast oesophogram and oesophagoscopy were performed, which were normal. The chylothorax quickly resolved and both drains were removed on day 6. Initial treatment of chylothorax aims to decompress the pleural space and minimise chyle production by not feeding the patient via the enteral route. Most authors recommend conservative management for 2 weeks or more unless certain parameters are met: average daily chyle loss of > 1.5 l for a 5-day period, or imminent nutritional complications. In this case, surgical management of the chylothorax and spinal fractures was planned. However, conservative management was successful, highlighting the fact that early aggressive surgical intervention for chyle leaks in blunt trauma is not necessary.
Topics: Accidents, Traffic; Adult; Chest Tubes; Chylothorax; Humans; Male; Multiple Trauma; Pneumothorax; Spinal Fractures; Thoracic Duct; Thoracic Vertebrae; Wounds, Nonpenetrating
PubMed: 17251600
DOI: 10.1136/emj.2006.042028 -
BMJ Case Reports 2009During a high speed road traffic accident, a 26-year-old man suffered multiple fractures of his thoracic vertebrae and bilateral pneumothoraces. The day after admission...
During a high speed road traffic accident, a 26-year-old man suffered multiple fractures of his thoracic vertebrae and bilateral pneumothoraces. The day after admission and commencement of nasogastric feeding, milky fluid was noted in his right chest drain. Feeding was stopped and a contrast oesophogram and oesophagoscopy were performed, which were normal. The chylothorax quickly resolved and both drains were removed on day 6. Initial treatment of chylothorax aims to decompress the pleural space and minimise chyle production by stopping enteral feeding. Most authors recommend conservative management for 2 weeks or more unless certain parameters are met: average daily chyle loss of >1.5 litres for a 5 day period, or imminent nutritional complications. In this case, surgical management of the chylothorax and spinal fractures was planned. However, conservative management was successful, highlighting the fact that early aggressive surgical intervention for chyle leaks in blunt trauma is not necessary.
PubMed: 21687029
DOI: 10.1136/bcr.01.2009.1417 -
Journal of Multidisciplinary Healthcare 2022Alagille syndrome (ALGS) is an autosomal dominant disorder characterized by involvement of various organ systems. It predominantly affects the liver, skeleton, heart,... (Review)
Review
Alagille syndrome (ALGS) is an autosomal dominant disorder characterized by involvement of various organ systems. It predominantly affects the liver, skeleton, heart, kidneys, eyes and major blood vessels. With myriads of presentations across different age groups, ALGS is usually suspected in infants presenting with high gamma glutamyl transpeptidase cholestasis and/or congenital heart disease. In children it may present with decompensated cirrhosis, intellectual disability or short stature, and in adults vascular events like stroke or ruptured berry aneurysm are more commonly noted. Liver transplantation (LT) is indicated in children with cholestasis progressing to cirrhosis with decompensation. Other indications for LT include intractable pruritus, recurrent fractures, hepatocellular carcinoma and disfiguring xanthomas. Due to an increased risk of renal impairment noted in ALGS, these patients would require optimized renal sparing immunosuppression in the post-transplant period. As the systemic manifestations of ALGS are protean and a wider spectrum is being increasingly elucidated, a multidisciplinary team needs to be involved in managing these patients. Moreover, many basic-science and clinical questions especially with regard to its presentation and management remain unanswered. The aim of this review is to provide updated insights into the management of the multi-system involvement of ALGS.
PubMed: 35237041
DOI: 10.2147/JMDH.S295441 -
Current Osteoporosis Reports Oct 2021Fractures are frequently encountered in paediatric practice. Although recurrent fractures in children usually unveil a monogenic syndrome, paediatric fracture risk could... (Review)
Review
PURPOSE OF REVIEW
Fractures are frequently encountered in paediatric practice. Although recurrent fractures in children usually unveil a monogenic syndrome, paediatric fracture risk could be shaped by the individual genetic background influencing the acquisition of bone mineral density, and therefore, the skeletal fragility as shown in adults. Here, we examine paediatric fractures from the perspective of monogenic and complex trait genetics.
RECENT FINDINGS
Large-scale genome-wide studies in children have identified ~44 genetic loci associated with fracture or bone traits whereas ~35 monogenic diseases characterized by paediatric fractures have been described. Genetic variation can predispose to paediatric fractures through monogenic risk variants with a large effect and polygenic risk involving many variants of small effects. Studying genetic factors influencing peak bone attainment might help in identifying individuals at higher risk of developing early-onset osteoporosis and discovering drug targets to be used as bone restorative pharmacotherapies to prevent, or even reverse, bone loss later in life.
Topics: Age Factors; Bone Density; Child; Fractures, Bone; Genetic Loci; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Multifactorial Inheritance; Osteoporosis; Phenotype
PubMed: 33945105
DOI: 10.1007/s11914-021-00680-0