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Journal of Pediatric Orthopedics Mar 2022Osteogenesis imperfecta is a collagen mutation-related disease characterized by bone fragility and other extraskeletal manifestations. Intramedullary fixation for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Osteogenesis imperfecta is a collagen mutation-related disease characterized by bone fragility and other extraskeletal manifestations. Intramedullary fixation for deformity correction or fracture is the standard care. Elongating rods are designed to accommodate growth, with the aim of preventing additional operations and/or complications associated with nonelongating rods. Although elongating rods have been in use for many years, estimates of the clinical outcomes vary. We conducted a systematic review and meta-analysis to synthesize the literature on outcomes of elongating rods and nonelongating rods. Meta-analysis was used to compare the complication rates and reoperation rates.
METHODS
We conducted the literature search, systematic review, and meta-analysis in accordance with Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) guidelines. Comparative cohort studies and large case series detailing complication rates and reoperation rates of elongating and nonelongating rods were included. Random effect models were used to summarize the complication rates and reoperation rates of intramedullary rod procedures.
RESULTS
A total of 397 studies were identified and 24 studies were included in the final cohort. Compared with rates from nonelongating rods, osteogenesis imperfecta Patients using elongating rods had a complication rate of 61% and a reoperation rate of 78%. Reoperation rates dropped with succeeding generations of elongating rods. Pooling data from 600 patients, we identified a 9% complication rate per rod per follow up year and 5% reoperation rate per rod and per follow up year in the cohort of elongating rod fixation. The Bailey-Dubow rod had the highest complication rate per rod per follow up year (12%), largely because of its T piece relate problems. The most popular fixator Fassier-Duval rod had a complication rate per rod per follow up year of 9%. About 68% of complications were mechanical-biological related.
CONCLUSION
Pooling data from published literature demonstrates the advantage of elongating rods over nonelongating rods. However, as high as 9% complication rate per rod per follow up year was associated with elongating fixation. Notably, most complications are both mechanical and biological related.
LEVEL OF EVIDENCE
Level III.
Topics: Fracture Fixation, Intramedullary; Humans; Internal Fixators; Lower Extremity; Osteogenesis Imperfecta; Reoperation
PubMed: 35034037
DOI: 10.1097/BPO.0000000000002040 -
Journal of Bone and Mineral Research :... Mar 2020High-resolution peripheral quantitative computed tomography (HR-pQCT) is a noninvasive imaging modality for assessing volumetric bone mineral density (vBMD) and... (Meta-Analysis)
Meta-Analysis
High-resolution peripheral quantitative computed tomography (HR-pQCT) is a noninvasive imaging modality for assessing volumetric bone mineral density (vBMD) and microarchitecture of cancellous and cortical bone. The objective was to (1) assess fracture-associated differences in HR-pQCT bone parameters; and (2) to determine if HR-pQCT is sufficiently precise to reliably detect these differences in individuals. We systematically identified 40 studies that used HR-pQCT (39/40 used XtremeCT scanners) to assess 1291 to 3253 and 3389 to 10,687 individuals with and without fractures, respectively, ranging in age from 10.9 to 84.7 years with no comorbid conditions. Parameters describing radial and tibial bone density, microarchitecture, and strength were extracted and percentage differences between fracture and control subjects were estimated using a random effects meta-analysis. An additional meta-analysis of short-term in vivo reproducibility of bone parameters assessed by XtremeCT was conducted to determine whether fracture-associated differences exceeded the least significant change (LSC) required to discern measured differences from precision error. Radial and tibial HR-pQCT parameters, including failure load, were significantly altered in fracture subjects, with differences ranging from -2.6% (95% confidence interval [CI] -3.4 to -1.9) in radial cortical vBMD to -12.6% (95% CI -15.0 to -10.3) in radial trabecular vBMD. Fracture-associated differences reported by prospective studies were consistent with those from retrospective studies, indicating that HR-pQCT can predict incident fracture. Assessment of study quality, heterogeneity, and publication biases verified the validity of these findings. Finally, we demonstrated that fracture-associated deficits in total and trabecular vBMD and certain tibial cortical parameters can be reliably discerned from HR-pQCT-related precision error and can be used to detect fracture-associated differences in individual patients. Although differences in other HR-pQCT measures, including failure load, were significantly associated with fracture, improved reproducibility is needed to ensure reliable individual cross-sectional screening and longitudinal monitoring. In conclusion, our study supports the use of HR-pQCT in clinical fracture prediction. © 2019 American Society for Bone and Mineral Research.
Topics: Bone Density; Cross-Sectional Studies; Fractures, Bone; Humans; Prospective Studies; Radius; Reproducibility of Results; Retrospective Studies
PubMed: 31643098
DOI: 10.1002/jbmr.3901 -
Current Osteoporosis Reports Apr 2021Atypical femur fractures (AFFs) are rare subtrochanteric or diaphyseal fractures regarded as side effects of bisphosphonates (BPs), possibly with a genetic background....
PURPOSE OF REVIEW
Atypical femur fractures (AFFs) are rare subtrochanteric or diaphyseal fractures regarded as side effects of bisphosphonates (BPs), possibly with a genetic background. Here, we summarize the most recent knowledge about genetics of AFFs.
RECENT FINDINGS
AFF has been reported in 57 patients with seven different monogenic bone disorders including hypophosphatasia and osteogenesis imperfecta; 56.1% had never used BPs, while 17.5% were diagnosed with the disorder only after the AFF. Gene mutation finding in familial and sporadic cases identified possible AFF-related variants in the GGPS1 and ATRAID genes respectively. Functional follow-up studies of mutant proteins showed possible roles in AFF. A recent small genome-wide association study on 51 AFF cases did not identify significant hits associated with AFF. Recent findings have strengthened the hypothesis that AFFs have underlying genetic components but more studies are needed in AFF families and larger cohorts of sporadic cases to confirm previous results and/or find novel gene variants involved in the pathogenesis of AFFs.
Topics: Bone Density Conservation Agents; Bone Diseases; Dimethylallyltranstransferase; Farnesyltranstransferase; Femoral Fractures; Genome-Wide Association Study; Geranyltranstransferase; Humans; Membrane Transport Proteins; Mutation
PubMed: 33587247
DOI: 10.1007/s11914-021-00658-y -
Professioni Infermieristiche 2010This work provides a systematic review of literature, a careful analysis, synthesis and critical review, gathering the relevant findings and results of 20 clinical... (Review)
Review
This work provides a systematic review of literature, a careful analysis, synthesis and critical review, gathering the relevant findings and results of 20 clinical studies on Osteogenesis Imperfecta all with the ultimate goal of generating an overview of nursing assistance addressed to the child with this rare chronic disease. The works come from texts considered scientifically validated. The review will serve as a stimulus to improve nursing care and lead nurses to care conscious choices based on scientific evidence, as it is only by an experienced and experimental evidence that can rise to the optimal treatment for each patient (R. Iovine, 2000).
Topics: Child; Humans; Osteogenesis Imperfecta; Patient Education as Topic; Pediatric Nursing
PubMed: 21266132
DOI: No ID Found -
Acta Dermato-venereologica Mar 2020Ehlers-Danlos syndromes (EDS) are a group of inherited connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and variable tissue...
Ehlers-Danlos syndromes (EDS) are a group of inherited connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and variable tissue fragility. However, there are limited published data on the dental manifestations of EDS. This review systematically assessed the spectrum of published dental anomalies in various types of EDS. Twenty-four individual case reports/series and 3 longer case-control studies, reporting on a total of 84 individuals with a clinical diagnosis of EDS, were included in the data analysis. The main dental features listed in classical EDS were pulp calcification and localized root hypoplasia. Common dental abnormalities observed in vascular EDS were pulp shape modifications (52.2%), exceeding root length (34.8%), and molar root fusion (47.8%). Dentinogenesis imperfecta is a consistent finding in osteogenesis imperfecta/EDS overlap syndrome. Data on dental manifestations in other types of EDS are both rare and generally inconclusive.
Topics: Dental Pulp Calcification; Ehlers-Danlos Syndrome; Humans; Tooth Abnormalities; Tooth Diseases; Tooth Root
PubMed: 32147746
DOI: 10.2340/00015555-3428 -
Clinical Orthopaedics and Related... Mar 2011Child abuse and neglect (CAN) is a serious problem that has major implications for the welfare of the child involved. Unexplained fractures are of particular concern to... (Review)
Review
BACKGROUND
Child abuse and neglect (CAN) is a serious problem that has major implications for the welfare of the child involved. Unexplained fractures are of particular concern to the orthopaedic surgeon, who must often consider alternative diagnoses to CAN.
QUESTIONS/PURPOSES
We therefore (1) determined which bone diseases most commonly mimic CAN; (2) what types of osteogenesis imperfecta (OI) are most commonly confused with CAN and why; and (3) what specific findings in OI and bone disease render a mistaken diagnosis of CAN more likely.
METHODS
A systematic review of the literature was performed. We identified studies that compared cases of CAN with cases in which patients had bone disease that resulted in an unexplained fracture. We also included studies in which patients with fractures resulting from underlying bony pathology were misclassified as CAN and were subsequently reclassified as bone disease as a result of further investigation. Our search netted only five studies that directly compared and contrasted CAN with metabolic or genetic bone disease in the same study.
RESULTS
The published literature suggests OI is most frequently confused with CAN, although metaphyseal dysplasia, disorders of phosphate metabolism, and temporary brittle bone disease are also documented in the literature identified by our search. Difficulty in differentiating these bony diseases from CAN stems from ambiguity in the history and physical examination at the time of presentation.
CONCLUSIONS
Bone disease is a diagnosis of exclusion in the differential diagnosis of CAN.
Topics: Bone Diseases; Child; Child Abuse; Child, Preschool; Crime Victims; Diagnosis, Differential; Fractures, Bone; Fractures, Spontaneous; Humans; Infant; Osteogenesis Imperfecta
PubMed: 20878560
DOI: 10.1007/s11999-010-1578-z -
Archives of Disease in Childhood Sep 2006To evaluate the currently available evidence for the effectiveness of bisphosphonates in children with low bone mineral density (BMD) and fragility fractures associated... (Review)
Review
AIMS
To evaluate the currently available evidence for the effectiveness of bisphosphonates in children with low bone mineral density (BMD) and fragility fractures associated with juvenile idiopathic arthritis (JIA), and the safety of bisphosphonates in JIA and other conditions.
METHODS
Literature databases were searched using a structured search strategy. The effectiveness review included any studies of children with JIA treated with bisphosphonates. The safety review also included studies of osteogenesis imperfecta. Quantitative data analysis was not undertaken because of the heterogeneity of the studies; findings were summarised using tables and narrative synthesis.
RESULTS
Ninety four studies were identified. Sixteen studies (78 JIA children) were included in the effectiveness review: one randomised controlled trial, three controlled cohort studies, 11 case series, and one case report. At baseline, children had low BMD below the expected values for age and sex matched children. In all studies, treatment with bisphosphonates increased BMD compared with baseline: the mean percentage increase in spine BMD ranged from 4.5% to 19.1%. Overall, studies were heterogeneous and of variable quality. A total of 59 papers were included in the safety review; treatment durations were up to three years. The most common side effect was a flu-like reaction with intravenous treatment. This occurred during the first infusion and was transient; the symptoms were managed with paracetamol and did not occur during subsequent cycles.
CONCLUSIONS
Bisphosphonates are a promising treatment for low BMD and fragility fractures in children with JIA. However, the quality of the current evidence is variable and better studies are needed to more clearly assess their role.
Topics: Adolescent; Arthritis, Juvenile; Bone Density Conservation Agents; Child; Diphosphonates; Female; Fractures, Bone; Humans; Male; Osteogenesis Imperfecta; Osteoporosis
PubMed: 16690698
DOI: 10.1136/adc.2006.093997 -
Prenatal Diagnosis Dec 2023To investigate the maternal and fetal safety of In utero stem cell transplantation (IUSCT).
OBJECTIVE
To investigate the maternal and fetal safety of In utero stem cell transplantation (IUSCT).
METHODS
Medline®, Embase and Cochrane library (1967-2023) search for publications reporting IUSCT in humans. Two reviewers independently screened abstracts and full-text papers.
RESULTS
Sixty six transplantation procedures in 52 fetuses were performed for haemoglobinopathies (n = 14), red cell/bleeding disorders (n = 4), immunodeficiencies (n = 15), storage disorders (n = 7), osteogenesis imperfecta (n = 2) and healthy fetuses (n = 10). The average gestational age was 18.9 weeks; of procedures reporting the injection route, cells were delivered by intraperitoneal (n = 37), intravenous (n = 19), or intracardiac (n = 4) injection or a combination (n = 3); most fetuses received one injection (n = 41). Haematopoietic (n = 40) or mesenchymal (n = 12) stem cells were delivered. The cell dose was inconsistently reported (range 1.8-3.3 × 10 cells total (n = 27); 2.7-5.0 × 10 /kg estimated fetal weight (n = 17)). The acute fetal procedural complication rate was 4.5% (3/66); the acute fetal mortality rate was 3.0% (2/66). Neonatal survival was 69.2% (36/52). Immediate maternal and pregnancy outcomes were reported in only 30.8% (16/52) and 44.2% (23/52) of cases respectively. Four fetal/pregnancy outcomes would also classify as ≥ Grade 2 maternal adverse events.
CONCLUSIONS
Short-, medium-, and long-term maternal and fetal adverse events should be reported in all IUSCT studies.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Infant; Pregnancy Outcome; Prenatal Care; Fetus; Gestational Age
PubMed: 37975679
DOI: 10.1002/pd.6459 -
The Cochrane Database of Systematic... Mar 2015Pain is one of the most common symptoms in children and young people (CYP) with life-limiting conditions (LLCs) which include a wide range of diagnoses including cancer.... (Review)
Review
BACKGROUND
Pain is one of the most common symptoms in children and young people (CYP) with life-limiting conditions (LLCs) which include a wide range of diagnoses including cancer. The current literature indicates that pain is not well managed, however the evidence base to guide clinicians is limited. There is a clear need for evidence from a systematic review to inform prescribing.
OBJECTIVES
To evaluate the evidence on the effectiveness of different pharmacological interventions used for pain in CYP with LLCs.
SEARCH METHODS
The following electronic databases were searched up to December 2014: CENTRAL (in the Cochrane Library), MEDLINE, EMBASE, PsycINFO and CINAHL. In addition, we searched conference proceedings and reference lists of included studies. For completeness, we also contacted experts in the field. No language restrictions were applied.
SELECTION CRITERIA
Randomised controlled trials (RCTs), quasi-randomised studies and other studies that included a clearly defined comparator group were included. The studies investigated pharmacological treatments for pain associated with LLCs in CYP. The treatment included those specifically developed to treat pain and those that acted as an adjuvant, where the treatment was not primarily developed to treat pain but has pain relieving properties. The LLC was identified by its inclusion in the Richard Hain Directory of LLCs.
DATA COLLECTION AND ANALYSIS
Citations were screened by five review authors. Data were extracted by one review author and checked by a second. Two review authors assessed the risk of bias of included studies. A sufficient number of studies using homogeneous outcomes was not identified so a meta-analysis was not possible.
MAIN RESULTS
We identified 24,704 citations from our database search. Nine trials with 379 participants fulfilled our inclusion criteria. Participants had cerebral palsy (CP) in five of the studies and osteogenesis imperfecta (OI) in the other four. Participants across the trials ranged in age from 2 to 19 years. All studies, apart from one cross-over trial, were parallel designed RCTs. Three of the trials on CP evaluated intrathecal baclofen (ITB) and two botulinum toxin A (BoNT-A). All of the OI trials evaluated the use of bisphosphonates (two alendronate and one pamidronate). No trials were identified that evaluated a commonly used analgesic in this patient group. Pain was a secondary outcome in five of the eight identified studies. Overall the quality of the trials was mixed. Only one study involved over 100 participants.For the two ITB studies for pain in CP, in the same study population but assessed at different time points in their disease, both found an effect on pain favouring the intervention compared to the control group (standard care or placebo) (mean difference (MD) 4.20, 95% confidence interval (CI) 2.15 to 6.25; MD 26.60, 95% CI 2.61 to 50.59, respectively). In these studies most of the adverse events related to the procedure or device for administration rather than the drug, such as swelling at the pump site. In one trial there were also eight serious adverse effects; these included difficulty swallowing and an epileptic seizure. The trial did not state if these occurred in the intervention group. At follow-up in both BoNT-A trials there was no evidence of a difference in pain between the trial arms among CP participants. The adverse events in the BoNT-A trials mostly involved those who received the intervention drug and involved seizures. Gastrointestinal problems were the most frequent adverse event in those who received alendronate. The trial investigating pamidronate found no evidence of a difference in pain compared to the control group. No adverse events were reported in this trial.
AUTHORS' CONCLUSIONS
Published, controlled evidence on the pharmacological interventions for pain in CYP with LLCs is limited. The evidence that is currently available evaluated pain largely as a secondary outcome and the drugs used were all adjuvants and not always commonly used in general paediatric palliative care for pain. Based on current data this systematic review is unable to determine the effects of pharmacological interventions for pain for CYP with LLCs. Future trials with larger populations should examine the effects of the drugs commonly used as analgesics; with the rising prevalence of many LLCs this becomes more necessary.
Topics: Adolescent; Alendronate; Baclofen; Botulinum Toxins, Type A; Cerebral Palsy; Child; Child, Preschool; Diphosphonates; Gastrointestinal Diseases; Humans; Injections, Spinal; Neuromuscular Agents; Osteogenesis Imperfecta; Pain; Pamidronate; Seizures; Young Adult
PubMed: 25768935
DOI: 10.1002/14651858.CD010750.pub2 -
Frontiers in Immunology 2022Mesenchymal stromal cells (MSCs) possess profound immunomodulatory and regenerative properties that are of clinical use in numerous clinical indications with unmet... (Meta-Analysis)
Meta-Analysis
Mesenchymal stromal cells (MSCs) possess profound immunomodulatory and regenerative properties that are of clinical use in numerous clinical indications with unmet medical need. Common sources of MSCs include among others, bone marrow (BM), fat, umbilical cord, and placenta-derived decidua stromal cells (DSCs). We here summarize our more than 20-years of scientific experience in the clinical use of MSCs and DSCs in different clinical settings. BM-MSCs were first explored to enhance the engraftment of autografts in hematopoietic cell transplantation (HCT) and osteogenesis imperfecta around 30 years ago. In 2004, our group reported the first anti-inflammatory use of BM-MSCs in a child with grade IV acute graft-versus-host disease (GvHD). Subsequent studies have shown that MSCs appear to be more effective in acute than chronic GvHD. Today BM-MSC-therapy is registered for acute GvHD in Japan and for GvHD in children in Canada and New Zeeland. MSCs first home to the lung following intravenous injection and exert strong local and systemic immunomodulatory effects on the host immune system. Thus, they were studied for ameliorating the cytokine storm in acute respiratory distress syndrome (ARDS). Both, MSCs and DSCs were used to treat SARS-CoV-2 coronavirus-induced disease 2019 (COVID-19)-induced ARDS. In addition, they were also used for other novel indications, such as pneumomediastinum, colon perforation, and radiculomyelopathy. MSC and DSCs trigger coagulation and were thus explored to stop hemorrhages. DSCs appear to be more effective for acute GvHD, ARDS, and hemorrhages, but randomized studies are needed to prove superiority. Stromal cell infusion is safe, well tolerated, and only gives rise to a slight fever in a limited number of patients, but no major side effects have been reported in multiple safety studies and metaanalysis. In this review we summarize current evidence from studies, animal models, and importantly our clinical experience, to support stromal cell therapy in multiple clinical indications. This encloses MSC's effects on the immune system, coagulation, and their safety and efficacy, which are discussed in relation to prominent clinical trials within the field.
Topics: Animals; COVID-19; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Hemorrhage; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Pregnancy; Respiratory Distress Syndrome; SARS-CoV-2
PubMed: 35371003
DOI: 10.3389/fimmu.2022.839844