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Orthopaedic Surgery Aug 2020To assess the effectiveness and safety of oral bisphosphonates in increasing bone mineral density (BMD), reducing fractures, and improving clinical function in patients... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess the effectiveness and safety of oral bisphosphonates in increasing bone mineral density (BMD), reducing fractures, and improving clinical function in patients with osteogenesis imperfecta (OI).
METHODS
Studies were eligible for inclusion if they were randomized controlled trials of directly comparing oral bisphosphonate therapy with placebo-group in OI patients. Data synthesis regarding to bone mineral density as measured by dual-energy X-ray absorptiometry (DEXA), decreased fracture incidence, change in biochemical markers of bone and mineral metabolism, bone histology, growth, bone pain, quality of life, and others were assessed, and meta-analysis done when possible.
RESULTS
From 98 potential references and six randomized controlled studies a total of 263 participants receiving oral bisphosphonates and 143 placebo treatments contributed data to meta-analysis. Pooled meta-analysis of three studies suggested that there was significant difference between bisphosphonate treated group and placebo in number of patients with at least one fracture (mean difference 0.53, 95% confidence interval 0.32-0.89, P = 0.02). Pooled meta-analysis of two studies suggested that significant difference was noted between bisphosphonate treated group and placebo in mean percentage change in spine BMD (T-score) (mean difference 28.43, 95% confidence interval 7.09-49.77, P = 0.009). The similar effect was shown in the term of mean change (Z-score) in spine BMD.
CONCLUSIONS
Significant improvement in lumbar areal BMD in patients affected with OI has been shown when treated with oral bisphosphonates, even though only a small population was enrolled. We cannot draw a definite conclusion that the increase in BMD can be translated into fracture reduction and clinical functional improvement. The optimal method, dose, type, initiation, and duration of oral bisphosphonates therapy still remains unclear. Well-designed, adequately-powered, placebo-controlled RCTs investigating the effects of oral bisphosphonates on fractures reduction and improvement in quality of life in both children and adults are studied here.
Topics: Bone Density; Bone Density Conservation Agents; Diphosphonates; Fractures, Bone; Humans; Osteogenesis Imperfecta; Randomized Controlled Trials as Topic
PubMed: 32589343
DOI: 10.1111/os.12611 -
Journal of Applied Oral Science :... 2023Osteogenesis imperfecta (OI) is a rare genetic disorder primarily caused by mutations in the genes involved in the production of type 1 collagen. OI is also known as... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Osteogenesis imperfecta (OI) is a rare genetic disorder primarily caused by mutations in the genes involved in the production of type 1 collagen. OI is also known as brittle bone disease.
OBJECTIVE
This study aims to describe the prevalence of dental anomalies (except dentinogenesis imperfecta) in individuals with OI, and compare the prevalence of dental anomalies between individuals with and without OI and between individuals with different types of OI.
SEARCH METHODS
Searches in PubMed, Web of Science, Scopus, Ovid, and gray literature were performed in October 2022.
SELECTION CRITERIA
Observational studies (with or without a comparison group) that evaluated the prevalence of dental anomalies in individuals with OI. Data collection and analysis: Data items were extracted by two authors. Quality assessment employing the Joanna Briggs Institute checklists and meta-analyses was conducted. Results were provided in prevalence values and odds ratio (OR) / 95% confidence interval (CI). Strength of evidence was determined.
RESULTS
Eighteen studies were included. Most prevalent dental anomalies in individuals with OI included pulp obliteration (46.4%), dental impaction (33.5%), dental impaction of second molars (27%), and tooth agenesis (23.9%). Individuals with OI type III/IV had 20.16-fold greater chance of exhibiting tooth discoloration in comparison with individuals with OI type I (CI: 1.10-370.98). In comparison with the group without OI, the individuals with OI had 6.90-fold greater chance of exhibiting dental impaction (CI: 1.54-31.00). High methodological quality was found in 47% of the studies. Strength of evidence was low or very low.
CONCLUSIONS
Pulp obliteration, dental impaction, and tooth agenesis were the most prevalent dental anomalies in the OI group. Individuals with OI were more likely to have dental impaction than individuals without OI. Individuals with OI type III/IV (severe-moderate) are more likely to have tooth discoloration than individuals with OI type I (mild).
Topics: Humans; Osteogenesis Imperfecta; Prevalence; Tooth Discoloration
PubMed: 37672427
DOI: 10.1590/1678-7757-2023-0040 -
Bone Reports Dec 2021There is no cure for osteogenesis imperfecta (OI), and current treatments can only partially correct the bone phenotype. Stem cell therapy holds potential to improve...
There is no cure for osteogenesis imperfecta (OI), and current treatments can only partially correct the bone phenotype. Stem cell therapy holds potential to improve bone quality and quantity in OI. Here, we conduct a systematic review and meta-analysis of published studies to investigate the efficacy of stem cell therapy to rescue bone brittleness in mouse models of OI. Identified studies included bone marrow, mesenchymal stem cells, and human fetal stem cells. Effect size of fracture incidence, maximum load, stiffness, cortical thickness, bone volume fraction, and raw engraftment rates were pooled in a random-effects meta-analysis. Cell type, cell number, injection route, mouse age, irradiation, anatomical bone, and follow up time were considered as moderators. It was not possible to investigate further parameters due to the lack of standards of investigation between the studies. Despite the use of mice in the majority of the investigations considered and the lack of sham mice as control, this study demonstrates the promising potential of stem cell therapy to reduce fractures in OI. Although their low engraftment, cell therapy in mouse models of OI had a beneficial effect on maximum load, but not on stiffness, cortical thickness and bone volume. These parameters all depend on bone geometry and do not inform on its material properties. Being bone fractures the primary symptom of OI, there is a critical need to measure the fracture toughness of OI bone treated with stem cells to assess the actual efficacy of the treatment to rescue OI bone brittleness.
PubMed: 34368408
DOI: 10.1016/j.bonr.2021.101108 -
JBMR Plus Oct 2019Osteogenesis imperfecta (OI) is a rare genetic connective tissue disorder that results in bone fragility and deformity. Management is multi-disciplinary. Although...
Osteogenesis imperfecta (OI) is a rare genetic connective tissue disorder that results in bone fragility and deformity. Management is multi-disciplinary. Although pharmacologic intervention with bisphosphonates (BP) is a standard of care for individuals with severe OI, no consensus or reviews were found that focus on the effects of bisphosphonates on function and mobility. PubMed, CINAHL, Cochrane Library, Web of Science, and PEDro databases were searched for eligible articles for this review. Methodological quality was assessed using the Cochrane Collaboration's tool for risk of bias. Twenty-six studies (801 children) were reviewed and five showed a low risk of bias. Included studies showed significant variability among clinical protocols for administering BP. Randomized controlled trials did not demonstrate a significant improvement in function and mobility with oral BP administration, while non-randomized open-label uncontrolled studies demonstrated that oral and intravenous BP administration objectively improved function and mobility. The most common outcome measure used by the studies included in this review was the Bleck score. Effect sizes (d = 0.28 - 4.5) varied among studies. This systematic review also summarized the apparent confounding variables affecting results of previous studies and provided suggestions to improve the quality of future studies.
PubMed: 31687649
DOI: 10.1002/jbm4.10216 -
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 -
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 -
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 -
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 -
Frontiers in Endocrinology 2020Bone biopsies have been obtained for many centuries and are one of the oldest known medical procedures in history. Despite the introduction of new noninvasive...
Bone biopsies have been obtained for many centuries and are one of the oldest known medical procedures in history. Despite the introduction of new noninvasive radiographic imaging techniques and genetic analyses, bone biopsies are still valuable in the diagnosis of bone diseases. Advanced techniques for the assessment of bone quality in bone biopsies, which have emerged during the last decades, allows in-depth tissue analyses beyond structural changes visible in bone histology. In this review, we give an overview of the application and advantages of the advanced techniques for the analysis of bone biopsies in the clinical setting of various rare metabolic bone diseases. A systematic literature search on rare metabolic bone diseases and analyzing techniques of bone biopsies was performed in PubMed up to 2019 week 34. Advanced techniques for the analysis of bone biopsies were described for rare metabolic bone disorders including Paget's disease of bone, osteogenesis imperfecta, fibrous dysplasia, Fibrodysplasia ossificans progressiva, X-linked osteoporosis, Loeys-Diets syndrome, osteopetrosis, Erdheim-Chester disease, and Cherubism. A variety of advanced available analytical techniques were identified that may help to provide additional detail on cellular, structural, and compositional characteristics in rare bone diseases complementing classical histopathology. To date, these techniques have only been used in research and not in daily clinical practice. Clinical application of bone quality assessment techniques depends upon several aspects such as availability of the technique in hospitals, the existence of reference data, and a cooperative network of researchers and clinicians. The evaluation of rare metabolic bone disorders requires a repertoire of different methods, owing to their distinct bone tissue characteristics. The broader use of bone material obtained from biopsies could provide much more information about pathophysiology or treatment options and establish bone biopsies as a valuable tool in rare metabolic bone diseases.
Topics: Biopsy; Bone Diseases; Fibrous Dysplasia of Bone; Humans; Loeys-Dietz Syndrome; Myositis Ossificans; Osteitis Deformans; Osteogenesis Imperfecta; Osteopetrosis; Osteoporosis; Rare Diseases
PubMed: 32714279
DOI: 10.3389/fendo.2020.00399