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International Journal of Orthopaedic... May 2019
Topics: Health Knowledge, Attitudes, Practice; Humans; Orthopedic Nursing; Osteogenesis Imperfecta; Transitional Care
PubMed: 30910468
DOI: 10.1016/j.ijotn.2018.11.005 -
Disability and Health Journal Jul 2019Osteogenesis Imperfecta (OI) is a rare genetic condition whose key characteristic is increased bone fragility. OI has the potential to impact upon all family members,...
BACKGROUND
Osteogenesis Imperfecta (OI) is a rare genetic condition whose key characteristic is increased bone fragility. OI has the potential to impact upon all family members, making it important to consider the challenges families face, how they cope and their support needs as the affected individual moves from childhood through to adult life.
OBJECTIVE
To conduct a mixed-methods systematic review investigating the experiences of families when a family member is affected with OI.
METHODS
A systematic search of seven electronic databases, relevant patient organisation websites and reference lists was conducted. Data extraction was performed for all studies that met the eligibility and quality criteria. Results were synthesised following the principles of thematic analysis.
RESULTS
One mixed-method, six qualitative and six quantitative studies were included in the review. Three overarching themes were identified through thematic analysis: Impact of OI on the psychosocial wellbeing of families, impact on family life and evolving roles and relationships. Fear of fractures and the uncertainty of when the next fracture will occur are key issues that permeate all areas of family life and impact upon all family members.
CONCLUSION
The experiences, coping strategies and support needs of families affected by OI were highly variable and changed over time. Future research should address the need for adaptive health and education interventions that support all family members.
Topics: Adaptation, Psychological; Disabled Persons; Family; Fear; Fractures, Bone; Health Services Needs and Demand; Humans; Osteogenesis Imperfecta; Uncertainty
PubMed: 30638886
DOI: 10.1016/j.dhjo.2018.12.003 -
World Journal of Pediatrics : WJP Feb 2019Bone remodeling is a lifelong process due to the balanced activity of osteoclasts (OCs), the bone-reabsorbing cells, and osteoblasts (OBs), and the bone-forming cells....
BACKGROUND
Bone remodeling is a lifelong process due to the balanced activity of osteoclasts (OCs), the bone-reabsorbing cells, and osteoblasts (OBs), and the bone-forming cells. This equilibrium is regulated by numerous cytokines, but it has been largely demonstrated that the RANK/RANKL/osteoprotegerin and Wnt/β-catenin pathways play a key role in the control of osteoclastogenesis and osteoblastogenesis, respectively. The pro-osteoblastogenic activity of the Wnt/β-catenin can be inhibited by sclerostin and Dickkopf-1 (DKK-1). RANKL, sclerostin and DKKs-1 are often up-regulated in bone diseases, and they are the target of new monoclonal antibodies.
DATA SOURCES
The authors performed a systematic literature search in PubMed and EMBASE to June 2018, reviewed and selected articles, based on pre-determined selection criteria.
RESULTS
We re-evaluated the role of RANKL, osteoprotegerin, sclerostin and DKK-1 in altered bone remodeling associated with some inherited and acquired pediatric diseases, such as type 1 diabetes mellitus (T1DM), alkaptonuria (AKU), hemophilia A, osteogenesis imperfecta (OI), 21-hydroxylase deficiency (21OH-D) and Prader-Willi syndrome (PWS). To do so, we considered recent clinical studies done on pediatric patients in which the roles of RANKL-RANK/osteoprotegerin and WNT-ß-catenin signaling pathways have been investigated, and for which innovative therapies for the treatment of osteopenia/osteoporosis are being developed.
CONCLUSIONS
The case studies taken into account for this review demonstrated that quite frequently both bone reabsorbing and bone deposition are impaired in pediatric diseases. Furthermore, for some of them, bone damage began in childhood but only manifested with age. The use of denosumab could represent a valid alternative therapeutic approach to improve bone health in children, although further studies need to be carried out.
Topics: Adrenal Hyperplasia, Congenital; Alkaptonuria; Biomarkers; Bone Remodeling; Bone Resorption; Child; Diabetes Mellitus, Type 1; Hemophilia A; Humans; Intercellular Signaling Peptides and Proteins; Osteogenesis Imperfecta; Osteoprotegerin; Prader-Willi Syndrome; RANK Ligand; Up-Regulation; Wnt Signaling Pathway
PubMed: 30343446
DOI: 10.1007/s12519-018-0198-7 -
JBMR Plus Jan 2018Atypical femoral fractures (AFFs) are uncommon and have been associated particularly with long-term antiresorptive therapy, including bisphosphonates. Although the... (Review)
Review
Atypical femoral fractures (AFFs) are uncommon and have been associated particularly with long-term antiresorptive therapy, including bisphosphonates. Although the pathogenesis of AFFs is unknown, their identification in bisphosphonate-naïve individuals and in monogenetic bone disorders has led to the hypothesis that genetic factors predispose to AFF. Our aim was to review and summarize the evidence for genetic factors in individuals with AFF. We conducted structured literature searches and hand-searching of conference abstracts/reference lists for key words relating to AFF and identified 2566 citations. Two individuals independently reviewed citations for (i) cases of AFF in monogenetic bone diseases and (ii) genetic studies in individuals with AFF. AFFs were reported in 23 individuals with the following 7 monogenetic bone disorders (): osteogenesis imperfecta (), pycnodysostosis (), hypophosphatasia (), X-linked osteoporosis (), osteopetrosis, X-linked hypophosphatemia (), and osteoporosis pseudoglioma syndrome (). In 8 cases (35%), the monogenetic bone disorder was uncovered after the AFF occurred. Cases of bisphosphonate-naïve AFF were reported in pycnodysostosis, hypophosphatasia, osteopetrosis, X-linked hypophosphatemia, and osteoporosis pseudoglioma syndrome. A pilot study in 13 AFF patients and 268 controls identified a greater number of rare variants in AFF cases using exon array analysis. A whole-exome sequencing study in 3 sisters with AFFs showed, among 37 shared genetic variants, a p.Asp188Tyr mutation in the gene in the mevalonate pathway, critical to osteoclast function, which is also inhibited by bisphosphonates. Two studies completed targeted gene sequencing, an heterozygous mutation was found in 1 case of a cohort of 11 AFFs, whereas the second study comprising 10 AFF cases did not find mutations in . Targeted sequencing of , , , and genes in 5 cases of AFF identified a variant in COL1A2 in 1 case. These findings suggest a genetic susceptibility for AFFs. A large multicenter collaborative study of well-phenotyped AFF cases and controls is needed to understand the role of genetics in this uncommon condition.
PubMed: 30283886
DOI: 10.1002/jbm4.10024 -
Oral Diseases May 2019The purpose of this systematic review was to evaluate the potential use of dental imaging assessment of trabecular bone structure in the maxillomandibular complex as an...
The purpose of this systematic review was to evaluate the potential use of dental imaging assessment of trabecular bone structure in the maxillomandibular complex as an adjuvant screening tool to identify systemic disorders. Five electronic databases and grey literature were searched. Studies were included if they investigated subjects with altered trabecular bone determined by dental radiographs. The QUADAS-2 assessed the risk of bias (RoB) among the studies, while the GRADE determined the strength of evidence. A total of 14 studies that included 1,466 individuals were considered eligible for the qualitative analysis. All studies presented an overall low RoB and low concern regarding applicability. Systemic disorders such as osteoporosis, osteogenesis imperfecta, diabetes, and primary hyperparathyroidism, with their respective control groups, were analyzed among the included studies. Osteoporosis was the condition presenting the most significant results, and 72% of the studies detected changes in the maxillomandibular trabecular bone structure. Studies exploring diabetic edentulous patients found less dense trabecular bone pattern (p < 0.05). In summary, periapical and panoramic radiographs, computed tomography, and cone beam computed tomography imaging could be considered useful for the assessment of the mandibular trabecular bone structure of patients affected by osteoporosis and patients with diabetes.
Topics: Bone Density; Cancellous Bone; Cone-Beam Computed Tomography; Diabetes Complications; Humans; Mandible; Osteoporosis; Radiography, Panoramic; Tomography, X-Ray Computed
PubMed: 30086203
DOI: 10.1111/odi.12950 -
Acta Paediatrica (Oslo, Norway : 1992) Mar 2018
Topics: Bone Density; Bone Density Conservation Agents; Child; Child, Preschool; Denosumab; Dose-Response Relationship, Drug; Drug Administration Schedule; Evidence-Based Medicine; Female; Humans; Injections, Subcutaneous; Male; Osteogenesis Imperfecta; Prognosis; Severity of Illness Index; Treatment Outcome
PubMed: 29154388
DOI: 10.1111/apa.14154 -
African Journal of Traditional,... 2017Patients with (OI) have abnormal bone modelling and resorption. The bone tissue adaptation and responsivity to dynamic and mechanical loading may be of therapeutic use... (Review)
Review
BACKGROUND
Patients with (OI) have abnormal bone modelling and resorption. The bone tissue adaptation and responsivity to dynamic and mechanical loading may be of therapeutic use under controlled circumstances. Improvements due to the wholebody vibration (WBV) exercises have been reported in strength, motion, gait, balance, posture and bone density in several osteopenic individuals, as in post-menopausal women or children with disabling conditions, as patients with OI. The aim of this investigation was to systematically analyse the current available literature to determine the effect of WBV exercises on functional parameters of OI patients.
MATERIALS AND METHODS
Three reviewers independently accessed bibliographical databases. Searches were performed in the PubMed, Scopus, Science Direct and PEDro databases using keywords related to possible interventions (including WBV) used in the management of patients with .
RESULTS
Three eligible studies were identified by searches in the analysed databases.
CONCLUSION
It was concluded that WBV exercises could be an important option in the management of OI patients improving the mobility and functional parameters. However, further studies are necessary for establishing suitable protocols for these patients.
Topics: Adolescent; Child; Child, Preschool; Exercise Therapy; Female; Humans; Male; Osteogenesis Imperfecta; Treatment Outcome; Vibration
PubMed: 28480432
DOI: 10.21010/ajtcam.v14i3.22 -
Neuro-Chirurgie Dec 2016Osteogenesis imperfecta is an inherited connective tissue disorder that causes bone fragility. Vascular complications have been described, but only few cases of ruptured... (Review)
Review
OBJECTIVE
Osteogenesis imperfecta is an inherited connective tissue disorder that causes bone fragility. Vascular complications have been described, but only few cases of ruptured intracranial aneurysm have been reported.
MATERIALS AND METHODS
We first described 2 familial cases of ruptured intracranial aneurysm and then conducted a systematic review of the literature.
RESULTS
A mother and her daughter with a typical history of osteogenesis imperfecta presented with subarachnoid hemorrhage, which was related to a posterior communicating artery aneurysm in both cases. The mother had early rebleeding and died. The aneurysm was excluded by coiling in the daughter. Despite occurrence of hydrocephalus and delayed cerebral ischemia, she had an excellent functional outcome. A systematic review of the literature identified seven additional cases. None of the cases were in fact familial. All patients had a previous medical history of multiple fractures. Seven aneurysms were resolved, three by surgical clipping and four by endovascular procedure. No periprocedural complication was reported. One patient died prematurely and 6 experienced good functional outcome.
CONCLUSIONS
We report the first familial cases of aneurysmal subarachnoid hemorrhage in osteogenesis imperfecta patients. Intracranial aneurysms are probably linked to a collagen pathology, which is at the origin of osteogenesis imperfecta. In cases of aneurysmal subarachnoid hemorrhage in an osteogenesis imperfecta family, intracranial aneurysm screenings in the relatives showing osteogenesis imperfecta should be considered.
Topics: Aneurysm, Ruptured; Cerebral Angiography; Computed Tomography Angiography; Embolization, Therapeutic; Family Health; Female; Humans; Hydrocephalus; Intracranial Aneurysm; Middle Aged; Osteogenesis Imperfecta; Rupture, Spontaneous; Ventriculoperitoneal Shunt
PubMed: 28120769
DOI: 10.1016/j.neuchi.2016.07.004 -
The Cochrane Database of Systematic... Oct 2016Osteogenesis imperfecta is caused by a genetic defect resulting in an abnormal type I collagen bone matrix which typically results in multiple fractures with little or... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Osteogenesis imperfecta is caused by a genetic defect resulting in an abnormal type I collagen bone matrix which typically results in multiple fractures with little or no trauma. Bisphosphonates are used in an attempt to increase bone mineral density and reduce these fractures in people with osteogenesis imperfecta. This is an update of a previously published Cochrane Review.
OBJECTIVES
To assess the effectiveness and safety of bisphosphonates in increasing bone mineral density, reducing fractures and improving clinical function in people with osteogenesis imperfecta.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Inborn Errors of Metabolism Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of journals and conference proceedings. We additionally searched PubMed and major conference proceedings.Date of the most recent search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Register: 28 April 2016.
SELECTION CRITERIA
Randomised and quasi-randomised controlled trials comparing bisphosphonates to placebo, no treatment, or comparator interventions in all types of osteogenesis imperfecta.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data and assessed the risk of bias of the included trials.
MAIN RESULTS
Fourteen trials (819 participants) were included. Overall, the trials were mainly at a low risk of bias, although selective reporting was an issue in several of the trials. Data for oral bisphosphonates versus placebo could not be aggregated; a statistically significant difference favouring oral bisphosphonates in fracture risk reduction and number of fractures was noted in two trials. No differences were reported in the remaining three trials which commented on fracture incidence. Five trials reported data for spine bone mineral density; all found statistically significant increased lumbar spine density z scores for at least one time point studied. For intravenous bisphosphonates versus placebo, aggregated data from two trials showed no statistically significant difference for the number of participants with at least one fracture, risk ratio 0.56 (95% confidence interval 0.30 to 1.06). In the remaining trial no statistically significant difference was noted in fracture incidence. For spine bone mineral density, no statistically significant difference was noted in the aggregated data from two trials, mean difference 9.96 (95% confidence interval -2.51 to 22.43). In the remaining trial a statistically significant difference in mean per cent change in spine bone mineral density z score favoured intravenous bisphosphonates at six and 12 months. Data describing growth, bone pain, and functional outcomes after oral or intravenous bisphosphonate therapy, or both, as compared to placebo were incomplete among all studies, but do not show consistent improvements in these outcomes. Two studies compared different doses of bisphosphonates. No differences were found between doses when bone mineral density, fractures, and height or length z score were assessed. One trial compared oral versus intravenous bisphosphonates and found no differences in primary outcomes. Two studies compared the intravenous bisphosphonates zoledronic acid and pamidronate. There were no significant differences in primary outcome. However, the studies were at odds as to the relative benefit of zoledronic acid over pamidronate for lumbosacral bone mineral density at 12 months.
AUTHORS' CONCLUSIONS
Bisphophonates are commonly prescribed to individuals with osteogenesis imperfecta. Current evidence, albeit limited, demonstrates oral or intravenous bisphosphonates increase bone mineral density in children and adults with this condition. These were not shown to be different in their ability to increase bone mineral density. It is unclear whether oral or intravenous bisphosphonate treatment consistently decreases fractures, though multiple studies report this independently and no studies report an increased fracture rate with treatment. The studies included here do not show bisphosphonates conclusively improve clinical status (reduce pain; improve growth and functional mobility) in people with osteogenesis imperfecta. Given their current widespread and expected continued use, the optimal method, duration of therapy and long-term safety of bisphosphonate therapy require further investigation. In addition, attention should be given to long-term fracture reduction and improvement in quality of life indicators.
Topics: Administration, Oral; Bone Density; Bone Density Conservation Agents; Diphosphonates; Fractures, Bone; Humans; Injections, Intravenous; Osteogenesis Imperfecta; Randomized Controlled Trials as Topic
PubMed: 27760454
DOI: 10.1002/14651858.CD005088.pub4 -
Quality of Life Research : An... Aug 2016Osteogenesis imperfecta (OI) is a genetic disorder (prevalence: 1:10,000), leading to bone fragility, frequent fractures, and varying degrees of physical limitations.... (Review)
Review
PURPOSE
Osteogenesis imperfecta (OI) is a genetic disorder (prevalence: 1:10,000), leading to bone fragility, frequent fractures, and varying degrees of physical limitations. Despite a substantial amount of research on the genetics, pathophysiology, and treatments related to OI, there remains a paucity of knowledge concerning the lived psychosocial experience of the OI population. This mixed-methods systematic review aimed to review, appraise, and synthesize the literature on the psychosocial experience of children and adults with OI with the goal of identifying implications for research, practice, and policy-making.
METHODS
Using a systematic methodology, quantitative, qualitative, and mixed-methods studies were accessed through database searching, screened, assessed for eligibility, and appraised. Data from the selected studies fulfilling the eligibility and quality criteria were extracted and synthesized using thematic analysis with an inductive approach.
RESULTS
A total of four qualitative and 20 quantitative studies, with various study designs and methodologies ranging in quality, were included in the review (n = 800; comprising 610 children and 175 adults with OI types I, III, IV, and V, ten parents and five healthcare professionals). Six themes were identified: intellectual feats, isolation and feeling different, fear of fractures, coping with challenges, adapting by learning new skills, and social relationships.
CONCLUSION
These findings highlighted key aspects of the experiences of children and adults with OI and will be essential for improving the quality and direction of research, tailoring clinical interventions addressing the psychosocial needs and quality of life of individuals with OI, and raising awareness among caregivers, healthcare professionals, administrators, and policy-makers associated with the OI population.
Topics: Adaptation, Psychological; Adult; Child; Female; Humans; Male; Osteogenesis Imperfecta; Sickness Impact Profile
PubMed: 26894269
DOI: 10.1007/s11136-016-1247-0