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Journal of Clinical Medicine Feb 2023Medication-related osteonecrosis of the jaw (MRONJ) is defined by the American Association of Oral and Maxillofacial Surgeons (AAOMS) as the presence of an exposed bone... (Review)
Review
Medication-related osteonecrosis of the jaw (MRONJ) is defined by the American Association of Oral and Maxillofacial Surgeons (AAOMS) as the presence of an exposed bone area in the maxillofacial region, present for more than eight weeks in patients treated with the use of antiresorptive or antiangiogenic agents, with no history of radiation or metastatic disease. Bisphosphonates (BF) and denosumab (DS) are widely used in adults for the management of patients with cancer and osteoporosis, and recently there has been an increase in their use in child and young patients for the management of disorders such as osteogenesis imperfecta (OI), glucocorticoid-induced osteoporosis, McCune-Albright syndrome (MAS), malignant hypercalcemia, and others. There are differences between case reports in adults compared to child and young patients related to the use of antiresorptive/antiangiogenic drugs and the development of MRONJ. The aim was to analyze the presence of MRONJ in children and young patients, and the relation with oral surgery. A systematic review, following the PRISMA search matrix based on the PICO question, was conducted in PubMed, Embase, ScienceDirect, Cochrane, Google Scholar, and manual search in high-impact journals between 1960 and 2022, publications in English or Spanish, including randomized and non-randomized clinical trials, prospective and retrospective cohort studies, cases and controls studies, and series and case reports. A total of 2792 articles were identified and 29 were included; all of them published between 2007 and 2022, identifying 1192 patients, 39.68% male and 36.24% female, aged 11.56 years old on average, using these drugs mainly for OI (60.15%); 4.21 years on average was the therapy time and 10.18 drug doses administered on average; oral surgery was observed in 216 subjects, reporting 14 cases of MRONJ. We concluded that there is a low presence of MRONJ in the child and youth population treated with antiresorptive drugs. Data collection is weak, and details of therapy are not clear in some cases. Deficiencies in protocols and pharmacological characterization were observed in most of the included articles.
PubMed: 36835951
DOI: 10.3390/jcm12041416 -
The Cochrane Database of Systematic... Oct 2008In osteogenesis imperfecta (OI) a genetic defect in type I collagen results in multiple fractures with little or no trauma. Bisphosphonates are used to attempt to reduce... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In osteogenesis imperfecta (OI) a genetic defect in type I collagen results in multiple fractures with little or no trauma. Bisphosphonates are used to attempt to reduce these fractures.
OBJECTIVES
To assess the effectiveness and safety of bisphosphonates in increasing bone mineral density (BMD), reducing fractures and improving clinical function in people with OI.
SEARCH STRATEGY
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearches of journals and conference proceedings. We searched PubMed and major conference proceedings.Register last searched: August 2008.
SELECTION CRITERIA
Randomised and quasi-randomised controlled trials comparing bisphosphonates to placebo, no treatment, or comparator interventions in all types of OI.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data and assessed trial quality.
MAIN RESULTS
Eight studies (403 participants) were included. Data for oral bisphosphonates versus placebo could not be aggregated. A significant difference favouring bisphosphonates in fracture risk reduction and number of fractures was noted in one trial. No differences were reported in the remaining three trials. Two trials reported data for spine BMD; one found significantly increased lumbar spine density z scores at 12 months and one reported a significant increase in lumbar spine BMD at 12, 24 and 36 months; both favouring bisphosphonates. For intravenous bisphosphonates versus placebo, aggregated data from two trials showed no significant difference for the number of participants with at least one fracture, RR 0.56 (95% CI 0.30 to 1.06). In the remaining trial no significant difference was noted in fracture incidence. For spine BMD, no significant difference was noted in the aggregated data from two trials, MD 9.96 (95%CI -2.51 to 22.43). In the remaining trial a significant difference in mean per cent change in spine BMD z score favoured intravenous bisphosphonates at 6 and 12 months. One trial compared oral versus intravenous bisphosphonates and found no differences in primary outcomes. Data describing growth, bone pain, and functional outcomes after bisphosphonate therapy were incomplete.
AUTHORS' CONCLUSIONS
Evidence suggests oral or intravenous bisphosphonates increase BMD in children and adults with OI. These were not shown to be different in their ability to increase BMD; it is unclear whether either treatment decreases fractures. Additional studies may determine whether bisphosphonates improve clinical status (reduce fractures and pain; improve growth and functional mobility) in this population. Optimal method, duration of therapy and long-term safety of bisphosphonate therapy requires further investigation.
Topics: Bone Density; Bone Density Conservation Agents; Diphosphonates; Fractures, Bone; Humans; Osteogenesis Imperfecta; Randomized Controlled Trials as Topic
PubMed: 18843680
DOI: 10.1002/14651858.CD005088.pub2 -
Clinical Genetics Sep 2023Tooth eruption is an important and unique biological process during craniofacial development. Both the genetic and environmental factors can interfere with this process.... (Meta-Analysis)
Meta-Analysis Review
Tooth eruption is an important and unique biological process during craniofacial development. Both the genetic and environmental factors can interfere with this process. Here we aimed to find the failure pattern of tooth eruption among five genetic diseases. Both systematic review and meta-analysis were used to identify the genotype-phenotype associations of unerupted teeth. The meta-analysis was based on the characteristics of abnormal tooth eruption in 223 patients with the mutations in PTH1R, RUNX2, COL1A1/2, CLCN7, and FAM20A respectively. We found all the patients presented selective failure of tooth eruption (SFTE). Primary failure of eruption patients with PTH1R mutations showed primary or isolated SFTE1 in the first and second molars (59.3% and 52% respectively). RUNX2 related cleidocranial dysplasia usually had SFTE2 in canines and premolars, while COL1A1/2 related osteogenesis imperfecta mostly caused SFTE3 in the maxillary second molars (22.9%). In CLCN7 related osteopetrosis, the second molars and mandibular first molars were the most affected. While FAM20A related enamel renal syndrome most caused SFTE5 in the second molars (86.2%) and maxillary canines. In conclusion, the SFTE was the common characteristics of most genetic diseases with abnormal isolated or syndromic tooth eruption. The selective pattern of unerupted teeth was gene-dependent. Here we recommend SFTE to classify those genetic unerupted teeth and guide for precise molecular diagnosis and treatment.
Topics: Humans; Tooth Eruption; Tooth, Unerupted; Core Binding Factor Alpha 1 Subunit; Tooth Abnormalities; Phenotype; Genotype; Chloride Channels
PubMed: 37448157
DOI: 10.1111/cge.14400 -
Genetics in Medicine : Official Journal... Oct 2023Skeletal dysplasia are heterogeneous conditions affecting the skeleton. Common nutrition issues include feeding difficulties, obesity, and metabolic complications. This...
PURPOSE
Skeletal dysplasia are heterogeneous conditions affecting the skeleton. Common nutrition issues include feeding difficulties, obesity, and metabolic complications. This systematic scoping review aimed to identify key nutrition issues, management strategies, and gaps in knowledge regarding nutrition in skeletal dysplasia.
METHODS
The databases Ovid MEDLINE, Ovid EMBASE, Ebsco CINAHL, Scopus, and Cochrane Central Register of Controlled Trials and Database of Systematic Reviews were searched. Reference lists and citing literature for included studies were searched. Eligible studies included participants with skeletal dysplasia and described: anthropometry, body composition, nutrition-related biochemistry, clinical issues, dietary intake, measured energy or nutrition requirements, or nutrition interventions.
RESULTS
The literature search identified 8509 references from which 138 studies were included (130 observational, 3 intervention, 2 systematic reviews, and 3 clinical guidelines). Across 17 diagnoses identified, most studies described osteogenesis imperfecta (n = 50) and achondroplasia or hypochondroplasia (n = 47). Nutrition-related clinical issues, biochemistry, obesity, and metabolic complications were most commonly reported, and few studies measured energy requirements (n = 5).
CONCLUSION
Nutrition-related comorbidities are documented in skeletal dysplasia; yet, evidence to guide management is scarce. Evidence describing nutrition in rarer skeletal dysplasia conditions is lacking. Advances in skeletal dysplasia nutrition knowledge is needed to optimize broader health outcomes.
Topics: Humans; Comorbidity; Dwarfism; Obesity; Osteochondrodysplasias; Systematic Reviews as Topic
PubMed: 37330695
DOI: 10.1016/j.gim.2023.100920 -
Pain Management Nursing : Official... Feb 2023The objective of this literature review was to evaluate multimodal therapies and interventions that help prevent progression and manage pain in children with OI. (Review)
Review
OBJECTIVES
The objective of this literature review was to evaluate multimodal therapies and interventions that help prevent progression and manage pain in children with OI.
DESIGN
A systematic review of literature utilizing PRISMA guidelines.
DATA SOURCES
The Cumulative Index to Nursing and Allied Health Literature (CINAHL) Complete, PubMed, PsycINFO, UpToDate, and ProQuest Nursing & Allied Health Source.
REVIEW/ANALYSIS METHODS
Existing literature on pain management in pediatric patients diagnosed with OI was reviewed and appraised. Fifteen studies met the criteria for review.
RESULTS
Results indicated that therapies addressing pain management are most effective when they use a multimodal approach that promotes bone strength, psychological support, reduces the risk of fractures, increases bone stability, and maintains physiological function. Four multimodal treatments for pain management in children with OI were identified including bisphosphonate therapy, surgical intervention, physical therapy, and psychosocial support.
CONCLUSIONS
Developing a finite understanding of the utilization of multimodal therapies to manage and treat pain can assist in engineering treatments that improve the quality of life for children diagnosed with OI.
Topics: Humans; Child; Diphosphonates; Quality of Life; Pain Management; Osteogenesis Imperfecta; Pain
PubMed: 36207231
DOI: 10.1016/j.pmn.2022.08.014 -
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 -
BioMed Research International 2014A rare disease afflicts less than 200,000 individuals, according to the National Organization for Rare Diseases (NORD) of the United States. Over 6,000 rare disorders... (Review)
Review
A rare disease afflicts less than 200,000 individuals, according to the National Organization for Rare Diseases (NORD) of the United States. Over 6,000 rare disorders affect approximately 1 in 10 Americans. Rare genetic bone disorders remain the major causes of disability in US patients. These rare bone disorders also represent a therapeutic challenge for clinicians, due to lack of understanding of underlying mechanisms. This systematic review explored current literature on therapeutic directions for the following rare genetic bone disorders: fibrous dysplasia, Gorham-Stout syndrome, fibrodysplasia ossificans progressiva, melorheostosis, multiple hereditary exostosis, osteogenesis imperfecta, craniometaphyseal dysplasia, achondroplasia, and hypophosphatasia. The disease mechanisms of Gorham-Stout disease, melorheostosis, and multiple hereditary exostosis are not fully elucidated. Inhibitors of the ACVR1/ALK2 pathway may serve as possible therapeutic intervention for FOP. The use of bisphosphonates and IL-6 inhibitors has been explored to be useful in the treatment of fibrous dysplasia, but more research is warranted. Cell therapy, bisphosphonate polytherapy, and human growth hormone may avert the pathology in osteogenesis imperfecta, but further studies are needed. There are still no current effective treatments for these bone disorders; however, significant promising advances in therapeutic modalities were developed that will limit patient suffering and treat their skeletal disabilities.
Topics: Bone Diseases; Bone and Bones; Humans; Osteogenesis; Rare Diseases
PubMed: 25530967
DOI: 10.1155/2014/670842 -
Gene May 2020Osteogenesis imperfecta (OI) is a rare disease characterized by increased bone fragility and predisposition to fractures, bone deformities and other major signs such as...
Rare splicing mutation in COL1A1 gene identified by whole exomes sequencing in a patient with osteogenesis imperfecta type I followed by prenatal diagnosis: A case report and review of the literature.
BACKGROUND
Osteogenesis imperfecta (OI) is a rare disease characterized by increased bone fragility and predisposition to fractures, bone deformities and other major signs such as dentinogenesis imperfecta, blue sclera and deafness. Over 90% of OI cases are caused by mutations in the COL1A1 and COL1A2 genes and the inheritance is autosomal dominant.
METHODS
We present a case of a couple requesting genetic counseling, because the man was diagnosed with OI on a clinical and radiological basis and the woman was pregnant. Whole exomes sequencing (WES) was performed in order to identify the mutation (s), followed by prenatal diagnosis.
RESULTS
WES identified a rare splicing mutation c.1155 + 1G > C in the COL1A1 gene recognized to be pathogenic and subsequently confirmed by next generation sequencing. The carrier state of the mutation was excluded for the fetus, so the pregnancy was further pursued and a healthy baby was born at term.
CONCLUSIONS
WES is a new and effective technique for detecting pathogenic variants in monogenic diseases and it is preferable to use such a technique in diseases with genetic heterogeneity especially when time does not allow another time-consuming diagnostic technique such classical Sanger sequencing. WES offers possibility to expand the global spectrum of OI pathogenic variants enabling the diagnosis of the disease.
Topics: Adult; Alternative Splicing; Collagen Type I; Collagen Type I, alpha 1 Chain; Exome; Female; Genotype; High-Throughput Nucleotide Sequencing; Humans; Male; Mutation; Osteogenesis Imperfecta; Pedigree; Pregnancy; Prenatal Diagnosis; Protein Isoforms; Exome Sequencing
PubMed: 32165296
DOI: 10.1016/j.gene.2020.144565 -
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 -
Orphanet Journal of Rare Diseases Aug 2012Little information is available on the prevalence, geographic distribution and mutation spectrum of genetic skeletal disorders (GSDs) in China. This study systematically... (Review)
Review
Little information is available on the prevalence, geographic distribution and mutation spectrum of genetic skeletal disorders (GSDs) in China. This study systematically reviewed GSDs as defined in "Nosology and Classification of genetic skeletal disorders (2010 version)" using Chinese biomedical literature published over the past 34 years from 1978 to 2012. In total, 16,099 GSDs have been reported. The most frequently reported disorders were Marfan syndrome, osteogenesis imperfecta, fibrous dysplasia, mucopolysaccharidosis, multiple cartilaginous exostoses, neurofibromatosis type 1 (NF1), osteopetrosis, achondroplasia, enchondromatosis (Ollier), and osteopoikilosis, accounting for 76.5% (12,312 cases) of the total cases. Five groups (group 8, 12, 14, 18, 21) defined by "Nosology and Classification of genetic skeletal disorders" have not been reported in the Chinese biomedical literature. Gene mutation testing was performed in only a minor portion of the 16,099 cases of GSDs (187 cases, 1.16%). In total, 37 genes for 41 different GSDs were reported in Chinese biomedical literature, including 43 novel mutations. This review revealed a significant imbalance in rare disease identification in terms of geographic regions and hospital levels, suggesting the need to create a national multi-level network to meet the specific challenge of care for rare diseases in China.
Topics: Bone Diseases; China; Genetic Diseases, Inborn; Humans; Publishing
PubMed: 22913777
DOI: 10.1186/1750-1172-7-55