SEARCH · PubMed Health

Results for “OSTEOGENESIS IMPERFECTA”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources

PubMed2004

Bone turnover markers in patients with osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a heterologous group of rare inherited bone disorders resulting from defect in collagen synthesis or function. In previous studies, bone turnover has been found either increased or low-normal. These contradictory results might result from the study population made of children with prior recent fractures. We measured serum total and bone alkaline phosphatase (total and bone AP) serum osteocalcin (sOC), serum type I collagen C-telopeptide breakdown products (sCTX), urinary free-deoxypyridinoline (ufDPD), and urinary cross-linked N-telopeptides of type I collagen (uNTX) in 39 male and 38 premenopausal patients with different types of OI aged between 18 and 51 years who had not experienced new clinical fracture during 12 months preceding the laboratory assessment. The study also includes a control group of 29 men and 26 women matched for age and gender. Most bone markers were 50-200% higher in patients than in controls. Only sCTX was comparable to that found in controls. From a sub-analysis of the data, a trend for higher bone resorption markers was observed for any OI type, but patients with OI type III and IV had significantly higher values in ufDPD and uNTX than patients with type I OI, and their sOC levels were not significantly higher than in controls. These results provide a strong rational for the use of anti-resorbing agent in OI.

Adolescent↗

PubMed1993

Defective pro alpha 2(I) collagen synthesis in a recessive mutation in mice: a model of human osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a heritable disorder of connective tissue associated with fractures, osteopenia, and short stature. OI results from mutations affecting the pro alpha 1 or pro alpha 2 gene of type I collagen. We describe a strain of mice with a nonlethal recessively inherited mutation (oim) that results in phenotypic and biochemical features that simulate moderate to severe human OI. The phenotype of homozygous oim mice includes skeletal fractures, limb deformities, generalized osteopenia, and small body size. Their femurs are smaller and demonstrate marked cortical thinning and fewer medullary trabeculae than those of wild-type mice. Breeding studies show the mutation is inherited in most crosses as a single recessive gene on chromosome 6, near the murine Cola-2 gene. Biochemical analysis of skin and bone, as well as isolated dermal fibroblast cultures, demonstrate that alpha 1(I) homotrimeric collagen accumulates in these tissues and is secreted by fibroblasts. Short labeling studies in fibroblasts demonstrate an absence of pro alpha 2(I) collagen chains. Nucleotide sequencing of the cDNA encoding the COOH-propeptide reveals a G deletion at pro alpha 2(I) nucleotide 3983; this results in an alteration of the sequence of the last 48 amino acids. The oim mouse will facilitate the study of type I collagen-related skeletal disease.

Amino Acid Sequence↗

PubMed2003

Intravenous neridronate in adults with osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a heritable disease of connective tissue, characterized by increased bone fragility. Bisphosphonates currently seems to be the most promising therapy, at least in children. We tested IV neridronate, an amino-bisphosphonate structurally similar to alendronate and pamidronate in adults with OI. Twenty-three men and 23 premenopausal women with OI were randomized to either iv neridronate (100 mg infused intravenously for 30 minutes every 3 months) or no treatment with a ratio of 2 to 1. Control patients were given the same bisphosphonate therapy at the end of the first year. Clinical evaluation included bone densitometry measurements using dual energy X-ray absorptiometry (DXA), fasting serum and urinary biochemistry every 6 months, and radiographs of the spine taken at baseline and after 12 and 24 months of follow-up. Spine and hip bone mineral density rose by 3.0 +/- 4.6% (SD) and by 4.3 +/- 3.9%, respectively, within the first 12 months of treatment, whereas small insignificant changes were observed in the control group. During the second year of follow-up, additional 3.91% and 1.49% increases were observed at the spine and hip, respectively. Markers of skeletal turnover significantly fell during neridronate treatment. Fracture incidence during neridronate treatment was significantly lower than before therapy and compared with controls. Neridronate iv infusions, administered quarterly, significantly increase bone mineral density and lowered the risk of clinical fracture in adults with OI. Bisphosphonate therapy seems to provide clinical benefits, not only to children with OI, but also to adult patients.

Adult↗

PubMedDate not supplied

Osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a genetically determined disorder of connective tissue characterized by bone fragility. The disease state encompasses a phenotypically and genotypically heterogeneous group of inherited disorders that result from mutations in the genes that code for type I collagen. The disorder is manifest in tissues in which the principal matrix protein is type I collagen (mainly bone, dentin, sclerae, and ligaments). Musculoskeletal manifestations are variable in severity along a continuum ranging from perinatal lethal forms with crumpled bones to moderate forms with deformity and propensity to fracture to clinically silent forms with subtle osteopenia and no deformity. The differential diagnosis includes other entities with multiple fractures, deformities, and osteopenia. Classification is based on the timing of fractures or on multiple clinical, genetic, and radiologic features. Molecular genetic studies have identified more than 150 mutations of the COL1A1 and COL1A2 genes, which encode for type I procollagen. Various systemic treatments have been attempted; however, these interventions have been ineffective or inconclusive or are still experimental. Gene therapy has the potential to increase the synthesis of type I collagen in mild variants and to correct mutations in severe variants, but there are a great number of technical difficulties to overcome. The goals of treatment of OI are to maximize function, minimize deformity and disability, maintain comfort, achieve relative independence in activities of daily living, and enhance social integration. Attainment of these goals requires a team approach to tailor treatment needs to the severity of the disease and the age of the patient. Nonoperative management is the mainstay of orthopaedic treatment, with the goals of preventing and treating fractures and enhancing locomotion. Operative intervention is indicated for recurrent fractures or deformity that impairs function.

Chromosomes, Human, Pair 17↗

PubMed1997

(G586V) substitutions in the alpha 1 and alpha 2 chains of collagen I: effect of alpha-chain stoichiometry on the phenotype of osteogenesis imperfecta?

Osteogenesis imperfecta (OI) is a congenital disease of connective tissue, most often caused by single amino acid substitutions of glycine residues within the triple helical region of collagen I. Collagen I consists of two alpha 1 chains and one alpha 2 chain. Thus, a substitution in the alpha 1(I) chain is thought to affect the function of the collagen molecule more than would a similar substitution in the alpha 2(I) chain, thereby causing more severe OI. Theoretically this hypothesis may be tested by comparing patients with identical substitutions in different alpha-chains. We present a Gly586Val substitution in the alpha 1(I) chain, and compare our findings to those resulting from Gly586Val substitutions in the alpha 2(I) chain (Forlino et al., 1994; Bateman et al., 1991). Our proband had lethal OI type II. Most alpha-chains of collagen I produced by his cultured fibroblasts were overmodified. The denaturation temperature of the abnormal collagen was 1.5 degrees C below normal. Cyanogen bromide cleavage and subsequent sequencing revealed a G-to-T base substitution at nucleotide 2420 of COL1A1, resulting in a Gly586Val substitution. The collagen findings were almost identical to those reported by Bateman et al. (1991) and Forlino et al. (1994), but the clinical phenotypes were different: the patients with the alpha 2(I) substitutions had OI type IV and III and not the lethal OI type II of our proband. It is known that identical biochemical aberrations in the same chain may have different phenotypic effects, both within families and between non-related patients. This must be taken into account in our cautious proposal that substitutions in the alpha 1(I) chain may have more serious consequences than similar substitutions in the alpha 2(I) chain.

Cells, Cultured↗

PubMedDate not supplied

Impact of alendronate on quality of life in children with osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a debilitating clinical condition characterized by fragile bone and skeletal deformity. Over the past decade frequent reports have suggested that the cyclical administration of intravenous pamidronate has a positive impact on bone density and skeletal fractures; however, the impact of such therapy on the quality of life (QOL) has rarely been reported. Alendronate, an oral bisphosphonate, is widely used to treat osteoporosis. The purpose of this study was to evaluate the impact of daily alendronate on QOL and bone parameters in children with OI. A prospective double-blind crossover study was designed in which placebo was alternated with daily alendronate. Twenty children with types I, III, and IV OI were recruited. Seventeen patients completed the study. Markers of QOL were measured in children with type III and IV OI (n = 15) using total mobility (PEDI), self-care (WeeFIM), well-being, pain, and use of analgesic scores. After 1 year of alendronate therapy, vertebral bone mineral density (BMD) improved from a change in standard deviation score (z-score) of 0.89 +/- 0.19 to -0.12 +/- 0.14 after 1 year of placebo (P < 0.001). All QOL markers, except for mobility score, improved in response to alendronate therapy. Change in height z-score also improved in response to 1 year of alendronate therapy (0.41 +/- 0.21 vs. -0.09 +/- 0.11, P < 0.05). Alendronate therapy did not alter serum levels of calcium, osteocalcin, parathyroid hormone (PTH), 1, 5 (OH)2 vitamin D, cholesterol, or urinary hydroxyproline or any other biochemical marker evaluated. Alendronate decreased by 56% urinary cross-linked N-telopeptide of type 1 collagen divided by urinary creatinine (uNTX/uCr). Daily alendronate therapy was well tolerated. Only two patients had mild gastrointestinal discomfort, responding to minor adjustments in alendronate intake. Daily alendronate therapy is safe and effective in improving QOL in children with OI.

Adolescent↗

PubMed2025

Real-world data of fracture rates and musculoskeletal disorders for patients living with osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a genetic disease characterized by bone fragility and recurrent fractures. Fracture rate has been advocated as an important endpoint for evaluating investigative therapies in OI, but real-world data on fracture burden in the OI population are lacking. This retrospective US claims database study aimed to quantify fracture rate and the occurrence of musculoskeletal disorders among patients with OI of all ages and in a subgroup of patients who were treated with ≥1 off-label therapies. 5722 patients with OI were identified in the IQVIA PharMetrics Plus database and 2095 (55.7% female; 35.1% peds; 20% with OI-related treatments; 87.1% commercial-insured) met eligibility criteria and were included in analyses. About 40% of patients with OI and 37% of those with off-label treatments had a fracture within 1 yr of diagnosis (index date for all OI) or treatment (index date for OI-treated). The annual average fracture rates of these groups were 0.84 and 0.98, respectively. Matched non-OI comparators had 3% fracture occurrence and a 0.03 annual fracture rate. Among patients with ≥1 fracture episode, the annualized median fracture rate was 2 per year for both OI and OI-treated cohorts and 1 for the non-OI cohort. Pediatric patients had the highest fracture occurrence and fracture rate, both among patients with OI and the subgroup of treated OI patients. Musculoskeletal disorders and diagnosed pain were more frequent in OI patients compared with the non-OI cohort, especially among pediatric age groups and adults 18-<45 yr. Pain and musculoskeletal disorders occurred frequently among OI patients, regardless of fracture occurrence, demonstrating impacts of OI beyond those that can be attributed to fractures. Together, these results highlight a high burden of fracture and other musculoskeletal disorders in a commercially insured population of OI patients, which are not effectively managed by current management strategies or off-label treatments.

bone and mineral diseases-other↗

PubMedDate not supplied

Increased cell surface expression of receptors for transforming growth factor-beta on osteoblasts from patients with Osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a heritable connective tissue disorder usually characterized by either a reduction in the production of normal collagen I or the synthesis of abnormal collagen. The variability in the clinical phenotype is not in each case sufficiently explained by the underlying mutation in the collagen I genes. Also, biochemical differences between mutant collagen from different tissues suggest additional regulatory mechanisms possibly involved in matrix deposition and maturation, two processes in which transforming growth factor-beta (TGF-beta) plays an important role. We, therefore, studied the cell surface expression and functional properties of TGF-beta receptors I, II and III on osteoblasts from a group of OI patients compared to healthy controls. Receptor number and affinity were determined by Scatchard analysis of binding data and TGF-beta receptor II gene expression was assessed by RT-PCR. Ligand-induced downregulation of TGF-beta receptors was analyzed to demonstrate the dynamic response to exogenous stimuli. All experiments were performed in parallel in human osteoblastic cells from OI patients and from age-matched controls. TGF-beta receptors I, II and III (betaglycan) were present on osteoblasts from both healthy donors and OI patients. The receptor numbers were significantly higher (29,000 per cell) on OI osteoblasts than on age-matched control osteoblasts (12,000 per cell) in spite of similar steady state levels for TGF-beta receptor II mRNA in OI and control cells. Furthermore, receptor affinity was not significantly different in OI osteoblasts (181 vs. 177 nM(-1)), and the receptor number did not depend on the culture substrate. With respect to dynamic adaption, ligand-induced downregulation of TGF-beta receptors was reduced in OI osteoblasts. In conclusion, the human osteoblastic cells from patients with OI investigated all have an elevated number of cell surface receptors for TGF-beta, without any evidence for a transcriptional regulation of TGF-beta receptor II. On the functional level, there is some evidence for an impaired adaptive behavior of receptor presentation, whereas receptor affinity is unchanged.

Cells, Cultured↗

PubMed2000

Static and dynamic bone histomorphometry in children with osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a genetic disorder characterized by increased bone fragility and low bone mass. Four clinical types are commonly distinguished. Schematically, type I is the mildest phenotype, type II is usually lethal, type III is the most severe form compatible with postnatal survival, and type IV is moderately severe. Although mutations affecting collagen type I are responsible for the disease in most patients, the mechanisms by which the genetic defects cause abnormal bone development have not been well characterized. Therefore, we evaluated quantitative static and dynamic histomorphometric parameters in tetracycline-labeled iliac bone biopsies from 70 children, aged 1.5 to 13.5 years, with OI types I (n = 32), III (n = 11), and IV (n = 27). Results were compared with those of 27 age-matched controls without metabolic bone disease. Biopsy core width, cortical width, and cancellous bone volume were clearly decreased in all OI types. Decreased cancellous bone volume was due to a 41%-57% reduction in trabecular number and a 15%-27% lower trabecular thickness. Regression analyses revealed that trabecular number did not vary with age in either controls or OI patients, indicating that no trabecular loss occurred. The annual increase in trabecular thickness was 5.8 microm in controls and 3.6 microm in type I OI, whereas no trabecular thickening was evident in type III and IV OI. Wall thickness, which reflects the amount of bone formed during a remodeling cycle, was decreased by 14% in a subgroup of 17 type I OI patients, but was not determined in the other OI types. The remodeling balance was less positive in type I OI than in controls, and probably close to zero in types III and IV. Surface-based parameters of bone remodeling were increased in all OI types, indicating increased recruitment of remodeling units. No defect in matrix mineralization was found. In conclusion, there was evidence of defects in all three mechanisms, which normally lead to an increase in bone mass during childhood; that is, modeling of external bone size and shape, production of secondary trabeculae by endochondral ossification, and thickening of secondary trabeculae by remodeling. Thus, OI might be regarded as a disease in which a single genetic defect in the osteoblast interferes with multiple mechanisms that normally ensure adaptation of the skeleton to the increasing mechanical needs during growth.

Adolescent↗

PubMed2026

Inhibition of EED enhances osteogenic differentiation and bone formation: a potential therapeutic strategy for osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a heterogeneous group of inherited connective tissue disorders primarily caused by dominant mutations in COL1A1 or COL1A2 that impair type I procollagen folding and secretion. Misfolded collagen accumulates in the endoplasmic reticulum (ER), triggering ER stress and osteoblast dysfunction, and bone fragility. Current pharmacologic therapy focuses on inhibiting bone resorption but has limited efficacy and does not address the underlying biology of the disease. The epigenetic regulator polycomb-repressive complex 2 (PRC2) has emerged as an important regulator of bone formation. Genetic and pharmacologic disruption of PRC2 enhanced osteogenic differentiation in WT cells. Here, we demonstrate that inhibition of the PRC2 through targeting its essential component embryonic ectoderm development (EED) enhances osteogenic differentiation, improves bone architecture in male Col1a2 +/G610C OI mouse models, modulates the integrated stress response (ISR), and improves ER morphology in OI cells. These findings identify EED inhibition as a novel epigenetic strategy to restore collagen homeostasis and improve skeletal integrity in OI.

ER stress↗

PubMed2003

[Osteoporosis in osteogenesis imperfecta].

Osteogenesis imperfecta (OI) is a kind of genetic osteoporosis, whose clinical severities vary from patients to patients. In type I OI, some patients appear normal without investigating bone mineral density (BMD) by DXA. In severe OI children, pamidronate infusion therapy is effective, however it is still uncertain when to stop the pamidronate therapy without having the problems of bone fracture healing. Also, the appropriate therapy for adult and post-menopoause OI patients remains to be clarified in future.

English Abstract↗

PubMed2005

[Osteogenesis imperfecta--lower limb in osteogenesis imperfecta].

The author of this paper asses lower extremity in 141 children with osteogenesis imperfecta, treated in University Children Hospital in Krakow in years 1988-2002: number of fractures, presence of the deformation, radiological findings, possibility of walking. Only 3 from this group did not suffer from lower extremity long bone fractures. In remaining patients, the number of fractures was 4 on average with type I and IV, and 46 fractures in children with type III osteogenesis imperfecta in each patient. Perinatal fractures appeared in 26 children with type II or III oi. In remaining, first fracture happened at the age of 23 months on average. 21% of the children had never walked before, and the rest of them started pionisation at the age of 20 months on average. Lower extremities deformations appeared in 113 children (80%). We assessed typical deformity pattern, based on clinical and radiological findings: varisation of femur and antecurvation of the tibia. The movement limitations in hips or knees was found in 29 children. Radiological changes in growth cartilage, so-called "popcorn calcification" were found in 15 children with type III of osteogenesis imperfecta.

Female↗

PubMed1996

Immunoreactivity of tenascin-C in dentin matrix in dentinogenesis imperfecta associated with osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a heterogeneous group of heritable connective tissue disorders, assigned to different mutations in type I collagen genes. A variety of structural abnormalities of dentin have been described in dentinogenesis imperfecta (DI) associated with OI. To clarify further the constitution of the dentin matrix in OI, we immunostained frozen and paraffin sections of deciduous teeth from four patients, each from a different family, with two monoclonal antibodies (MAbs) to the matrix glycoprotein tenascin-C (TN-C). One of the MAbs recognizes an epitope common to all TN-C isoforms (BC-4), and the other is specific for a splicing variant (BC-2). Normal teeth, oral mucosa, and skin were analyzed for comparison. Staining patterns with the two MAbs did not differ markedly. Normal dentin matrix and odontoblasts were lacking reactivity, but the pulp stained clearly. TN-C reactivity was present in the dentin matrix of all teeth obtained from two patients with different OI phenotypes and DI, and in one out of three teeth from one patient who also had DI. The reactivity was distributed in layers, but the staining patterns varied from one patient to another and from tooth to tooth. Intratubular staining seen in a tooth from the patient with clinically and histologically normal teeth was comparable with that present in normal deciduous teeth. The variation in TN-C expression suggests that, besides genetic heterogeneity, epigenetic factors could influence the composition of the dentin matrix in OI.

Adolescent↗

PubMed2004

[Osteogenesis imperfecta--upper limb in osteogenesis imperfecta].

The authors of this paper discuss upper extremity in children with osteogenesis imperfecta: fractures frequency, presence of the deformity, radiological data as well as ability to use the limb. Fractures of the upper extremity and shoulder ring occurred in 93 (66%) among 141 children with oi that were treated in the ward in years 1988-2002. Most of the fractures occurred in children with type III oi in Sillence classification, this was a group were deformities appeared most frequently. Generally, deformities were found in 33% of the children with oi. Typical arm deformity was posterior bending, in forearm dorsal bending. Varus elbow occurred often (11%). We found in the x-rays capitis radius dislocation (3.5%), interosseus membrane ossification (2.1%), pseudoarthrosis of the forearm bones (2.1%). The causes of the deformities and opportunities to prevent them were discussed.

Arm Injuries↗

PubMed1979

[Osteogenesis imperfecta cystica (Fairbank)--a special form of osteogenesis imperfecta congenita (Vrolik) (author's transl)].

Two patients, aged 13 and 19 years, with osteogenesis imperfecta congenita (Vrolik) have been seen at the rehabilitation centre at Neckargemund. The younger patient showed the typical appearances of osteogenesis imperfecta cystica (Fairbank), while the older patient failed to show these changes in the skeleton. Contrary to the frequently expressed view that patients with osteogenesis imperfecta congenita always die in the perinatal period, they may survive for a considerable length of time. The change of osteogenesis imperfecta congenita (Vrolik) into osteogensis imperfecta cystica (Fairbank) has been described as a sequence in the occasional survivors by Spranger, but is not a necessary condition for survival. Osteogenesis imperfecta cystica should be regarded as an extremely rare special type of Vrolik's disease.

Adolescent↗

PubMed1992

Unusual dentinal changes in dentinogenesis imperfecta associated with osteogenesis imperfecta. A case report.

A case is described of a boy with dentinogenesis imperfecta associated with osteogenesis imperfecta. The dentin of extracted deciduous teeth was found to show an abrupt transition to a normal tubular structure before a reversion to the more typical structure seen in dentinogenesis imperfecta. This change in the dentin appeared to have occurred in a chronologic manner. The possibilities that either a metabolic disturbance or a temporary reduced expression of the mutant gene had caused the abnormality and could account for the unusual histologic findings are discussed.

Child↗

PubMed2003

Dentinogenesis imperfecta associated with osteogenesis imperfecta: report of two cases.

Osteogenesis imperfecta (OI) is a heritable systemic disorder of the connective tissue. Dentinogenesis imperfecta (DI), which is sometimes an accompanying symptom of OI, belongs to a group of genetically conditioned dentin dysplasias and is characterized clinically by an opalescent amber appearance of the dentin. Although the teeth of DI cases wear more easily and excessively compared to normal teeth, they do not appear to be more susceptible to dental caries than normal teeth. Two cases of DI associated with OI are presented in this paper, with 1 case suffering from nursing bottle caries. The purposes of this paper are to present the dental and skeletal characteristics of moderately and mildly involved DI associated with OI, and to discuss the possible methods of dental treatment. Patients with OI and opalescent teeth should be evaluated as soon as the deciduous teeth erupt; immediate dental involvement and oral hygiene instruction can be of help in reducing the necessity of extensive dental care.

Child↗

PubMed2005

[Role of the bone mineral density investigation through measuring of peripheral dual-energetic x-ray absorption in prevention of fractures in children with osteogenesis imperfecta].

The Osteogenesis imperfecta is hereditary disturbance of collagen biosynthesis. Illness is characterized by frequent fractures that consequently cause functional disturbance of locomotor system as well as deformation of long tubular bones. The distinguishing feature of this illness is the secondary osteoporosis. The latter in its turn worsens clinical course and the outcome of the illness. The purpose of the present work was the study of bone mineral density in children with osteogenesis imperfecta through application of dual energetic x-ray absorption measurements. In total 32 patients 1-15 years of age with osteogenesis imperfecta have been investigated. The patients have been divided into three age groups. Measurement of distal and proximal sections of radius and elbow (ulna) bones was carried out using peripheral dual-energetic x-ray absorption measurements in order to determine the bone mineral density. Results of the bone mineral density (BMD) measurements have proved that children with osteogenesis imperfecta have lower indices in comparison with children of the corresponding age group and has been registered as 3,76 times lower for 1-7 years old children; 2,3 times lower for 7-12 years old children and 1,89 times lower for children 13-15 years of age. Having studied the correlation between downgraded bone mineral density and number of fracture cases, it was registered that the lower is BMD of cortical layer, the higher is the number of fracture cases. Investigating the bone mineral density in children with osteogenesis imperfecta provides opportunity to reveal potential high risk patients with predisposition to the development of fractures and to provide corresponding treatment and preventive measures in these patients.

Absorptiometry, Photon↗