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At least 19 recordsLinked to original sources
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 &#x2265;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&#xa0;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 &#x2265;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&#xa0;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↗
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↗
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↗
PubMed2026

A Novel Splice Variant in the COL1A1 Gene Leads to Exon 46 Skipping and Osteogenesis Imperfecta.

BACKGROUND: Osteogenesis imperfecta (OI) is a clinical and genetic disorder characterised by bone fragility, growth deficiency and skeletal deformity. Ninety per cent of OI cases are attributable to autosomal dominant variants in the COL1A1 and COL1A2 genes. METHODS: Candidate variants were identified and verified through trio whole-exome sequencing (trio-WES), copy number variation sequencing (CNV-seq) and Sanger sequencing. Minigene splicing assays were performed in HeLa and HEK293T cells with pcDNA3.1 and pcMINI-C vectors to investigate the function of the candidate variants. A systematic review of COL1A1 splicing variants and the corresponding genotype-phenotype spectrum was performed. RESULTS: Trio-WES revealed a novel heterozygous variant in the C-terminal region of the COL1A1 gene: NM_000088.4:c.3423+5G>A. Sanger sequencing confirmed the variant in both the proband (II-2) and her foetus (III-1) who were clinically suspected of having OI. The c.3423+5G>A variant causes complete skipping of Exon 46, as demonstrated by a minigene splicing assay. We retrieved 419 COL1A1 splicing variants from PubMed, excluded 15 without phenotypic data and 2 linked to Ehlers-Danlos syndrome and stratified the remaining 402 variants into three types on the basis of splice site location: (1) Variants at canonical splicing sites (77.8%, 313/402) mostly cause mild phenotypes, whereas a minority may be severe. (2) Intron variants in other locations, such as splice region variants (17.9%, 72/402), usually cause mild clinical phenotypes, and deep intronic splice variants (0.4%, 2/402) that may result in severe phenotypes. (3) Other variants (3.7%, 15/402), such as exon variants or fragment loss, are extremely rare. We also preliminarily discuss the mechanisms underlying phenotypic variability and the characteristics of C-terminal variants. CONCLUSIONS: This intron variant in COL1A1 was classified as likely pathogenic and was confirmed to disrupt COL1A1 expression. The summary analysis results also revealed a correlation among splicing variants, C-terminal region variants and disease, suggesting that variant location provides a useful framework for prognosis prediction.

Female↗
PubMed1975

Management of pregnancy in osteogenesis imperfecta: new perspectives.

Osteogenesis imperfecta during pregnancy presents increased risk to mother and fetus. In addition to the well-known skeletal changes, other recently recognized metabolic abnormalities also may lead to maternal and fetal problems during labor and delivery. A discussion of risk factors and their managment is presented. The importance of considering the possibility of fetal osteogenesis imperfecta is stressed, and cesarean section is presented as the method of choice for delivery. Important genetic factors including the lack of correlation between the severity of involvement of parent and offspring and the use of pyrophosphate analyses are discussed. An illustrative case is presented.

Adult↗
PubMed1979

In vitro sulfate turnover in osteogenesis imperfecta congenita and tarda.

Sulfate (35SO4(-2)) uptake was studied in confluent skin fibroblasts from three patients with osteogenesis imperfecta "congenita," six patients with osteogenesis imperfecta "tarda," three clinically unaffected relatives of an osteogenesis imperfecta tarda patient, and four controls. Only two of the osteogenesis imperfecta congenita cell strains showed an increased uptake of sulfate, all other cell strains being comparable to the control group. The degradation rate of glycosaminolgycans in mutants as seen by the chase experimentas was comparable to that found in the normal control cell strains. Glucose oxidation was normal in the osteogenesis imperfecta cell strains having an abnormal sulfate uptake. This rules out the possibility of an hypermetabolic state of these cells. These findings do not warrant the use of 35SO4(-2) incorporation in cultured cells as a tool for prenatal diagnosis of osteogenesis imperfecta.

Cells, Cultured↗
PubMed1979

Surgical findings and results of stapedectomy in patients with osteogenesis imperfecta.

Nine patients with osteogenesis imperfecta tarda and stapedial fixation (12 ears) are presented. Surgical findings as well as the immediate and long-term results of stapedectomy are described and compared with the results of previous authors. We found firmly fixed footplates in all 12 ears. Only 2 ears had thick and soft footplates. In 10 ears the stapes crura were abnormally slender and brittle, but only 1 had fractured. In 4 ears a troublesome bleeding tendency occurred during the operation. Both the immediate and the long-term hearing results were in general satisfactory.

Adult↗
PubMed1979

Osteogenesis imperfecta. A study of 160 family members.

Osteogenesis imperfecta, a genetic disease characterized by blue sclera, fragile bones, and hearing loss, was studied in 160 descendants of a single, affected individual. One hundred twenty family members in four generations were at risk of inheriting the gene for osteogenesis imperfecta. Fifty-six percent (68/120) had blue sclera, and, of this group, 66% had fragile bones, and 47% of those tested had hearing loss. The onset of hearing loss was usually in the second or third decade, and was primarily of the conductive type. The incidence of sensorineural hearing loss was only slightly less than the incidence of conductive hearing loss. To out knowledge, this is the largest reported kindred study of osteogenesis imperfecta. The genetic transmission of this disease as an autosomal dominant was confirmed.

Adolescent↗
PubMed1979

Bone mineral content in osteogenesis imperfecta tarda and in otosclerosis.

In 22 patients with osteogenesis imperfecta and in 63 patients with otosclerosis the bone mineral content in peripheral bones was determined by photon absorptiometry. The bone mineral content proved significantly reduced in patients with osteogenesis imperfecta as compared with normals and with patients with otosclerosis. In the latter patients the bone mineral content was normal. These findings support the assumption that stapedial fixation in otosclerosis and in osteogenesis imperfecta is of different aetiology.

Adolescent↗
PubMedDate not supplied

Operative treatment of spine deformity in osteogenesis imperfecta.

There has been little mention in the literature of scoliosis associated with osteogenesis imperfecta. The purpose of this study was to investigate the problem of spine deformity in a series of osteogenesis imperfecta patients and to review the operative treatment of 8 patients. A series of 49 patients (ranging in age from 8 months to 57 years, average 12 years) with osteogenesis imperfecta were studied. Thirty-five (71%) of these patients had scoliosis ranging from 7 degrees to 105 degrees (average 42 degrees). The more severely involved patients (OIC and OITI groups) demenostrated a higher incidence (80%) of scoliosis and a greater average degree of curvature (42 degrees) as compared to the mildly involved (OITII) group with a 50% incidence of scoliosis with an average curvature of 26 degrees. Attempts to control these curves by bracing have been difficult and usually had to be abandoned. Eight of these patients underwent spine stabilization in an attempt to control curve progression. All 8 patients had posterior spine fusions. One of these patients had an anterior fusion preceding the posterior fusion because of a significant kyphotic deformity. Harrington instrumentation was used in 5 patients. One patient could not be instrumented secondary to severe osteoporosis while the remaining 2 patients were treated by the Risser technique. Postoperatively, either cast or brace protection was used. Only minimal improvement in the curves was achieved. Spine stabilization rather than curve correction is the goal of spine fusion in osteogenesis imperfecta. An important finding was that there was no change in the pre- and postoperative activity and ambulatory status in these patients. Preliminary follow-up (9-12 months) in all 8

Adolescent↗
PubMed1979

Metaphyseal fractures in osteogenesis imperfecta.

Forty-one children with osteogenesis imperfecta have been reviewed. A minority (7/41) showed small metaphyseal fractures, resembling those seen in non-accidental injury, but in all of these there was obvious generalized bone disease so that confusion with non-accidental injury did not occur.

Battered Child Syndrome↗
PubMed1979

[Expanding intramedullary rods in the treatment of osteogenesis imperfecta (author's transl)].

Eleven cases of osteogenesis imperfecta were treated by corrective osteotomies and fixation with expanding intramedullary rods. The authors have used the Bailey-Dubow nail. Despite a short follow-up (average one year) they think that the device will avoid future repeated changes of rods during the growing period. Several technical pitfalls are described. It is thought that the same technique could be applied to congenital pseudarthrosis of the tibia.

Bone Nails↗
PubMed1979

Genetic heterogeneity in osteogenesis imperfecta.

An epidemiological and genetical study of osteogenesis imperfecta (OI) in Victoria, Australia confirmed that there are at least four distinct syndromes at present called OI. The largest group of patients showed autosomal dominant inheritance of osteoporosis leading to fractures and distinctly blue sclerae. A large proportion of adults had presenile deafness or a family history of presenile conductive hearing loss. A second group, who comprised the majority of newborns with neonatal fractures, all died before or soon after birth. These had characteristic broad, crumpled femora and beaded ribs in skeletal x-rays. Autosomal recessive inheritance was likely for some, if not all, of these cases. A third group, two thirds of whom had fractures at birth, showed severe progressive deformity of limbs and spine. The density of scleral blueness appeared less than that seen in the first group of patients and approximated that seen in normal children and adults. Moreover, the blueness appeared to decrease with age. All patients in this group were sporadic cases. The mode of inheritance was not resolved by the study, but it is likely that the group is heterogeneous with both dominant and recessive genotypes responsible for the syndrome. The fourth group of patients showed dominant inheritance of osteoporosis leading to fractures, with variable deformity of long bones, but normal sclerae.

Adolescent↗
PubMed1977

Valvular heart disease in osteogenesis imperfecta.

Aortic and mitral valve abnormalities have been reported which clearly appear to be related to the underlying connective tissue disorder in two patients, a father and daughter, with osteogenesis imperfecta. Although this appears to occur with a much lower prevalence and lesser severity than in the Marfan syndrome, the true prevalence of cardiac connective tissue involvement is not known, and the orthopedic complications of osteogenesis imperfecta may have overshadowed attention to cardiovascular abnormalities. In evaluating patients with osteogenesis imperfecta, careful attention should be paid to cardiovascular findings and if valvular lesions are noted, patients should be instructed regarding the need for antibiotic prophylaxis for dental and surgical procedures. The valvular lesions can progress, and regular follow-up cardiovascular evaluation should be planned. Finally, despite potential problems with tissue friability and healing and a possible tendency for increased bleeding, successful valve replacement can be carried out if necessitated by cardiac disability.

Adult↗
PubMedDate not supplied

Spondylolisthesis resulting from osteogenesis imperfecta: report of a case.

Spondylolisthesis resulting from osteogenesis imperfecta has been very rarely documented in the literature. The possibility that osteofragility of the isthmus of the fifth lumbar vertabral can cause spondylolisthesis is noteworthy in the case of a 40-year-old man with trias fragilitas ossium hereditaria.

Adult↗
PubMed1979

[Treatment of osteogenesis imperfecta with (+)-catechin (author's transl)].

4 girls aged 4--12 years with various forms of osteogenesis imperfecta were treated with (+)-catechin for several months. Bone punch biopsies from the iliac crest were investigated by electron microscopy before and during treatment. The frequency of fractures decreased clinically. There were no radiographic changes in the bones and there were no side effects. Electron microsopy showed a dilated coarse endoplasmatic reticulum with infrequent ribosomes, thin collagen fibrils and decreased predominantly disseminated mineralisation before treatment. Under the influence of treatment electron microscopical aspects of the bone improved. The cisternae of the endoplasmatic reticulum were arranged parallel with densely packed ribosomes, collagen fibrils were wider and in closely packed bundles and mineralisation was clearly improved. The electron microscopic findings are evidence for a possibly beneficial influence of (+)-catechin in some cases of osteogenesis imperfecta.

Benzopyrans↗
PubMed1977

[Pathophysiology and metabolism in osteogenesis imperfecta (author's transl)].

The tissue changes in osteogenesis imperfecta apparently lie in the collagen and in the glycosaminoglycans. The collagen shows structural development disturbance and incomplete calcification. The tissue glycosaminoglycans are increased. The basis probably lies in a disturbed ATP metabolism (Solomons and Millar, 1973). An increased pyrophosphate concentration explains the decreased calcification and the structural changes. The increased osteolysis could be explained by increased quantities of cAMP.

Bone Resorption↗