Mutations in COL1A1 and COL1A2 and dental aberrations in children and adolescents with osteogenesis imperfecta - A retrospective cohort study.

Osteogenesis imperfecta (OI) is a heterogeneous group of disorders of connective tissue, caused mainly by mutations in the collagen I genes (COL1A1 and COL1A2). Dentinogenesis imperfecta (DGI) and other dental aberrations are common features of OI. We investigated the association between collagen I mutations and DGI, taurodontism, and retention of permanent second molars in a retrospective cohort of 152 unrelated children and adolescents with OI. The clinical examination included radiographic evaluations. Teeth from 81 individuals were available for histopathological evaluation. COL1A1/2 mutations were found in 104 individuals by nucleotide sequencing. DGI was diagnosed clinically and radiographically in 29% of the individuals (44/152) and through isolated histological findings in another 19% (29/152). In the individuals with a COL1A1 mutation, 70% (7/10) of those with a glycine substitution located C-terminal of p.Gly305 exhibited DGI in both dentitions while no individual (0/7) with a mutation N-terminal of this point exhibited DGI in either dentition (p = 0.01). In the individuals with a COL1A2 mutation, 80% (8/10) of those with a glycine substitution located C terminal of p.Gly211 exhibited DGI in both dentitions while no individual (0/5) with a mutation N-terminal of this point (p = 0.007) exhibited DGI in either dentition. DGI was restricted to the deciduous dentition in 20 individuals. Seventeen had missense mutations where glycine to serine was the most prevalent substitution (53%). Taurodontism occurred in 18% and retention of permanent second molars in 31% of the adolescents. Dental aberrations are strongly associated with qualitatively changed collagen I. The varying expressivity of DGI is related to the location of the collagen I mutation. Genotype information may be helpful in identifying individuals with OI who have an increased risk of dental aberrations.

No osteonecrosis in jaws of young patients with osteogenesis imperfecta treated with bisphosphonates.

BACKGROUND: Recent reports of osteonecrosis of the jaw (ONJ) after dental surgery in patients treated with second- and third-generation nitrogen-containing bisphosphonates instigated this retrospective study. As treatment with bisphosphonates in patients with osteogenesis imperfecta (OI) has become an important symptomatic therapy, especially for severe forms of the disease, we found it important to investigate whether healing after surgical exposure of jaw bone was influenced by the bisphosponate treatment in our group of children, adolescents and young adults with OI. SUBJECTS AND METHODS: Disodiumpamidronate was given as monthly intravenous infusion to 64 patients with OI aged 3 months to 20.9 years at the start of treatment (mean 8.1, median 7.7). During 0.5-12.5 years of treatment (mean 4.5, median 4.0), a total individual dose of 140-4020 mg/m(2) disodiumpamidronate was given (mean 1623 and median 1460). Ten patients continued with oral alendronate and two with zoledronic acid therapy. In 22 of these patients, 38 dental surgery procedures were performed at the age of 3.4-31.9 years (mean 12.2, median 12.3) after 0.03-7.9 years of treatment (mean 3.6, median 3.4). RESULTS: Despite long-term intravenous monthly disodiumpamidronate treatment, none of the 64 patients had any clinical signs of ONJ. CONCLUSIONS: The risk of ONJ in these patients must be considered so low that the patients with indications for treatment should be treated and get the chance to experience the well-documented beneficial effect for children with severe OI.

Assessment of dysplastic dentin in osteogenesis imperfecta and dentinogenesis imperfecta.

Two semiquantitative scoring systems, Clinical Radiographic Score (CRS) and Dysplastic Dentin Score (DDS), were introduced for analyzing degree of dysplastic manifestations in dentin. The utility of both systems was demonstrated in a large material of teeth from patients with dentinogenesis imperfecta (DI) and osteogenesis imperfecta (OI). Twenty teeth from healthy controls, 81 teeth from 40 patients with OI, and 18 teeth with DI without OI (DI type II) were examined. The degree of dysplasia was correlated with type and form of OI and type of DI. The median DDS did not differ between DI associated with OI (DI type I) and DI type II. DDS in OI patients without clinical signs of DI was above that of control teeth. Both circumpulpal and mantle dentin showed increased DDS, although circumpulpal dentin was more severely affected. The median DDS was highest for the most severe type of non-lethal OI (type III). DDS increased significantly with form (severity) of OI. A significant association between DDS and CRS was found, although diagnosis of DI in less severe cases was not possible based on radiographic or clinical signs alone. Thus, the DDS system proved valuable when the CRS system based on radiographic/clinical manifestations failed, the most significant finding being subclinical histological manifestations of DI in patients with OI but without clinical or radiographic signs of DI. These subtle dysplastic changes are most likely an expression of genetic disturbances associated with OI and should not be diagnosed as DI, but rather be termed histologic manifestations of dysplastic dentin associated with OI.

Dental aberrations in children and adolescents with osteogenesis imperfecta.

The aim of this investigation was to study dental aberrations in a large sample of unrelated patients with different types and forms of osteogenesis imperfecta (OI). Sixty-eight non-related index patients aged 0.3 to 20 years (mean, 10 years) were examined clinically. Panoramic radiographs from 49 patients were analyzed. Dentinogenesis imperfecta (DI) type I was found in 27 of 65 patients and was significantly more common in OI type III than in types I and IV and in patients with a severe form of the disease. The presence or absence of DI showed almost complete accordance between affected parents and children and between affected siblings. Moreover, agenesis was found in 11 of 49 patients, apically extended pulp chambers in 20 of 48 patients, and impaction of second permanent molars in 7 of 19 patients older than 15 years. The percentage of patients with no apparent dental aberrations was approximately the same in patients with OI type I and type III and in patients with mild and severe form of the disease. The high prevalence of dental aberrations in OI stresses the importance of clinical and radiographic odontologic examination as part of the clinical investigation. In patients with mild forms of the disease, in whom the medical diagnosis is uncertain, demonstration of disturbances in dental development can be crucial for establishing the OI diagnosis. C