Altered oral microbiome, but normal human papilloma virus prevalence in cartilage-hair hypoplasia patients.

BACKGROUND: Cartilage-hair hypoplasia (CHH) is a rare syndromic immunodeficiency with metaphyseal chondrodysplasia and increased risk of malignancy. In this cross-sectional observational study, we examined HPV status and oral microbiome in individuals with CHH. Oral brush samples were collected from 20 individuals with CHH (aged 5-59 years) and 41 controls (1-69 years). Alpha HPVs (43 types) were tested by nested PCR followed by bead-based probe hybridization. Separately, beta-, gamma-, mu- and nu- HPV types were investigated, and a genome-based bacterial microbiome sequencing was performed. RESULTS: We found a similar alpha HPV prevalence in individuals with CHH (45%) and controls (36%). The HPV types of individuals with CHH were HPV-16 (25%), 27, 28, and 78, and of controls HPV-3, 16 (21%), 27, and 61. Beta HPV positivity and combined beta/gamma/mu/nu prevalence was detected in 11% and 11% of individuals with CHH and in 5% and 3% of the controls, respectively. Individuals with CHH differed from the controls in bacterial microbiota diversity, richness, and in microbial composition. Individuals with CHH had lower abundance of species Mitsuokella sp000469545, Parascardovia denticolens, Propionibacterium acidifaciens, UMGS1907 sp004151455, Salinicola halophilus, Haemophilus_A paraphrohaemolyticus, Fusobacterium massiliense, and Veillonella parvula, and higher abundance of Slackia exigua. CONCLUSIONS: Individuals with CHH exhibit similar prevalence of HPV DNA but different bacterial microbiota on their oral mucosa compared to healthy controls. This may partly explain the previously observed high prevalence of oral diseases in CHH, and regular oral examination is warranted.

Oral findings in patients with cartilage-hair hypoplasia - cross-sectional observational study.

BACKGROUND AND OBJECTIVES: Cartilage-hair hypoplasia (CHH) is a rare chondrodysplasia with associated primary immunodeficiency. The aim of this cross-sectional study was to examine oral health indicators in individuals with CHH. METHODS: In total, 23 individuals with CHH, aged between 4.5 and 70 years, and 46 controls aged between 5 and 76 years were clinically examined for periodontal disease, presence of oral mucosal lesions, tooth decay, masticatory system function, and malocclusions. A chairside lateral flow immunoassay test of active-matrix metalloproteinase was obtained from all the adult participants with a permanent dentition. Laboratory signs of immunodeficiency were recorded for individuals with CHH. RESULTS: Individuals with CHH and controls had similar prevalence of gingival bleeding on probing (median 6% vs. 4%). Oral fluid active-matrix metalloproteinase concentration was greater than 20 ng/ml in 45% of study subjects in both groups. However, deep periodontal pockets, 4 mm or deeper, were more common in individuals with CHH as compared to the controls (U = 282.5, p = 0.002). Similarly mucosal lesions were significantly more common in individuals with CHH (30% vs. 9%, OR = 0.223, 95%CI 0.057-0.867). The median sum of the number of decayed, missing due to caries, and filled teeth was nine for the individuals with CHH and four for controls. In the CHH cohort, 70% displayed an ideal sagittal occlusal relationship. Malocclusion and temporomandibular joint dysfunction prevalence were similar in both study groups. CONCLUSIONS: Individuals with CHH have more frequently deep periodontal pockets and oral mucosal lesions than general population controls. Routine intraoral examination by a dentist at regular intervals should be recommended to all individuals with CHH.

Examination performance of dentistry students during the COVID-19 pandemic.

CONCLUSIONS: Our results imply that online teaching did not systematically improve or worsen the examination performance of undergraduate students of dentistry. Our findings have important policy implications for educational practices in the future. The observed annual grade variation might reflect the effectiveness of remote teaching, changes in students' performance, or non-systematic grading. MATERIALS AND METHODS: Using administrative data from the University of Helsinki, the examination performance during the years 2018 and 2019 was compared with that of 2020. OBJECTIVE: The global COVID-19 pandemic has led to an increase in remote teaching and online assessment in higher education. The examination performance of undergraduate students of dentistry was evaluated to assess any possible association between the altered learning environment and learners' performance. RESULTS: In 16 out of 22 courses (73%) taught remotely during the pandemic, a statistically significant difference (p < .05) between the awarded grades was observed, as compared to the two previous years. Annual variation in examination grades was common even before the onset of remote teaching, but more so after it. The grade variation during the pandemic was nearly as prevalent towards falling grades (26%) as towards rising grades (36%), implying a multifactorial cause possibly unrelated to remote teaching.

Early orthodontic treatment in a Finnish public health centre: a retrospective cross-sectional study.

OBJECTIVES: The aim of this observational cross-sectional one-centre study was to assess whether the previously described national orthodontic treatment practises and international recommendations are implemented in a public health care centre in Finland. We also assessed early treatment practices and appliances used. METHODS: The study group comprised 801 children born in 2011 and 2012 residing in the Riihimäki health centre catchment area in Finland, representing 80% of the age cohort. The patient records were examined for data on orthodontic treatment, timing of treatment, appliances used, and occlusal traits. RESULTS: The children had been examined by four orthodontist specialists and two orthodontic postgraduate students. Mean age at occlusal examination had been 9 years. Of the children, 212 (26%) were undergoing or had undergone orthodontic treatment. An additional 4.4% were scheduled for treatment. The proportion of children deemed to need treatment was significantly different between the different orthodontists. The most frequently used appliances were quad-helix (30%), eruption guidance appliance (20%), head gear (14%), fixed appliances (10%), protraction facemask (10%), and passive mandibular lingual arch (6%). CONCLUSIONS: Nearly one-third of children aged less than 12 years in the health centre were currently or had been in orthodontic treatment. Approximately half had received treatment with either quad-helix or eruption guidance appliance.

Effects of a 2-Year Early Childhood Vitamin D3 Intervention on Tooth Enamel and Oral Health at Age 6-7 Years.

INTRODUCTION: The aim of the study was to compare the effects of a 30 µg/day versus 10 µg/day vitamin D supplementation, given during the two first years of life, on oral health at the age of six to 7 years. METHODS: In 2013-2016, we conducted a randomized, double-blinded, clinical trial from age 2 weeks to 2 years of daily vitamin D3 supplementation (10 vs. 30 µg), including 975 healthy infants. For the present follow-up study at age 6-7 years, a sample of 123 children underwent oral examination by investigators blinded to the intervention group. Tooth enamel defect and caries findings, oral rinse active matrix metalloproteinase-8 levels, and tooth eruption were recorded. The intervention groups were compared with χ2 and Mann-Whitney U tests. Associations of the oral health outcomes were evaluated with correlation analysis and logistic regression. RESULTS: Of the children (median age 7.4 years, 51% boys), 56% belonged to the 30 µg intervention group. Developmental defect of enamel (DDE) was found in 39% of the children in the 10 µg intervention group and in 53% of the 30 µg group (p = 0.104). In total, 94% of children were vitamin D sufficient (25[OH]D ≥50 nmol/L) and 88% had caries-free teeth. No associations were found between vitamin D intervention group in infancy and oral health or the presence of DDE. CONCLUSION: Daily supplementation with 10 µg vitamin D3 in the Northern Hemisphere seems adequate in healthy children younger than 2 years in ensuring good oral health at early school age.

Longitudinal analysis of the quality of orthodontic treatment outcome and stability of occlusal traits.

OBJECTIVES: To assess the quality and stability of orthodontic treatment outcome relative to the initial malocclusion. MATERIAL AND METHODS: The study was performed in one public health care clinic in Finland. Study subjects comprised 51 orthodontic patients (age range 12.7-18.7 years). Pre-treatment medical records and lateral skull radiographs were analysed for malocclusion type. The main reasons for orthodontic treatment were mandibular retrognathia, Class II distal bite, deep bite and crowding. At the end of a retention phase (Examination 1), the quality of treatment outcome was assessed using the occlusal morphology and function index (OMFI) and patients were asked about treatment satisfaction. Stability of occlusal traits and patient satisfaction were re-evaluated after a two-year follow-up (Examination 2). Occlusal characteristics descriptive statistics were performed. RESULTS: At Examination 1, all six morphological criteria for acceptability were fulfilled by 76% and all functional criteria by 82% of the patients. All OMFI criteria were met by 67% of the patients. At Examination 2, 68% of the patients fulfilled all morphological and 82% all functional criteria of acceptability. At Examination 2, all the OMFI criteria were still met by 64% of the patients and 92% expressed satisfaction with own occlusion. The main reasons for unacceptability were deficiencies in canine relationship and overbite, in addition to functional protrusion interferences. CONCLUSIONS: In the evaluated health care clinic, patient satisfaction and the quality of treatment outcome were high. However, deep bite showed a tendency for relapse.

Craniofacial and Craniocervical Features in Cartilage-Hair Hypoplasia: A Radiological Study of 17 Patients and 34 Controls.

Background: Biallelic mutations in the non-coding RNA gene RMRP cause Cartilage-hair hypoplasia (CHH), a rare skeletal dysplasia in which the main phenotypic characteristic is severe progressive growth retardation. Objective: This study compared the cranial dimensions of individuals with CHH to healthy subjects. Methods: Lateral skull radiographs of 17 patients with CHH (age range 10 to 59 years) and 34 healthy individuals (age range 10 to 54 years) were analyzed for relative position of the jaws to skull base, craniofacial height and depth, as well as vertical growth pattern of the lower jaw, anterior cranial base angle, and the relationship between the cervical spine and skull base. Results: We found that the length of the upper and lower jaws, and clivus were significantly decreased in patients with CHH as compared to the controls. Anterior cranial base angle was large in patients with CHH. Basilar invagination was not found. Conclusion: This study found no severe craniofacial involvement of patients with CHH, except for the short jaws. Unexpectedly, mandibular deficiency did not lead to skeletal class II malocclusion. Clinical Impact: Although the jaws were shorter in patients with CHH, they were proportional to each other. A short posterior cranial base was not associated with craniocervical junction pathology.

Dental and dentoalveolar dimensions in individuals with osteogenesis imperfecta.

OBJECTIVE: This cross-sectional study compared tooth and dental arch dimensions of individuals with Osteogenesis imperfecta (OI) and healthy controls. MATERIAL AND METHODS: The 37 OI patients and 37 controls were aged 10 to 74 years. Mesio-distal tooth size, dental arch dimensions, and palatal height were measured from dental models. The differences between the patient and control groups were analysed statistically with a t-test, chi-square test, and Mann-Whitney U test. RESULTS: The average mesio-distal tooth size of individuals with OI was smaller by 0.1 to 0.8 mm, corresponding to 1.4 to 7.3% of the size of the tooth. The patients and controls showed similar anterior-posterior lengths of maxillary and mandibular arches. The OI patient group exhibited increasingly wider maxillary dental arches posterior to the canines and a shallow palate. CONCLUSIONS: Reduced tooth size is a developmental feature of OI and a shallow palate a characteristic possibly associated with previously documented imparity of vertical jaw development. Observed posterior widening of the dental arches may follow from altered tongue position. Smaller tooth size can be favourable from orthodontic point of view in alleviating crowding, but it might further predispose to fracturing of teeth which is a considerable risk associated with dentine abnormality. The shallow jawbones may initiate development of posterior open bite, rare in general population but relatively often encountered in OI.

Positive airway pressure therapy for obstructive sleep apnea in patients with Osteogenesis imperfecta: a prospective pilot study.

BACKGROUND: Obstructive sleep apnea (OSA) is prevalent in individuals with Osteogenesis imperfecta (OI). To date, no study has investigated treatment of OSA in adult individuals with OI using positive airway pressure (PAP). This observational pilot study examined the adherence of adults with OI to treatment of OSA with PAP therapy, and the evolution of self-experienced sleepiness and depression symptoms before and after treatment. METHODS: We included 20 patients, with a mean age of 51 years, who represented varying severity of OI and displayed an apnea and hypopnea index ≥ 5 /sleeping hour as recorded by an overnight polysomnography. PAP therapy was proposed to all patients. Epworth Sleepiness Scale (ESS) questionnaire to evaluate daytime sleepiness, and a validated self-rating depression questionnaire to identify possible depression, were completed prior to PAP therapy and repeated after a minimum of one year. The datasets supporting the conclusions of this article are included within the article. RESULTS: From the 20 patients, 15 initiated PAP therapy, and two patients later interrupted it. The mean PAP follow-up period was 1230 days. At baseline, an abnormally high ESS score was reported by 29% of the respondents, and an abnormally high number of symptoms suggesting depression by 29%. Follow-up questionnaires were completed by 60% of the patients, of whom 83% were adherent to PAP treatment. ESS score and depression symptoms did not decrease significantly with PAP therapy. CONCLUSIONS: Patients with OI accepted well PAP therapy and remained compliant. Sleepiness and depression persisted unaltered despite good PAP adherence. These unexpectedly poor improvements in symptoms by PAP therapy may be due to subjective depression symptoms and the complexity of factors underlying persisting sleepiness in OI. Further research is needed to confirm this novel finding.

Treatment compliance of adolescent orthodontic patients with headgear activator and twin-block appliance assessed prospectively using microelectronic wear-time documentation.

BACKGROUND: Success of orthodontic removable appliance treatment relies on patient compliance. The aim of this quantitative and qualitative study was to explore the compliance and self-reported experience of adolescents in orthodontic treatment with headgear activator (HGA) or twin-block (TB) appliance. MATERIALS/METHODS: The study group comprised 52 adolescents with a mean age of 12.6 (±1.3) years at the start of the treatment. The patients were treated at a free-of-charge public dental clinic. Participants were randomly allocated to two equal groups to be treated with either HGA or TB. Patient compliance was evaluated as appliance wear time and subjective experience. Appliance wear time was recorded with Theramon® microchip, and the self-reported subjective experience using a questionnaire. RESULTS: In total, 30 patients completed the treatment during the follow-up period. HGA was worn on average 7 hours per day and TB 9 hours per day by those patients, who successfully completed the treatment. During a mean observation period of 13 months (range 7-23 months), the mean actual wear time was 43 per cent less than the advised 12 or 18 hours per day in the whole patient group, and 55 per cent in those patients, who completed the treatment. Compliance level was unrelated to the appliance type. LIMITATIONS: Study assessed a relatively small number of patients. CONCLUSIONS/IMPLICATIONS: Adolescent patients wear HGA and TB less than advised. Individual variation in treatment adherence is considerable. Thereby, microelectronic wear-time documentation can be a cost-effective mean of identifying non-compliance.

Is sleep apnea underdiagnosed in adult patients with osteogenesis imperfecta? -a single-center cross-sectional study.

BACKGROUND: Patients with Osteogenesis imperfecta (OI) suffer from increased bone fracture tendency generally caused by a mutation in genes coding for type I collagen. OI is also characterized by numerous co-morbidities, and recent data from questionnaire studies suggest that these may include increased risk for sleep apnea, a finding that lacks clinical evidence from cohort studies. In this cross-sectional study, 25 adults with OI underwent clinical otorhinolaryngology examination as well as overnight polysomnography to address the question. The participants were aged between 19 and 77 years, and ten of them had mild clinical OI phenotype, seven had a moderately severe phenotype, and eight had a severe phenotype. RESULTS: We found obstructive sleep apnea (apnea hypopnea index ≥5/h) in as many as 52% of the OI patients in the cohort. Unexpectedly, however, no correlation was present between sleep apnea and daytime sleepiness, experienced bodily pain, severity of OI, Mallampati score, or neck circumference. CONCLUSIONS: Seeing that the usual predictors showed no association with occurrence of sleep apnea, we conclude that obstructive sleep apnea may easily be left as an undetected disorder in individuals with OI. Recurrent nocturnal hypoxia due to episodes of apneas can even affect bone metabolism, thereby further aggravating bone fragility in patients with OI.

Fatigue and disturbances of sleep in patients with osteogenesis imperfecta - a cross-sectional questionnaire study.

BACKGROUND: Persisting fatigue has been reported to be a common complaint by individuals with connective tissue disorders, including Osteogenesis imperfecta (OI). This controlled study evaluated in an adult OI population the subjective experience of fatigue, affecting daily life. Sleep disturbances and chronic pain were examined as hypothesized underlying factors. METHODS: This cross-sectional study analyzed the answers of 56 OI patients and 56 matched healthy controls to a questionnaire, designed to evaluate levels of experienced fatigue and bodily pain, as well as the presence or absence of symptoms related to sleep disturbances or sleep apnea. The relationships between fatigue, pain, and sleep disturbances were evaluated with correlation analysis and regression analysis. RESULTS: Fatigue was reported by 96%, and daily pain by 87% of the individuals with OI. Notably, the level of fatigue was similarly experienced by patient respondents and controls. In total, 95% of the patients and 77% of the controls reported one to several sleep disturbance symptoms. These symptoms as well as previously diagnosed sleep apnea were statistically significantly more prevalent in the patient group than in the controls (p < 0.05). Likewise, the experienced bodily pain was statistically highly significantly more severe among the respondents with OI (p < 0.001), and correlated with the reported fatigue. CONCLUSIONS: In comparison with age-matched controls, adults with OI do not differ in experienced fatigue, unlike hypothesized. Therefore, sleep disturbances, which based on the frequency of reported related symptoms and previous sleep apnea diagnoses appear to be common in OI patients, may remain undiagnosed.

Timing of dental development in osteogenesis imperfecta patients with and without bisphosphonate treatment.

Bisphosphonates have established their role as medical therapy for pediatric osteogenesis imperfecta (OI) patients. Since bisphosphonates have also been shown to delay tooth development in animal models, we aimed to assess whether the medication has a similar effect on children with OI. In this cross-sectional study, bisphosphonate-treated OI patients of whom dental panoramic tomograph was taken between 3 and 16years of age formed the study group. The patients, 22 in total, had been treated with pamidronate, zoledronic acid or risedronate for at least one year before the radiography. Developmental stage of the permanent teeth, resorption of the deciduous teeth, and number of the erupted permanent teeth were radiographically assessed in the left mandibular quadrant. Dental panoramic tomographs of 50 OI patients, naïve to bisphosphonates, and of 50 healthy individuals of the same age were used as controls. The dental development was statistically significantly accelerated in the OI group naïve to bisphosphonates showing median advancement of dental age by 0.63years from chronological age and median increase in the number of erupted teeth by 0.31 as compared to Finnish norms. Bisphosphonate-treated OI patients displayed, however, age-appropriate dental development. The OI patients not treated with bisphosphonates also showed statistically significantly faster resorption of the deciduous teeth than the treated ones, and displayed an altered interrelationship between the resorption stage of an individual primary tooth and the developmental stage of the succedaneous permanent tooth, unlike the OI patients treated with bisphosphonate. No correlation between either cumulative bisphosphonate dose or between treatment length and any measured component of the dental development was found. To conclude, OI itself was found to lead to advanced dental development. Bisphosphonate treatment had a delaying effect in all the three aspects studied, resulting in a rate of dental development indistinguishable from normal.

Cranial base pathology in pediatric osteogenesis imperfecta patients treated with bisphosphonates.

OBJECT: Cranial base pathology is a serious complication of osteogenesis imperfecta (OI). Our aim was to analyze whether bisphosphonate treatment, used to improve bone strength, could also prevent the development of craniocervical junction pathology (basilar impression, basilar invagination, or platybasia) in children with OI. METHODS: In this single-center retrospective study the authors analyzed the skull base morphology from lateral skull radiographs and midsagittal MR images (total of 94 images), obtained between the ages of 0 and 25 years in 39 bisphosphonate-treated OI patients. The results were compared with age-matched normative values and with findings in 70 OI patients who were not treated with bisphosphonates. In addition to cross-sectional data, longitudinal data were available from 22 patients with an average follow-up period of 7.6 years. The patients, who had OI types I, III, IV, VI, and VII, had been treated with zoledronic acid, pamidronate, or risedronate for 3.2 years on average. RESULTS: Altogether 33% of the 39 bisphosphonate-treated patients had at least 1 cranial base anomaly, platybasia being the most prevalent diagnosis (28%). Logistic regression analysis suggested a higher risk of basilar impression or invagination in patients with severe OI (OR 22.04) and/or older age at initiation of bisphosphonate treatment (OR 1.45), whereas a decreased risk was associated with longer duration of treatment (OR 0.28). No significant associations between age, height, or cumulative bisphosphonate dose and the risk for cranial base anomaly were detected. In longitudinal evaluation, Kaplan-Meier curves suggested delayed development of cranial base pathology in patients treated with bisphosphonates but the differences from the untreated group were not statistically significant. CONCLUSIONS: These findings indicate that cranial base pathology may develop despite bisphosphonate treatment. Early initiation of bisphosphonate treatment may delay development of craniocervical junction pathology. Careful followup of cranial base morphology is warranted, particularly in patients with severe OI.

Association between joint hypermobility, scoliosis, and cranial base anomalies in paediatric Osteogenesis imperfecta patients: a retrospective cross-sectional study.

BACKGROUND: Joint hypermobility is a common clinical characteristic of patients with Osteogenesis imperfecta (OI), a disorder with serious comorbidities of scoliosis and cranial base anomalies. This study aimed at evaluating how prevalent joint hypermobility is in paediatric OI patients, and to find out whether it serves as a potential predictive marker of the different spinal complications; scoliosis and craniovertebral anomalies (basilar impression and basilar invagination). METHODS: In this cross-sectional one-center study we analysed retrospectively clinical patient records and radiographs of 47 OI patients, aged 1-19 years, some of whom were treated with bisphosphonates. Presence of joint hypermobility, scoliosis, and craniovertebral anomalies was recorded and possible connections between the phenomena were explored with correlation analysis. RESULTS: Joint hypermobility was found in 70% of the patients. Scoliosis and cranial base anomalies had developed in 26%. The presence of spinal complications was independent of the bisphosphonate treatment status and joint hypermobility. CONCLUSIONS: Scoliosis and craniovertebral anomalies are strongly associated in paediatric OI patients. Joint hypermobility that is much more common appears, however, to be a poor predictor.

Prevalence and natural course of craniocervical junction anomalies during growth in patients with osteogenesis imperfecta.

Pathology in the craniocervical junction is a serious complication of osteogenesis imperfecta (OI). Our aim was to analyze the prevalence and natural course of craniocervical junction anomalies in patients with OI during growth. In a one-center retrospective study, we analyzed lateral skull radiographs and midsagittal magnetic resonance images of 76 patients with either type I, III, or IV OI. The material included longitudinal series of 31 patients. In total, 150 patient images taken at ages 0 to 39 years were analyzed and compared with age-matched control data. Craniocervical anomalies were observed in 37% of patients and in all OI types studied. Of the three types of anomalies, basilar invagination was seen in 13%, basilar impression in 15%, and platybasia in 29% of the patients. From those with an abnormal finding, 44% displayed more than one type of anomaly. At a group level, we found no evidence of progression of craniocervical junction pathology with age. We provide longitudinal and cross-sectional data on craniocervical junction dimensions in growing patients with OI and, based on those, suggest a radiological management strategy for diagnosis of cranial base pathology. A higher risk of having any of the pathological conditions was associated with a lower height Z-score. Careful follow-up of cranial base anomalies particularly in subjects with OI and severe growth failure is warranted.

Cranial base abnormalities in osteogenesis imperfecta: phenotypic and genotypic determinants.

Cranial base abnormalities are an important complication of osteogenesis imperfecta (OI), a hereditary bone fragility disorder that in most patients is caused by mutations affecting collagen type I. To elucidate which clinical characteristics are associated with the occurrence of cranial base abnormalities in OI, we compared cephalometric results of 187 OI patients (median age 12.0 years, range 3.4 to 47 years; 96 female) with those of 191 healthy subjects and related findings to clinical descriptors of the disease. Overall, 41 patients (22%) had at least one unambiguously abnormal skull base measure. Multivariate logistic regression analysis in patients with OI types I, III, and IV (n = 169) revealed that height Z-score [odds ratio (OR) = 0.53, 95% confidence interval (CI) 0.43-0.66, p < .001]--but not age, gender, scleral hue, lumbar spine areal bone mineral density, or a history of bisphosphonate treatment--was a significant independent determinant of skull base abnormalities. Among patients with a height Z-score below -3, 48% had a skull base abnormality regardless of whether they had received bisphosphonate treatment in the first year of life or not. Genotype-phenotype correlations were evaluated in patients with detectable mutations in COL1A1 or COL1A2, the genes coding for collagen type I (n = 140). Skull base abnormalities were present in 6% of patients with haploinsufficiency (frameshift or nonsense) mutations, in 43% of patients with helical glycine substitutions caused by COL1A1 mutations, in 32% of patients with helical glycine substitutions owing to COL1A2 mutations, and in 17% of patients with splice-site mutations affecting either COL1A1 or COL1A2. However, multivariate logistic regression analysis showed that height Z-score but not the type of collagen type I mutation was independently associated with the prevalence of skull base abnormalities. In conclusion, this study shows that clinical severity of OI, as expressed by the height Z-score, was the strongest predictor of skull base abnormalities. We did not find evidence for the hypothesis that bisphosphonate treatment protects against skull base abnormalities.

Dimensions of the craniocervical junction in longitudinal analysis of normal growth.

INTRODUCTION: Abnormal configuration of the craniocervical junction in the form of basilar impression or invagination, with often-associated platybasia, is a clinically significant cause of neurological symptoms particularly in patients with inherited diseases affecting the connective tissue. To better understand the course of development of these basilar abnormalities and further define their diagnostic criteria in children, we analysed longitudinally changes in the vertical dimensions of the craniocervical junction and in the flexion of the anterior skull base in normal growing individuals. METHODS: The distance of the odontoid process to four reference lines and the anterior skull base angle was measured in consecutive series of at least five lateral skull radiographs of 30 females and 23 males. Their mean age was 6.4 years at the beginning and 22.4 years at the end of the observation period. RESULTS: In young children, the odontoid process was situated in a caudal relation to the skull base structures and reached a level similar to that of adults approximately at the age of 7 years in both males and females. Cross-sectional observation of the results camouflages, however, how the intra-individual changes were markedly non-linear. Changes in the anterior skull base angle remained nonsignificant. CONCLUSIONS: Normal values for McRae's, Chamberlain's and McGregor's measurements and the more recently documented D-M measurement are age dependent. We provide reference values specific for ages from 4 years. A notable deviation from the documented values indicates a need of further examination.