R.R. van Rijn

Classification of Osteogenesis Imperfecta revisited.

In 1979 Sillence proposed a classification of Osteogenesis Imperfecta (OI) in OI types I, II, III and IV. In 2004 and 2007 this classification was expanded with OI types V-VIII because of distinct clinical features and/or different causative gene mutations. We propose a revised classification of OI with exclusion of OI type VII and VIII since these types have been added because of genetic criteria (autosomal recessive inheritance) while the clinical and radiological features are indistinguishable from OI types II-IV. Instead, we propose continued use of the Sillence criteria I, II-A, II-B, II-C, III and IV for clinical and radiological classification of OI with additional mentioning of the causative mutated gene to this classification. OI type V and VI are still part of this revised classification, because of the distinguishing clinical/radiological and/or histological features observed in these types.

Osteogenesis Imperfecta: A Review with Clinical Examples.

Osteogenesis imperfecta (OI) is characterized by susceptibility to bone fractures, with a severity ranging from subtle increase in fracture frequency to prenatal fractures. The first scientific description of OI dates from 1788. Since then, important milestones in OI research and treatment have, among others, been the classification of OI into 4 types (the ‘Sillence classification’), the discovery of defects in collagen type I biosynthesis as a cause of most cases of OI and the use of bisphosphonate therapy. Furthermore, in the past 5 years, it has become clear that OI comprises a group of heterogeneous disorders, with an estimated 90% of cases due to a causative variant in the COL1A1 or COL1A2 genes and with the remaining 10% due to causative recessive variants in the 8 genes known so far, or in other currently unknown genes. This review aims to highlight the current knowledge around the history, epidemiology, pathogenesis, clinical/radiological features, management, and future prospects of OI. The text will be illustrated with clinical descriptions, including radiographs and, where possible, photographs of patients with OI.

Normal Values for Tibial Quantitative Ultrasonometry in Caucasian Children and Adolescents (Aged 6 to 19 Years)

Abstract Bone densitometry in children is a relatively new topic of interest within the field of osteoporosis. Bone densitometry techniques using an X-ray source have the disadvantage of radiation exposure. Also on some systems, motion artifacts are caused by long scan times. Tibial quantitative ultrasonometry (QUS) is ideally suited for children as it is radiation free and the interactive measurement provides real-time quality control. In this prospective study, we present data from 596 healthy children—309 girls, mean age 12.9 years (range 6.1–19.9), and 287 boys, mean age 12.3 years (range 6.1–19.6) from Rotterdam, The Netherlands. For all subjects, a short questionnaire regarding overall health was completed. To assess skeletal age, an X-ray of the left hand was taken and tibial QUS of the right tibia was performed using the SoundScan™ Compact. A statistically significant correlation was found between age and speed of sound (SOS)—r2boys= 0.52 and r2girls= 0.63 (both P < 0.001) and between skeletal age and SOS—r2boys= 0.56 and r2girls= 0.63 (both P < 0.001). In boys, significant increase of mean SOS is seen between Tanner stages II and III and between IV and V. In girls there is a significant increase of mean SOS among all Tanner stages, except stages II and III. This is the first study to present normative tibial QUS data for Caucasian children and adolescents. In this study, normative data relative to skeletal age are also provided, facilitating the implementation of this technique in children with growth disorders showing dissociation between calendar and skeletal age.

A paediatric bone index derived by automated radiogrammetry

SummaryHand radiographs are obtained routinely to determine bone age of children. This paper presents a method that determines a Paediatric Bone Index automatically from such radiographs. The Paediatric Bone Index is designed to have minimal relative standard deviation (7.5%), and the precision is determined to be 1.42%.IntroductionWe present a computerised method to determine bone mass of children based on hand radiographs, including a reference database for normal Caucasian children.MethodsNormal Danish subjects (1,867), of ages 7–17, and 531 normal Dutch subjects of ages 5–19 were included. Historically, three different indices of bone mass have been used in radiogrammetry all based on

Bone mineral assessment with tibial ultrasonometry and dual-energy X-ray absorptiometry in long-term survivors of acute lymphoblastic leukemia in childhood.

A = \pi {\text{ }}T{\text{ }}W\left( {{\text{1}} - T/W} \right)

Of small bones and big mistakes; bone densitometry in children revisited

, where T is the cortical thickness and W the bone width. The indices are the metacarpal index A/W2, DXR-BMD = A/W, and Exton-Smith’s index A/(WL), where L is the length of the bone. These indices are compared with new indices of the form A/(WaLb), and it is argued that the preferred index has minimal SD relative to the mean value at each bone age and sex. Finally, longitudinal series of X-rays of 20 Japanese children are used to derive the precision of the measurements.ResultsThe preferred index is A/(W1.33L0.33), which is named the Paediatric Bone Index, PBI. It has mean relative SD 7.5% and precision 1.42%.ConclusionsAs part of the BoneXpert method for automated bone age determination, our method facilitates retrospective research studies involving validation of the proposed index against fracture incidence and adult bone mineral density.

Intermediate and long-term adverse effects of radioiodine therapy for differentiated thyroid carcinoma - A systematic review

We have evaluated the applicability of a new Digital X-ray Radiogrammetry (DXR) system in a Dutch Caucasian pediatric population. For this study we enrolled 535 healthy participants who all signed an informed consent form. In addition, 20 children suffering from inflammatory bowel disease (IBD) and juvenile chronic arthritis (JCA) were enrolled. Radiographs of the left hand were obtained from all participants. From the healthy population a subset of children with a history of forearm fractures were separately analyzed. Measurements consisted of DXR (X-posure®; Pronosco-Sectra, Linköping, Sweden). Five hundred thirty-five subjects were enrolled in the study. Twenty-two subjects (4.3%) were discontinued (age 3–10 years), all because of a nonrecognizable radiograph by the DXR system. The short-term coefficient of variation of DXR in this population was 0.59%. Significant differences in DXR-BMD between boys and girls for the ages of 11, 12, 16, 17, and 18 years were found. There were also significant differences in DXR-BMD between the sequential Tanner stages. For 88 subjects repeat radiographs were available (mean interval 1.8 years). In all cases an increase in DXR-BMD was seen Girls with IBD, JCA, or a history of forearm fractures and boys with IBD showed a significantly lower DXR-BMD compared with healthy controls. We show that DXR is an applicable technique in children. Also, in a small subpopulation it is possible to discriminate children with a high risk of low BMD.

Radiology in suspected non-accidental injury: Theory and practice in the Netherlands

Acute lymphoblastic leukemia (ALL) in childhood is a serious disease that can affect growth and the attainment of maximal peak bone mass. The latter has recently been recognized as a risk factor for the development of osteoporosis later in life. To determine long-term effects of the disease itself and its treatment, we assessed the bone status of a group of long-term survivors of childhood ALL, all treated with high doses of steroids (dexamethasone) and methotrexate and without cranial irradiation. All 21 subjects enrolled in this cross-sectional study were diagnosed to have non-high-risk precursors acute lymphoblastic leukemia (12 boys and 9 girls, mean age 16.5 yr, range 12.2-25.4 yr). Standard deviation (SD) scores were calculated using a tibial ultrasound device and spinal dual-energy X-ray absorptiometry (DXA) device as bone assessment techniques. SD scores of those two different bone assessment techniques were compared. The mean SOS (speed of sound) SD scores (SDS) of the tibia (mean 0.26, standard deviation [sd] 1.00) were not significantly different from our reference value of 0. There was no significant difference between the SOS SDS in boys and girls. With DXA, no significant difference was seen between the mean BMD SDS and the reference data and no significant difference in BMD between boys and girls was found. The individual mean SDS for bone mineral density (BMD) of lumbar spine are 0.24 (sd 1.02), total body 0.17 (sd 1.00), and apparent BMD (BMAD) 0.07 (sd 1.09). Spearmans correlation between mean SOS SDS and mean BMD of lumbar spine was 0.47, mean SOS SDS and mean BMAD SDS was 0.43, and mean SOS SDS and mean BMD of total body was 0.49. These correlations were significant at the 0.05 level (two tailed). Despite high-dose dexamethasone and methotrexate used for treatment of these children with ALL, no long-term side effects on the bone mineral status of the subjects, measured with DXA or tibial ultrasonometry, could be determined.