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This review examines the role of skeletal maturity ('bone age', BA) assessment in clinical practice. BA is mainly used in children with the following conditions: short stature (addressed in part 1 of this review), tall stature, early or late puberty, and congenital adrenal hyperplasia (all addressed in part 2). Various manual and automatic methods of BA assessment have been developed. Healthy tall children tend to have advanced BA and healthy short children tend to have delayed BA in comparison to chronological age. Growth hormone (GH) treatment of children with GH deficiency leads to a catch-up in BA that is usually appropriate for the height of the child. Response to GH is dependent on BA delay in young children with idiopathic short stature, and GH dosage appears to affect BA acceleration. In chronic renal failure, BA is delayed until puberty but then increases due to increased sensitivity of the growth plate to sex steroids, thus further impairing adult height. The assessment of BA provides an important contribution to the diagnostic workup and management of children with short stature. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

BoneXpert, an automated method for analysis of hand radiographs of children, has recently been developed and validated in European children. It determines Tanner-Whitehouse (TW) and Greulich Pyle (GP) bone ages (BA). The purpose of this work is to validate BoneXpert BA in Japanese children and determine the following two properties of the method: (1) The accuracy of the BA, i.e. the standard deviation from an experienced Japanese TW BA rater. (2) The precision of the BA, i.e. BoneXpert's ability to yield the same BA value on a repeated radiograph. The data consist of two studies: 185 radiographs of 22 normal children followed longitudinally from approximately 7 years to full maturity, and 284 radiographs of 22 patients with growth hormone deficiency treated with growth hormone and gonadotropin-releasing hormone analogue followed from an age of 4-11 years to almost full maturity. All radiographs were rated manually according to the TW-Japan system. BoneXpert processed all images, and the accuracy (SD) of TW-Japan BA was 0.72 years (95% CI 0.68-0.76). The precision error (SD) on a single determination of GP BA was 0.17 years (95% CI 0.15-0.19). It is concluded that BoneXpert performs as well in Japanese children as it does in Caucasian children. This study accomplishes a calibration of BoneXpert to the TW-Japan standard, which performs well for the entire BA range from 4 years up to full maturity. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Background and aims : Treatment with GH in short children has focused on height development. Little is known about the concomitant changes in muscle mass, bone structure and bone strength. Methods : Muscle area as well as parameters of bone architecture (bone mineral content, BMC; volumetric cortical density, total bone area, TBA; cortical area, cortical thickness, CT; and marrow area) were measured by means of pQCT (Stratec) at 65% of the proximal length of the forearm. The strength–strain index (SSI) was calculated as an indicator of bone strength. Results : Prepubertal children with GHD (mean values: age; 7.2 years; height SDS=−2.9 SDS; GH dose: 30 μg/kg/d) were followed at 0, 6, 12 (n =74) and 24 (n =55) months. Prepubertal children with SGA (mean values: age: 7.1 years; height SDS=−3.4 SDS; GH dose: 55 μg/kg/d) were followed at 0, 6, 12 (n =47) and 24 (n =35) months. Both groups showed a similar increase in height. At GH start, muscle mass and bone characteristics were lower than normal but similar in SGA vs. GHD. Muscle area (mean values, SDS) increased from −3.0 to −1.5 in SGA and from −2.4 to −1.0 in GHD. Bone geometry changed in a biphasic mode, with an increase in total bone area and lowering of bone mineral content (BMC) during the first 12 months, followed by an increase of BMC and CT thereafter. SSI (mean values, mm3) improved from 78 to 114 in GHD and from 62 to 101 in SGA after 24 months on GH. The increment in terms of SDS did not reach significance in SGA. SSI correlated positively with muscle area before and during GH treatment. Conclusions : Bone strength and muscle mass are impaired in prepubertal children with GHD and SGA. Exogenous GH can indirectly improve bone structure and strength by inducing an increase in muscle mass. Our findings support the assumption that, in SGA, there is impaired tissue responsiveness to GH. [Copyright &y& Elsevier]

Conventional analyses of growth hormone (GH) treatment in children focus mainly on height development. We aimed to investigate the complex effects of GH on three components of the body, namely, muscle, fat and bone, by means of peripheral quantitative computed tomography. This method, in which a component of the body is taken to represent the whole, is non-invasive and suitable for children. Our study group comprised 74 pre-pubertal children with GH deficiency (mean age, 7.2 years; height standard deviation score [SDS], –2.9) who received recombinant human GH treatment (30 μg/kg/day [0.03 mg/kg/day]) for 12 months (55 of the children received treatment for up to 24 months). Within 2 years, mean height SDS increased from –2.9 to –1.5, muscle surface area SDS rose from –2.4 to 1.0, while fat surface area SDS decreased from 0.1 to –1.0. Grip strength SDS increased from –1.0 to –0.3, whereas the ratio of strength to muscle area did not change. We thus observed that changes in body compartments (including bone) occur during GH treatment; we also found evidence showing a specific pattern of dynamics over time. In view of the limited literature available on muscle development during GH therapy in children, we explore the potential role and significance of these response variables in the assessment of GH therapy. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Two methods of determining puberty onset (Preece- Baines model 1 (PB1) and Tanner staging) were used to calculate total pubertal growth (TPG) in adolescents with growth hormone deficiency (GHD). Patients and Methods: 34 patients (11 girls) met the following inclusion criteria: isolated GHD, >2 years growth hormone therapy prior to puberty onset, regular weight-adjusted GH dosage, known final height (age >21 years or height velocity <0.5 cm/year), no induction of puberty. PB1 was used to define age and height at onset of the pubertal growth spurt (‘take-off’). Results: The results (mean ± SD) were as follows: in girls, mean age at take-off was 9.8 years; 2.0 ± 1.1 years before breast stage B2. In boys, mean age at take-off was 11.3 years; 1.4 ± 0.8 years before testes volume >3 ml. Height at take-off was lower than at Tanner stage 2 by 12.4 ± 7.6 cm in girls and 7.7 ± 5.3 cm in boys. TPG was thus markedly greater (p < 0.001) using the PB1 method, as compared with Tanner stage2. Peak height velocity was normal. Final height was –0.5 ± 0.7 SDS in females and –0.4 ± 0.9 SDS in males. Conclusions: The method of measuring TPG from take-off is more objective, and has potentially greater implications for GH therapeutics than the Tanner stage method. In our study, 40% of TPG occurred before ‘breast stage B2’ was attained in GHD girls; whereas 23% of TPG occurred before ‘testes >3 ml’ in GHD boys. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]