GH and GnRH analog treatment in children who enter puberty at short stature

It is well known that height at the onset of puberty is closely related to final height. To improve final height of short children who enter puberty at short stature, twenty-one short boys and six short girls were treated with a combination of GH and GnRH analog. The boys started the combination treatment at a mean age of 12.0 years when their mean height was 128.5 cm (-2.74 SD) and the girls at a mean age of 10.68 years when their mean height was 126.4 cm (-2.23 SD). The boys discontinued GnRH at a mean age of 16.88 years after a mean treatment period of 4.89 years when their height was 153.7 cm (-2.75 SD), and the girls at a mean age of 13.89 years after a mean treatment period of 3.20 years when their height was 143.3 cm (-1.94 SD). Bone age maturation significantly decelerated during the combination treatment. Bone age rarely exceeded 14 years in boys and did not exceed 13 years in girls. Bone age maturation during combination treatment decelerated after bone age 12 years in boys and 10.5 years in girls. On average, bone age matured at a mean rate of 0.48 years a year in boys and 0.56 years a year in girls during the combination treatment. During the combination treatment, height velocity did not decelerate rapidly and remained at 3-5 cm/year for a longer duration because of the bone age deceleration, although a definite pubertal growth spurt was not observed. As a consequence, the mean projected height SDS for bone age increased 1.50 (+/- 0.76) SD in boys and 1.24 (+/- 0.49) SD during the combination treatment. Although most of the patients have not yet reached their final height, combined GnRH analog and GH treatment should increase the pubertal height gain and the adult height in short children who enter puberty early for height, when the post-GST growth is taken into account. The combination treatment seems more effective in boys than in girls. This improvement is attributed to the lengthening of the treatment period by slower bone maturation and maintained growth velocity.     

Reference values for height and weight in Prader-Willi syndrome based on 315 patients

The spontaneous growth of 315 patients (109 girls and 208 boys) with Prader-Willi syndrome (PWS) was analysed in a mixed longitudinal and cross-sectional manner. 33 patients were seen in the department between 1970 and 1994; height and weight of 76 patients from Germany were evaluated by means of a questionnaire with detailed measuring instructions, and 206 definite cases were added from the literature. Mean ( SD) length of newborn babies with PWS was 50.2+/-2.8 cm (145 boys) and 48.9 3.3 cm (79 girls). Mean weight at birth was 2945 570 g in boys and 2782+/-594 g in girls. During the 1st year, the children's growth was nearly normal, thereafter short stature was present in approximately 50% of PWS patients. Between 3 and 13 years of age, the 50th percentile for height in PWS is roughly identical with the 3rd percentile in healthy controls. Body weight was normal for all boys and girls during the first 2 years. Thereafter, a rapid weight gain occurred; after an age of 10 years weight-for-height index in nearly all patients exceeded the normal range. The extent of pubertal growth was reduced for the group. Mean adult height was 161.6+/-8.1 cm (23 males) and 150.2+/-5.5 cm (21 females). Head circumference for age was normal for boys and girls. CONCLUSION: Reference data on spontaneous development of growth and weight gain of children with Prader-Willi syndrome are described allowing a better counselling of patients and parents.     

Craniofacial parameters during growth from the deciduous to permanent dentition--a longitudinal study

Data on the dynamics of craniofacial growth, obtained by simple non-invasive measurements, are scarce in comparison with those collected by cephalometric methods. The aim of this study was to measure a number of craniofacial parameters, and to evaluate their changes during transition from the deciduous to the permanent dentition. A sample of 61 subjects (32 boys and 29 girls) were followed longitudinally by annual examination from an initial mean age of 4.7 years to a final mean age of 11.8 years. Conventional anthropometric instruments were employed to measure six craniofacial variables: G-Op, Eu-Eu, Zy-Zy, Go-Go, N-Gn and N-Pr. The data were analysed using basic summary statistics and a longitudinal regression model. A difference between males and females was found for all variables during the study period. During the transition from deciduous to mixed dentition (4.7-7.5 years), the cranial breadth and length (Eu-Eu and G-Op) decreased followed by an increase during the mixed dentition. All other parameters showed a continuous increase, which was highest for the variables defining facial height.     

Head posture and cervicovertebral anatomy as mandibular growth predictors

In this study, the separate and the combined influence of head posture and cervicovertebral anatomy on mandibular growth direction was analysed. The subjects, 20 boys and 16 girls, were a subsample of 12-year-old Chinese children in Hong Kong, all with initial and 2-5-year follow-up lateral cephalometric radiographs recorded in natural head position (NHP). Postural variables were measured in terms of craniovertical, craniocervical, and cervicohorizontal angulations. Morphological variables of the craniocervical junction region were measured in terms of intervertebral space and atlantoaxial dimensions. Mandibular growth was estimated as the direction of displacement of prognathion in relation to the sella nasion line when superimposing on stable cranial base structures. The data were analysed with a multiple regression model, separately for boys and girls. In both sexes the height of the atlas dorsal arch showed a statistically significant correlation (P < 0.01) with mandibular growth direction (boys r = 0.54 and girls r = 0.62), while the craniovertical angulation correlated significantly only for the boys (NSL/VER r = 0.59, P < 0.01; C1/VER r = 0.49, P < 0.05). However, atlas dorsal arch height (DORS C1) combined with cervicohorizontal angulation (OPT/HOR) in girls and with craniovertical angulation (NSL/VER; C1/VER) in boys, displayed a significantly (P < 0.05) increased correlation (r = 0.76 and 0.71, respectively). Combination of atlas morphology and head posture predicts mandibular growth direction better than either variable alone.     

Pressure-flow studies: an evaluation of within-testing reproducibility--validity of the measured parameters

Growth and maturation during adolescence has not been well described in rural African populations, although it may represent the missing link between high levels of preschool stunting and nearly 'normal' adult heights. In 1995 the homes of subjects aged 10.3-17.5 years, living in a rural area of Senegal, were visited, and all adolescents present, 1527 boys and 1126 girls, were included in the analysis. A number of girls were absent because they worked in the capital city Dakar. Resident girls (n = 705) had significantly higher means than boys for all anthropometric variables (weight, body mass index, arm circumference and muscle arm circumference, triceps and subscapular skinfolds), except for height and head circumference. Girls who had just returned from seasonal migration to Dakar (n = 415) were, on average, 2 kg heavier, but not taller, than resident girls (p < 0.0001). The girls fell off in height from 11 to 13 years compared to the NCHS reference and then 'caught up' until the age of 17, while boys fell off during the entire age span. Mean age at menarche was estimated at 16.1 years (95% fiducial CI: 15.8-16.4) from status quo data by probit analysis. No significant difference was found between residents and migrants. Postmenarcheal girls had better nutritional status than premenarcheal girls in terms of height, weight, body mass index, percentage body fat and arm muscle circumference (p < 0.0001). In conclusion, puberty, as assessed by age at menarche, is delayed by about 3 years in this population, probably due to malnutrition.     

The prevalence of epilepsy follows the distribution of onchocerciasis in a west Ugandan focus

A study was made to determine whether skeletal alterations usually produced by rapid maxillary expansion may be compensated for in time by growth and/or comprehensive orthodontic treatment. In 30 patients, orthodontic treatment was started with rapid maxillary expansion, followed by fixed appliances, not combined with any other form of orthopedic device. Mean treatment time was 3.1 years. Nine measurements from the Ricketts analysis were studied, based on lateral cephalometric radiographs. Records were taken before orthodontic treatment and after completion of active therapy. A statistical analysis was made of the nine variables used, reflecting the vertical and anteroposterior skeletal proportions of the face, contrasting the changes before and after treatment. Of all the variables studied, the four that change with age according to the Ricketts analysis (mandibular plane angle, maxillary height, facial depth and facial convexity), yielded statistically significant differences after treatment, indicative of normal growth. The five remaining variables that remain constant with age according to the Ricketts analysis (facial axis, lower facial height, total facial height, palatal plane inclination and maxillary depth) showed no significant changes after treatment, also indicative of normal growth.     

Growth charts, growth velocity and bone development in childhood obesity

OBJECTIVE: To compare the growth charts of obese subjects (4-18 years) with the Tanner's growth curves and to analyze the growth velocities and bone age of obese children in prepuberty and adolescence. Moreover to compare the relationship between the serum insulinemic and glycemic levels and height standard deviation score (HSDS). DESIGN: Growth charts: this study included 1250 obese subjects (669 males, 581 females) observed between 1981 and 1993 and divided into seven age categories (4-6, 7-8, 9-10, 11-12, 13-14, 15-16, 17-18 years). Growth velocities: yearly growth velocities of 579 obese subjects (325 males, 254 females) were compared to growth velocities of 473 controlled children of the same sex, chronological age and pubertal stage. Bone age (BA) of 846 obese subjects (470 males, 376 females) was estimated. Blood analysis: insulin secretion of 70 obese children was considered and compared to 70 lean controls of equal chronological age and sex. MEASUREMENTS: Growth rate, standardized height and other physical characteristics of the children were measured by trained examiners. All subjects were evaluated singularly for at least 4 years with a follow-up every 6 months. BA was estimated by radiograph of the left hand and wrist using the Tanner-Whitehouse II system by a single observer. For the insulin secretion study and glycemic levels oral glucose tolerance test (OGTT) was performed using a glucose load of 1.75 g/kg per body weight. Plasma insulin was assessed by a double antibody radioimmunoassay. RESULTS: In adipose children the growth charts, referred to 97th centile, 50th centile and 3rd centile, were superior to those of the normal population up to the age of 13 and 12.5 years for male and for female respectively; growth decreases at the above age in both sexes. The obese subjects were equal in height to the non obese subjects as they reached their 18th birthday. The growth velocity (cm/yr) of the obese child, in the age range considered here, does not show differences when compared with the lean child in the prepubertal status (P not significant) but decreases during Tanner's stage II, III IV in boys and girls (P < 0.0001). BA is more advanced over chronological age (delta BA-CA) in both sexes. The increase of BA over CA does not show a remarkable difference during pubertal maturation in boys (P not significant); whereas in girls the delta BA-CA decreases with advancing sexual maturation (P < 0.0001). Our obese subjects have significantly higher plasma insulinemic levels compared with the lean controls (P < 0.0001). Moreover there is a positive correlation between plasma insulinemic levels and HSDS (r = 0.881, P < 0.0001). We did not observe a correlation between serum glycemic levels and HSDS. CONCLUSION: Our data demonstrate that the growth increase in an obese child starts in the first years of life. The statural advantage acquired in the first years of life would be exploited and maintained up to the beginning of puberty and with a growth velocity equal to that of the lean subject. Skeletal maturation is strongly increased in both sexes. Bone age remained advanced during the entire period of pubertal development. During puberty obese subjects demonstrate a less notable growth spurt when compared with lean subjects. The growth advantage gradually decreases and final adult height of obese and normal subjects is equal.     

Protection of both auditory hair cells and auditory neurons from cisplatin induced damage

Knowledge about body composition is important in metabolic and nutritional studies. In this cross-sectional study the body composition of 403 healthy white Dutch children and adolescents was evaluated by using dual-energy X-ray absorptiometry (DXA). Possible determinants of body composition were analyzed. In 85 subjects the results of bioelectrical impedance analysis (BIA) were compared with DXA. Fat mass, lean tissue mass, and bone mineral content were greater in older boys and girls. Percentage body fat was greater in older girls but not in boys and it was higher in girls than in boys at all ages. From the age of 14 y boys had higher lean tissue mass and bone mineral content than girls. Tanner stage had a significant relation with body composition in both sexes. Percentage body fat was lower in boys in stage 4 than in stage 3 and was higher in consecutive Tanner stages in girls. After adjustment for age, Tanner stage was significantly positively related to lean tissue mass and bone mineral content in boys and girls and to percentage body fat and fat mass in girls. The profession of the parents and the education of the father had a significant negative correlation with percentage body fat and fat mass in girls (P < 0.01). Physical activity was related to lean tissue mass (P = 0.001) but not to fat mass in boys after adjustment for age. A high correlation and a small difference was found between lean body mass by BIA and lean tissue mass by DXA. Body composition in healthy Dutch children and adolescents is related to age, sex, Tanner stage, socioeconomic status, and physical activity.     

Correlation between maximum bite force and facial morphology in children

The correlation between maximum bite force and facial morphology was studied in 54 boys, 8 to 16 years old, and 66 girls, 7 to 17 years old. Bite force was measured at the first molars with a miniature bite force recorder. Facial morphology was evaluated on profile cephalograms. In addition, the number of teeth in contact in the intercuspal position was recorded with occlusal foils. In the girls, maximum bite force was correlated with the inclination of the mandible, the size of the gonial angle, and the ratio between posterior and anterior face heights. The correlations implied a large bite force with a small mandibular inclination and gonial angle, a large posterior face height in relation to the anterior face height, and a small bite force with the opposite facial characteristics. These correlations were nonexistent or weaker in boys. In both sexes, bite force was correlated with the number of occlusal contacts. Elimination of the influence of age and occlusal contact in the group of girls by the use of partial correlations reduced the correlation between bite force and facial morphology. A significant correlation with the size of the gonial angle remained, however, and the correlation with mandibular inclination was close to significance. In addition to the correlations found with facial morphology, the study clearly demonstrated the need to take gender and occlusal contacts into consideration in future studies of masticatory muscle function and strength in relation to facial morphology.     

Accuracy of final height prediction and effect of growth-reductive therapy in 362 constitutionally tall children

Height reduction by means of treatment with high doses of sex steroids in constitutionally tall stature (CTS) is a well known, though still controversial, therapy. The establishment of the effect of such therapy is dependent on the height prediction method applied. We evaluated the reliability of various prediction methods together with the subjective clinician's judgment in 143 untreated children (55 boys and 88 girls) with CTS and the effect of height-reductive therapy in 249 tall children (60 boys and 159 girls) treated with high doses of sex hormones (cases). For this purpose, we compared the predicted adult height with the attained height at a mean adult age of 25 yr and adjusted the therapeutic effect for differences in bone age (BA), chronological age (CA), and height prediction between untreated and treated children. At the time of the height prediction, controls were significantly shorter, had more advanced estimated BAs (except for the BA according to Greulich and Pyle in boys), had lower target heights, and had smaller adult height predictions compared with the CTS patients (P < 0.05). At the time of the follow-up, CTS patients were significantly taller than controls for both boys and girls (P < 0.02). In controls, a large variability was found for the errors of prediction of the various prediction methods and in relation to CA. The prediction according to Bailey and Pinneau systematically overestimated adult height in CTS children, whereas the other prediction methods (Tanner-Whitehouse prediction and index of potential height) systematically underestimated final height. The mean (SD) absolute errors of the prediction methods varied from 2.3 (1.8) to 5.3 (4.3) cm in boys and from 2.0 (1.9) to 3.7 (3.5) cm in girls. They were significantly negatively correlated with CA (r = [minus 0.27 to -0.65; P < 0.05), except for the Tanner-Whitehouse prediction in boys, indicating that height prognosis is more reliable with increasing CA. In addition, experienced clinicians gave accurate height predictions by evaluating the growth chart of the child while taking into account various clinical parameters, such as CA, BA, and pubertal stage. The effect of sex hormone therapy was assessed by means of multiple regression analysis while adjusting for differences in height prediction, CA, and BA at the start of therapy between treated and untreated children. The mean (SD) adjusted effect varied from -0.5 (2.4) to 0.3 (1.4) cm in boys and from -0.6 (2.1) to 2.4 (1.4) cm in girls. The adjusted height reduction was dependent on the BA at the time of start of sex hormone therapy and was more pronounced when treatment was started at a younger BA. In boys, the treatment effect was significantly negative at BAs exceeding 14-15 yr. After cessation of therapy, additional mean (SD) growth of 2.4 (1.2) and 2.7 (1.1) cm was observed for boys and girls, respectively. The mean (SD) BA according to Greulich and Pyle at that time was 17.1 (0.7) yr for boys and 15.2 (0.6) yr for girls. These data demonstrate that height prediction in children with CTS is inaccurate in boys, but clinically acceptable in girls. With increasing age, height prognosis became more accurate. Overall, the height-reducing effect of high doses of sex hormones in children with CTS was limited, especially in boys. However, a significant effect of treatment was observed when treatment was started at BAs less than 14-15 yr, depending on the method of BA assessment. In boys, treatment appeared to be contraindicated at BAs older than 14-15 yr, because androgen administration caused extra growth instead of growth inhibition. It is recommended that referral should take place early, preferably before puberty, for careful monitoring of growth and height prediction. Moreover, it is recommended not to discontinue therapy before complete closure of the epiphyses of the hand has occurred to avoid considerable posttreatment growth.     

Growth in stature in fragile X families: a mixed longitudinal study

The effect of fragile X on growth in stature was estimated in individuals aged 5-20 years from 50 fragile X families. The multivariate normal model for pedigree analysis was applied to the mixed longitudinal data, which varied with regard to intervals between the measurements and their number in individual subjects, totalling 349 measurement data points from fragile X families, and 292 data points from unrelated normal subjects. The results of genetic and regression analysis showed that, in fragile X boys and girls, total pubertal height gain is impaired, whereas the rate of growth during the preadolescent period is increased, compared with the growth rate of nonfragile X subjects. Moreover, the growth parameters in fragile X males were found to be correlated with the size of CGG trinucleotide expansion. The hypothesis of premature activation of the hypothalamo-pituitary gonadal axis is postulated as the cause of growth impairment in fragile X boys and girls, which should be verified by data on the timing of pubertal stages, hormone levels, and bone maturation.     

Growth changes in children and adolescents with short-term diabetes

OBJECTIVE: Height and weight changes during the first 3 years of diabetes were prospectively followed in 152 diabetic children and adolescents. RESEARCH DESIGN AND METHODS: The study sample consisted of 152 Caucasian diabetic patients (84 boys; 68 girls) followed from diabetes onset in the Paediatric Diabetes Unit and 80 Caucasian normal subjects (49 boys; 31 girls) assessed in the Outpatient General Paediatric Clinic of the same hospital for routine examination and not affected by problems that might influence growth. Diabetic patients and control subjects were consecutively enrolled in the study between 1989 and 1992; diabetic patients with positive markers for celiac disease (positive antiendomysial antibodies) and thyroid disease (positive antimicrosomial antibodies) or any other chronic disease were not considered in the study. Mean age of diabetic patients (8.9 +/- 4.1 years) and control subjects (8.5 +/- 4.2 years) at recruitment in the study was similar. RESULTS: At onset of diabetes, the mean height expressed as the height standard deviation score (HSDS) was significantly greater than the expected values (P < 0.0001) and was independent of sex and pubertal stage. During the first 3 years of diabetes, HSDS decreased significantly (F = 6.9; P < 0.001). Meanwhile, growth velocity as standard deviation score (SDS) decreased significantly between the 1st and 2nd year (-0.12 +/- 2.1; -0.76 +/- 2.6, respectively; P < 0.05), but it was similar between the 2nd and 3rd year of diabetes. Weight expressed as SDS increased significantly during the first 2 years of diabetes but not thereafter. Height changes during the study period were independent from pubertal stage and sex. Metabolic control and insulin requirement, in our series, were not clearly related to height and weight changes. CONCLUSIONS: Diabetic patients at onset of diabetes are taller than age- and sex-matched nondiabetic subjects. During the first years of the disease, linear growth decreases independently of metabolic control and weight changes.     

Systematisation of anthropometric data of 17-year-old schoolgirls from Tartu, Estonia

An anthropometric study of 358 healthy schoolgirls at the age from 17 to 18 years from all secondary schools of Tartu was carried out. 42 single body measurements and 11 skinfolds were measured, and 45 indices and body composition characteristics were derived from them. The data were systematised into 5 height-weight SD-classes according to the correspondence between height and weight. There were 3 classes with relative correspondence between height and weight: 1. short and light girls, 2. medium-height and medium-weight girls, 3. tall and heavy girls and 2 classes with the largest relative non-correspondence between height and weight: 4. pycnics, 5. leptosomes. In addition to the well-known differences between pycnics and leptosomes it was also shown that in the classes small--medium--big statistically significant gradual changes take place. The increase in the fullness of the body and in the amount of soft tissue was in positive correlation with total body fat and subcutaneous body fat and with bone-muscle rate in the cross-sectional area of the arm and the thigh. The increase in height was connected with proportional changes in the whole skeleton. As the proportions of fat, muscles and bones are in mutual correlation, for establishing of norms for these proportions it is necessary to take the body size into consideration.     

Gender differences in body fat content are present well before puberty

To determine whether gender differences in body fat could be detected in prepubertal children using dual energy X-ray absorptiometry (DEXA), body composition was measured in 20 healthy boys aged 3-8 y matched for age, height and weight with 20 healthy girls. Although boys and girls did not differ in age, height, weight, body mass index (BMI) or bone mineral content, the boys had a lower percentage of body fat (13.5 +/- 5.1 vs 20.4 +/- 6.1%, P < 0.01), a lower fat mass (3.2 +/- 2.0 vs 4.9 +/- 3.1 kg, P < 0.01), and a higher bone-free lean tissue mass (18.6 +/- 4.3 vs 17.0 +/- 3.5 kg, P < 0.01) than the girls. Girls had approximately 50% more body fat than the boys. This is the first DEXA study to show that boys aged 3-8 y have less body fat than girls of similar age, height and weight. Thus, this technology demonstrates that significant gender differences in body composition are evident, well before the onset of puberty.     

Muscle strength and hormonal levels in adolescents: gender related differences

The purpose of the present investigation was to study muscle strength in adolescents and its relationship to serum levels of testosterone and growth hormone in both genders. Thirty active adolescents (15 boys; age range 11 -12 y/o) participated in the first study. Isokinetic muscle strength of the dominant knee extensors (KE) was determined at 0, 12, 20, 30, 120, 180 and 240 deg/sec using a Cybex 340 dynamometer. The assessment of pubertal status was accomplished using the criteria of Tanner. Serum levels of total testosterone (T) and growth hormone (GH) were determined using radioimmunoassay techniques. Boys had higher (p< 0.001) T levels but no differences in muscle strength were detected between genders. Fifty-seven additional subjects representing three age groups (11-12 y/o, n=18; 13-14, n=21; 17-18, n=18) participated in the second study. A significant increase in peak torque (absolute and corrected for body weight) with age was observed in both genders. There were no significant gender differences in strength for the two youngest age groups, but boys were stronger than girls in the oldest age group (group 3). Testosterone and GH levels increased with age in boys but not in girls. Gender related differences in T were found in groups 2 and 3. A positive correlation (r=0,64 boys; r=0.46 girls) between testosterone levels and absolute muscle strength was seen in both genders. Our results suggest that increases in anabolic hormones precede muscle strength gains in adolescent males. In addition, gender related differences in muscle strength during adolescents cannot be explained solely on the basis of difference in body size or T levels.     

The interrelationships between facial areas and other body dimensions

The data from 35 premenarchial Gujarati, Hindu girls, selected at random, in the age range of 120 months to 144 months were collected to find out statistically the nature and the values of correlation coefficients among various facial areas and other body dimensions such as body weight, stature, chronological and skeletal ages. The correlation coefficients between skeletal, chronological, height and weight ages ranged from 0.413 to 0.8105 showing moderately high association. Height and weight ages turned out to be the most reliable indicators of growth and development of facial areas in this age group and the chronological age as in ineffectual indicator of the same. Maxillary and mandibular areas showed a high value of correlation coefficients (0.67) while the orbitoethmoidal area did not show any correlation with any age variables or with other facial areas. The mandibular areas showed the highest correlation with weight age (0.63) and lowest with chronological age (0.431). The maxillary area showed highest correlation with chronological age (0.62) and lowest with skeletal age (0.42). Fifteen empirical formulae have been developed by which average value of facial areas could be predicted from the other variables.     

Pattern rate and interpattern interval in development of matching simple auditory-visual patterns.

Assessed the possibility that previous failures to find evidence of more rapid inter- than intramodal development of matching of simple auditory and visual patterns have occurred because of the exclusive use of slow patterns and short interpattern intervals. In Exp I 32 1st- and 32 3rd-grade boys were compared in inter- and intramodal matching of fast or slow spatiotemporal patterns with long or short interpattern intervals. In Exp II the same comparisons were made for 32 2nd- and 32 4th-grade boys using temporal patterns. In both studies modality was a within-Ss variable, whereas age, pattern rate, and interpattern interval were between-Ss variables. Results indicate that in Exp I 3 separate indices of sensitivity coincided in indicating a significant effect of pattern rate but not of interpattern interval. The more rapid development of inter- than of intramodal matching for fast but not for slow patterns provided support for the hypothesis that auditory–visual integration increases with age at least in boys. In Exp II there was no indication of differential inter- and intramodal development under any condition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Bone alkaline phosphatase and collagen markers as early predictors of height velocity response to growth-promoting treatments in short normal children

OBJECTIVE: A number of long-term research studies are in progress to evaluate the effects of treatment with GH on growth and final height in children with short stature but no demonstrable abnormality of GH secretion. Such treatment is invasive, expensive and carries some risk to the child. An early indication of growth response would allow restriction of treatment to those children most likely to benefit, but anthropometric measurements are relatively subjective, insensitive and imprecise. The aim of this study was to evaluate bone alkaline phosphatase, procollagen Type I C-terminal propeptide, procollagen Type III N-terminal propeptide and the cross-linked carboxy-terminal telopeptide of Type I collagen as early biochemical predictors of height velocity response to growth-promoting treatments in short normal children. DESIGN: A prospective intervention study, partially placebo controlled on a double blind basis. PATIENTS: Fifty healthy children with familial short stature or constitutional delay in growth and puberty (8 girls, 42 boys, ages 5.5-16.5 years and all either prepubertal (45) or in very early puberty (5 boys) at the start of treatment) were treated with placebo (6), GH alone (32), GH plus oxandrolone (8) or GH plus testosterone (4). MEASUREMENTS: Bone alkaline phosphatase and the collagen markers were measured at the start of treatment and 3 months later. Height velocity was calculated at the start of treatment and again after one year. RESULTS: Pre-treatment biochemical marker concentrations did not predict height velocity response after one year. Increments in all markers after 3 months were significantly correlated with height velocity increments after one year of treatment, the highest correlations being observed for bone alkaline phosphatase (r = 0.67, P < 0.0001) and procollagen Type III N-terminal propeptide (r = 0.57, P < 0.0001). Highly significant correlations (P < 0.0001) were also observed between bone alkaline phosphatase and procollagen Type I C-terminal propeptide (r = 0.55) and between procollagen Type III N-terminal propeptide and the cross-linked carboxy-terminal telopeptide of Type I collagen (r = 0.62). Multiple linear regression with stepwise selection of variables identified bone alkaline phosphatase and procollagen Type III N-terminal propeptide as the only two independent variables that contributed significantly to the prediction of height velocity response after one year (analysis of variance, P < 0.0001). Together they predicted 59% of the variability in height velocity response after a year. CONCLUSIONS: The best early predictors of height velocity response were bone alkaline phosphatase (a protein found in hypertrophic chondrocytes in the epiphyseal growth plate, in calcifying matrix vesicles and in mature osteoblasts) and procollagen Type III N-terminal propeptide, a marker of interstitial fibril biosynthesis in soft tissues. Using these markers, GH treatment could be targeted to those children most likely to benefit in the medium term.     

Dietary protein restriction and selective preference for a protein-containing diet in the golden hamster (Mesocricetus auratus)

The corrected midparental height method was introduced by Tanner in 1970 (Tanner method) and is commonly used to estimate target height in children to evaluate the effectiveness of growth-promoting therapies. It has not been established if the equation used to compute target height should be the same for children with short, normal, or tall parents. In this study, we examined the predicted target height values by parental heights in a large population-based study (n = 2402). A simple linear function of midparental height (x) was proposed to estimate target height (y): y = 45.99 + 0.78x (boys), y = 37.85+0.75x (girls), with a 95% predicted interval of about +/-10 cm. The prediction model was similar for boys and girls in SD scores (SDS), and was not affected by assortative mating or difference in parental heights. The model may underestimate the potential stature by about 2 cm for children with midparental height below -2 SDS, or 163 cm. In comparison, the Tanner method may lead to a 6-cm error in underestimating target height for these children. The function would be a better choice than the Tanner method for estimating target height in the clinical evaluation of growth promotion treatments because it is common that short children also have short parents. Children with very short parents will usually be much taller than their parents in adult stature, and we believe that a different function should be developed. The results support the proposed nondominant, non-sex-linked, polygenic inheritance in stature. The estimated heritability values were 0.75-0.78 in cm or 0.55-0.60 in SDS.