We report reference values for osteocalcin and bone and liver alkaline phosphatase (ALP) isoforms in serum from 114 healthy children and adolescents, age 7-16 y. The bone and liver ALP isoforms were measured by high performance liquid chromatography (HPLC). Six ALP isoforms were separated and quantified in all samples: one bonelintestinal (BA), two bone (Bl and B2), and three liver ALP isoforms (Ll, L2, and L3). It is especially important to make distinctions between ages and gender during puberty in the interpretation of biochemical markers of bone. We observed that girls reached adult levels for osteocalcin, total ALP, and bone ALP isoforms, BA, B 1, and B2, earlier than boys. Girls in the oldest age group (15-16 y) and in the pubertal stage groups IV-V, reached higher levels than boys for the calculated ratio B l B 2 due to a more rapid decline of B2 compared with B 1.ALP is one of the most thoroughly investigated enzymes in the routine clinical chemistry laboratory and the most frequently used biochemical marker for osteoblastic bone formation. At least four human gene loci are encoding for the ALP isoenzymes; "tissue nonspecific," placental, germ cell, and small intestinal locus (1). ALP from the tissue nonspecific locus is expressed in tissues such as bone, liver, and kidney. Different carbohydrate side chains or maybe remaining fragments of the in situ cell membrane glycosyl-phosphatidylinosit01 anchor, or both, yields "tissue-specific" structures in the ALP isoforms from this gene locus (2). In concordance with strict isoenzyme definition (3), bone and liver ALP should be referred to as isoforms of the same isoenzyme.Osteocalcin (bone-Gla protein) is a bone matrix protein of 49 amino acid residues (molecular mass 5800 D) containing three calcium binding y-carboxyglutamic acids which is mainly synthesized in bone by osteoblasts. Only a small amount is synthesized in dentine by odontoblasts. The synthe- Reference values in healthy children and adolescents for total ALP have frequently been reported (6, 7). However, reference values in children and adolescents for bone and liver ALP (8-12), and osteocalcin (13-16) are more sparse. Age, sex, race, pubertal, and skeletal maturation are some factors that reflect reference value differences for osteocalcin and the bone ALP isoforms.We have recently described a new HPLC method which can detect six different ALP isoforms; one bonelintestinal (BIT), two bone (B1 and B2), and three liver ALP isoforms (Ll, L2 and L3) (17,18). This study describes reference values in Unit, Department of Clinical Chemistry, Linkoping University Hospital, S-581 85 Linkohealthy children and adolescents, age 7-16 y, for osteocalcin ping, Sweden.

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The spontaneous growth process in Turner's syndrome is characterized by a progressive decline in height velocity during childhood and no pubertal growth spurt. Therefore, therapy aimed at improving height during childhood as well as increasing final height is desirable for most girls with Turner's syndrome. Forty-five girls with Turner's syndrome, 9-16 yr of age (mean age, 12.2 yr), were allocated to three study groups. Group 1 (n = 13) was initially treated with oxandrolone alone; after 1 yr of treatment, GH without (group 1a; n = 6) or with (group 1b; n = 7) ethinyl estradiol was added. Group 2 (n = 17) was treated with GH plus oxandrolone. Group 3 (n = 15) was treated with GH, oxandrolone, and ethinyl estradiol. The dosage were: GH, 0.1 IU/kg.day; oxandrolone, 0.05 mg/kg.day; and ethinyl estradiol, 100 ng/kg.day. A height of 150 cm or more was achieved in 61%, 75%, and 60% of the girls in groups 1, 2, and 3, respectively. The most impressive increase in height was seen in group 2. In this group the mean final height was 154.2 cm (SD = 6.6), which is equivalent to a mean net gain of 8.5 cm (SD = 4.6) over the projected final height. In group 3, in which ethinyl estradiol was included from the start of therapy, the initially good height velocity decelerated after 1-2 yr of treatment. Their mean final height was 151.1 (SD = 4.6) cm, equivalent to a mean net gain of 3.0 cm (SD = 3.8). A similar growth-decelerating effect of ethinyl estradiol was seen in group 1b. We conclude that in girls with Turner's syndrome who are older than 9 yr of age, treatment with GH in combination with oxandrolone results in significant growth acceleration, imitating that in normal puberty, leading to a more favorable height during childhood. This mode of treatment also results in a significantly increased final height, permitting a great number of the girls to attain a final height of more than 150 cm. However, early addition of estrogen decelerates the height velocity and reduces the gain in height.

BackgroundRecent studies suggest that adolescent adiposity is established already in preadolescence. Earlier studies have confirmed a strong tracking of obesity from adolescence to adulthood. Our aim was to examine the diagnostic accuracy of a population-derived protocol for identification of preschool children at risk for obesity in preadolescence.Methodology/Principal FindingsWe analysed data obtained for child health surveillance up to age 5 from 5778 children born in a Swedish county in 1991. The basic data set included age, sex, and weight and height measurements from the regular checkups between ages 1.5 and 5. Data not routinely collected in the child health centre setting were disregarded. The children were at age 10 randomly assigned to protocol derivation and validation cohorts and assessed for obesity according to IOTF criteria. The accuracy of predicting obesity in the validation cohort was measured using decision precision, specificity, and sensitivity. The decision protocol selected 1.4% of preschool children as being at obesity risk. The precision of the protocol at age 10 was 82% for girls and 80% for boys, and the specificity was 100% for both boys and girls. The sensitivity was higher for girls (41%) than for boys (21%). The relative risk for obesity at age 10 estimated by the odds ratio for individuals selected by the protocol compared to non-selected peers was 212.6 (95% confidence interval 56.6 to 798.4) for girls and 120.3 (95% CI 24.5 to 589.9) for boys.Conclusion/SignificanceA simple and inexpensive decision protocol based on BMI values proved to have high precision and specificity for identification of preschool children at risk for obesity persisting into adolescence, while the sensitivity was low especially for boys. Implementation and further evaluations of the protocol in child health centre settings are warranted.