Short stature in Duchenne muscular dystrophy: a study of 34 patients

In Duchenne muscular dystrophy (DMD), short stature is a feature of unknown cause. This cross-sectional study of 34 male patients (mean age 8.0 y, age range 1.2-13.7 y) was conducted to examine the relationship between auxological parameters, markers of growth and the extent of muscular weakness. Weight and length at birth (SDS +/- SD; 0.0 +/- 1.2; 0.2 +/- 1.5) and target height SDS (-0.2 +/- 0.7) were normal. Height (HT) SDS (-1.0 +/- 1.1) was lower than the normal population (p < 0.001) and did not correlate with age. Body mass index SDS (-0.1 +/- 1.6) was normal. Tests of insulin-like growth factor-I SDS (-0.6 +/- 1.2) and insulin-like growth factor binding protein-3 SDS (0.1 +/- 1.3) ruled out a severe derangement in the GH-IGF-axis. The carboxy-terminal propeptide of type I procollagen (PICP) SDS (0.6 +/- 1.5) was normal, but bone-specific alkaline phosphatase (BAP) SDS (-1.7 +/- 0.8) was low (p <0.001). HT SDS did not correlate with BAP SDS. The Vignos scale, a grading of muscular function (score: 0 = unaffected; 11 = confined to bed) (median (range): 3 (0-9)) correlated strongly with age (r = 0.77, p < 0.0001), but did not correlate with HT SDS, PICP SDS or BAP SDS. In conclusion, DMD patients are significantly shorter than the normal population, though the HT SDS does not change with age. Growth hormone deficiency does not seem to be the cause of short stature in DMD. Significantly low BAP levels are probably the result of the reduced muscle mass, which leads to a lower biomechanical load on the bone and thus a reduction in bone turnover. The short stature observed in our study is unlikely to be the result of muscular weakness.     

Bone mineralisation in premature infants cannot be predicted from serum alkaline phosphatase or serum phosphate

BACKGROUND: The bone mineral content of premature infants at term is lower than in mature infants at the same postconceptional age. Serum alkaline phosphatase and serum phosphate are often used as indicators of bone mineralisation. OBJECTIVE: To analyse the association between bone mineral content and serum alkaline phosphatase and serum phosphate. METHODS: Serum alkaline phosphatase and phosphate were measured at weekly intervals during admission in 108 premature infants of gestational age below 32 weeks (mean (SD) gestational age 29 (2) weeks; mean (SD) birth weight 1129 (279) g). Bone mineral content was measured at term (mean gestational age 41 weeks) by dual energy x ray absorptiometry and corrected for body size. RESULTS: Serum alkaline phosphatase was significantly negatively associated with serum phosphate (p < 0.001). Bone mineral content was not associated with mean serum alkaline phosphatase (p = 0.8), peak serum alkaline phosphatase (p = 0.5), or mean serum phosphate (p = 0.2) at term. CONCLUSION: Routine measurements of serum alkaline phosphatase and serum phosphate are of no use in predicting bone mineralisation outcome in premature infants.     

Growth velocity and plasma alkaline phosphatase activity in the preterm infant

The relationship between growth and plasma alkaline phosphatase activity differs in the preterm infant when compared with older children and adolescents. 18 preterm infants were studied over the first 12 postnatal weeks; growth velocity and plasma alkaline phosphatase activity were measured serially. Plasma calcium, inorganic phosphate, the vitamin D metabolites and parathyroid hormone were assayed at a median age of 3 and 6 weeks. There was an overall significant negative correlation between growth and plasma alkaline phosphatase activity (r = -0.37; P less than 0.005); this was more marked in a group where the plasma alkaline phosphatase activity exceeded the preterm reference range. Plasma 1,25-dihydroxycholecalciferol and inorganic phosphate were lower in this group at 3 weeks but not at 6 weeks when compared with infants where plasma alkaline phosphatase activity did not exceed the reference range. There was no difference in caloric intake between the groups. In the preterm infant biochemical rickets is common and unlike older children and adolescents an increase in plasma alkaline phosphatase activity correlates with decreased rather than increased growth.     

血清大分子碱性磷酸酶测定对新生儿阻塞性黄疸早期诊断价值的研究

目的　探讨血清大分子碱性磷酸酶 (HMAP)在新生儿胆道闭锁、新生儿肝炎中的差异性 ,以寻找新的对阻塞性黄疸早期诊断有鉴别意义的实验室指标。方法　阻塞性黄疸患儿 3 1例 ,其中胆道闭锁 15例 ,新生儿肝炎 16例 ;非阻塞性黄疸和健康儿各 3 0例作对照。全部标本各取血清1ml,储存于 -80℃冰箱内备检。采用患儿血清中提纯的HMAP做抗原 ,制备特异性单克隆抗体 ,以硝酸纤维素膜片为固相 ,用此特异性单克隆抗体建立测定血清中HMAP的免疫催化方法。同时测定患儿血清碱性磷酸酶总活性 (TALP)和γ 谷氨酰转肽酶 (γ GT) ,并做肝胆B超和肝胆核素扫描检查。所得数据做统计学处理 ,分析比较不同测定值的敏感性与特异性。结果　 15例胆道闭锁患儿血清HMAP阳性 14例 ,阳性率为 93 3 % ;16例新生儿肝炎患儿血清HMAP阳性 2例 ,阳性率为 12 5% ,两组比较 ,差异有非常显著意义 (P <0 0 0 5)。在临床资料的统计学处理中 ,两组仅大便颜色差异有显著性 ,其余均无统计学意义。胆道闭锁组和新生儿肝炎组血生化的TALP、γ GT和肝胆核素扫描结果差异均有显著性 ,但其敏感性与特异性分别为 80 0 %、73 3 %、86 7%和 62 5%、68 8%、62 5% ,明显低于HMAP的敏感性 ( 93 3 % )和特异性 ( 87 5% )。结论　血清HMAP在新生儿阻塞     

Maternal serum alkaline phosphatase and fetal maturity

Total as well as heat stable alkaline phosphatase activity was determined in sera of 70 normal pregnant mothers. Rise in activity was observed with advancement of gestation and was due to increased concentration of heat stable fraction. Statistically significant differences in levels between various gestational age groups suggest the assay of this enzyme for assessment of fetal maturity. Total alkaline phosphatase activity of 15 K.A. units/dl or more, with more than 50% of it being heat stable fraction, indicated a mature fetus (37 weeks or more gestation).     

Bone metabolism biomarkers, body weight, and bone age in healthy Brazilian male adolescents

Eighty-seven male volunteers were grouped according to bone age (BA): 10-12 years (n=25), 13-15 years (n=36), and 16-18 years (n=26), and the following were recorded for each: weight (kg), height (m), BMI (kg/m(2)), calcium intake from three 24-h food recalls (mg/day), puberty evaluation by Tanner stages, bone biomarker (BB) evaluation, serum osteocalcin (OC), bone alkaline phosphatase (BAP), carboxyterminal telopeptide (S-CTx), and bone mineral density (BMD) evaluations by dual-energy X-ray absorptiometry (g x cm(2)) in the lumbar spine, proximal femur, and the whole body. BBs showed similar behaviors, and very high median values were observed for individuals aged 13-15 years (BAP = 155.50 IU/L, OC = 41.63 ng/mL, S-CT x =2.09 ng/mL). Lower median BB values were observed with advancing BA between 16 and 18 years (BA P =79.80 IU/L, O C =27.80 ng/mL, S-CT x =1.65 ng/mL). Stepwise multiple regression analysis showed body weight associated with BA as independent variables with greater determination power for S-CTx (r(2) = 0.40) and OC (r(2)=0.21). For BAP, stepwise analysis showed body weight and whole-body BMD (r(2) = 0.34). All predictive models showed significance ( p < 0.01). A high turnover for both bone formation and resorption biomarkers, particularly from 13 to 15 years of BA, were observed along with very low values in the 16-18 age range. Weight and BA were significant in determining predictive equations of OC and of S-CTx, whereas for BAP, weight and BMD of full body were selected.     

Effect of zinc supplementation on growth hormone secretion, IGF-I, IGFBP-3, somatomedin generation, alkaline phosphatase, osteocalcin and growth in prepubertal children with idiopathic short stature

Controversy exists about the effect of zinc on growth and the GH-IGF system. Zinc supplementation has been shown to stimulate linear growth in zinc-deficient children. However the mechanism of this effect has not been well characterized. Furthermore, the effect of zinc supplementation on non-zinc-deficient short children is unknown. We investigated the effect of zinc supplementation on endogenous GH secretion, serum IGF-I and IGFBP-3 concentrations, IGF-I and IGFBP-3 generation in response to exogenous GH, bone formation markers, and linear growth of non-zinc-deficient children with idiopathic short stature. We analyzed prospectively serum zinc, IGF-I, IGFBP-3, alkaline phosphatase, osteocalcin, and GH response to clonidine test, and performed a somatomedin generation test before and 6 weeks after zinc supplementation in 22 (16 M, 6 F) prepubertal children with idiopathic short stature. Serum IGF-I increased from 67.4+/-70.6 to 98.2+/-77.3 ng/ml (p <0.001), IGFBP-3 from 2326+/-770 to 2758+/-826 ng/ml (p <0.001), alkaline phosphatase from 525+/-136 to 666+/-197 U/l (p <0.0001), and osteocalcin from 16.8+/-10.6 to 25.8+/-12.8 ng/ml (p <0.05) after zinc supplementation despite there being no difference in GH response to clonidine after zinc supplementation (peak GH 11.6+/-6.9 vs 13.4+/-7.8 ng/ml, GH area under the curve during clonidine test 689+/-395 vs 761+/-468, NS). Percent change in IGF-I and IGFBP-3 during the somatomedin generation test was not significantly affected by zinc supplementation (118% vs 136% and 57% vs 44%, respectively). There was no significant correlation between percentage increase in zinc levels and percentage increase in parameters tested. Height SDS or weight SDS did not improve significantly in 17 patients who continued on zinc supplementation for at least 6 months (6-12 months) (-2.59 vs -2.53 SDS and -1.80 vs -1.67 SDS, respectively). Zinc supplementation increased basal IGF-I, IGFBP-3, alkaline phosphatase and osteocalcin without changing GH response to clonidine. Zinc supplementation did not affect sensitivity to exogenous GH as tested by IGF-I and IGFBP-3 generation test. These results suggest a direct stimulatory effect of zinc on serum IGF-IGFBP-3, alkaline phosphatase and osteocalcin. Despite improvements in the above parameters, zinc supplementation to children with idiopathic short stature with normal serum zinc levels did not significantly change height or weight SDS during 6-12 months follow-up.     

Maternal serum urea resistant alkaline phosphatase in Down syndrome pregnancy

BACKGROUND: The normal levels of alkaline phosphatase (AP) activity in maternal serum are virtually the same as those observed in Down syndrome (DS) pregnancies at 14-20 weeks' gestation. Using urea inhibition of AP, we observed an atypical AP isoenzyme in the neutrophils of mothers with trisomy 21 fetuses. AIM: To assess the use of urea as a selective inhibitor of serum AP in order to seek a possible diagnostic difference between normal and DS pregnancies. STUDY DESIGN AND SUBJECTS: Serum AP samples from 24 DS pregnancies and 204 control cases were examined at 12-22 weeks' gestation with and without 2.5 M urea AP inhibition at 18 degrees C for 2 h. The levels of AP activity obtained without urea and the percentage urea AP inhibition were analyzed in the two groups. RESULTS: Without urea treatment, no significant difference of total alkaline phosphatase activity levels was detected between the 204 normal controls and the 24 DS samples. Using 2.5 M urea AP inhibition, after 120 min of exposure at 18 degrees C, the residual activity, as a percentage of initial values of AP, showed significantly higher resistance in the DS samples (> or = 50 IU/l of total AP activity) at 15-22 weeks' gestation. However, at 12-14 weeks (< or = 45 IU/l of total AP activity), no significant difference was found between the DS and control cases. CONCLUSION: Serum urea resistant alkaline phosphatase in DS pregnancies showed a significant difference only at 15-22 weeks' gestation, compared with normal controls.     

Characterization of serum alkaline phosphatase in infancy and childhood

In 364 serum samples of cord blood, infants, children, and adults alkaline phosphatase was characterized by means of L-phenylalanine inhibition, L-homoarginine inhibition, heat inactivation, acrylamide gel disc electrophoresis, and neuraminidase sensitivity. The increase of serum alkaline phosphatase in cord blood serum and in infant's and children's serum in comparison with adult levels was attributed mainly to the bone enzyme and in smaller proportion to the intestinal enzyme. Using acrylamide gel disc electrophoresis, an increase in the frequency of subjects with an intestinal alkaline phosphatase band with increasing age values was found.This work was supported by the National Research Council.     

Plasma insulin-like growth factors (IGFs), IGF-Binding proteins (IGFBPs), acid-labile subunit (ALS) and IGFBP-3 proteolysis in individuals with clinical characteristics of Sotos syndrome

OBJECTIVE: Sotos syndrome is an overgrowth syndrome of poorly understood aetiology. We investigated whether this syndrome is related to alterations in plasma insulin-like growth factors (IGFs), IGF-binding proteins (IGFBPs), acid-labile subunit (ALS) and serum IGFBP-3 proteolysis. DESIGN: Based on clinical criteria, 32 patients with clinical characteristics of Sotos syndrome (median age 8.4 years, range 1.8-48.4) were categorised into three groups: typical (n = 10, group 1), dubious (n = 12, group 2) and atypical (n = 10, group 3). Blood samples were obtained from 29 patients. MEASUREMENTS: Plasma IGF-I, IGF-II, E-II (pro-IGF-II and E-domain fragments), IGFBP-2, IGFBP-3, IGFBP-4, IGFBP-6 and ALS were measured by specific radioimmunoassays (RIAs). Except for E-II immunoreactivity, the concentrations were compared with those of age references, and expressed as standard deviation scores (SDS). IGFBP-3 proteolysis was assessed by incubation of serum with [125I]-IGFBP-3, followed by gel electrophoresis and was then compared with that in normal serum and third trimester pregnancy serum. RESULTS: Patients in group 1 showed significantly reduced plasma levels of IGF-II (median -0.9 SDS; p = 0.01), IGFBP-4 (-0.5 SDS; p = 0.02) and IGFBP-3 (-1.0 SDS; p = 0.01). Mean IGFBP-3 proteolysis was higher than in normal standard serum (61% vs 37%; p < 0.01) but lower than in third trimester pregnancy serum (94%; p < 0.01). Plasma IGF-I showed a tendency towards low values (median -0.9 SDS; p = 0.09), IGFBP-6 and ALS a tendency towards elevated levels (median values +0.8 SDS; p = 0.07 and +2.3 SDS; p = 0.09), and IGFBP-2 was normal. The mean value of E-II immunoreactivity was 8.7 nmol/l, similar to that in pooled normal plasma (8.6 nmol/l). Plasma and serum parameters in groups 2 and 3 were similar to reference values with the exception of plasma IGFBP-3 (in groups 2 and 3 median < or = -1.1 SDS; p < or = 0.02) and ALS (in group 3 median +1.3 SDS; p < 0.01). CONCLUSIONS: Patients with typical Sotos syndrome show low plasma IGF-II, IGFBP-3, IGFBP-4, and increased proteolysis of IGFBP-3 in serum. The extent to which these findings are associated with the pathophysiology of Sotos syndrome remains uncertain.     

Urinary hydroxyproline: relationship to growth, bone mineral content, and serum alkaline phosphatase level in premature infants

There is little information on urinary hydroxyproline (UHP) excretion in premature infants. We hypothesized that UHP excretion would positively correlate with growth in premature infants, and that there would be correlations between UHP excretion and serum alkaline phosphatase concentration as well as bone mineral content (BMC). Twenty-six premature infants (birth weight, less than 1,300 g; gestational age, less than or equal to 32 weeks) received one of four oral feedings. Seven received mother's own milk (HM), and eight received mothers own milk fortified with 0.85 g/dl of bovine whey, 90 mg/dl of Ca, and 45 mg/dl of P. Six and five infants received Similac, 20 cal/oz (SIM) and Similac Special Care, 20 cal/oz, respectively. Measurements of UHP, serum alkaline phosphatase, BMC (photon absorptiometry), and growth were made during the 1st 7 weeks of life. The lowest UHP excretion was in the HM group. For all infants, there was a significant correlation between UHP excretion (mg/day) and absolute weight (r = 0.64, p less than 0.001), as well as rate of weight gain (r = 0.50, p less than 0.01). The UHP excretion (milligrams per day) also correlated with absolute length (r = 0.41, p less than 0.01) and rate of gain in length (centimeters per week) (r = 0.70, p less than 0.001). The UHP excretion did not correlate significantly with BMC or serum alkaline phosphatase concentration. We conclude that UHP excretion is increased in the growing premature infant compared to older infants and adults and is a good marker for somatic growth in this population.(ABSTRACT TRUNCATED AT 250 WORDS)     

Placental alkaline phosphatase in pediatric adrenocortical cancer

The germline R337H mutation in the TP53 gene is considered to be responsible for the increased incidence of adrenocortical tumors (ACTs) in children from Brazil. High level production of hormones in ACTs (>95%) cause virilization alone (60%), Cushing syndrome (<5%), the mixed type (30%), or other rarer manifestations. ACT probably develops owing to events occurring during the final stages of intrauterine life based on the very common early onset of signs and symptoms shortly after birth. In this study, we determined by immunohistochemistry and enzyme assays whether placental alkaline phosphatase (PLAP) is expressed in pediatric ACTs. Immunohistochemical analysis revealed positive p53 expression in 88% of the tested ACTs (29 of 33). PLAP was detected at a slightly lower frequency based on immunohistochemical (17 of 33, 51%) and enzyme activity analyses (9 of 16, 56%). In conclusion, probably at a certain time point during adrenocortical development (end of gestation to early postnatal period), some fetal zone cells survive owing to defective apoptosis and develop into childhood ACT, maintaining some characteristics of the embryonal period, such as PLAP expression. Further studies of PLAP should investigate the functional role, if any, of PLAP in such tumors.     

Leukocyte alkaline phosphatase (LAP) activity in health and infections of infancy

Leukocyte alkaline phosphatase (LAP) activity was determined in healthy neonates and 1–12 months old infants. As compared to the control values of 142±13.85 (range 118–163), in the neonatal infections of bacterial origin, the LAP score fell down to 115.92±35.91 (range 79–202) with p-value of <0.05; while in the nonbacterial infections the values were 120.91±15.68 (range 95–151) with a p value of <0.01. During the postneonatal period of infancy, healthy controls had values of 100.5±7.41 (range 88–113) which rose to 147.7±28.42 (range 90–205) in bacterial infections with a p value of <0.001 but in the nonbacterial infections, the score observed was 95.8±13.50 (range 80–118) with a p value of >0.05. The diagnostic importance of the test was assessed.     

Evaluation of the activity of tartrate-resistant acid phosphatase isoform 5b in normal Chinese children--a novel marker for bone growth

BACKGROUND: Most parents are very concerned about the height of their children. Biochemical markers of bone formation and resorption may provide useful clinical predictors for bone growth. Tartrate-resistant acid phosphatase 5b (TRAcP 5b) has been advocated as a biomarker of osteoclast activity and bone resorption. However, the TRAcP 5b levels of children at different ages are still unknown. It is necessary to accumulate and analyze the data for healthy children at different ages. OBJECTIVES: We use an improved immunoassay for bone TRAcP 5b to examine sera from children to see whether it is a significant marker of bone growth. METHODS: Serum, including cord blood, was collected from 404 normal Chinese children (age range 0-17 years; 225 male, 179 female). The venous blood was withdrawn from the peripheral vein and stored at 4 degrees C before centrifugation for serum collection. All sera were stored at -70 degrees C and thawed at 37 degrees C immediately before TRAcP 5b levels were measured. Bone-specific alkaline phosphatase (BAP) was also used for comparison with TRAcP 5b levels at different ages. RESULTS: TRAcP 5b levels were extremely high in infants of both genders, gradually decreasing with age (p <0.001). A second peak in TRAcP 5b values occurred at 12-13 and 10-11 years in males and females, respectively (p <0.001). Age alone, as well as age-related changes between the male and female groups, were independent predictors of TRAcP 5b levels (p <0.001). There was no significant between-gender difference in serum TRAcP 5b levels for any age group (p = 0.682). BAP values did not show a significant second peak in females. Age and gender alone, as well as the age-related changes between male and female groups, were independent predictors of BAP values (p <0.001). CONCLUSION: Preliminary results were established for serum TRAcP 5b and BAP values of normal Chinese children of different ages. Elevated serum TRAcP 5b values were observed during infancy and puberty for both genders. The pattern of this age-related change in serum TRAcP 5b levels is similar to the shape of the standard height velocity curve for healthy children. Values of BAP were less specific than TRAcP 5b. These data may prove valuable as a normal reference in future research about bone markers.     

Serum leptin and leptin binding activity in children and adolescents with hypothalamic dysfunction

Marked disturbance in eating behaviour and obesity are common sequelae of hypothalamic damage. To investigate whether these were associated with dysfunctional leptin central feedback, we evaluated serum leptin and leptin binding activity in 37 patients (age 3.5-21 yr) with tumour or trauma involving the hypothalamic-pituitary axis compared with 138 healthy children (age 5.0-18.2 yr). Patients were subdivided by BMI <2 SDS or > or = 2 SDS and healthy children and children with simple obesity of comparable age and pubertal status served as controls. Patients had higher BMI (mean 1.9 vs 0.2 SDS; p <0.001), a greater proportion had BMI > or = 2 SDS (54% vs 8%; p <0.001) and higher serum leptin (mean 2.1 vs 0.04 SDS; p <0.001) than healthy children. Serum leptin (mean 1.1 vs -0.1 SDS; p = 0.004) and values adjusted for BMI (median 0.42 vs 0.23 microg/l:kg/m2; p = 0.02) were higher in patients with BMI <2 SDS. However, serum leptin adjusted for BMI was similar in patients with BMI > or = 2 SDS compared to corresponding controls (1.08 vs 0.95; p = 0.6). Log serum leptin correlated with BMI SDS in all subject groups but the relationship in patients with BMI <2 SDS was of higher magnitude (r = 0.65, slope = 0.29, p =0.05 for difference between slopes) than in healthy controls (r = 0.42, slope = 0.19). Serum leptin binding activity (median 7.5 vs 9.3%; p = 0.02) and values adjusted for BMI (median 0.28 vs 0.48 % x m2/kg; p <0.001) were lower in patients than in healthy children. The markedly elevated leptin levels with increasing BMI in non-obese patients with hypothalamic-pituitary damage are suggestive of an unrestrained pattern of leptin secretion. This along with low leptin binding activity and hence higher free leptin levels would be consistent with central leptin insensitivity.     

Growth in children with X-linked hypophosphataemic rickets

Currently, X-linked hypophosphataemic rickets (XLHR) is most commonly treated with a combination of phosphate and vitamin D, but there is conflicting evidence about the effects of this treatment on linear growth. In all, 25 patients with XLHR (current age range, 4.1–22.1 years; median, 8.2 years) were studied to determine whether there was any improvement in height SDS during treatment. The duration of therapy was 2.9–15.0 years (median, 5.7 years). Measurements before the age of 2 years or after the onset of puberty were excluded to remove the effects of measurement difficulties in small infants and of variation in pubertal timing. The growth of these patients was compared with a similar group of untreated historical controls. Patients treated with calcitriol and phosphate for at least 2 years before the onset of puberty (n = 22) had a significantly better mean height SDS than the historical controls (-1.23 compared with —2.05 for the historical controls; p = 0.02). Among patients treated with calcitriol and phosphate for at least 2 years (n = 21), the change in height SDS had a positive correlation with the duration of therapy ( r = 0.51; p = 0.02). The growth of children with XLHR treated with combination therapy was thus significantly better than that of historical controls.     

Increased respiratory burst response and alkaline phosphatase activity in human cord blood neutrophils

The priming effect of a bacterial lipopolysaccharide (LPS) on subsequent respiratory burst activity induced by either the chemoattractant formylmethionyl-leucyi-phenylalaninc (fMLP) or phorbol myristate acetate (PMA; a protein kinase C activator) was studied in human ncutrophils isolated from cord blood and adult peripheral blood. Cells from adults, but not from newborn babies, were primed by LPS pretreatment. The content and release of β-glucuronidase and vitamin-B12 binding protein, or marker for the azurophilic and specific granules, respectively, was similar for cells from infants and adult controls. In contrast, alkaline phosphatase activity was significantly increased in the cord blood neutrophils compared to neutrophils from adult peripheral blood. The latency of the alkaline phosphatase activity was, however, similar. Thus, the primed response of cord blood neutrophils could not be explained by an increased release of azurophilic or specific granule content. If the increased alkaline phosphatase activity of curd cells represents an increased number of secretory vesicles, however, then this would indicate a rapid turnover leading to delivery of new receptors and oxidase components to the cell membrane.     

Long-term monitoring of treatment with recombinant human growth hormone by serial determinations of type III procollagen-related antigens in serum

Inasmuch as recombinant human growth hormone is now more generally available for the treatment of different types of short stature, there is a need for better short-term indicators of treatment success. In healthy children, serum concentrations of antigens related to the aminoterminal propeptide of type III procollagen (P-III-NP) closely follow the growth velocity curve. P-III-NP was measured longitudinally in 20 children with growth hormone deficiency during 6 months of human growth hormone substitution therapy. Two different radioimmunoassay systems were used; one recognizes predominantly the intact propeptide showing a lesser affinity to a smaller monomeric peptide (RIAgnost assay), while the other assay detects both forms equally (FAB assay). These results were compared to the growth response [median 5.6 (0.4 to 13.9) cm in 6 months] and to other established growth correlated parameters (somatomedin C, alkaline phosphatase). A relatively better growth response correlated significantly with high pretreatment P-III-NP (RIAgnost assay) values (r = 0.56) and delayed bone age (r = -0.70). A combination of these parameters in multiple regression analysis increased the cumulative prediction value to above 60% (r2 = 0.61). On the other hand, P-III-NP (FAB assay) values proved to be best in monitoring treatment, correlating with the individual growth rate during the first 3 months (r = 0.40; p less than 0.05), during the consecutive 3 months (r = 0.66; p less than 0.001), and during the total 6-month period (r = 0.46; p less than 0.05). All other parameters showed associations to growth only during some treatment periods.(ABSTRACT TRUNCATED AT 250 WORDS)     

Biochemical markers of bone turnover in the diagnosis of renal osteodystrophy in dialyzed children

In this study we investigated the value of biochemical markers of bone turnover in the diagnosis of renal osteodystrophy in dialysis patients. The study was carried out in 22 chronic renal failure patients (mean age: 16.1 +/- 4.5) being treated with chronic dialysis. There were three groups according to intact parathormone (iPTH) levels: Group I (n: 6): iPTH levels were less than 200 pg/ml; Group II (n: 9): iPTH levels were between 201 and 500 pg/ml; and Group III (n: 7). iPTH levels were higher than 501 pg/ml. We investigated iPTH, bone alkaline phosphatase, total serum alkaline phosphatase, osteocalcin, serum type 1 procollagen peptide (PICP) and insulin-like growth factor-1 (IGF-1) levels in all patients. In group III mean bone alkaline phosphatase level (126.0 +/- 10.95) was significantly higher than in both group I and group II (52.16 +/- 22.8, 57.35 +/- 16.21) (p < 0.001). Mean osteocalcin level (35.13 +/- 2.93) in group I was significantly lower than in group III (40.52 +/- 2.83) (p < 0.05). Serum alkaline phosphatase, PICP and IGF-1 levels were not different between the groups (p > 0.05). There was a significant positive correlation between bone alkaline phosphatase and iPTH (r = 0.80, p < 0.0001). Serum osteocalcin correlated with both bone alkaline phosphatase and iPTH (correlation) coefficients were r = 0.44 and r = 0.51 respectively, p < 0.05). It is concluded that bone alkaline phosphatase and osteoocalcin combined with iPTH level seem to be useful noninvasive markers of bone metabolism in dialysis patients.     

Studies Alkaline Phosphatase during Development Part II: Changes in alkaline phosphatase activity and isozyme patterns in the serum of healthy children and of children with various diseases

In order to clarify the organ origins of high serum alkaline phosphatase in children during development and in children with various diseases, the serum alkaline phosphatase activity and isozyme patterns of children, umbilical cord blood and pregnant woman were investigated by the agar gel electrophoresis and heat stability test. In two infant autopsy cases, isozyme patterns were also investigated in several organs. 1) Serum alkaline phosphatase activity of children was about 2.5 to 3 times as high as that of adults. In the group below 1 year of age and the group between 11 and 15 years of age, the levels were higher than in other groups. 2) Alkaline phosphatase isozyme pattern in normal serum was showed as a single band (band III) around the α₂-globulin fraction in all groups. 3) The alkaline phosphatase isozyme patterns in normal serum were divided into a pattern with non-shifting peak after heat treatment at 56°c for 10 minutes and another with shifting peak to α₁-globulin side. In younger groups, the pattern with non-shifting peak was more frequently seen and with growing the pattern with shifting peak increased. In adults, the peak shifted in all cases after heat treatment. 4) The decreasing rate of alkaline phosphatase activity of normal serum by heat treatment was within the range of about 70–80% in each age group without remarkable differences. No calculation was possible in adult group, because the activity was markedly low. 5) Serum alkaline phosphatase activity of pregnant women showed slightly higher than umbilical cord blood, about 3 times higher than in normal adults. The isozyme patterns were different between sera of pregnant women and umbilical cord blood. The decreasing rate of alkaline phosphatase activity after heat treatment (56°c for 10 minutes) was less in serum of pregnant women than in other sera, showing greater heat stability. 6) Serum alkaline phosphatase was always high in diseases of liver and bone. Five bands of alkaline phosphatase activity were noted in the sera of normal subjects, pregnant women and children with various diseases. In liver diseases without marked obstruction and in bone diseases, the alkaline phosphatase isozyme pattern appeared in α₂-globulin band (band III). In liver diseases with marked obstruction, α₁-globulin band (band II originated from the liver) and β-globulin band (band V probably from intestine) appeared. In one case, an Albumin-α₁ globulin band (band I) appeared. 7) The alkaline phosphatase isozyme patterns in liver, bone, small intestine and kidney showed different electrophoretic migration rates indicating organ specificity. 8) To sum up, serum alkaline phosphatase of the healthy children appeared to be originated from liver and bone. During childhood the alkaline phosphatase predominantly consists of bone origin, while in adults, major activity appeared to be hepatic origin.