Artificially low cortical bone mineral density in Turner syndrome is due to the partial volume effect.

UNLABELLED: We aimed to show that the decrease in the cortical bone mineral density (BMD) in the radius in Turner syndrome (TS) is artificially caused by the partial volume effect. We confirmed that the partial volume effect-corrected cortical BMD is not decreased in TS compared to in the healthy controls. Other factors are responsible for the increased fracture rate in TS. INTRODUCTION: Decreased cortical bone mineral density (BMD) has been reported in Turner syndrome (TS), using peripheral quantitative computerised tomography, and it is perceived as one of the major factors leading to increased fracture risk. We tested the hypothesis that low cortical BMD in the radius is caused artificially by the partial volume effect. METHODS: A cross-sectional study was conducted at the university hospital referral centre between March and October 2013. Thirty-two participants with TS who consented to the study were included (mean age 15.3 ± 3.2 years). We assessed the cortical BMD in the radius as well as the tibia, where the cortex is thicker compared with the radius. RESULTS: Whereas the cortical BMD was decreased in the radius (mean ± SD Z-score -0.6 ± 1.5, p = 0.037), it was increased in the tibia (mean Z-score 0.83 ± 1.0, p < 0.001). After correcting the cortical BMD for the partial volume effect, the mean Z-score was normal in the radius in TS (0.4 ± 1.3, p = 0.064). The corrected cortical BMD values were similar in the radius and tibia (1108 ± 52 vs. 1104 ± 48, group difference p = 0.75). CONCLUSIONS: The cortical BMD is not decreased in TS. The partial volume effect is responsible for previous findings of decreased cortical BMD in the radius. Altered bone geometry or other factors rather than low cortical BMD likely play a role in the increased fracture risk in TS.

Long-term Surveillance of Children with Congenital Hypothyroidism: Data from the German Registry for Congenital Hypothyroidism (AQUAPE "Hypo Dok").

BACKGROUND: The German study group for quality assurance in pediatric endocrinology and the University of Ulm have established a software ("Hypo Dok") for the documentation of longitudinal data of patients with congenital primary hypothyroidism (CH). Aim of this study was to analyse the long-term follow-up of patients with CH and to compare treatment with current guidelines. METHODS/PATIENTS: Anonymised data of 1,080 patients from 46 centres were statistically analysed. RESULTS: Newborn screening result was available at a mean age of 7.3 days. Confirmation of the diagnosis was established at 8.4 days and therapy was started at 11 days. The average screening TSH was 180.0 mIU/L. During the first 3 months mean levothyroxine (LT4) dose was 10.7 µg/kg/day or 186.0 µg/m²/day. Weight-, BMI- and height-SDS did not differ significantly from the normal population. Only 25% of the patients (n=262) underwent formal EQ/IQ-testing. Their average IQ was 98.8 ± 13.2 points. DISCUSSION: In Germany screening, confirmation and start of treatment of CH are within the recommended time frame of 14 days. Initial LT4-doses are adequate. The auxological longterm outcome of young CH patients is normal. The implementation of standardized IQ testing has to be improved in routine patient care. CONCLUSION: Longitudinal data of patients with CH was analysed and compared to current guidelines. Confirmation and start of treatment are according to the recommendations. However standardised IQ testing requires improvement.

Musculoskeletal pain: a new algorithm for differential diagnosis of a cardinal symptom in pediatrics.

Musculoskeletal pain (MSP) is a common childhood complaint associated with multiple differential diagnoses, including cancer. Considering the expanding spectrum of diagnostics, evaluat-ing a young patient with MSP is a challenge today, particularly for non-specialists in a primary care setting. Since childhood cancer is rare and most cardinal symptoms mimic rather non-serious diseases, misdiagnosis is not uncommon, but of significant prognostic relevance. To build the appropriate bridge between primary and secon-dary care for a child presenting with MSP, thereby preventing treatment delay and longterm sequelae, initial evaluation should follow a comprehensive, multidisciplinary, systematic and stepwise approach, which unites the patient's individual anamnestic, psychosocial, and clinical charac-teristics. After a systematic review of the literature, we generated multidisciplinarily quality-assured recommendations for efficient, rational and cost-effective primary care assessment of pediatric MSP. The algorithm promotes the identification and structured interpretation of the patient's individual clinical clues. It should serve the primary care physician to recognize when further intervention, rather than reassurance and follow-up, is needed using the minimum amount of testing to make an appropriate, prompt diagnosis in the clinical situation "child presenting with MSP". A German version of this algorithm has been published in the Guideline-Portal of The Association of the Scientific Medical Societies ("Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften", AWMF) in November 2013.

Measuring procedures to determine the Cobb angle in idiopathic scoliosis: a systematic review.

BACKGROUND: Scoliosis of the vertebral column can be assessed with the Cobb angle (Cobb 1948). This examination is performed manually by measuring the angle on radiographs and is considered the gold standard. However, studies evaluating the reproducibility of this procedure have shown high variability in intra- and inter-observer agreement. Because of technical advancements, interests in new procedures to determine the Cobb angle has been renewed. This review aims to systematically investigate the reproducibility of various new techniques to determine the Cobb angle in idiopathic scoliosis and to assess whether new technical procedures are reasonable alternatives when compared to manual measurement of the Cobb angle. METHOD: Systematic review. Studies examining procedures used to determine the Cobb angle were selected. Two review authors independently selected studies for inclusion, extracted data and assessed risk of bias. Statistical results of reliability and agreement were summarised and described. RESULTS: Eleven studies of new measuring procedures were included, all reporting the reproducibility. The new procedures can be divided into computer-assisted procedures, automatic procedures and smartphone apps. CONCLUSIONS: All investigated measuring procedures showed high degrees of reliability. In general, digital procedures tend to be slightly better than manual ones. For all other measurement procedures (automatic or smartphone), results varied. Studies implementing vertebral pre-selection and observer training achieved better agreement.

[Childhood and adolescent obesity--consequences for the locomotor system and treatment options. Musculoskeletal complications of overweight children and adolescents]. / Kindliche Adipositas - Folgen für den Bewegungsapparat und Therapieansätze. Muskuloskelettale Komplikationen bei Übergewicht und Adipositas im Kindes- und Jugendalter.

The aim of this article is to present the most relevant musculoskeletal complications known to be associated with being overweight or obese in childhood and adolescence in order to help the clinicians and physiotherapists in the diagnostic and management of these patients. Various musculoskeletal problems like slipped capital femoral epiphysis and Blount disease are well-known complications. More recent studies describe the effects of overweight on musculoskeletal pain and controversial influences on fracture rates. Reduced physical activity is a contributing factor in obesity, but also effects bone mineral accrual. Reduced postural stability and increased falls may be the reason for increased fracture rates. Furthermore these data show relevant changes of locomotion studied by gait analysis. Longitudinal kinematic studies may be needed to understand the entire aspect of gait development in overweight children. Obesity is still a serious health problem and has a relevant impact on the development of a child's musculoskeletal system. Obesity affects the locomotor sytem both functionally and structurally. Future studies are necessary to help us better understand the pathophysiology and development of optimal therapeutic strategies.

[Perioperative enhanced recovery after surgery program for Ivor Lewis esophagectomy : First experiences of a high-volume center]. / Perioperatives "Enhanced-recovery-after-surgery"-Programm der Ivor-Lewis-Ösophagektomie : Erste Erfahrungen eines High-volume-Zentrums.

BACKGROUND AND OBJECTIVE: Transthoracic esophagectomy is generally accepted as the standard of surgical care for patients with esophageal cancer. Despite improvements in the perioperative management this surgical procedure is associated with a clinically relevant morbidity. Fast-track protocols (synonym: enhanced recovery after surgery, ERAS) are conceived to perioperatively maintain the physiological homoeostasis and thereby to accelerate postoperative rehabilitation and reduce morbidity. In this prospective observational study the initial experiences of a high-volume center with the implementation of an ERAS protocol after transthoracic esophagectomy were analyzed. MATERIAL AND METHODS: A total of 26 patients with esophageal cancer and a low index of comorbidities prior to hybrid Ivor Lewis esophagectomy were included in this study. According to an ERAS protocol all patients underwent a standardized perioperative treatment pathway aiming to discharge the patients from the inpatient treatment on postoperative day 10. The primary outcome parameter was the rate of major complications (Clavien-Dindo IIIb/IV), which was compared to a cohort of 52 non-ERAS patients. RESULTS AND CONCLUSION: The ERAS programs with the various core elements can be implemented in patients scheduled for transthoracic esophagectomy, although the organizational and personnel expenditure of this fast-track protocol is high. The length of hospital stay appears to be reduced without compromising patient safety. The limiting variable of the ERAS protocol remains the early and adequate enteral feeding load of the gastric conduit before discharge on postoperative day 10.

Insulin binding to antibodies is a risk factor for inexplicable severe hypoglycaemia in children with type-1 diabetes mellitus.

BACKGROUND: Type-1 diabetic individuals differ with regard to both, the formation of circulating insulin antibodies, and the incidence of severe hypoglycaemia. AIM OF THE STUDY: To assess the association of insulin binding to antibodies with the incidence of severe hypoglycaemia. PATIENTS AND METHODS: In a cross sectional study, 73 children with type-1 diabetes mellitus (median age 14 years, duration of diabetes 6 years) were investigated, 22 of whom had experienced severe hypoglycaemia during the past 18 months, and 51 had never experienced severe hypoglycaemia. Of the patients with severe hypoglycaemia 16 had experienced severe unexplained hypoglycaemias, and 6 had experienced severe hypoglycaemias which were explicable (by missed meals, unplanned physical exercise etc.). Insulin binding was measured in a blinded central laboratory by radioimmunoassay, and expressed as ratio bound/unbound insulin; a binding >15% was considered relevant insulin binding. RESULTS: A total of 38 patients displayed relevant insulin binding (17 of whom had experienced severe hypoglycaemia), and 35 patients did not (5 of whom had experienced severe hypoglycaemia; p=0.0055, Fisher's exact test). Patients with relevant insulin binding were younger (12.2 vs 14.5 years, p=0.006) than patients without relevant insulin binding. From the 16 patients with inexplicable severe hypoglycaemia, 15 displayed relevant insulin binding, compared to 2 of the 6 patients with explicable severe hypoglycaemia (p=0.009). The association of any severe hypoglycaemia, and of inexplicable severe hypoglycaemia, with relevant insulin binding was significant (odds ratio 4.8 (95%CI 1.5-15.2), and 22.1(95%CI 2.7-179.6), p<0.006). Patients with/without relevant insulin binding, or with/without severe hypoglycaemia, did not differ significantly regarding sex, duration of diabetes, number of insulin injections per day, HbA1c and C-peptide levels (ANOVA). CONCLUSION: Insulin binding to antibodies >15% appears to be a strong risk factor for inexplicable severe hypoglycaemias in type-1 diabetic children.

Clinical characteristics of type 2 diabetes mellitus in overweight European caucasian adolescents.

AIM: To present the clinical features of Type 2 diabetes mellitus (T2DM) in overweight European Caucasian children and adolescents. METHODS: We report the clinical characteristics of 16 non-syndromal overweight European Caucasian adolescents with T2DM (10 boys, 6 girls, SDS-BMI in median +2.8, range +1.6 to +3.4) treated in 5 specialised centres for obesity and diabetes. RESULTS: None of the adolescents manifested with ketoacidosis. 13 were asymptomatic (3 adolescents with polyuria), 12 showed features of metabolic syndrome (dyslipidaemia or hypertension), 8 demonstrated acanthosis nigricans and 12 had relatives with T2DM. 11 adolescents were extremely obese and all patients were pubertal. Mean age at diagnosis was 14.2 years (range 11.0 - 16.9). Median insulin was 19 microU/ml, insulin resistance index (HOMA) 8.5, C-peptide 2.3 ng/ml, HbA1c 6.9 %, fasting blood glucose 176 mg/dl and blood glucose at 2 hours with the oGTT 229 mg/dl at manifestation. Fasting blood glucose and HBA1c were in the normal range in 4 and 6 adolescents respectively, while oGTT always fitted the diagnosis of T2DM. CONCLUSION: Since T2DM occurred in Caucasian overweight adolescents and is frequently asymptomatic, it is essential that clinicians perform diagnostic procedures to identify T2DM in high-risk groups of overweight Caucasian adolescents (extreme obesity, features of metabolic syndrome, relatives with T2DM).

Determinants of radial bone density as measured by PQCT in pre- and postmenopausal women: the role of bone size.

The aim of the present study was to examine the influence of anthropometric, hormonal, and geometric factors on the variability of radial bone mineral density (BMD) in women. In 583 healthy pre- and postmenopausal females (aged 40-60 years) radial total (BD) and trabecular BMD (TBD) was measured by peripheral quantitative computerized tomography at the nondominant distal forearm. In addition, 29 women who had suffered a Colles' fracture after minor trauma were also evaluated. There was no age-dependent change in radial BD and TBD before menopause. We found a negative correlation between BMD and age and years since menopause (YSM) in postmenopausal women (BD = 422.73 - 2.342 age - 6.308YSM; r = 0.36, p = 0.0001, n = 128). The variation of YSM, body mass index (BMI), and age accounted for 20% of the variability of BD in postmenopausal women. In contrast, in premenopausal women, only 3% of the variability could be explained by anthropometric variables. Bone mineral content (BMC) and bone area, but not BMD at the distal radius, were significantly correlated to grip strength (r = 0.25, p = 0.006 for BMC, r = 0.26, p = 0.003 for area). The cross-sectional bone area of the CT slice showed a significant increase with aging (y = 263.02 + 1.25x; r = 0.14, p = 0.0009). There was a strong negative correlation between bone area and BD and TBD (y = 516.04 - 0.668x; r = -0.57, p < 0.0001 for BD). If BMD is normalized for BA, variation is reduced by 32% (for BD) and 10% (for TBD), respectively. Women with Colles' fracture had a significantly lower TBD normalized for BA (fracture group [-0.71 +/- 0.88] vs. normals (0.03 +/- 0.99]; p = 0.00009). Our results show that YSM and BMI are predictors of postmenopausal BMD. However, radial BMD is influenced strongly by geometric variables such as cross-sectional bone area.

Asp361Val Mutant of alkaline phosphatase found in patients with dominantly inherited hypophosphatasia inhibits the activity of the wild-type enzyme.

Hypophosphatasia is characterized by the hypomineralization of bone associated with the mutation of the tissue-nonspecific alkaline phosphatase (TNSALP) gene. Although the disease is usually autosomal recessive, an autosomal dominant form is also recognized. Approximately 50 mutations have been found in the TNSALP gene in patients with hypophosphatasia. However, the mutations identified to date do not seem to account for the dominantly inherited form of the disease. We have examined a German family in which the father and all 4 children were affected with hypophosphatasia, whereas the mother was healthy. The affected members of this family showed premature loss of deciduous teeth at or shortly before 2 yr of age and low levels of serum ALP with elevated levels of urinary phosphoethanolamine. DNA analysis by direct sequencing revealed a heterozygous missense mutation that caused the conversion of amino acid Asp to Val at position 361 (D361V) in the patients. Another substitution was detected in exon 12 (Val to Ala conversion at codon 505: V505A) in 1 allele of the mother and 3 children, indicating no association of the substitution with the disease. Reconstruction experiments demonstrated that the D361V mutant protein lost its enzymatic activity and that it inhibited the function of wild-type enzyme when coexpressed in COS-7 cells. On the other hand, the V505A mutant exhibited enzymatic activities equal to those of the wild-type ALP. It is likely that the mutant D361V protein forms dimers with the wild-type protein, and the protein-protein interaction contributes to the dominant effect of the mutant D361V. The mutation that causes D361V is the first one proven to be associated with the dominant form of hypophosphatasia.

Urinary excretion of galactosyl-hydroxylysine is a marker of growth in children.

Galactosyl-hydroxylysine (Gal-Hyl) is the predominant product of the posttranslational glycosylation of skeletal collagen. Urinary Gal-Hyl excretion is regarded as a marker of bone resorption in adults, but little information is available on the validity of this parameter in pediatric age groups. Using 24-h urine samples from 88 healthy children and adolescents ages 4-18 yr, reference ranges were established for this age group, and values were compared with measurements in children with overt GH deficiency (n = 14) or Ullrich-Turner syndrome (n = 21). When expressed relative to body weight (Gal-Hyl/wt), urinary Gal-Hyl excretion was 3.2 to 4.7 times higher in subjects 4-16 yr of age than in adults. Highest values were observed in very young children and during the pubertal growth spurt. In the total population, urinary Gal-Hyl/wt was closely related to growth velocity (r = 0.72) and significantly correlated with the urinary excretion of both hydroxyproline (r = 0.74) and deoxypyridinoline (r = 0.88; P < 0.001 each). Urinary Gal-Hyl/wt was significantly lower in children with GH deficiency or Ullrich-Turner syndrome than in healthy children (P < 0.001 each). The urinary excretion of Gal-Hyl was significantly correlated with growth velocity in GH-deficient children (r = 0.69; P = 0.004) but not in patients with Ullrich-Turner syndrome. In the latter, the increase in urinary Gal-Hyl excretion after 3 months of treatment with recombinant human GH correlated significantly with the increase in growth velocity after 12 months of treatment (r = 0.76; P = 0.002). We conclude that the urinary excretion of Gal-Hyl is a valid and potentially useful index of skeletal growth in children.

Age at menarche and cortical bone geometry in premenopausal women.

Previous studies have suggested that the timing of puberty might have an impact on the adult skeleton. What composite of bone structure could be affected by the timing of puberty is unknown at present. In this study, we evaluated the relationship between age at menarche and bone cortex geometry at the distal radius. Using peripheral quantitative computed tomography, we determined total area of the radial cross section, cortical bone area, periosteal cortical perimeter, endosteal cortical perimeter, and cortical width in 169 healthy premenopausal women aged 40-45 years. When stratified according to age at menarche (early, <12 years In = 22]; intermediate, 12-14 years [n = 118]; late, >14 years [n = 29]), only endosteal cortical perimeter varied significantly between the groups (p = 0.02, by analysis of variance), the mean value being 10% higher in the late compared to the early menarche group. However, weight and body mass index also exhibited significant variations between groups. After adjustment for weight the differences in endosteal cortical perimeter remained significant (p = 0.03). In multiple regression analysis, endosteal cortical perimeter was the only parameter of cortex geometry, which was independently associated with age at menarche. In a model including height and weight, age at menarche explained about 2% of the variability in endosteal cortical perimeter (p = 0.04). These data suggest that the bone marrow cavity of the distal radius may be slightly larger when puberty occurs later. Whether this marginal effect influences fracture risk in later life appears questionable.

A new and accurate prediction model for growth response to growth hormone treatment in children with growth hormone deficiency.

OBJECTIVE: To identify parameters which predict individual growth response to recombinant human GH (rhGH) therapy and to combine these parameters in a prediction model. DESIGN: Fifty-eight prepubertal patients with GH deficiency (17 females) participated in this prospective multicenter trial with 1 year of follow-up. METHODS: Auxological measurements, parameters of GH status and markers of bone metabolism were measured at baseline and at 1, 3 and 6 months after the start of rhGH treatment. Correlations with height velocity during the first 12 months of treatment (HV+12) were calculated. Prediction models were derived by multiple regression analysis. RESULTS: The model which best predicted HV+12 combined the following parameters: pretreatment bone age retardation as a fraction of chronological age, pretreatment serum levels of IGF-I, urinary levels of deoxypyridinoline (a marker of bone resorption) after 1 month of treatment and height velocity after 3 months of treatment. This model explained 89% of the variation in HV+12 with a standard deviation of the residuals of 0.93 cm/year. Defining successful rhGH therapy as a doubling of pretreatment height velocity, the model had a specificity of 90% and a sensitivity of 100% in predicting therapeutic success. CONCLUSIONS: This model is an accurate and practicable tool to predict growth response in GH-deficient children. It may help to optimize rhGH therapy by individual dose adjustment and contribute to improved overall outcomes.

Posterior pituitary ectopia: another hint toward a genetic etiology.

We report the MR and clinical findings of two patients with growth hormone deficiency and posterior pituitary ectopia (PPE). Possible causes of PPE are discussed.

Free deoxypyridinoline in urine and serum--results in children and adolescents.

The urinary excretion of the collagen crosslinking compound dexoypyridinoline (DPD) is considered a specific index of bone resorption. Here we report on the levels of free (i.e., non peptide-bound) DPD in the urine and serum of subjects from 5 to 19 years of age, as determined by a new radioimmunoassay. Reference values for free DPD were established using 24-h urine collections from 118 healthy children and serum samples from 133 children with acute febrile illnesses. Serum and urine levels of free DPD were compared in samples from 23 short, normal children. Additionally, total (the sum of peptide-bound and free) DPD was measured by high-performance liquid chromatography in the 24-h urine collections. Urinary-free DPD was significantly correlated with total DPD (r = 0.90; P < 0.001) and declined steadily with age. Serum levels of free DPD ranged from 0.9 to 5.7 nmol/l and varied with age in boys only. No significant association was found between serum and urine levels of free DPD (r = 0.08; P = 0.37). In conclusion, urinary-free DPD did not reflect enhanced bone turnover during the time of puberty. Free DPD serum levels are very low, which may be due to rapid clearance via the kidneys.

Insulin-like growth factor binding protein-3 levels during early and late follow-up after surgery in acromegalic patients.

Disease activity in acromegaly is accurately reflected by growth hormone (GH) concentration during oral glucose tolerance test (OGTT) and insulin-like growth factor-I (IGF-I) levels, representing an integrated index of GH activity. This prospective study was performed to evaluate whether plasma IGF binding protein 3 (IGFBP-3) might also reflect the hormonal disease activity in pituitary acromegaly after operative treatment during early and late follow-up. Twenty-two acromegalic patients were studied. Data were obtained pre-, intra- and post-operatively in 13 cases. In 9 patients the acromegalic activity was studied only after treatment. The hormonal assessment included repeated blood samples for estimation of IGF-I, IGFBP-3 and repeated OGTTs. In each case 100 sigma g octreotide (Sandostatin lambda, Sandoz, Basel) was injected to test the acute response of GH, IGF-I and IGFBP-3. Intraoperatively, GH levels were estimated to examine acutely the influence of tumour reduction on GH levels. Patients were considered cured when GH levels (GH60min) were less than 2 ng/ml during OGTT 4 weeks after surgery. The data outlined that in patients with normalized GH60min levels, normalized IGFBP-3 levels were noticed 4 weeks and 12 months post-operatively. In non-cured patients normalized IGFBP-3 concentrations were found in 11 out of 15 cases in the late post-treatment phase. In contrast only 1 of 7 cured patients had persistently elevated IGF-I levels within the first month post-operatively, whereas no case of the non-cured patients had IGF-I values in the normal range. Despite these observations a strong correlation of IGF-I and IGFBP-3 did not exist before one year post-operatively -- either in the cured or in the non-cured patients. Serum IGFBP-3 in patients with pituitary acromegaly does not provide a predictive value of appreciable magnitude concerning cure or non-cure from the disease- whether examined early or late in the post-operative period. Absolute levels of IGFBP-3 may thus cause misinterpretation concerning cure of acromegalics after surgery.

Vitamin D receptor genotypes and changes of bone density in physically active German women with high calcium intake.

Polymorphisms at the vitamin D receptor (VDR) gene have been reported to mediate important differences in bone mineral density (BMD) and bone metabolism. In this longitudinal study we examined the relationships between VDR genotypes and bone metabolism, changes in BMD and changes in ultrasound transmission velocity in a population of healthy unrelated German women. The study population comprised 50 physically active women (aged 43.3 to 62.8 years, 14 premenopausal, 36 postmenopausal) with a daily calcium intake of (mean +/- SD) 1045 +/- 338 mg, who had earlier participated in a longitudinal study on the association of physical activity and bone density and bone turnover. Each participant was genotyped for the BsmI polymorphism at the VDR gene locus. Markers of bone turnover (alkaline phosphatase, osteocalcin, procollagen type I C-terminal propeptide, collagen type I C-terminal telopeptide, tartrate-resistant acid phosphatase) were measured at baseline. BMD (determined by peripheral quantitative computed tomography at the distal radius) and ultrasound transmission velocity through bone (at calcaneus, patella and thumb) were analysed at baseline and 15 months later. The genotypic groups did not differ significantly (p > 0.05) in any of the parameters determined at baseline. Neither were there any differences between these groups in the changes of BMD or ultrasound transmission velocity during the study period. Thus, we conclude that in physically active German women with a relatively high calcium intake the impact of VDR genotypic polymorphisms on bone density, bone metabolism and changes in bone density may be of limited importance.

Chemiluminescence immunometric assay for measuring osteocalcin in healthy children.

Osteocalcin (OC) was measured in serum samples from 92 children and adolescents (57 females, 35 males) by a two-site chemiluminescence immunometric assay (Nichols Institute Diagnostics, USA), which recognizes the 1-19 region of the whole molecule as well as the large N-terminal midregion fragment representing the main part of OC in serum. The highest OC levels are measured between the age of 10-15 years. The linear correlations between OC and alkaline phosphatase were 0.65 (p < .01) for total alkaline phosphatase (TAP) and 0.61 (p < 0.1) for bone alkaline phosphatase (BAP).

The bone behind a low areal bone mineral density: peripheral quantitative computed tomographic analysis in a woman with osteogenesis imperfecta.

Areal bone mineral density (BMD) is the most widely used densitometric parameter. However, this approach makes it difficult to understand the structural basis of bone diseases, because a large number of bone properties are integrated into a single number. This is exemplified in the present case of a 27-year-old woman with osteogenesis imperfecta type I. Peripheral quantitative computed tomographic analysis at the radial metaphysis and at the radial diaphysis revealed a decreased areal BMD at both sites (z score -3.9 and -3.4, respectively). Yet, the structural basis for this decrease was different for the two locations: At the distal radius areal BMD was decreased because volumetric BMD was very low, whereas bone size was above the mean of the reference range. At the proximal radius areal BMD was decreased, because bone size was very low but volumetric BMD was above average. Bone mineral content of the radial diaphysis was very low for forearm muscle size, a finding which is compatible with Frost's hypothesis that the mechanostat setpoint is increased in osteogenesis imperfecta.

The "muscle-bone unit" in children and adolescents: a 2000 overview.

In former views hormones, calcium, vitamin D and other humoral and nonmechanical agents dominated control of postnatal bone strength (and "mass") in children and adolescents. However later evidence that led to the Utah paradigm of skeletal physiology revealed that this control depends strongly on the largest mechanical loads on bones. Trauma excepted, muscles cause the largest loads and the largest bone strains, and these strains help to control the biological mechanisms that determine whole-bone strength. That makes the strength of children's load-bearing bones depend strongly on growing muscle strength and how bones respond to it. Most hormones and other nonmechanical agents that affect bone strength can help or hinder that "bone strength-muscle strength" relationship but cannot replace it. In addition some agents long thought to exert bone effects by acting directly on bone cells, affect muscle strength too. In that way they could affect bone strength indirectly. Such agents include growth hormone, adrenalcorticosteroid analogs, androgens, calcium, genes, vitamin D and its metabolites, etc. Thus bone and muscle do form a kind of operational unit. It is part of the Utah paradigm that supplements earlier views with later evidence and concepts. The paradigm explains how the "bone strength-muscle strength" relationship works. This article provides an overview of that physiology, and some of its implications for pediatric endocrinologists.