Published online August 14, 2006
PEDIATRICS Vol. 118 No. 3 September 2006, pp. e627-e634 (doi:10.1542/peds.2005-2193)
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow P3Rs: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when P3Rs are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My File Cabinet
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bechtold, S.
Right arrow Articles by Schwarz, H. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bechtold, S.
Right arrow Articles by Schwarz, H. P.
Related Collections
Right arrow Endocrinology

ARTICLE

Early Manifestation of Type 1 Diabetes in Children Is a Risk Factor for Changed Bone Geometry: Data Using Peripheral Quantitative Computed Tomography

Susanne Bechtold, MD, Isa Dirlenbach, MD, Klemens Raile, MD, Vera Noelle, MD, Walter Bonfig, MD and Hans Peter Schwarz, MD, PhD

Division of Pediatric Endocrinology, University Children's Hospital, Munich, Germany


   ABSTRACT
TOP
 ABSTRACT
Methods
 Biochemical Parameters
 pQCT
 Grip Force Analysis
 Statistical Analysis
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
OBJECTIVE. Normal to severely decreased bone mineral density has been reported in children with type 1 diabetes. To detect possible abnormalities in bone mineralization, geometry, and muscle bone unit, we measured selective parameters in children with type 1 diabetes using peripheral quantitative computed tomography.

METHODS. Measurements of the radius by peripheral quantitative computed tomography were made to assess cortical and trabecular bone characteristics as well as muscle mass in 88 patients (42 girls, 46 boys) at a mean age of 11.7 ± 3.0 years, a mean disease duration of 5.6 ± 3.7 years, and a mean manifestation age of type 1 diabetes of 6.1 ± 3.5 years. Height, weight, Tanner stage, insulin regimen, and glycosylated hemoglobin values were recorded. Bone metabolism was studied by measurement of bone formation and bone resorption parameters. Dynamic muscle force was measured using a grip strength device.

RESULTS. Overall, cortical, trabecular, and total bone mineral density were within the reference range. Total and cortical bone cross-sectional area and muscle mass were low in prepubertal patients, and total cross-sectional area was low in early puberty. Adolescent patients showed normal bone and muscle parameters. Grip strength and recreational physical activity were normal in all in relation to a healthy reference population. In a subgroup of 18 patients, early manifestation of type 1 diabetes was detected as a risk factor for altered bone development with significantly reduced cortical bone mineral density and total, cortical, and muscle cross-sectional area (–0.9 ± 1.3 SD, –2.1 ± 1.3 SD, –1.6 ± 0.7 SD, and –1.0 ± 0.7 SD, respectively). Bone characteristics were not influenced by metabolic control, disease duration, or insulin regimen.

CONCLUSIONS. Manifestation of type 1 diabetes at an early age may impair bone development. Longitudinal data are needed to determine whether this impairment persists into adolescence and adulthood.

Key Words: type 1 diabetes • osteopenia • bone mineral density • bone geometry • peripheral quantitative computed tomography

Abbreviations: BMD—bone mineral density • pQCT—peripheral quantitative computed tomography • CSA—cross-sectional area • HbA1c—hemoglobin A1c • IGF-1—insulin-like growth factor-1 • aP—alkaline phosphatase • CICP—C-terminal propeptide of type I collagen • iPTH—intact parathyroid hormone • DpD—deoxypyridinoline • SDS—SD score

Children and adolescents with type 1 diabetes seem to have an increased risk for decreased bone mass. Several studies have documented a lower bone mineral density (BMD) and postponed attainment of peak bone mass and an increased risk for osteoporosis and related complications later in life.1–6 However, other studies found normal levels of bone mass and BMD.7–9

It still is a matter of debate whether a specific generalized diabetic bone disease, often called diabetic osteopathy or diabetic osteopenia, actually exists and what the clinical relevance of this disorder would be. There is no general agreement on the relative importance of several diabetes-specific characteristics, such as age at onset, disease duration, and glycemic control or insulin regimen, on bone health.9

The majority of studies have reported bone mass and BMD in children with type 1 diabetes using dual-energy x-ray absorptiometry. This method measures bone mineral content and bone area to determine apparent BMD. Especially in pediatrics, this method has limitations because of the 2-dimensional measurement and therefore height dependence. Furthermore, no information on bone geometry and the bone-muscle relation can be gained with this method.

The objectives of the present cross-sectional study were to evaluate BMD and bone and muscle geometry in patients with type 1 diabetes using peripheral quantitative computed tomography (pQCT). Interpretation of bone density measurements is incomplete without taking into account the interrelationship with the muscle mass.10 Muscle cross-sectional area (CSA), bone mass, BMD, and bone geometry can be assessed by a single measurement using pQCT.


   Methods
TOP
 ABSTRACT
 Methods
Biochemical Parameters
 pQCT
 Grip Force Analysis
 Statistical Analysis
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
The study population included 88 white children and adolescents (42 girls, 46 boys) with type 1 diabetes. Mean age was 11.7 ± 3.0 years, and mean disease duration was 5.6 ± 3.7 years. The mean age at manifestation of type 1 diabetes was 6.1 ± 3.5 years (range: 0.7–14.6 years). All participants of the study were observed regularly at the diabetes outpatient clinic of the University Children's Hospital, Munich, and met the following criteria: (1) first diagnosis of type 1 diabetes made before 18 years of age; (2) no evidence of diabetic retinopathy, neuropathy, or nephropathy; (3) no intake of medications, hormones, vitamins, or calcium preparation in the preceding 6 months aside from insulin and, if necessary, thyroid hormones; (4) no chronic disease apart from celiac disease or thyroiditis under control; (5) no hospitalization or ketoacidosis in the preceding 6 months; and (6) no restriction of physical activity. All patients were examined every 3 months. Some were treated with a conventional regimen of 2 injections (n = 5); most patients had multiple injections (3–4 daily) of regular and neutral protamine hagedorn insulin (n = 73) or an insulin pump therapy (n = 10). Diabetic control was monitored by measurements of hemoglobin A1c (HbA1c) levels at 3-months intervals. The HbA1c level was measured by DCA 2000 (Bayer AG, Leverkusen, Germany), based on specific inhibition of latex immunoagglutination. Normal values of HbA1c as established in our laboratory ranged from 4.0% to 6.0%. Moreover, an average HbA1c was calculated for each patient, and the mean of 4 measurements during the previous 12 months was taken.

Anthropometric data were compared with the cross-sectional German growth data of Kromeyer et al.11 The pQCT results were compared with those in a German reference population using an identical method. The reference population consisted of participants in the Dortmund Nutritional and Anthropometric Longitudinally Designed study, an observational study that investigated the interrelations of nutrition, growth, and metabolism in healthy children. The results in this reference population have been described before.12–14

Height was measured in a standing position to the next 1 mm using a digital telescopic wall-mounted stadiometer (Ulmer Stadiometer; Prof E. Heinze, Ulm, Germany). Weight was determined to the nearest 0.1 kg using an electronic scale (Seca 753 E; Vogel and Hanke, Hamburg, Germany) with the children clothed in underwear. The BMI was calculated (weight/height2) and compared with the German normative data by Kromeyer et al.11 Forearm length was measured at the nondominant forearm as the distance between the ulnar styloid process and the olecranon using a caliper. The stage of sexual development was determined in all study participants using the grading system by Tanner for breast development in girls and genital status in boys.15 Forty-four (50%) patients were prepubertal (Tanner stage 1), 17 (19%) were early pubertal (Tanner stages 2 and 3), and 27 (31%) were adolescent (Tanner stages 4 and 5). Patients were interviewed regarding their time spent for physical activity in comprehensive and recreational sports using a structured questionnaire as previously described.16


   Biochemical Parameters
TOP
 ABSTRACT
 Methods
 Biochemical Parameters
pQCT
 Grip Force Analysis
 Statistical Analysis
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Yearly routine blood and urine analyses were conducted before pQCT measurement. Serum concentration of calcium and phosphorus and routine chemistry were measured in addition to insulin-like growth factor-1 (IGF-1), alkaline phosphatase (aP), C-terminal propeptide of type I collagen (CICP), 25-OH-vitamin D, and intact parathyroid hormone (iPTH). Collagen cross-link deoxypyridinoline (DpD) was determined from the second morning void of urine. IGF-1 was measured by immunoenzymetric assay OCTEIA IGF-1 (IDS, Boldon, United Kingdom), CICP by enzyme immunoassay (F. Metra Biosystems, Osnabrück, Germany), aP by Monotest (Roche Diagnostica, Mannheim, Germany), and DpD by enzyme-linked immunosorbent assay (Quidel Metra Biosystems, San Diego, CA). 25-OH-vitamin D was measured using a radioimmunoassay (Nichols Institute Diagnostics, Paris, France), and iPTH was measured using an electrochemiluminescence immunoassay (Roche Diagnostics). The university's ethics committee approved the study protocol, and informed consent was obtained from all patients and/or their parents.


   pQCT
TOP
 ABSTRACT
 Methods
 Biochemical Parameters
 pQCT
Grip Force Analysis
 Statistical Analysis
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Two sites of the nondominant radius were analyzed by pQCT, the distal metaphysis (4% site) and the proximal diaphysis (65% site) as previously described.12–14,17 A pQCT scanner (XCT 2000; Stratec Inc, Pforzheim, Germany) that was equipped with a low-energy (38 keV) radiograph tube was used. The effective radiation dose is ~0.1 µSv from radiation source of 45 kV at 150 µA. For the measurement, the scanner was positioned on the distal forearm and a scout view was conducted to position the scanner at the site on the radius whose distance to the radial articular surface corresponded to 4% and 65% of forearm length. At both sites, a 2-mm-thick single tomographic slice was sampled at a voxel size of 0.4 mm. Image processing and calculation of numerical values were made using the manufacturer's software package (version 5.40; Stratec Inc). At the distal radius (metaphyseal site), total and trabecular BMD were calculated, and at the proximal radius (diaphyseal site), total and cortical BMD, total CSA, cortical CSA, and muscle CSA were calculated by the manufacturer's software.

Only measurements of good quality without movement artifacts were taken for analysis. To establish the variability of the measurements, we measured the forearm of 6 adult volunteers 3 times with repositioning of the forearm. Reproducibility was 1.08% for trabecular BMD and 1.42% for total BMD at the metaphysis and 1.30% for CSA, 1.36% for total BMD, and 1.11% for cortical BMD at the diaphysis. The accuracy of the previous version (XCT-960) was determined using the European forearm phantom, and average accuracy values between 1.9% and 1.4% for CSA and BMD values were reported.18 Calibration of the machine was performed with phantoms provided by the manufacturer every other day (single slice) or once a month (multiple slices), respectively.


   Grip Force Analysis
TOP
 ABSTRACT
 Methods
 Biochemical Parameters
 pQCT
 Grip Force Analysis
Statistical Analysis
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Maximal isometric grip force of the nondominant hand was determined with a standard adjustable-handle Jamar Dynamometer (Preston, Jackson, MI) as described before.19 The dynamometer was held freely, without support, with flexed elbow, which did not touch the trunk. The participants were told to exert maximal force on the dynamometer. The maximum value of 3 trials was noted. The results in kilograms, as indicated by the scale of the dynamometer, were converted by the factor of 9.81 to calculate grip force unit in Newtons. Reference data were taken from the participants in the Dortmund Nutritional and Anthropometric Longitudinally Designed study.19


   Statistical Analysis
TOP
 ABSTRACT
 Methods
 Biochemical Parameters
 pQCT
 Grip Force Analysis
 Statistical Analysis
RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Results in patients with type 1 diabetes were converted into gender-, age-, and height-specific SD scores (SDSs) using the formula SDS = [(test result for a patient) – (age- or height-specific mean in reference population)]/(age- or height-specific SD in reference population). To evaluate whether a parameter was significantly different from the results of an age-matched healthy population, the difference of the mean SDS to 0 was assessed by Student's 2-tailed t test for unpaired observations. A significant difference was assumed when the 95% confidence interval of the mean SDS did not include 0. Pearson's product-moment correlation was used to determine r values for possible influencing factors on BMD and geometry parameters. We used a general univariate linear regression analysis to evaluate the covariant effects using significance levels of the 2-sided P < .05. All statistical analyses were performed using the SPSS software package (version 12.0 for windows; SPSS Inc, Chicago, IL).


   RESULTS
TOP
 ABSTRACT
 Methods
 Biochemical Parameters
 pQCT
 Grip Force Analysis
 Statistical Analysis
 RESULTS
DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Auxologic and Clinical Data
The main clinical features of the cross-sectional study population are shown in Table 1. Patients with diabetes showed normal SDSs for height but significant higher SDSs for weight and therefore for BMI (P < .05). Fourteen (15.9%) of 88 patients had a BMI of >90th percentile; 3 of these had a BMI >97th percentile. There was no significant difference between genders for BMI. Most patients were in moderate to acceptable metabolic control with a mean HbA1c of 7.6 ± 1.3% (range: 5.5%–11.8%) at time of radial pQCT and 7.6 ± 1.1% (range: 5.8%–10.5%) on average during 12 months before the evaluation. Eight and 3 patients had an average HbA1c of >9.0% and >10.0%, respectively. HbA1c values and daily insulin dose per body weight were similar in boys and girls. There was no significant influence of Tanner stage on SDSs for height, weight, and BMI; tendencies were seen: older patients had higher HbA1c levels, and higher recent and average HbA1c values were associated with higher insulin dose per kilogram body weight per day. Four patients had biopsy-proven celiac disease without detectable antibodies as a result of good dietary compliance, and 2 patients had euthyroid Hashimoto thyroiditis without hormone replacement. All were well within the range for height, weight, BMI, and HbA1c of all patients with type 1 diabetes.


View this table:
[in this window]
[in a new window]

  		TABLE 1 Characteristics of the Studied Patients With Type 1 Diabetes

 
Bone Densitometric Results
Radial Metaphysis (4% Site)
Total BMD was normal, whereas trabecular BMD was even higher in patients with type 1 diabetes than in healthy control subjects, irrespective of age, gender, and Tanner stage. A reevaluation of the scout view scan revealed that 6 patients had a 4% measurement too close to the growth plate and were excluded for the distal BMD analysis. Using the new logarithmic approach of data analysis as suggested by Rauch et al,20 trabecular BMD was 0.45 ± 1.0 in girls and 0.08 ± 1.2 in boys (Fig 1). Only prepubertal and female patients still had significantly higher trabecular BMD values in relation to the reference population. BMI correlated significantly (P < .01) with metaphyseal total and trabecular BMD (r = 0.31 and 0.3, respectively; Table 2).


Figure 1
View larger version (17K):
[in this window]
[in a new window]

  		FIGURE 1 Metaphyseal trabecular BMD of patients with type 1 diabetes. Upper, female patients; lower, male patients.

 

View this table:
[in this window]
[in a new window]

  		TABLE 2 BMD and Bone-Geometry Parameters With Muscle Mass of the Studied Patients With Type 1 Diabetes Divided According to Gender and Tanner Stage Groups

 
Radial Diaphysis (65% Site)
Cortical BMD was normal in relation to the reference population, whereas total CSA, cortical CSA, and muscle CSA were significantly reduced. Especially the younger patients showed smaller CSA values (Figs 2 and 3). The dynamic function of the muscle measured by grip strength was significantly higher in relation to the healthy reference population.


Figure 2
View larger version (22K):
[in this window]
[in a new window]

  		FIGURE 2 Diaphyseal total bone CSA of patients with type 1 diabetes. Upper, female patients; lower, male patients. {square}, patients with ≥2 pathologic parameters.

 

Figure 3
View larger version (21K):
[in this window]
[in a new window]

  		FIGURE 3 Diaphyseal cortical bone CSA of patients with type 1 diabetes. Upper, female patients; lower, male patients. {square}, patients with ≥2 pathologic parameters.

 
Separating the genders, no significant difference in BMD and bone-geometry parameters was detectable. However, in staging the patients with type 1 diabetes according to Tanner, there were great differences. In prepubertal patients (Tanner stage 1; n = 44), patients with type 1 diabetes had lower SD levels for total, cortical, and muscle CSA. In early puberty (Tanner stages 2 and 3; n = 17), only a lower total CSA was detectable, and in adolescent patients (Tanner stages 4 and 5; n = 27), bone-geometry and muscle CSA were normal. There was no significant influence of insulin regimen on bone and muscle parameters. There was a positive correlation between total CSA and age and diabetes duration (r = 0.66 and 0.62; P < .01). Muscle CSA SD values correlated significantly (P < .01) with total CSA (r = 0.61) and cortical CSA (r = 0.67). There was also a significant correlation (P < .01) between grip strength and diaphyseal total CSA (r = 0.81), cortical CSA (r = 0.90), and muscle CSA (r = 0.92).

To look for potential confounders, we designed 4 different models of multiple linear regression using diaphyseal total and cortical CSA as the dependent variables and present HbA1c, average HbA1c, insulin dose, and type 1 diabetes duration as the independent variables. Age, gender, and Tanner stage were used as covariates. No significant influence of the independent variables on diaphyseal total and cortical CSA was detectable.

Subgroup Analysis
Participants with ≥2 BMD, bone-geometry, or muscle CSA parameters that were more than –2 SD below reference (group A; n = 18, 7 girls) were compared with the remaining patients with type 1 diabetes (group B; n = 70, 35 female). Those in group A were significantly younger at time of pQCT measurement and initial diagnosis (P < .05). Height, weight, and BMI in group A were normal for age but significantly lower than those in group B. The duration of type 1 diabetes, daily insulin dose, and current and average HbA1c were not significantly different. Diaphyseal total CSA was significantly reduced in both groups versus reference; however, only cortical BMD and cortical and muscle CSA were significantly reduced in group A (P < .01). Neither group was large enough to examine the effects of pubertal maturation by Tanner stage (Table 3).


View this table:
[in this window]
[in a new window]

  		TABLE 3 Subgroup Analysis

 
Sports
Mean time spent for recreational physical activity was reported as 6.7 hours per week, with girls spending 5.9 hours per week and boys spending 7.4 hours per week. Forty patients with type 1 diabetes (21 boys, 19 girls) took part regularly in competitive sports. Greater recreational activity correlated with age (P < .05) but not with HbA1c levels or insulin doses. These results are not different from data reported by Raile et al16 for German children and adolescents who were aged 6 to 18 years and had diabetes. Grip strength was significantly higher in our study population in relation to healthy control patients (P < .01) and increased with age and hours of physical activity per week (P < .01).

Biochemical Results
Serum calcium, phosphorus, aP (328 ± 120 U/L), and IGF-1 (189 ± 79 ng/mL), CICP (298 ± 148 µg/L) as well as 25-OH vitamin D (110 ± 45 nmol/L) and iPTH (36 ± 15 pg/mL) were within the reference range for age, gender, and season. Urinary excretion of DpD (13.9 ± 6.1 nmol/mmol) was normal. There was no correlation of bone turnover parameters with BMD or bone-geometry parameters or with HbA1c values. IGF-1 correlated significantly with SD values of total, cortical, and muscle CSA (r = 0.32, 0.28, and 0.26, respectively; P < .05).


   DISCUSSION
TOP
 ABSTRACT
 Methods
 Biochemical Parameters
 pQCT
 Grip Force Analysis
 Statistical Analysis
 RESULTS
 DISCUSSION
CONCLUSIONS
 REFERENCES
 
BMD and bone mineral content have been measured in children and adolescents with type 1 diabetes using different methods. Studies that used dual-energy x-ray absorptiometry of the spine found lower BMD values that suggested that type 1 diabetes in the young may compromise peak bone mass and increase the risk for osteoporosis in adult age.21–24 However, there is a great variability in number of patients investigated, auxologic data, and metabolic control of the patients with type 1 diabetes as well as normative data, possibly caused by different measurement techniques.2,9,25 In our study, BMD values (total, trabecular, and cortical) were within the reference range. Bone-geometry parameters, specifically total and cortical CSA and muscle CSA, were low, although patients were not compromised in height for age and gender.

Looking for possible factors that influence the bone and muscle development, several important observations were made. The BMI in our study population was significantly higher in relation to the reference population. The older the patients, the higher the BMI and the indices of bone geometry were more normalized. It could be speculated that BMI and/or pubertal development exerts a protective or normalizing effect on bone.26

In analogy to our results, the effect of metabolic control on BMD and bone mass development has been excluded by several authors.9,27 However, we do not exclude the possibility that children with poorly controlled diabetes over a prolonged period of time might have more significant bone deficits than our patients.28 Additional disease-specific parameters such as insulin dose, insulin treatment regimen, or duration of disease had no significant influence on BMD and bone-geometry parameters.27 Gunczler et al21 described a decreased BMD of the lumbar spine in children a few months after the onset of clinical type 1 diabetes. After a period of 3 to 5 years, a stabilization of BMD values was noted by McNair et al.29 They suggested a defect in bone mass accretion early in the course of type 1 diabetes that then ameliorates with time. This observation is in accordance with our finding that total, cortical, and muscle CSA were reduced only in the youngest, prepubertal group. In the early pubertal group, only total CSA levels were reduced, and in the adolescent group, all parameters of bone-geometry and muscle CSA were within reference ranges. After clinical manifestation of type 1 diabetes, an initial derangement of bone development may take place, possibly followed by a catchup in bone development over a long period of time. However, patients with a very early manifestation of type 1 diabetes may fail to experience such a catchup in bone development. In a subanalysis, we compared patients who had ≥2 low values in one of the bone parameters or muscle CSA (group A) with the rest of the study population (group B). It is interesting to note that patients of group A were significantly younger at clinical manifestation of type 1 diabetes and still were younger at the time of pQCT measurement; they were also significantly shorter and weighed less. Cortical BMD and total, cortical, and muscle CSA were significantly lower in group A compared with both group B and the reference population. It could be speculated that an early age at onset of type 1 diabetes in a critical phase of growth and development could adversely influence bone development; this also was described by Lettgen et al.3

Physical exercise is encouraged and has favorable metabolic effects in patients with type 1 diabetes. The degree of physical fitness and engagement was normal in our patient population when compared with healthy children who were of similar age and gender and did not have diabetes.16 Inadequate physical activity therefore is an unlikely cause of low muscle CSA in our patients. Muscle CSA values were not influenced by parameters of metabolic control, insulin dose, or duration of type 1 diabetes. As expected, muscle CSA correlated significantly with total and cortical CSA levels, putting emphasis on the importance of the muscle–bone unit.10 The elevated grip strength in our study population probably was attributable to an intensive motivation of the patients by the examiner. This short-time dynamic muscle force as measured by grip strength and our questionnaire may not really reflect physical fitness. A more detailed evaluation of the type, duration, and intensity of physical activity would be necessary.

With regard to the pathogenesis of altered bone parameters, it has been suggested that the absence of the anabolic action of insulin and IGF-1 on the skeleton might be the key, especially when metabolic control is unsatisfactory.30 Insulin deficiency may cause a reduction of osteoblast cell number.31 Animal and human models of type 1 diabetes as well as histomorphic studies have demonstrated impaired bone turnover. The number and the function of osteoblasts were decreased.31 On the contrary, in a study by De Leeuw et al,32 normal trabecular bone volume and structure but reduced magnesium content of the trabecular bone was reported in iliac crest biopsies in adult patients with type 1 diabetes. The finding of normal parameters of bone formation and resorption in our study might be related to the relatively good metabolic control of the patients. We found a weak but significant correlation of IGF-1 levels with total, cortical, and muscle CSA. This may be attributable to advancing age, growth velocity, and puberty.

Limitations of our study were its cross-sectional character and the problem of growth plate artifacts at the distal radius, which made a reevaluation of the scout view scan necessary. Exact positioning of the reference line is difficult but essential, especially in younger patients.


   CONCLUSIONS
TOP
 ABSTRACT
 Methods
 Biochemical Parameters
 pQCT
 Grip Force Analysis
 Statistical Analysis
 RESULTS
 DISCUSSION
 CONCLUSIONS
REFERENCES
 
Younger patients with type 1 diabetes seem to have altered bone geometry with reduced total and cortical CSA as well as lower muscle mass. However, this effect on bone and muscle seems to become normalized over time. Patients with early onset of type 1 diabetes may be more affected by metabolic derangement that is caused by the clinical manifestation that results especially in altered bone geometry than patients with an onset of type 1 diabetes later in life. Longitudinal data on bone development in patients with early and with late onset of type 1 diabetes will be needed to draw final conclusions about whether subnormal peak bone mass is associated with early manifestation of type 1 diabetes and accounts for the diabetic osteopenia in adult patients.


   FOOTNOTES
 
Accepted Mar 20, 2006.

Address correspondence to Susanne Bechtold, MD, University Children's Hospital, Lindwurmstrasse 4, D-80337 Munich, Germany. E-mail: susanne.bechtold{at}med.uni-muenchen.de

The authors have indicated they have no financial relationships relevant to this article to disclose.


   REFERENCES
TOP
 ABSTRACT
 Methods
 Biochemical Parameters
 pQCT
 Grip Force Analysis
 Statistical Analysis
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 

  1. Rosenbloom AL, Lezotte DC, Weber FT, et al. Diminution of bone mass in childhood diabetes. Diabetes. 1977;26 :1052 –1055[Abstract]
  2. Weber G, Beccaria L, de Angelis M, et al. Bone mass in young patients with type 1 diabetes. Bone Miner. 1990;8 :23 –30[CrossRef][ISI][Medline]
  3. Lettgen B, Hauffa B, Möhlmann C, Jeken C, Reiners C. Bone mineral density in children and adolescents with juvenile diabetes: selective measurement of bone mineral density of trabecular and cortical bone using peripheral quantitative computed tomography. Horm Res. 1995;43 :173 –175[ISI][Medline]
  4. Gunczler P, Lanes R, Paz-Martinex V, et al. Decreased lumbar spine bone mass and low bone turnover in children and adolescents with insulin-dependent diabetes mellitus followed longitudinally. J Pediatr Endocrinol Metab. 1998;11 :413 –419[ISI][Medline]
  5. Heap J, Murray MA, Miller SC, Jalili T, Moyer-Mileur LJ. Alterations in bone characteristics associated with glycemic control in type 1 diabetes mellitus adolescents. J Pediatr. 2004;144 :56 –62[CrossRef][ISI][Medline]
  6. Moyer-Mileur LJ, Dixon SB, Quick JL, Askew EW, Murray MA. Bone mineral acquisition in adolescents with type 1 diabetes. J Pediatr. 2004;145 :662 –669[CrossRef][ISI][Medline]
  7. Roe TF, Mora S, Costin G, Kaufman F, Carlson ME, Gilsanz V. Vertebral bone density in insulin-dependent diabetic children. Metabolism. 1991;40 :967 –971[CrossRef][ISI][Medline]
  8. Ponder SW, McCormik DP, Fawcett HD, et al. Bone mineral density of the lumbar vertebrae in children and adolescents with insulin-dependent diabetes mellitus. J Pediatr. 1992;120 :541 –545[CrossRef][ISI][Medline]
  9. De Schepper J, Smitz J, Rosseneu S, Bollen P, Louis O. Lumbar spine bone mineral density in diabetic children with recent onset. Horm Res. 1998;50 :193 –196[CrossRef][ISI][Medline]
  10. Schönau E. The development of the skeletal system in children and the influence of muscular strength. Horm Res. 1998;49 :27 –31[CrossRef][ISI][Medline]
  11. Kromeyer-Hauschild K, Wabitsch M, Kunze D, et al. Perzentile für den Body-mass-Index für das Kindes- und Jugendalter unter Heranziehung verschiedener deutscher Stichproben [Percentiles of body mass index in children and adolescents evaluated from different regional German studies]. Monatsschr Kinderheilkd. 2001;149 :807 –818[CrossRef]
  12. Neu C, Manz F, Rauch F, Schönau E. Bone density and bone size at the distal radius in healthy children and adolescents: a study using peripheral quantitative computed tomography. Bone. 2001;28 :227 –232[Medline]
  13. Neu C, Manz F, Rauch F, Schönau E. Modeling of cross-sectional bone size and geometry at the proximal radius: a study of normal bone development using peripheral quantitative computed tomography. Osteoporosis Int. 2001;12 :538 –547[CrossRef][ISI][Medline]
  14. Bechtold S, Rauch F, Noelle V, et al. Musculoskeletal analyses of the forearm in young women with Turner syndrome: a study using peripheral quantitative computed tomography. J Clin Endocrinol Metab. 2001;86 :5819 –5823[Abstract/Free Full Text]
  15. Tanner JM. Growth at adolescence. In: The Development of the Reproductive System. 2nd ed. Oxford, United Kingdom: Blackwell; 1962;28 –39
  16. Raile K, Kapellen T, Schweiger A, et al. Physical activity and competitive sports in children and adolescents with type 1 diabetes. Diabetes Care. 1999;22 :1904 –1905[Free Full Text]
  17. Schönau E, Neu CM, Rauch F, Manz F. The development of bone strength at the proximal radius during childhood and adolescence. J Clin Endocrinol Metab. 2001;86 :613 –618[Abstract/Free Full Text]
  18. Augat P, Gordon CL, Lang TF, Iida H, Genant HK. Accuracy of cortical and trabecular bone measurements with peripheral computed tomography (pQCT). Phys Med Biol. 1998;43 :2873 –2883[CrossRef][ISI][Medline]
  19. Rauch F, Neu CM, Wassmer G, et al. Muscle analysis by measurement of maximal isometric grip force: new reference data and clinical applications in pediatrics. Pediatr Res. 2002;51 :505 –510[ISI][Medline]
  20. Rauch F, Schönau E. Peripheral quantitative computed tomography of the distal radius in young subjects: new reference data and interpretation. J Muskuloskelet Neuronal Interact. 2005;5 :119 –126
  21. Gunczler P, Lanes R, Paoli M, Martinez V, Villarel O, Weisinger JR. Decreased bone mineral density and bone formation markers shortly after diagnosis of clinical type 1 diabetes mellitus. J Pediatr Endocrinol Metab. 2001;14 :525 –528[ISI][Medline]
  22. Ersoy B, Goksen D, Darcan S, Mavi E, Ozturk C. Evaluation of bone mineral density in children with diabetes mellitus. Indian J Pediatr. 1999;66 :375 –379[Medline]
  23. Pascual J, Argent J, Lopez MG, et al. Bone mineral density in children and adolescents with diabetes mellitus type 1 of recent onset. Calcif Tiss Int. 1998;62 :31 –35[CrossRef][ISI][Medline]
  24. Haffner SM, Bauer RL. The association of obesity and glucose and insulin concentrations with bone density in premenopausal and postmenopausal women. Metabolism. 1993;42 :97 –104[CrossRef][ISI][Medline]
  25. Munoz-Torres M, Jordan E, Escobar-Jimenez F, Lopez-Ibarra P, Luna J. Bone mineral density measured by dual x-ray absorptiometry in Spanish patients with insulin-dependent diabetes mellitus. Calcif Tissue Int. 1996;58 :316 –319[CrossRef][ISI][Medline]
  26. Matthiassen B, Nielsen S, Ditzel J, Rodbro P. Long-term bone loss in insulin-dependent diabetes mellitus. J Intern Med. 1990;227 :325 –327[ISI][Medline]
  27. Hui SL, Epstein S, Johnston CC. A prospective study of bone mass in patients with type 1 diabetes. J Clin Endocrinol Metab. 1985;60 :74 –81[Abstract]
  28. Valario G, del Puente A, Esposito-Puente A, Buono P, Mozzillo E, Franzese A. The lumbar bone mineral density is affected by long-term poor metabolic control in adolescents with type 1 diabetes mellitus. Horm Res. 2002;58 :266 –272[CrossRef][ISI][Medline]
  29. McNair P, Christiansen C, Christiansen MS, et al. Development of bone loss in insulin-treated diabetes: a 1 1/2 years follow-up study in sixty patients. Eur J Clin Invest. 1981;11 :55 –59[ISI][Medline]
  30. Terada M, Inaba M, Yano Y. Growth-inhibitory effect of high glucose concentration on osteoblast-like cells. Bone. 1998;22 :17 –23[Medline]
  31. Bouillon R, Bex M, Van Herck E, et al. Influence of age, sex and insulin on osteoblast function: osteoblast dysfunction in diabetes mellitus. J Clin Endocrinol. 1995;80 :1194 –1202[Abstract]
  32. De Leeuw I, Vertommen J, Abs R. The magnesium content of the trabecular bone in diabetic subjects. Biomedicine. 1978;29 :16 –17[ISI][Medline]
PEDIATRICS (ISSN 1098-4275). ©2006 by the American Academy of Pediatrics



This article has been cited by other articles:


Home page
 Diabetes CareHome page
S. Bechtold, S. Putzker, W. Bonfig, O. Fuchs, I. Dirlenbach, and H. P. Schwarz
Bone Size Normalizes With Age in Children and Adolescents With Type 1 Diabetes
Diabetes Care, August 1, 2007; 30(8): 2046 - 2050.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow P3Rs: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when P3Rs are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My File Cabinet
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bechtold, S.
Right arrow Articles by Schwarz, H. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bechtold, S.
Right arrow Articles by Schwarz, H. P.
Related Collections
Right arrow Endocrinology