Pediatric Radiology

, Volume 36, Issue 5, pp 415–420

The potential of digital X-ray radiogrammetry (DXR) in the assessment of osteopenia in children with chronic inflammatory bowel disease

Authors

    • Department of Pediatric Radiology, Institute of Diagnostic and Interventional RadiologyFriedrich-Schiller-University Jena
  • Joerg Blume
    • Department of Gastroenterology, Clinic of PediatricsFriedrich-Schiller-University Jena
  • Joachim Boettcher
    • Department of Pediatric Radiology, Institute of Diagnostic and Interventional RadiologyFriedrich-Schiller-University Jena
  • Gabriele Lehmann
    • Department of Rheumatology and Osteology, Clinic of Internal MedicineFriedrich-Schiller-University Jena
  • Diana Tuchscherer
    • Department of Pediatric Radiology, Institute of Diagnostic and Interventional RadiologyFriedrich-Schiller-University Jena
  • Alexander Pfeil
    • Department of Pediatric Radiology, Institute of Diagnostic and Interventional RadiologyFriedrich-Schiller-University Jena
  • Anika Kramer
    • Department of Pediatric Radiology, Institute of Diagnostic and Interventional RadiologyFriedrich-Schiller-University Jena
  • Ansgar Malich
    • Department of Pediatric Radiology, Institute of Diagnostic and Interventional RadiologyFriedrich-Schiller-University Jena
  • Eberhard Kauf
    • Department of Gastroenterology, Clinic of PediatricsFriedrich-Schiller-University Jena
  • Gert Hein
    • Department of Rheumatology and Osteology, Clinic of Internal MedicineFriedrich-Schiller-University Jena
  • Werner A. Kaiser
    • Department of Pediatric Radiology, Institute of Diagnostic and Interventional RadiologyFriedrich-Schiller-University Jena
Original Article

DOI: 10.1007/s00247-005-0093-y

Cite this article as:
Mentzel, H., Blume, J., Boettcher, J. et al. Pediatr Radiol (2006) 36: 415. doi:10.1007/s00247-005-0093-y
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Abstract

Background

Loss of bone mass is a known complication of chronic inflammatory bowel disease (IBD) in children. The gold standard in the evaluation of bone mineral density (BMD) is dual energy X-ray absorptiometry (DXA).

Objective

In this preliminary study we evaluated digital X-ray radiogrammetry (DXR) which estimates BMD (DXR-BMD) from hand radiographs in children with IBD.

Materials and methods

A total of 26 children with IBD (10 girls, 16 boys; age range 10–18 years) underwent DXR for the calculation of DXR-BMD and metacarpal index (DXR-MCI) using the Pronosco X-posure system. The results were compared with a local reference database and correlated with the results of DXA.

Results

DXR-BMD was 0.36–0.56 g/cm2 (median 0.46 g/cm2) in Crohn disease patients and 0.38–0.63 g/cm2 (median 0.48 g/cm2) in ulcerative colitis patients. DXR-MCI was 0.29–0.49 in Crohn disease patients and 0.28–0.53 in ulcerative colitis patients. The Z-scores were reduced to <−1 SD in five Crohn disease patients and in six ulcerative colitis patients. The coefficients (r) for the correlations between DXR-BMD and DXA-BMD were 0.78 for the lumbar spine and 0.61 for the proximal femur (P<0.01), and between DXR-MCI and DXA-BMD were 0.78 for the lumbar spine and 0.51 for the proximal femur (P<0.01).

Conclusions

DXR seems to be able to estimate cortical osteopenia in children with chronic IBD. The DXR results showed a positive correlation with DXA results.

Keywords

Inflammatory bowel diseaseOsteopeniaDigital X-ray radiogrammetryBone mineral densityMetacarpal indexDual energy X-ray absorptiometry

Introduction

Osteopenia is a common clinical feature of chronic inflammatory bowel disease (IBD) in children and adults. Osteoporosis is characterized by a low bone mass and microarchitectural deterioration of cortical and trabecular bone tissue. The risk of fracture increases with diminished biomechanical competence of the skeletal parts. Osteopenia and osteoporosis are well-described complications in patients with chronic IBD. The mechanisms contributing to bone loss in Crohn disease and ulcerative colitis are unclear [1]. Many factors such as corticosteroid use, the IBD itself, which activates cytokines interacting with bone metabolism, smoking, physical inactivity, malnutrition, sex hormone deficiency and disturbances in calcium homeostasis due to malabsorption and vitamin D deficiency have been implicated [2]. Reports of skeletal fragility in children with IBD indicate the importance of regular monitoring of bone mineral density (BMD) [3]. Klaus et al. [3] found that in patients with Crohn disease and reduced bone density, the prevalence of vertebral fractures was increased by 22%. Although the absolute risk of fracture is probably relatively low in the majority of patients with IBD, a few patients suffer significant morbidity as a result of fractures.

Dual-energy X-ray absorptiometry (DXA) is the most common method for detection of osteoporosis because it is rapid, precise and delivers a minimal dose of ionizing radiation. As the correlation between BMD and the risk of fracture is well documented in postmenopausal osteoporosis, DXA is recommended as a screening procedure for osteoporosis in adults, especially in postmenopausal women. Bone evaluation by DXA is increasingly used in children to quantify bone mass [4]. However, DXA has its drawbacks, including cost, lack of widespread availability for paediatric use, radiation, and difficult interpretation of data in children and adolescents [5]. Difficult interpretation in children is based on the lack of uniform reference data and the influence of puberty, weight and especially height on BMD [6]. Conventional radiographs have long been used to estimate BMD. Historically, the first technique for the quantification of bone mass was radiogrammetry, which measures the phalangeal width and cortical thickness and the results are expressed as a cortical index [7]. But manual radiogrammetry is a time-consuming technique. The implementation of high-quality film scanners, improved computer technique and software to automatically evaluate the cortical BMD and the metacarpal index (MCI) has led to renewed interest in radiogrammetry. In many studies in adults, BMD values determined by digital X-ray radiogrammetry (DXR-BMD) have been comparable with the values determined by DXA (DXA-BMD), which is currently the recommended method for the evaluation of BMD [8].

In this preliminary study we evaluated children with chronic IBD to identify patients with reduced BMD. The DXR-BMD results were compared with DXA-BMD results to evaluate the potential clinical relevance of DXR in children.

Materials and methods

Patients

The study population consisted of 26 children and adolescents (10 girls, 16 boys; age range 10–18 years; median 14.3 years; Table 1) diagnosed with Crohn disease (n=11) or ulcerative colitis (n=15) according to accepted international criteria. A history of previous fractures was not an exclusion criterion. Exclusion criteria were visible fractures of the investigated forearm, immobilization and other diseases that may have affected BMD. Children were eligible if they were younger than 18 years. The local ethics committee was informed about the character of the study and approved the study design.
Table 1

Clinical characteristics of the study group

 

Crohn disease

Ulcerative colitis

No. of patients (female/male)

11 (3/8)

15 (7/8)

Age (years)

 Median

15.0

13.8

 Range

12–18

10–17

Skeletal age (years)

 Median

14.2

14

 Range

10.5–18.5

8.5–18

No. of attacks

 Median

3.4

3.5

 Range

1–10

1–7

Illness duration (months)

27.6

25.3

Corticosteroids

 Yes/no

8/3

14/1

 Duration (months)

19.2

19.6

BMI (kg/m2)

 Median

18.6

19.5

 Range

13.9–22.6

15.6–25.3

Height (m)

 Median

1.58

1.61

 Range

1.42–1.82

1.39–1.82

Radiographs

In all patients, conventional radiographs of the non-dominant left hand were performed for the evaluation of skeletal age, known to be retarded in patients with chronic IBD. The use of the left hand was based on the fact that the original Greulich and Pyle atlas used the left hand. The consecutively sampled radiographs were obtained in a single centre. Standardized PA radiographs of the left hand were taken on a single film (Kodak Trimax Regular 400) using the following parameters: MPG 80 (General Electric, Milwaukee, Wis.), filter 1.0 mm aluminium + 0.1 mm copper, film focus distance 1 m, small focus 0.6 mm, tube voltage 45 kVp, exposure 3.2–4 mAs.

Digital X-ray radiogrammetry

The Pronosco X-posure system (version V.2, Sectra, Sweden) was used to determine DXR-BMD and DXR-MCI based on radiogrammetry. The 26 consecutively sampled radiographs were used for the analysis of DXR-BMD. As the technique has recently been described in detail elsewhere [911], the calculation of DXR-BMD (g/cm2) is only summarized here. The system consists of a computer and a flatbed scanner. The scanner is calibrated and quality-assurance testing is done on a daily basis. It takes 5 min to scan and analyze a radiograph, which is done automatically by the system. The system self checks the quality of the scanned image and interrupts the measurement when quality is inadequate. The computer algorithms automatically define regions of interest (ROIs) around the narrowest parts of metacarpals II, III and IV and detect the outer and inner edges of the cortical bone. Manual correction of the ROIs is not possible. The average cortical thickness of the second to fourth metacarpals is calculated. The cortical volume per area (VPA) is calculated for each bone. The DXR-BMD is computed on the basis of the VPA with a correction for porosity. Porosity is the fraction of cortical bone that is not occupied by compact cortical bone. The metacarpal index (DXR-MCI) is an expression of the mean cortical thickness normalized to the mean outer bone diameter (width).

Dual energy X-ray absorptiometry

BMD and bone mineral content of the lumbar spine (vertebrae L1–L4) and of the left trochanteric and femoral neck region and the femoral head were measured by means of DXA using a Hologic scanner (Hologic QDR 4500, Hologic, Bedford, Mass.). DXA measurement and radiography of the left hand were performed on the same day in all patients.

Data analysis

The evaluated DXR data were analyzed according to a regional database of healthy German Caucasian children and adolescents [12]. The DXR-BMD and the DXA results were corrected for skeletal age for further analysis. The data were compared to those of age- and sex-matched children and an individual standard deviation (SD) was calculated for each subject. It is necessary to compare the evaluated BMD with those of healthy gender-, age- and race-matched controls, which can be expressed as Z-scores. The Z-score is defined as the SD of the measured BMD in relation to the mean for the child’s age and sex. The Z-scores were calculated using the formula: (BMD patient − BMD control)/SD control [12]. Z-scores for DXR-BMD, DXR-MCI and DXA-BMD L1–L4 were evaluated. It was not possible to evaluate Z-scores for the DXA-BMD of the proximal femur due to missing reference values. Currently there are no defined ranges for osteopenia and osteoporosis in children. In the current study we defined a reduced BMD with a Z-score less than −1 SD as osteopenia and severely reduced bone mass as a Z-score less than −2.5 SD.

Data were analyzed using the Statistical Package of Social Sciences, version 11.0 (SPSS, Chicago, Ill.). The significance level was set to P<0.05. In order to test short-term in vivo precision of the system in children, all radiographs were scanned twice with repositioning between the measurements. The evaluated DXR-BMD and DXR-MCI were correlated with the DXA-BMD findings. The findings of bone densitometry were correlated with clinical parameters (glucocorticoid exposure, years since diagnosis, number of acute attacks, patient’s age).

Results

The DXR system recognized the metacarpals of all 26 patients and the DXR parameters could be calculated successfully in all these patients. Repeated measurements of the radiographs yielded a precision (coefficient of variation, CV%) of 0.45% in our population. DXR-BMD ranged from 0.357 to 0.559 g/cm2 (median 0.457 g/cm2) in patients with Crohn disease and from 0.319 to 0.634 g/cm2 (median 0.47 g/cm2) in patients with ulcerative colitis. DXR-MCI ranged from 0.287 to 0.486 (median 0.378) in Crohn patients and from 0.257 to 0.535 (median 0.394) in ulcerative colitis patients. The distribution of osteodensitometric parameters using DXR and DXA is listed in Table 2. Figure 1 demonstrates the distribution of BMD values at different sites measured with different methods.
Table 2

Osteodensitometric measurements in children with Crohn disease and ulcerative colitis. Values are medians (SD)

 

Crohn disease (n=11)

Ulcerative colitis (n=15)

Total (n=26)

DXA-BMD L1–L4 (g/cm2)

0.69 (0.11)

0.71 (0.16)

0.70 (0.14)

DXA-BMD L1–L4 Z-score

−2.64 (1.08)

−1.71 (1.35)

−2.28 (1.31)

DXA-BMD proximal femur (g/cm2)

0.80 (0.14)

0.81 (0.12)

0.81 (0.13)

DXR-BMD (g/cm2)

0.46 (0.08)

0.48 (0.08)

0.47 (0.08)

DXR-BMD Z-score

−1.53 (0.75)

−0.64 (0.93)

−1.13 (0.95)

DXR-MCI

0.38 (0.07)

0.39 (0.09)

0.39 (0.08)

DXR-MCI Z-score

−0.64 (0.89)

−0.39 (1.18)

−0.61 (1.05)

https://static-content.springer.com/image/art%3A10.1007%2Fs00247-005-0093-y/MediaObjects/247_2005_93_Fig1_HTML.gif
Fig. 1

Relationship between DXA-BMD and DXR parameters (DXR-BMD and DXR-MCI) in patients with chronic IBD (n=26)

In patients with Crohn disease, the median Z-score for DXR-BMD was −1.53 (range −2.90 to −0.33) and in patients with ulcerative colitis −0.64 (range −2.42 to +2.30) in comparison to the values for age- and sex-matched normal volunteers [12]. Following adjustment for skeletal age, the evaluated DXR-BMD Z-scores were reduced to <−1 SD in 15/26 patients (57.7%) with IBD. In one patient with Crohn disease the DXR-BMD Z-score was reduced to a score <−2.5 SD (3.8%). In eight patients with Crohn disease (30.7%) and in six patients with ulcerative colitis (23.1%), DXR-BMD was reduced to a Z-score between −1 and −2.5 SD in comparison to regional normative data (53.8%). Normal values of DXR-BMD were found in 11 patients (42.4%). The median Z-score in Crohn patients for DXR-MCI was −0.64 (range −2.55 to 0.75) and in patients with ulcerative colitis −0.39 (range −2.42 to 2.30).

The Z-scores for DXR-BMD, DXR-MCI and DXA-BMD L1–L4 are shown separately for patients with Crohn disease and ulcerative colitis in Table 2. There were significant correlations (P<0.01) between the estimated Z-score equivalents using the DXR-BMD and DXA-BMD in the lumbar spine (r=0.58). The DXR-BMD Z-score in Crohn patients (median −1.53 SD) was reduced more than in patients with ulcerative colitis (median −0.64 SD). The DXA-BMD Z-score in Crohn patients was also more reduced in the lumbar spine (median −2.64 SD) than in patients with ulcerative colitis (median −1.71 SD). The evaluated Z-score in these patients was reduced to <−1 SD in 22/26 patients (84.6%), but these data were corrected only for skeletal age and not for height.

Significant correlations (P<0.01) between DXR-BMD and the standard method DXA-BMD in the lumbar spine (r=0.78) and the proximal femur (r=0.61) were found (Table 3). Investigation of the association between the DXR parameters and the clinical parameters demonstrated close correlations between the DXR-BMD and skeletal age (r=0.81), height (r=0.78), weight (r=0.76), and body mass index (BMI) (r=0.59). The clinical parameters (cumulative dose of glucocorticoids, duration of the disease and number of periods of inflammatory activity) showed no significant association.
Table 3

Association (in terms of correlation coefficient, r) between DXR parameters, DXA-BMD and clinical parameters in the study group of children with chronic IBD (n=26)

 

DXR-BMD

DXR-MCI

DXA-BMD L1–L4

0.78**

0.78**

DXA-BMD proximal femur

0.61**

0.51**

Exposure to glucocorticoids

−0.17

−0.28

Years since diagnosis

0.21

0.18

Number of acute attacks

0.23

0.15

Skeletal age

0.81**

0.70**

Chronological age

0.61**

0.54**

Height

0.78**

0.57**

Weight

0.76**

0.56**

BMI

0.59**

0.47*

**P<0.01, *P<0.05

Discussion

Osteopenia and osteoporosis are, among others, extraintestinal sequelae of chronic IBD, with a prevalence of 5.3–38% [13]. The increased prevalence of osteopenia and osteoporosis is a significant complication in both children [14] and adults [15]. Osteoporosis is associated with a high risk of fractures of the spine, hip and radius resulting in significant morbidity and mortality [16]. This has even been reported in young patients with chronic bowel disease [17, 18]. The relationship between BMD and fracture risk is continuous; a reduction of 1 SD in BMD is associated with an approximately twofold increase in relative risk of fracture [19]. According to WHO guidelines, the definition of osteoporosis is based on the measurement of BMD with a T-score of less than −2.5 [16]. As was expected, our data confirmed lower BMD values in patients suffering from IBD. In our patients the DXR-BMD Z-score was reduced to <−1.0 SD in 57.7% of the patients, which is within the range of findings in the literature [20]. Harpavat et al. [20] reported that about 56% of patients have lumbar spine BMD Z-scores <−1 SD. Based on DXA, 84.6% of our patients had a Z-score <−1.0 SD. This result would imply that the use of DXR leads to under-diagnosis of osteoporosis compared with DXA. However, it is generally agreed that the cut-off values for osteopenia or osteoporosis used in DXA cannot be applied to other techniques. Furthermore, DXR studies in patients with osteoporosis and osteoporotic fractures are necessary for the evaluation of relevant cut-off values that can be used if DXR is to be implemented as a clinical routine.

Patients with IBD and low BMD should be identified and then treated according to accepted guidelines [21]. Adequate nutritional status should be achieved and long-term corticosteroid treatment should be avoided. The association between corticosteroid therapy and bone loss, particularly in the trabecular bone of the lumbar spine is well documented [22]. In the present study we did not observe a significant relationship between treatment with corticosteroids and BMD, although there was a trend towards a negative correlation between the duration of corticosteroid therapy and a reduction in BMD in the lumbar spine, femur and metacarpals. This is in agreement with the finding of Jahnsen et al. [1] who were unable to demonstrate a significant correlation between treatment with corticosteroids and BMD changes [1]. BMI reflects nutritional status and a low BMI may also indicate poorly controlled chronic IBD. Bolotin et al. [23] and Tothill et al. [24] have shown that DXA is susceptible to changes in body composition irrespective of the real BMD.

In our study there was a significant correlation between BMI and the results of DXR, which is supported by the findings of a recent study [25]. This is an interesting finding because DXR should not be hampered by changes in the soft tissues. So, DXR seems to be a promising technique for quantification of small alterations in cortical BMD. However, this was only a cross-sectional study with a small heterogeneous study population. The activity of the disease seems to be a further contributory factor to bone loss in patients with chronic IBD [1], but we did not observe a significant correlation between the number of periods of high activity of the disease and the results of DXA versus DXR. This finding confirms the conclusions of Cowan et al. [26] who found no association between disease activity and bone mineralization. They suggested that the relatively small number of patients in their study was insufficient to demonstrate an association. The small number of patients in our study led to the same problem.

The possibility of identifying patients with decreased BMD is a key factor in preventing or treating severe osteopenia. At present, DXA is the most commonly used method in clinical practice for the evaluation of BMD in the spine and hip. However, DXA has its drawbacks. Radiation exposure and the high cost of the equipment reduce its widespread availability [27]. The interpretation of DXA results in a paediatric population is complicated because of the influence of puberty, weight and height on BMD [5, 6]. Positioning is also more difficult in children because DXA apparatus is designed for adults. There are also limitations in the precise setting of the ROI in follow-up studies because of the growth of bones. However, the main disadvantage is that DXA does not correct for AP depth and the results are significantly influenced by bone size. So children with smaller bones will automatically show a lower bone density. A further point is movement of children; DXA requires the patient to be immobile.

The comparison of DXR and DXA revealed a strongly significant correlation between the different parameters in our patients. Furthermore, DXR-MCI showed a significant correlation with DXA-BMD, supporting the findings in the literature [10, 28]. Repeated measurements of radiographs yielded a CV of 0.45% for DXR-BMD in our population. In previously published studies, the CV ranged from 0.6% to 0.68% in adults [9, 10] and was 0.59% in a paediatric population [12]. DXR is a low-cost convenient method that has effectively been used for the evaluation of several patients with reduced BMD [10, 28, 29]. There are some reports regarding the use of DXR in children [11, 12, 30]. An advantage of DXR in children is that DXR-BMD can be evaluated using conventional and digitally acquired radiographs of the non-dominant hand that have already been obtained in many children with chronic diseases (e.g. oncologic patients, patients suffering from chronic inflammatory diseases) as a routine method for the evaluation of skeletal age. Therefore, the additional use of ionizing radiation for an estimation of bone status is unnecessary in these patients.

A further advantage of the DXR method in comparison to other osteodensitometric methods is the fact that there is no influence of soft-tissue thickness on BMD calculations. Finally, in the DXR method DXR-BMD and DXR-MCI are calculated without any influence of the operator. With the DXR device used in our study only cortical BMD was calculated. Consequently, density loss at trabecular sites would not be detectable using DXR. Another potential limitation of DXR is the peripheral location of the measurement. The values of BMD as determined by DXA and DXR are not directly comparable [28, 29]. This applies especially to the lumbar spine as the central part of BMD does not correlate with DXR sufficiently well because of the trabecular bone partitions. Thus the DXR method does not estimate the extent of demineralization of the whole skeleton and consequently DXR cannot replace DXA. However, our study was limited by its retrospective character, and general conclusions have to be reserved for further prospective studies of a larger population.

In conclusion, alterations of bone mass are common in both children and adolescents with chronic IBD. We were able to show in a small population of children with Crohn disease and ulcerative colitis that DXR-BMD was reduced as expected. Our data showed that DXR, which allowed a precise determination of cortical BMD, seems to be a technique that can be applied to children. The observed correlation with DXA supports the potential clinical relevance of DXA in children.

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© Springer-Verlag 2006