|Year : 2020 | Volume
| Issue : 2 | Page : 101-106
Evaluation of bone mineral density in type I diabetic children attending the diabetes clinic of Alexandria University Children’s Hospital
Salma M Saleh Elsayed1, Mohamed H Gouda2, Doaa M Emara3, Shaymaa Elsayed A Meguid1
1 Department of Pediatric, Pediatric Endocrinology and Diabetology Unit, Alexandria University, Alexandria, Egypt
2 Department of Pediatric, Alexandria University, Alexandria, Egypt
3 Department of Radiodiagnosis, Alexandria University, Alexandria, Egypt
|Date of Submission||28-Mar-2020|
|Date of Decision||02-Apr-2020|
|Date of Acceptance||04-Apr-2020|
|Date of Web Publication||5-Oct-2020|
Shaymaa Elsayed A Meguid
Department of Pediatric Endocrinology and Diabetology, Alexandria University, Alexandria, 21526
Source of Support: None, Conflict of Interest: None
Introduction Type 1 diabetes mellitus (T1DM) is associated with reduced bone mineral density (BMD). Potential pathogenic mechanisms of T1DM-related bone damage may include the deficiency of insulin and insulin-like growth factors. Early identification of reduced BMD is useful in reducing the bone loss and fracture risk. We can get a quick, noninvasive, and accurate quantitation of bone mass by using dual-energy X-ray absorptiometry (DEXA scan).
Aim The aim was to assess BMD in children with T1DM of 5-year duration or more and to evaluate its relation with the glycemic control.
Patients and methods This study included 30 children with T1DM attending the diabetic clinic in Alexandria University Children’s Hospital, Egypt. They were compared with 30 apparently healthy children of matched age and sex. Thorough history taking and clinical examination were done with emphasis on age and duration of diabetes and history of fractures. Laboratory investigations were done including renal functions, serum calcium (Ca), phosphorus (P), alkaline phosphatase, and glycosylated hemoglobin (HbA1C). BMD was assessed by DEXA scan at the spine (L2–L4) and at the femur.
Results The mean age of the diabetic cases was 12.2 years, with mean of 7.6 years as duration of diabetes. There was no significant difference between the two groups regarding the serum levels of Ca and P, but alkaline phosphatase was significantly higher in diabetic cases than in controls. A total of nine diabetic cases (30%) had low bone density (Z score < −2 SD by DEXA scan). The diabetic cases had lower mean BMD results than in control group.
Conclusion Reduced BMD is common in children with T1DM. The authors recommend assessing children with T1DM by DEXA scan for early identification of reduced BMD to reduce the fracture risk.
Keywords: bone mineral density, dual-energy X-ray absorptiometry, type 1 diabetes mellitus
|How to cite this article:|
Saleh Elsayed SM, Gouda MH, Emara DM, Meguid SA. Evaluation of bone mineral density in type I diabetic children attending the diabetes clinic of Alexandria University Children’s Hospital. Alex J Pediatr 2020;33:101-6
|How to cite this URL:|
Saleh Elsayed SM, Gouda MH, Emara DM, Meguid SA. Evaluation of bone mineral density in type I diabetic children attending the diabetes clinic of Alexandria University Children’s Hospital. Alex J Pediatr [serial online] 2020 [cited 2020 Oct 20];33:101-6. Available from: http://www.ajp.eg.net/text.asp?2020/33/2/101/297246
| Introduction|| |
The concomitance of type 1 diabetes mellitus (T1DM) and low bone mineral density (BMD) is a commonly discussed subject in the literature, as there is still some debate about the effect of the disease on bone mass during childhood, and the problem is considered as a public health issue .
It has been reported that bone loss might be considered as a late complication of T1DM, and this makes evaluation of bone health in T1DM follow-up a mandatory issue .
Measuring BMD is best done by dual-energy X-ray absorptiometry (DEXA) scan. In children, DEXA consists mainly of an examination of the lumbar spine and proximal femur, but it may include the whole body. The reference population to which the child is compared must be noted, and adjustment should be done for sex, height, weight, radiographic bone age, pubertal staging, and ethnicity ,.
For diagnosis in pediatric age groups, measured BMD values must be compared with an almost normal matching pediatric database, yielding an age, sex, and ethnicity-matched value to result in what is called a Z score, which is the score used to assess BMD in children. Typically Z scores of −2 or lower are considered to be below the expected range for age ,.
| Aim|| |
The aim was to assess BMD in children and adolescents with T1DM of 5 years duration or more and to evaluate its relation with the glycemic control.
| Patients and methods|| |
We included 30 children and adolescents with T1DM who were diagnosed since the past 5 years or more and attending the diabetic clinic in Alexandria University Children’s Hospital. They were compared with 30 apparently healthy children of matched age and sex. Patients with chronic kidney disease or history of and disease or drug intake that may alter bone metabolism were excluded.
Thorough history taking and clinical examination were done with emphasis on age and duration of diabetes, stage of puberty by Tanner staging, and history of fractures. BMI was calculated. Laboratory investigations were done, including renal functions, serum calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), and glycosylated hemoglobin (HbA1C).
BMD was assessed by DEXA scan at the spine (L2–L4) and at the femur. The device of DEXA scan was made in USA, model 2016; its company is GE Health Care. It was expressed as SD units (Z values) in relation to the age-matched reference population. Z score of less than or equal to −2 denotes low BMD, BMD between −2 and −1 denotes low normal BMD, and values of greater than or equal to −1 are accepted as normal. Calcium profile and DEXA scans were done to the control group.
Informed consent was taken from all the patients’ guardians. Ethical approval was obtained from Medical Ethics Committee of Faculty of Medicine, Alexandria University, in October 2016.
| Results|| |
In the diabetic group, half the patients were males and half of them were females, and their mean age at presentation was 12.23±2.55 years. However, in the control group, 17 (56.7%) were males and 13 (43.3%) were females, and their mean age was 11.03±3.39 years. There was no significant difference between the two groups regarding age, sex, and BMI. Half of the patients were prepubertal (Tanner I), and the other half were postpubertal.
It was observed that 27 (90%) patients were diagnosed since 5–10 years and three (10%) patients were diagnosed since greater than 10 years. The mean duration of diabetes was 7.6±2.22 years, with a range of 5–14 years.
Most patients (93.3%) had no history of bone fractures, whereas only two (6.7%) patients had past history of bone fractures (both of them with fracture humerus once or before after accidental trauma). The mean of HbA1c levels of the patients was 10.58%. The mean of total daily insulin dose was 1.06 U/kg/day. All the patients had serum creatinine and blood urea nitrogen within normal range. The mean glomerular filtration rate of the patients was 148.5 ml/min/m2.
The mean calcium level of the patient group was 9.41±0.91 mg/dl compared with 9.2±0.44 mg /dl for the controls. There was no significant statistical difference between the two groups regarding serum calcium and phosphorus levels. Hypocalcemia was found in four (13.3%) patients and only in one member of the control group. A total of 26 (86.7%) patients had high ALP levels compared with 21 (70%) controls. There was a statistically significant difference between the mean of ALP levels in patients and controls, as it was higher in the patients group (259.7±105.8 U/l) than in the controls group (176.4±76.99 U/l), with P value of 0.001 ([Table 1]).
|Table 1 Comparison between the two studied groups according to calcium profile|
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It was noticed that 12 (40%) patients have low normal bone density (Z score from −1 to −2 SD) compared with nine (30%) controls, whereas nine (30%) patients were found to have low bone density (Z score <−2 SD) compared with four (13.3%) controls. Approximately 56.7% of the control group were found to have normal bone density (Z score >−1 SD) in comparison with only 30% in the patient group, who were found to have normal bone density. There was a significant difference between both groups regarding DEXA scan results in general, where patients were found to have lower bone density mean (−1.34±1.22 SD) than controls (−0.58±1.15 SD) with P value 0.01 ([Table 2]).
|Table 2 Comparison between the two studied groups according to DEXA scan results (Z scores)|
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The difference between both groups was statistically significant regarding lumbar spine results, with P value 0.01, as it was found that the mean value of DEXA scan Z score at the spine in the patient group was −1.25±1.3, and for the control group, it was −0.49±1.15. However, there was no significant difference between both groups regarding femur results, as it was found that the mean value of DEXA scan Z score at the femur in the patient group was −0.33±1.22 and for the control group it was 0.12±1.27 ([Table 2]).
Descriptive data of the diabetic cases with low bone density
There were nine diabetic patients with low bone density, comprising four males and five females, and their mean age was 13.06±2.72 years. Overall, six of them were using premixed insulin regimen, and only three of them were using basal bolus regimen. Only one patient had past history of bone fracture (fracture humerus) whereas the others did not have and only two of them were diabetics since more than 10 years, whereas the rest were diagnosed since 5–10 years. Only two of them had hypocalcemia, and only one patient had high phosphorus level. A total of eight (88.9%) patients of this group had high ALP levels, whereas only one patient had normal ALP level. All of the nine patients were poorly controlled with HbA1c levels >more than .5%.
Correlation group between DEXA scan results and other parameters for the patients
There was a significant negative correlation between duration of the DM and DEXA scan results, with P value of 0.05. There was no significant relation between levels of HbA1C, BMI, sex, or pubertal stages of the patients and DEXA scan results of the patients ([Figure 1]).
|Figure 1 Correlation between dual-energy X-ray absorptiometry scan results (Z score) and duration of diabetes mellitus (years) for patients (n=30).|
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| Discussion|| |
The present study showed no significant statistical difference between diabetic cases and control groups regarding serum levels of calcium and phosphorus, but the mean ALP levels in patients was significantly higher than in the controls group.
In agreement to our results, Abdel Dayem et al.  did not find any statistically significant difference between patients and controls groups regarding serum calcium and phosphorus levels. Moreover, Ersoy et al.  found similar results.
Unlike our study, Hamed et al.  reported that the mean calcium level of their patients was 8.81±1.22 mg/dl, whereas it was 9.85±1.01 mg/dl in the control group, and this showed statistically significant difference between both groups. Moreover, the mean phosphorus level was 5.08±1.35 mg/dl in the patient group, which was significantly lower than that of control group (3.99±0.94 mg/dl). However, ALP levels did not show any significant statistical difference between both groups.
These contradictory results may be attributed to the fact that results of biochemical markers of bone remodeling are difficult to interpret, especially in children, as they reflect the processes of growth and remodeling that occur simultaneously during childhood and adolescence. Average values and inter-individual variation are many times greater in children than in adults.
In the present study, nine (30%) patients had low bone density compared with four (13.3%) controls, whereas 12 (40%) patients had low normal bone density compared with nine (30%) controls, and in general, diabetics had lower BMD values (mean=−1.34±1.22) than controls (mean=−0.58±1.15), and there was a statistically significant difference between DEXA scan results of both groups.
The mean DEXA scan Z score results of lumbar spine for patients was −1.22±1.28 compared with −0.57±1.21 for the controls, and this was statistically significant, but the difference between both groups regarding DEXA scan results of the femur was not significant.
Trabecular bone seems to be more sensitive to mineral changes than cortical bone and the explanation to the more evident bone mineralization changes found in lumbar spine DEXA scan results is the relatively high fraction of trabecular bone present in the spine more than other sites ,. The occurrence of low or low normal BMD in the control group may be explained by the presence of vitamin D deficiency or bad nutritional habits that may affect their bone health.
Similar to these results, Gunczler et al.  studied 23 prepubertal children with T1DM with a mean age of 9.5±2.2 years in comparison with controls in Venezuela and observed that lumbar spine BMD was reduced in diabetic children significantly when compared with healthy controls, where the mean lumbar spine Z scores was −0.89±1.2 for the patients and was −0.27±0.68 for the controls.
Moreover, in the study done by Abd El Dayem et al. , three (7.3%) patients, seven (16.7%) patients, and 17 (41.5%) patients out of 47 had low bone density at the lumbar spine, right femur, and total body, respectively. However, the results were worse in the study by Hamed et al.  where of 36 patients, two (5.6%) patients had low bone density and 30 (83.3%) patients had low normal bone density. Ersoy et al.  found that BMD of lumbar spine values were significantly lower in diabetics than in controls.
Moreover, Onder et al.  found that 10 (10%) patients had low BMD and 25 (25%) patients had BMD in the low range of normality and Sayarifard et al.  reported low BMD and BMD in the low range of normality in 17 (15.2%) and 25 (22.3%) of their patients, respectively.
However, in contrast to our results, Maggio et al.  reported that the BMD results were similar among T1DM and healthy subjects and no significant difference was found between both groups. Moreover, Mosso et al.  studied a group of 30 patients with T1DM and observed that lumbar spine BMD was more affected than femur BMD, but the difference was not significant, and in general, they found that diabetic children had a normal mean BMD at all sites evaluated, except for two patients who had low BMD at the spine level.
This discrepancy between reports is probably because of several factors, such as using different methods for BMD measurement, different designs of studies, and different patient selection criteria.
In the present study, there was no significant relation between sex of the patients and their DEXA scan results. Similarly, Sayarifard et al.  studied 112 diabetic children (57 females and 55 males) in Tehran, Iran. Their ages ranged from 4 to 14 years. They were in line with our results regarding this point.
In contrast to our results, Léger et al.  did a cross-sectional study on 127 white children (73 boys and 54 girls) with T1DM (ages ranged from 6 to 20 years) in Paris, France, and found that BMD of diabetic girls was higher significantly than control girls, whereas in boys, BMD was similar between both groups.
Unlike our results, Heilman et al.  found that male sex was associated with lower BMD in diabetic children, and this can be explained by the presence of more prepubertal boys than girls in their sample, and by considering that puberty is an important stage for the peak bone mass gain, it is proposed that the delayed pubertal pattern may be a reason that diabetic boys have lower BMD.
The mean duration of diabetes in our cases was 7.8 years, and there was a significant negative correlation between duration of the disease and DEXA scan results. On the contrary, a study by Gunczler et al.  showed decreased BMD of the lumbar spine in children a few months after the onset of T1DM, indicating that genetic predisposition may be the main predisposing factor rather than the long-term metabolic consequences of the disease.
However, Maggio et al. , who studied 27 children with T1DM with ages ranging from 6.8 to 16 years, and a mean disease duration of 3.2±2.3 years in Geneva in 2010, found no significant relations between diabetic and control groups.In the present study, no significant relation between BMI of the patients and DEXA scan results was found. In contrast to our results, Abd El Dayem et al . observed a significant positive correlation between BMD and BMI of their patients (mean BMI=22±8), which can be explained by the fact that whole-body bone mineral content increases with the rise of body mass index during childhood and adolescence.
The mean HbA1c level in the present study was 10.58±2.05%. Unfortunately, most of the patients are poorly controlled owing to poor compliance, mainly reluctance to commit to a healthy lifestyle, which is very essential for good control of diabetes and also low socioeconomic status plays a role in the very high percentage of poorly controlled subjects. There was no significant relation between the levels of HbA1c and DEXA scan results of the diabetic patients in the present study.
Similar results were observed in Hamed et al. , as the mean level of HbA1c in their patients was 9.14±1.9%, with 22 (61.1%) patients being poorly controlled. They also found no relation between glycemic control and results of DEXA scans. In contrast, a significant negative correlation was found in the studies by Abd El Dayem et al.  and Sayarifard et al. .
A relatively good metabolic control and short disease duration can explain the lack of associations between HbA1c and BMD in some studies and the fact that HbA1c result is only indicative of short-term glycemic control period, and it would not be expected to reflect cumulative bone damage measured by BMD.
This study had unfortunately some limitations: the relatively small number of patients. Although all results have been tested statistically, this made a restriction on generalizing these results and calls for a larger study to confirm these preliminary findings.
Moreover, an important parameter such as 25-OH vitamin D could not be done in all cases owing to their high costs, and it should be added in future studies regarding similar topics to have more clear results about the relation between diabetes and bone metabolism such as measuring some markers of bone metabolism like parathormone hormone and osteocalcin that may be used for the early detection of impaired bone metabolism in diabetics even before DEXA scan results are affected.
Children with T1DM possess multiple risk factors for skeletal fragility probably because of increased disease duration and poor metabolic control. However, because decreased BMD prevention is supported by nutritional, physical, and endocrinal factors, it should be initiated early by encouraging good metabolic control in diabetic children. Physical activity, adequate sunlight exposure and supplementing infants and children with calcium and vitamin D supplements or fortified food might be a safe and effective strategy for reducing the risk and also in the management of T1DM-related bone complications.
Conclusion and recommendations
From the present study we concluded the following:
- BMD of the diabetic group was significantly lower than that of the control group.
- There was no significant difference between patients and controls regarding serum calcium and phosphorus levels but ALP levels were significantly higher in diabetics than in the control group.
- There was a significant negative correlation between duration of the disease and DEXA scan results, but no significant relation between levels of HbA1C, BMI, sex, or pubertal stages of the patients and DEXA scan results was found.
So, we recommend the following:
- Doing DEXA scan as a part of routine screening of diabetes complications in children, especially in cases with longer duration of the disease.
- Conducting further trials on a wide scale to determine effects of several variables, such as biochemical markers of bone turnover and lifestyle interventions on BMD and metabolism in diabetic children.
The research was supported by Alexandria Faculty of Medicine.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2]