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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 33  |  Issue : 3  |  Page : 755-759

The association between osteoporosis and diabetic neuropathy in patients with type 2 diabetes


1 Department of Internal Medicine, Faculty of Medicine, Menoufia University, Shibin El-Kom, Menoufia Governorate, Egypt
2 Department of Clinical Pathology, Faculty of Medicine, Menoufia University, Shibin El-Kom, Menoufia Governorate, Egypt

Date of Submission21-Nov-2018
Date of Decision22-Dec-2018
Date of Acceptance30-Dec-2018
Date of Web Publication30-Sep-2020

Correspondence Address:
Hytham R Badr
Department of Internal Medicine, Faculty of Medicine, Menoufia University, Shibin El-Kom, Menoufia Governorate
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_380_18

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  Abstract 


Objective
The objective of this study was to evaluate the association between osteoporosis and diabetic peripheral neuropathy in patients with type 2 diabetes mellitus (T2DM).
Background
Diabetic complications and osteoporotic fractures are two of the most important causes of morbidity and mortality in older patients. There is increased fracture rate associated with T2DM, despite these patients having greater bone mineral density. Osteocalcin, one of the bone turnover markers, is a peptide secreted by bone cells and reflects bone formation and consequently indicates bone remodeling status; which is the major mechanism underlying osteoporosis.
Patients and methods
This case–control study was done on 78 patients with T2DM. They were classified into two groups. Group I (neuropathy group) included 39 patients with diabetic neuropathy. Group II (control group) included 39 patients without diabetic neuropathy. Dual-energy X-ray absorptiometry (DEXA) and serum osteocalcin measurement were done for both the studied groups.
Results
There was no significant difference between the two studied groups in the DEXA scan results; the mean least T-score of the neuropathy group was −1.4 and that of the control group was −1.2 (P = 0.27). The mean osteocalcin level of the neuropathy group was 35.8, whereas that of the control group was 13.8, showing significant difference between the two groups (P = 0.03).
Conclusion
Osteoporosis is more prevalent in T2DM with microvascular complications, and serum osteocalcin level is better in its diagnosis than DEXA scan.

Keywords: diabetes mellitus, diabetic neuropathy, diabetic osteoporosis, osteocalcin, osteoporosis


How to cite this article:
El-Kafrawy NA, El-Najjar MM, Shehab Eldin WA, Alhelbawy MG, Badr HR. The association between osteoporosis and diabetic neuropathy in patients with type 2 diabetes. Menoufia Med J 2020;33:755-9

How to cite this URL:
El-Kafrawy NA, El-Najjar MM, Shehab Eldin WA, Alhelbawy MG, Badr HR. The association between osteoporosis and diabetic neuropathy in patients with type 2 diabetes. Menoufia Med J [serial online] 2020 [cited 2020 Oct 22];33:755-9. Available from: http://www.mmj.eg.net/text.asp?2020/33/3/755/296678




  Introduction Top


Diabetic complications and osteoporotic fractures have many common features including genetic susceptibility, environmental factors, and molecular mechanisms. Bone microarchitecture is compromised by type 2 diabetes mellitus (T2DM) through inducing abnormal bone cell function and matrix structure, with increased osteoblast apoptosis, diminishment in its differentiation, and enhanced osteoclast-mediated bone resorption [1],[2].

There is increased fracture rate associated with T2DM, despite these patients having greater bone mineral density. The improper redistribution of bone mass, notably, increased trabecular bone density with decreased intracortical bone, results in compromised bending load in patients with T2DM. There is little to no evidence linking T2DM to osteopenia and osteoporosis [3].

Osteocalcin (OSN) is an independent predictor for osteoporosis and osteoporotic fractures, and it has been suggested that its production is diminished by negative regulation of osteoblasts in diabetes condition [4],[5].

Diabetic peripheral neuropathy is one the most common diabetes-related microvascular complications and can result in significant increase in morbidity, such as chronic pain, foot ulcerations, amputations, and mortality [6].

The aim of this study was to evaluate the association between diabetic neuropathy as an early microvascular diabetic complication and osteoporosis.


  Patients and Methods Top


This case–control study was approved from the Ethical Committee of Faculty of Medicine, Menoufia University, and the patients gave an informed consent. The study was done on 78 patients with T2DM. The patients attended the Internal Medicine Department, Menoufia University, in the period from September 2017 till September 2018.

The diagnosis of type 2 diabetes was carried out and/or confirmed following the American Diabetes Association criteria, which includes a fasting blood glucose of at least 126 mg/dl, random (nonfasting) blood glucose of at least 200 mg/dl, a blood glucose more than 200 mg/dl at 2 h during a standard oral glucose tolerance test, or hemoglobin A1c more than 6.5% [7].

Patients were excluded if informed consent was not obtained, they had no diabetes, onset of diabetes was before the age of 30 years, or they were on treatment for osteoporosis.

The patients were classified into two groups. Group I (neuropathy group) included 39 patients with diabetic neuropathy. Group II (control group) included 39 patients without diabetic neuropathy.

After taking a written consent, data such as age, sex, duration of T2DM were obtained. Clinical examination was done with special emphasis on blood pressure, BMI, and foot examination for signs of peripheral neuropathy.

Fasting blood sugar, 2-h postprandial blood sugar using oral glucose tolerance test, serum creatinine (Scr), blood urea, dual-energy X-ray absorptiometry (DEXA), and serum OSN were done for both the studied groups.

Blood sugar was measured by Gmate blood glucose test strips (Philosys Co. Ltd, Gunsan-si Jeollabuk-do, Korea).

Scr measurement was carried out using Integra 400 autoanalyzer (Roch, Mannheim, Germany). It is determined by measuring the increase in absorbance at 512 nm. The expected value is 0.7–1.5 mg/dl. Blood urea examination was carried out using the same autoanalyzer. It is determined by a kinetic test with urease and glutamate dehydrogenase.

Urinary albumin–creatinine ratio was calculated by dividing urinary albumin concentration in milligrams by creatinine concentration in urine in grams.

Human OSN ELISA kit (Chongqing Biospes Company, Chongqing, China) was used to measure serum OSN level.

The DEXA scan (Wipro GE Healthcare Pvt Ltd, Kadugodi Industrial, Bengaluru, India) uses X-ray equipment and a computer to measure bone density.

Clinical and laboratory data of the cases were tabulated.

Statistical analysis

Data entry, coding, and analysis were conducted using SPSS Statistics for Windows, version 20.0, released 2011 (IBM Corp., Armonk, New York, USA). Description of quantitative variables was in the form of mean ± SD, and description of qualitative variables was by frequency and percentage. χ2-test was used to assess the relationship between two qualitative groups, t-test and Mann–Whitney test were to assess the relationship between two quantitative groups, and Fisher's exact test was used to assess the relationship between two or more qualitative groups. P value less than 0.05 was set to be statistically significant.


  Results Top


The study was done on 78 patients with T2DM. Each group contained 17 (43.6%) males and 22 (56.4%) females, with no significant difference between the two groups (P = 1).

Regarding hypertension, there were 25 (64.1%) hypertensive and 14 (35.9%) nonhypertensive patients in the neuropathy group, whereas in the control group, there were 23 (59%) hypertensive and 16 (41%) nonhypertensive patients, with no significant difference between the two groups (P = 0.64) [Table 1].
Table 1: Baseline qualitative data of the studied groups

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The mean age of the neuropathy group was 54.9 years, and that of the control group was 54.8 years, with no significant difference between the two groups (P = 0.13). Regarding BMI, the mean BMI of the neuropathy group was 32.9 kg/m 2 and that of the control group was 32.1 kg/m 2, with no significant difference between the two groups (P = 0.42). In contrast, there was a significant difference between the two groups regarding the duration of diabetes, with a mean of 7.8 years in the neuropathy group and 4.6 years in the control group (P = 0.036) [Table 2].
Table 2: Baseline quantitative data of the studied groups

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Regarding diabetes control of the studied groups, the mean fasting blood glucose of the neuropathy group was 234.6 mg/dl and was 227.1 mg/dl in the control group, with no significant difference between the two groups (P = 0.61), whereas the mean 2-h postprandial blood glucose of the neuropathy group was 341.5 mg/dl and was 327.1 mg/dl in the control group, which was also nonsignificant statistically (P = 0.41) [Table 2].

Regarding the kidney function tests of the studied groups, the mean Scr of the neuropathy group was 1.1 mg/dl and that of the control group was 0.94 mg/dl, showing highly significant difference between the two groups (P = 0.00). The mean blood urea of the neuropathy group was 32.7 mg/dl and that of the control group was 30.1 mg/dl, showing significant difference between the two groups (P = 0.026), whereas the mean urinary albumin–creatinine ratio of the neuropathy group was 576.03 mg/g and that of the control group was 17.6 mg/g, showing also highly significant difference between the two groups (P = 0.00) [Table 2].

The DEXA scan results showed no significant difference between the studied groups. The mean T-score of the spine of the neuropathy group was −1.03 and that of the control group was −0.83 (P = 0.19). The mean T-score of the hip of the neuropathy group was −0.3 and that of the control group was −0.15 (P = 0.41). The mean T-score of the forearm of the neuropathy group was −1.01 and that of the control group was −0.83 (P = 0.27), and the mean least T-score of the neuropathy group was −1.4 and that of the control group was −1.2 (P = 0.27) [Table 3].
Table 3: Dual-energy X-ray absorptiometry scan results of the studied groups

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According to DEXA scan, in the neuropathy group, there were eight (20.5%) patients with normal bone density, 29 (74.4%) patients with osteopenia, and two (5.1%) patients with osteoporosis, whereas in the control group, there were 10 (25.6%) patients with normal bone density, 28 (71.8%) patients with osteopenia, and one (2.6%) patient with osteoporosis, with no significant difference between the two groups (P = 0.75) [Table 4] and [Figure 1].
Table 4: Bone condition and osteocalcin level of the studied groups

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Figure 1: Bone condition of the studied groups.

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The mean OSN level of the neuropathy group was 35.8, whereas that of the control group was 13.8, showing significant difference between the two groups (P = 0.03) [Table 4] and [Figure 2].
Figure 2: Osteocalcin level of the studied groups.

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  Discussion Top


In our study, there was no significant difference between the two groups regarding sex. Timar et al. [8] found that 43.9% of patient with neuropathy and 45.4% of patients without neuropathy were males, which was also nonsignificant. This was in agreement with Kasim et al. [9], who found that 41.6% of patient with neuropathy and 49.8% of patients without neuropathy were males.

Regarding hypertension, we found that there was no significant difference between the two groups. In agreement with our study, Jaiswal and colleagues found that there was no significant difference between the two groups showing that 8.9% of T2DM with neuropathy were hypertensive and 11.4% of T2DM patients without neuropathy were hypertensive. The small percentage of hypertensive patients in comparison with our study may be owing to the younger age of participants (22 ± 3.5 years). In contrast to our results, Kasim and colleagues found that the percentage of hypertensive patients in the diabetic neuropathy group was 69% and in the non-neuropathy group was 20.8%, showing significant difference between the two groups. This also may be owing to age concern in that study, as the neuropathy group included only 18% of patients below 50 years old and the non-neuropathy group included 84.4% of patients below 50 years old [9],[10].

There was no significant difference in the mean age of the two groups. In contrast to our results, Timar et al. [8] found that the mean age of the overt neuropathy group was 64.5 years old and that of the nonovert neuropathy group was 59 years old, which was highly significant difference. This may be owing to the difference in randomization of patients; our patients are randomized as neuropathy or not, whereas Timar et al. [8] randomized as overt neuropathy or nonovert.

Regarding BMI, there was no significant difference between the two groups. In agreement with our results, Jaiswal et al. [10] found that the mean BMI of the neuropathy group was 35.1 kg/m 2 and that of the control group was 35.6 kg/m 2, with no significant difference between the two groups.

In contrast, there was a significant difference between the two groups regarding the duration of diabetes. This result was similar to that found by Jaiswal et al. [10] with 8.6 years in the neuropathy group and 7.6 years in the control group.

When we focused on the investigations of osteoporosis and bone condition, we found that there was no significant difference between the two studied groups regarding DEXA scan results, but there was a significant difference in the OSN level between the two groups.

This finding is supported by Asokan et al. [11] who found that there was no difference between the diabetic and nondiabetic patients regarding the DEXA scan results, and this may be owing to the fact that obesity is widespread in T2DM patients, and this is strongly associated with higher bone mineral density and may also be owing to hormonal factors, including insulin, estrogen and leptin.

However, this finding is not in agreement with Prakash et al. [12] who found that the incidence and prevalence of osteoporosis increase in diabetic patients than others; however, that study's results may be conflicting as they recruited the patients from the outpatient department of orthopedics [11].

In contrast, Maghbooli et al. [4] found that OSN level was elevated in diabetic patients with microvascular complications than patients without complications, and this is supported by our results.

This finding may be owing to oxidative stress because of high glucose levels in the blood which interact with several proteins to generate a higher concentration of advanced glycation endproducts. Accumulated advanced glycation endproducts in the body may stimulate apoptosis of osteoblasts, thereby contributing to the defective bone formation [13],[14].


  Conclusion Top


Our study found that OSN level – as a marker of osteoporosis – is elevated in diabetic patients with microvascular complications in the form of peripheral neuropathy, whereas DEXA scan is not greatly helpful in diagnosis of osteoporosis in diabetic patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Chau D, Edelman S. Osteoporosis and diabetes. Clin Diabetes 2002; 20:153–157.  Back to cited text no. 2
    
3.
Sundararaghavan V, Mazur M, Evans B, Liu J, Ebraheim N. Diabetes and bone health: latest evidence and clinical implications. Ther Adv Musculoskelet Dis 2017; 9:67–74.  Back to cited text no. 3
    
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Maghbooli Z, Shabani P, Gorgani-Firuzjaee S, Hossein-nezhad A. The association between bone turnover markers and microvascular complications of type 2 diabetes. J Diabetes Metab Disord 2016; 15:51–54.  Back to cited text no. 4
    
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Singh S, Kumar D, Lal A. Serum osteocalcin as a diagnostic biomarker for primary osteoporosis in women. J Clin Diagn Res 2015; 9:RC04–RC07.  Back to cited text no. 5
    
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Pop-Busui R, Boulton A, Feldman E, Bril V, Freeman R, Malik R, et al. Diabetic neuropathy: a position statement by the American Diabetes Association. Diabetes Care 2017; 40:136–154.  Back to cited text no. 6
    
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American Diabetes Association. Standards of medical care for patients with diabetes mellitus. Diabetes Care 2017; 40:13–18.  Back to cited text no. 7
    
8.
Timar B, Timar R, Gaiă L, Oancea C, Levai C, Lungeanu D. The impact of diabetic neuropathy on balance and on the risk of falls in patients with type 2 diabetes mellitus: a cross-sectional study. PLoS ONE 2016; 11:e0154654.  Back to cited text no. 8
    
9.
Kasim K, Amar M, El-Sadek A, Abdel-Gawad S. Peripheral neuropathy in type-II diabetic patients attending diabetic clinics in Al-Azhar University Hospitals, Egypt. Int J Diabetes Mellitus 2010; 2:20–23.  Back to cited text no. 9
    
10.
Jaiswal M, Divers J, Dabelea D, Isom S, Bell R, Martin C, et al. Prevalence of and risk factors for diabetic peripheral neuropathy in youth with type 1 and type 2 diabetes: SEARCH for Diabetes in Youth Study. Diabetes Care 2017; 40:1226–1232.  Back to cited text no. 10
    
11.
Asokan A, Jaganathan J, Philip R, Soman R, Sebastian S, Pullishery F. Evaluation of bone mineral density among type 2 diabetes mellitus patients in South Karnataka. J Nat Sci Biol Med 2017; 8:94–98.  Back to cited text no. 11
    
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Prakash S, Jatti R, Ghagane S, Jali S, Jali M. Prevalence of osteoporosis in type 2 diabetes mellitus patients using dual energy X-ray absorptiometry (DEXA) scan. Int J Osteoporos Metab Disord 2017; 10:10–16.  Back to cited text no. 12
    
13.
Alikhani M, Alikhani Z, Boyd C, MacLellan CM, Raptis M, Liu R, et al. Advanced glycation end products stimulate osteoblast apoptosis via the MAP kinase and cytosolic apoptotic pathways. Bone 2007; 40:345–353.  Back to cited text no. 13
    
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Shaaban MA, Dawod AA, Nasr MA. Role of iron in diabetes mellitus and its complications. Menoufia Med J 2016; 29:11–16.  Back to cited text no. 14
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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