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Immunohistochemical features of the bone tissue of the lower extremities in patients with type 2 diabetes mellitus

https://doi.org/10.14341/DM12812

Abstract

Background: Diabetic neuroosteoarthropathy is a serious disabling complication of diabetes mellitus, which, in the absence of timely correct treatment, can lead to high amputations of the affected limb. At present, the reasons and mechanism of the development of Charcot’s foot are not completely clear. It is extremely important to determine the pathophysiological mechanisms of DNOAP formation and to search for reliable markers-predictors of this pathology.

Aim: To study the immunohistochemical characteristics of the bone tissue of the lower extremities in patients with diabetic neuroosteoarthropathy in comparison with patients with diabetes mellitus without this pathology.

Materials and methods: During the foot surgery, a bone fragment of the foot was harvested for immunohistochemical study of receptor markers for PINP, PIIINP, and RAGE in the group of patients with DNOAP compared with the control group.

Results: The study included 20 patients with type 2 diabetes mellitus and were divided into 2 groups: 10 patients with DNOAP made up group 1, 10 patients without DNOAP — group 2.

Patients in both groups were comparable in AGE, experience with type 2 diabetes, and glycemic control.

During the immunohistochemical study, a significant increase in the staining intensity of receptor markers for PINP, PIIINP, and AGE was recorded in the group of patients with DNOAP compared with the control group (p <0.05).

Conclusion: For the first time, an immunohistochemical study of markers of bone resorption and AGE was carried out in persons with DNOAP. The results obtained indicate impaired collagen formation and, as a consequence, impaired bone formation and bone resorption in patients with DNOAP: in group 1, a statistically significant increase in the expression of PINP, PIIINP, and RAGE was revealed.

About the Authors

A. Yu. Tokmakova
Endocrinology Research Centre
Russian Federation

Alla Yu. Tokmakova - MD, PhD; eLibrary SPIN: 7479-7043.


Competing Interests:

no



E. A. Kogan
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Evgeniya A. Kogan - MD, PhD, Professor; eLibrary SPIN: 2709-2449


Competing Interests:

no



E. L. Zaitseva
Endocrinology Research Centre
Russian Federation

Ekaterina L. Zaitseva - MD, PhD; eLibrary SPIN: 1075-3022.

11 Dm.Ulyanova street, 117036 Moscow


Competing Interests:

no



S. A. Demura
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Sofia A. Demura - MD, PhD; eLibrary SPIN: 9220-4883


Competing Interests:

no



N. V. Zharkov
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Nikolay V. Zharkov - senior laboratory assistant; eLibrary SPIN: 8812-9731


Competing Interests:

no



M. M. Kalandiya
Endocrinology Research Centre
Russian Federation

Mariya M. Kalandiya - PhD student


Competing Interests:

no



G. R. Galstyan
Endocrinology Research Centre
Russian Federation

Gagik R. Galstyan - MD, PhD, Professor; eLibrary SPIN: 9815-7509


Competing Interests:

no



References

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2. Strotman PK, Reif TJ, Pinzur MS. Charcot Arthropathy of the Foot and Ankle. Foot & Ankle International. SAGE Publications; 2016 Oct 8;37(11):1255–63. doi:10.1177/1071100716674434

3. Mascarenhas J V., Jude EB. The Charcot Foot as a Complication of Diabetic Neuropathy. Curr Diab Rep. 2014;14(12):1-9. doi:10.1007/s11892-014-0561-6

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Supplementary files

1. Figure 1. Histological picture of bone tissue in diabetic neuroosteoarthropathy: A - fields of bone osteolysis with ingrowth into foci of destruction of granulation tissue with hyalinosis of the walls of microvessels and swelling of the endothelium. Granulation tissue contains pronounced inflammatory infiltrates and sclerotic changes. In the foci of osteolysis, a large number of osteoclasts are found; B - bone tissue without pathological changes in patients with diabetes mellitus (control).
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2. Figure 2. Immunohistochemical picture of PINP expression in bone tissue: A - high expression of the marker in fibroblastic elements and cells of the inflammatory infiltrate of granulation tissue, as well as in osteoclasts in patients with diabetic neuroosteoarthropathy; B - weak expression of the marker in individual osteoblasts and bone marrow cells in control patients.
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3. Figure 3. Immunohistochemical picture of PIIINP expression in bone tissue: A - high expression of the marker in fibroblastic elements and cells of the inflammatory infiltrate of granulation tissue, as well as in osteoclasts in patients with diabetic neuroosteoarthropathy; B - weak expression of the marker in individual osteoblasts and bone marrow cells in control patients.
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4. Figure 4. Immunohistochemical picture of expression of AGE receptors in bone tissue. A - moderate expression of the marker in fibroblastic elements and cells of the inflammatory infiltrate of granulation tissue, as well as in osteoclasts in patients with diabetic neuroosteoarthropathy; B - weak expression of the marker in individual osteoblasts and bone marrow cells in control patients. Figure 5. Immunohistochemical characterization of PINP, PIIINP and AGE in bone biopsies with diabetic neuroosteoarthropathy (Charcot's foot) and without it (control).
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Review

For citations:


Tokmakova A.Yu., Kogan E.A., Zaitseva E.L., Demura S.A., Zharkov N.V., Kalandiya M.M., Galstyan G.R. Immunohistochemical features of the bone tissue of the lower extremities in patients with type 2 diabetes mellitus. Diabetes mellitus. 2021;24(5):448-455. (In Russ.) https://doi.org/10.14341/DM12812

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ISSN 2072-0351 (Print)
ISSN 2072-0378 (Online)