The study of new biomarkers of bone metabolism of sclerostin and cathepsin K in patients with type 2 diabetes mellitus

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BACKGROUND: Deterioration of bone tissue in type 2 diabetes mellitus (T2D): lead to the increased bone brittleness and to higher risk of low-energy fractures.

AIM: to study serum levels of sclerostin and cathepsin K in assessing bone metabolism in patients with type 2 diabetes mellitus.

MATERIAL AND METHODS: 102 postmenopausal women aged from 46 to 67 years were examined. All patients were divided into 4 groups: the first group included 39 patients with type 2 diabetes (T2DM) and postmenopausal osteoporosis (PO), the second group — 25 patients with PO without T2DM, the third group included 21 patients with T2DM but without PO, and the fourth group (control) — 17 people. Patinets of all groups were tested for ionized calcium, phosphorus, total alkaline phosphatase (ALP), parathyroid hormone, 25 (OH) vitamin D, bone mineral density in groups I, II, and IV, levels of sclerostin and cathepsin Kin seru, were also obtained.

RESULTS: No statistically significant differences have been observed between groups in sclerostin levels, a positive correlation was found between sclerostin and НbА (r=0.43; p=0.009) in the group of patients with T2DM and PO, a negative correlation was found between sclerostin and ionized calcium (r=–0.45; p=0.037) in the group of patients with PO. Cathepsin C in the first group was lower than in the second group (p=0.046), but taking into account Bonferroni correction this difference was not statistically significant. In the first and third groups, 25 (OH) vitamin D was lower than in the groups without T2D. The ALP negatively correlated with the duration of the postmenopause (r=–0.39 and r=–0.64; р=0.05, respectively).

CONCLUSIONS: Cathepsin С was lower in patients with T2DM2 and PO, which may indirectly indicate a decreased bone resorption. Concentration of sclerostin, which plays a key role in the mechanism of inhibiting osteoblastogenesis, positively correlated with НbА.

Guzel M. Nurullina

Izhevsk State Medical Academy

Author for correspondence.
ORCID iD: 0000-0002-4394-8446
SPIN-code: 5885-7116

Russian Federation, 281, Kommunarov street, Izhevsk, 426034


Guzyal I. Akhmadullina

Izhevsk State Medical Academy

ORCID iD: 0000-0003-1876-2516
SPIN-code: 4171-1245

Russian Federation, 281, Kommunarov street, Izhevsk, 426034


  1. Ogurtsova K, Da Rocha Fernandes JD, Huang Y, et al. IDF diabetes atlas: global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Res Clin Pract. 2017;128:40-50. doi:
  2. Janghorbani M, Van Dam RM, Willett WC, Hu FB. Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture. Am J Epidemiol. 2007;166(5):495-505. doi:
  3. Ferrari S. Diabetes and bone. Calcif Tissue Int. 2017;100(2):107-108. doi:
  4. Ялочкина Т.О., Белая Ж.Е. Низкотравматичные переломы и костное ремоделирование при сахарном диабете 2-го типа. // Ожирение и метаболизм. — 2017. — Т. 14. — № 3. — С. 11-18. [Yalochkina TO, Belaya ZhE. Fragility fractures and bone remodeling in type 2 diabetes mellitus. Obesity and Metabolism. 2017;14(3):11-18. (In Russ.)]. doi:
  5. Мельниченко Г.А., Белая Ж.Е., Рожинская Л.Я., и др. Фeдe рaльныe клиничecкиe рeкoмeндaции пo диaгнocтикe, лeчeнию и прoфилaктикe оcтeoпoрoзa. // Проблемы Эндокринологии. — 2017. — Т. 63. — № 6. — С. 392-426. [Melnichenko GA, Belaya ZhE, Rozhinskaya LYa, et al. Russian federal clinical recommendations on diagnostics, treatment and prevention of osteoporosis. Problems of Endocrinology. 2017;63(6):392-426. (In Russ.)]. doi:
  6. Гржибовский А.М., Иванов С.В., Горбатова М.А. Сравнение количественных данных трех и более независимых выборок с использованием программного обеспечения Statistica и SPSS: параметрические и непараметрические критерии. // Наука и Здравоохранение. — 2016. — № 4. — С. 5-29. [Grzhibovskiy AM, Ivanov SV, Gorbatova MA. Analysis of quantitative data in two non-independent groups using statistica and SPSS software: parametric and non-parametric tests. Science & Healthcare. 2016; (4):5-29. (In Russ.)].
  7. Zaidi M, Troen B, Moonga BS, Abe E. Cathepsin K, osteoclastic resorption, and osteoporosis therapy. J Bone Miner Res. 2001; 16(10):1747-1749. doi:
  8. Xu F, Ye YP, Dong YH, et al. Inhibitory effects of high glucose/insulin environment on osteoclast formation and resorption in vitro. J Huazhong Univ Sci Technolog Med Sci. 2013;33(2):244-249. doi:
  9. Orimo H. The mechanism of mineralization and the role of alkaline phosphatase in health and disease. J Nippon Med Sch. 2010;77(1):4-12. doi:
  10. Hygum K, Starup-Linde J, Harslof T, et al. Mechanisms in endocrinology: diabetes mellitus, a state of low bone turnover — a systematic review and metaanalysis. Eur J Endocrinol. 2017;176(3):R137-R157. doi:
  11. Руяткина Л.А., Ломова А.В., Руяткин Д.С., и др. Параметры костного метаболизма у женщин с сахарным диабетом 2-го типа в пре- и постменопаузе в основании дифференцированного выбора антиостеопоротической терапии. // Остеопороз и остеопатии. — 2013. — Т. 16. — № 3. — С. 8-12. [Ruyatkina LA, Lomova AV, Ruyatkin DS, et al. Parameters of bone metabolism in pre- and postmenopausal women with type 2 diabetes mellitus in the rationale for the choice of anti-osteoporotic therapy. Osteoporosis and Bone Diseases. 2013;16(3):8-12. (In Russ.)]. doi:
  12. Hay E, Bouaziz W, Funck-Brentano T, Cohen-Solal M. Sclerostin and bone aging: a mini-review. Gerontology. 2016;62(6):618-623. doi:
  13. Ardawi MS, Akhbar DH, Alshaikh A, et al. Increased serum sclerostin and decreased serum IGF-1 are associated with vertebral fractures among postmenopausal women with type-2 diabetes. Bone. 2013;56(2):355-362. doi:
  14. Wu Y, Xu SY, Liu SY, et al. Upregulated serum sclerostin level in the T2DM patients with femur fracture inhibits the expression of bone formation/remodeling-associated biomarkers VIA antagonizing WNT signaling. Eur Rev Med Pharmacol Sci. 2017;21(3):470-478.
  15. Ardawi MS, Al-Kadi HA, Rouzi AA, Qari MH. Determinants of serum sclerostin in healthy pre- and postmenopausal women. J Bone Miner Res. 2011;26(12):2812-2822. doi:
  16. Raska IJr, Raskova M, Zikan V, Skrha J. Prevalence and risk factors of osteoporosis in postmenopausal women with type 2 diabetes mellitus. Cent Eur J Public Health. 2017;25(1):3-10. doi:
  17. Garcia-Martin A, Rozas-Moreno P, Reyes-Garcia R, et al. Circulating levels of sclerostin are increased in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab. 2012;97(1):234-241. doi:
  18. Yamamoto M, Yamauchi M, Sugimoto T. Elevated sclerostin levels are associated with vertebral fractures in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab. 2013;98(10):4030-4037. doi:
  19. Daniele G, Winnier D, Mari A, et al. Sclerostin and insulin resistance in prediabetes: evidence of a cross talk between bone and glucose metabolism. Diabetes Care. 2015;38(8):1509-1517. Doi:

Supplementary files

Supplementary Files Action
1. Fig. 1. Diagram of the magnitude of the content of cathepsin K in the 1st, 2nd and 4th groups. View (776KB) Indexing metadata
2. Fig. 2. Correlation of HbA1c and sclerostin concentration in the 1st group (r = 0.43; p = 0.009). View (126KB) Indexing metadata
3. Fig. 3. Correlation of the concentration of sclerostin and ionized calcium in the 2nd group (r = –0.45; p = 0.037). View (149KB) Indexing metadata


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Copyright (c) 2019 Nurullina G.M., Akhmadullina G.I.

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