Calcified Tissue International

, Volume 103, Issue 6, pp 599–605 | Cite as

The Association Between Osteocalcin and Chronic Inflammation in Patients with Type 2 Diabetes Mellitus

  • Ippei Kanazawa
  • Sayuri Tanaka
  • Toshitsugu Sugimoto
Original Research


Osteocalcin acts as an endocrine hormone to regulate energy homeostasis. Although several in vivo and in vitro studies suggest that osteocalcin is involved in chronic inflammation, the association between osteocalcin and chronic inflammation in humans is unknown. In this cross-sectional study, 246 patients with type 2 diabetes mellitus (T2DM) were recruited to investigate the association of bone turnover markers with chronic inflammation parameters such as high-sensitive C-reactive protein (hsCRP), ferritin, and leukocyte subtype counts. Bone-specific alkaline phosphatase (BAP), total osteocalcin (OC), undercarboxylated OC (ucOC), and urinary N-terminal cross-linked telopeptide of type-I collagen (uNTX) were measured. Multiple regression analysis adjusted for age, duration of diabetes, body mass index, estimated glomerular filtration rate, and hemoglobin A1c showed that serum OC levels were significantly and negatively associated with hsCRP, ferritin, basophil count, and monocyte count (β = − 0.18, p = 0.013; β = − 0.22, p = 0.031; β = − 0.14, p = 0.038; and β = − 0.17, p = 0.012, respectively). Moreover, serum ucOC levels were significantly and negatively associated with hsCRP, ferritin, total leukocyte count, neutrophil count, and monocyte count (β = − 0.24, p = 0.007; β =− 0.37, p = 0.003; β = − 0.21, p = 0.007; β = − 0.24, p = 0.002; and β = − 0.20, p = 0.011, respectively). The ratio of ucOC to OC was significantly and negatively associated with ferritin (β = − 0.31, p = 0.014). However, neither BAP nor uNTX was associated with any chronic inflammation parameters. This is the first study to show that serum OC and ucOC levels were negatively associated with chronic inflammation parameters such as hsCRP, ferritin, and leukocyte subtypes in patients with T2DM. Therefore, OC could be a therapeutic target for protecting against chronic inflammation.


Osteocalcin Undercarboxylated osteocalcin Chronic inflammation Type 2 diabetes mellitus 



This study was partly supported by research grant from Eli Lilly Japan.

Author Contributions

Study design and conduct: IK. Collected and analyzed the data: IK and ST. wrote the paper: IK and TS. Approving final version: All authors. IK takes responsibility for the integrity of the data analysis.

Compliance with Ethical Standards

Conflict of interest

Ippei Kanazawa, Sayuri Tanaka, and Toshitsugu Sugimoto declare that they have no conflicts of interest.

Human and Animal Rights and Informed Consent

This study was approved by IRB of our university and informed consent was waived because no intervention and further examinations were performed.


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Internal Medicine 1Shimane University Faculty of MedicineIzumoJapan

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