The Presence of Thyroid-Stimulation Blocking Antibody Prevents High Bone Turnover in Untreated Premenopausal Patients with Graves' Disease

PLoS One. 2015 Dec 9;10(12):e0144599. doi: 10.1371/journal.pone.0144599. eCollection 2015.

Abstract

Osteoporosis-related fractures are one of the complications of Graves' disease. This study hypothesized that the different actions of thyroid-stimulating hormone receptor (TSHR) antibodies, both stimulating and blocking activities in Graves' disease patients might oppositely impact bone turnover. Newly diagnosed premenopausal Graves' disease patients were enrolled (n = 93) and divided into two groups: patients with TSHR antibodies with thyroid-stimulating activity (stimulating activity group, n = 83) and patients with TSHR antibodies with thyroid-stimulating activity combined with blocking activity (blocking activity group, n = 10). From the stimulating activity group, patients who had matched values for free T4 and TSH binding inhibitor immunoglobulin (TBII) to the blocking activity group were further classified as stimulating activity-matched control (n = 11). Bone turnover markers BS-ALP, Osteocalcin, and C-telopeptide were significantly lower in the blocking activity group than in the stimulating activity or stimulating activity-matched control groups. The TBII level showed positive correlations with BS-ALP and osteocalcin levels in the stimulating activity group, while it had a negative correlation with the osteocalcin level in the blocking activity group. In conclusion, the activation of TSHR antibody-activated TSH signaling contributes to high bone turnover, independent of the actions of thyroid hormone, and thyroid-stimulation blocking antibody has protective effects against bone metabolism in Graves' disease.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Autoantibodies / blood*
  • Bone Remodeling / immunology*
  • Case-Control Studies
  • Female
  • Graves Disease / blood
  • Graves Disease / immunology*
  • Humans
  • Immunoglobulins, Thyroid-Stimulating / blood*
  • Immunoglobulins, Thyroid-Stimulating / immunology*
  • Receptors, Thyrotropin / blood
  • Thyroid Function Tests
  • Thyroid Hormones / blood*

Substances

  • Autoantibodies
  • Immunoglobulins, Thyroid-Stimulating
  • Receptors, Thyrotropin
  • Thyroid Hormones
  • thyroid stimulation-blocking antibody
  • thyrotropin-binding inhibitory immunoglobulin

Grants and funding

This work was funded by Seoul National University Hospital (Grant No. 04-2015-0900). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.