The effect of glucocorticoids on Thrombospondin-1, Osteocalcin and the Thrombospondin-1:Osteocalcin ratio in humans.

Abstract

Thrombospondin-1 (TSP1), a matricellular protein, and Osteocalcin (OCN), a noncollagenous protein secreted by osteoblasts, are known to be up- and down-regulated, respectively, by glucocorticoids. The aim of this study was to determine whether a ratio between TSP1:OCN was altered by changes in glucocorticoid activity in humans. Prospective observational study. Tertiary university hospital in Queensland, Australia. Patients with Cushing's syndrome (CS, n=19), asthma or giant cell arteritis on chronic prednisolone treatment (PRED, n=13), adrenal insufficiency (AI, n=16) and healthy volunteers (HV, n=20). Plasma TSP1 and serum total OCN were measured by immunoassay at 0800h, 1200h and 1600h in patients with CS, patients with AI taking replacement glucocorticoids, HV before and after 4mg dexamethasone and PRED patients predose at 800 and 4hours post-dose at 1200hours. Plasma TSP1 in CS was higher (P<.0001), and serum OCN was lower (P<.0001) than HV. The TSP1:OCN ratio in HV increased significantly after 4mg dexamethasone (P<.0001) and in AI after taking their hydrocortisone replacement therapy (P<.001). PRED patients had a higher TSP1:OCN ratio compared with HV at both 800 and 1200hours (both P<.001), but no significant change occurred from pre- to post-dose. A TSP1:OCN ratio of >73 at 800hours differentiated CS from HV with a sensitivity of 95% and a specificity of 100%. The TSP1:OCN ratio is elevated in patients on prednisolone and in patients with CS compared with healthy volunteers. It may be a useful biomarker of total body glucocorticoid activity in humans.