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

ABSTRACT

OBJECTIVE: 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 TSP1OCN was altered by changes in glucocorticoid activity in humans. DESIGN: Prospective observational study. SETTING: Tertiary university hospital in Queensland, Australia. PATIENTS AND MEASUREMENTS 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 4 mg dexamethasone and PRED patients predose at 800 and 4 hours post-dose at 1200 hours. RESULTS: Plasma TSP1 in CS was higher (P < .0001), and serum OCN was lower (P < .0001) than HV. The TSP1OCN ratio in HV increased significantly after 4 mg dexamethasone (P < .0001) and in AI after taking their hydrocortisone replacement therapy (P < .001). PRED patients had a higher TSP1OCN ratio compared with HV at both 800 and 1200 hours (both P < .001), but no significant change occurred from pre- to post-dose. A TSP1OCN ratio of >73 at 800 hours differentiated CS from HV with a sensitivity of 95% and a specificity of 100%. CONCLUSIONS: The TSP1OCN 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.