Thursday, May 28, 2009

Deletereous Effects of Glucocorticoid Replacement on Bone in Women after Long-Term Remission of Cushing's Syndrome

María-José Barahona1,   N Sucunza1,   E Resmini1,   JM Fernández-Real2,   W Ricart2,   JM Moreno2,   T Puig3,   AM Wägner1,   J Rodriguez-Espinosa1,   J Farrerons4,   SM Webb1,

1Endocrinology and Medicine Departments and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBER-ER, Unidad 747), ISCIII, Barcelona; Hospital Sant Pau, Universitat Autònoma de Barcelona

2Endocrinology Department, Institut d'Investigació Biomèdica de Girona (IDIBGI) and CIBER Fisiopatologia de la Obesidad y Nutrición CB06/03/010; Hospital Josep Trueta, Girona

3Epidemiology Department, Hospital Sant Pau, Universitat Autònoma de Barcelona, Spain

4Internal Medicine Department, Hospital Sant Pau, Universitat Autònoma de Barcelona, Spain


Corresponding author: María-José Barahona, Department of Endocrinology, Hospital Mútua de Terrassa, Pl Dr Robert 5, 08221 Terrassa, Barcelona, Spain. Tel: +34-93-7365050. Fax: +34-93-7365059. Email:

Funding: Supported by a grant from the Instituto de Salud Carlos III (FIS 05/0448). M.J. Barahona was supported by a fellowship from CIRIT (FI 03/1102).

Conflict of Interest: The authors do not have any conflicts of interest.


Objective: Endogenous hypercortisolism as well as high dose and long-term glucocorticoid (GC) therapy reduce bone mass. Patients in remission after successful treatment of Cushing's syndrome (CS) often present hypoadrenalism and require long-term GC replacement. The aim of our study was to evaluate whether this GC “replacement” had any further effect on bone in women after long-term remission of CS.


Methods: Thirty-seven women (mean age: 50 ± 14 years, 27 of pituitary and 10 of adrenal origin) with cured CS (mean time of cure: 11 ± 6 years), 14 with active CS and 85 sex, BMI and age-matched controls, were enrolled. Bone mineral density (BMD) and bone mineral content (BMC) were measured by dual-energy x-ray absorptiometry scanning. Bone biochemical markers were also measured. Duration and dose of GC replacement, and duration of endogenous hypercortisolism were calculated.


Results: Cured and active CS patients had less BMC, BMD and osteocalcin than controls (p<0.01). These differences were observed in estrogen-sufficient women, but not in those with estrogen- deficiency. Duration of GC treatment (mean: 42 months (2-420)) and endogenous hypercortisolism (mean: 70 months (13-241)) negatively correlated with BMC and lumbar spine BMD. After regression analysis, the main predictor of abnormal BMC and BMD was the duration of GC replacement (p<0.01).


Conclusions: Patients treated for CS persistently have less bone mass despite long-term cure. Both duration of endogenous hypercortisolism and mainly exogenous “replacement” therapy with GC, negatively affect the bone mass. Thus, the additional deleterious effect of GC for the treatment of adrenal axis suppression should be considered.



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