| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
CLINICAL STUDY |
1 Institute of Medicine, University of Bergen, 5020 Bergen, Norway2 Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway3 Institute of Social Sciences in Medicine, University of Bergen, Bergen, Norway4 Department of Rheumatology5 , The Hormone Laboratory6 Centre for Clinical Genetics and Molecular Medicine, Haukeland University Hospital, 5021 Bergen, Norway7 Department of Medicine, University Hospital of North Norway, Tromsø, Norway8 Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway9 Department of Medicine, St Olavs Hospital, Trondheim, Norway10 Insitute of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway11 Faculty of Medicine, University of Oslo, Oslo, Norway12 Section of Endocrinology, Rikshospitalet University Hospital, Oslo, Norway13 Department of Endocrinology, Aker University Hospital, Oslo, Norway14 Department of Endocrinology, Christchurch Hospital, Canterbury, New Zealand15 Department of Medicine, University of Cambridge, Cambridge, UK
(Correspondence should be addressed to K Løvås; Email: kristian.lovas{at}med.uib.no)
Context: Patients with primary adrenal insufficiency (Addison's disease) receive more glucococorticoids than the normal endogenous production, raising concern about adverse effects on bone.
Objective: To determine i) the effects of glucocorticoid replacement therapy on bone, and ii) the impact of glucocorticoid pharmacogenetics.
Design, setting and participants: A cross-sectional study of two large Addison's cohorts from Norway (n=187) and from UK and New Zealand (n=105).
Main outcome measures: Bone mineral density (BMD) was measured; the Z-scores represent comparison with a reference population. Blood samples from 187 Norwegian patients were analysed for bone markers and common polymorphisms in genes that have been associated with glucocorticoid sensitivity.
Results: Femoral neck BMD Z-scores were significantly reduced in the patients (Norway: mean –0.28 (95% confidence intervals (CI) –0.42, –0.16); UK and New Zealand: –0.21 (95% CI –0.36, –0.06)). Lumbar spine Z-scores were reduced (Norway: –0.17 (–0.36, +0.01); UK and New Zealand: –0.57 (–0.78, –0.37)), and significantly lower in males compared with females (P=0.02). The common P-glycoprotein (ABCB1) polymorphism C3435T was significantly associated with total BMD (CC and CT>TT P=0.015), with a similar trend at the hip and spine.
Conclusions: BMD at the femoral neck and lumbar spine is reduced in Addison's disease, indicating undesirable effects of the replacement therapy. The findings lend support to the recommendations that 15–25 mg hydrocortisone daily is more appropriate than the higher conventional doses. A common polymorphism in the efflux transporter P-glycoprotein is associated with reduced bone mass and might confer susceptibility to glucocorticoid induced osteoporosis.
This article has been cited by other articles:
|
|
 |
|
  M. M. Erichsen, K. Lovas, B. Skinningsrud, A. B. Wolff, D. E. Undlien, J. Svartberg, K. J. Fougner, T. J. Berg, J. Bollerslev, B. Mella, et al. Clinical, Immunological, and Genetic Features of Autoimmune Primary Adrenal Insufficiency: Observations from a Norwegian Registry J. Clin. Endocrinol. Metab., December 1, 2009; 94(12): 4882 - 4890. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
