UNLABELLED: 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.
UNLABELLED: 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.
Authors: Nathalie Alos; Ronald M Grant; Timothy Ramsay; Jacqueline Halton; Elizabeth A Cummings; Paivi M Miettunen; Sharon Abish; Stephanie Atkinson; Ronald Barr; David A Cabral; Elizabeth Cairney; Robert Couch; David B Dix; Conrad V Fernandez; John Hay; Sara Israels; Caroline Laverdière; Brian Lentle; Victor Lewis; MaryAnn Matzinger; Celia Rodd; Nazih Shenouda; Robert Stein; David Stephure; Shayne Taback; Beverly Wilson; Kathryn Williams; Frank Rauch; Kerry Siminoski; Leanne M Ward Journal: J Clin Oncol Date: 2012-06-25 Impact factor: 44.544