This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chiodini, I. Articles by Scillitani, A. Search for Related Content PubMed PubMed Citation Articles by Chiodini, I. Articles by Scillitani, A. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Cushing's Syndrome Steroids

Alterations of Bone Turnover and Bone Mass at Different Skeletal Sites due to Pure Glucocorticoid Excess: Study in Eumenorrheic Patients with Cushing’s Syndrome

Division and Research Unit of Endocrinology (I.C., M.T., V.T., A.S.), Division of Internal Medicine (V.C.), Departments of Clinical Pathology (S.F., M.P., A.D.G.), Radiology (G.G., M.C.), and Nuclear Medicine (S.Mo.), Scientific Institute Casa Sollievo della Sofferenza, San Giovanni Rotondo; Division of Endocrinology, Istituto Auxologico Italiano (A.L.), Scientific Institute San Giuseppe, Piancavallo; and Istituto di Clinica Medica II, Policlinico Umberto I (S.Mi.), Rome, Italy

Address all correspondence and requests for reprints to: Dr. Iacopo Chiodini, Division and Research Unit of Endocrinology, IRCCS Ospedale Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo (FG), Italy.

The aim of the present investigation was to study the effect of glucocorticoid excess on bone mass and turnover not influenced by other diseases known to affect skeleton and/or by different gonadal status and sex. We studied several markers of bone turnover and bone mineral density (BMD) by both quantitative computed tomography (at spine and forearm) and dual x-ray absorptiometry (at spine and three femoral sites) in 18 eugonadal female patients affected by Cushing’s syndrome (CS) compared to 24 eugonadal healthy female subjects matched for age and body mass index.

In CS patients, serum bone Gla protein, a marker of osteoblastic function, was reduced (3.28 ± 2.3 vs. 6.47 ± 2.5; P < 0.01), and bone resorption was increased, as indicated by increased urinary hydroxyproline (36.6 ± 12 vs. 29.0 ± 9.1, P < 0.05) and urinary deoxypyridinoline (22.1 ± 8.0 vs. 16.4 ± 6.3; P < 0.05). BMD was significantly (P < 0.05 or P < 0.01) reduced at all sites, except cortical forearm, in CS patients compared to controls. By comparing z-scores of reduced BMD in CS patients, spinal trabecular BMD was found to be the most severely affected. Furthermore, disease activity, as measured by urinary free cortisol, was significantly correlated with bone Gla protein (r = -0.57; P < 0.02), urinary hydroxyproline (r = 0.57; P < 0.02), urinary deoxypyridinoline (r = 0.48, P < 0.05), and BMD measured at spine and femur.

Our results show that compared to matched control subjects, female eumenorrheic CS patients have reduced osteoblastic function, increased bone resorption, and reduced BMD, and that the severity of these abnormalities is statistically related to the severity of disease activity, as indicated by urinary free cortisol. Moreover, our data suggest a site and tissue specificity of the effect of glucocorticoid excess on bone mass.

This article has been cited by other articles:

				I. Chiodini, V. Morelli, B. Masserini, A. S. Salcuni, C. Eller-Vainicher, R. Viti, F. Coletti, G. Guglielmi, C. Battista, V. Carnevale, et al. Bone Mineral Density, Prevalence of Vertebral Fractures, and Bone Quality in Patients with Adrenal Incidentalomas with and without Subclinical Hypercortisolism: An Italian Multicenter Study J. Clin. Endocrinol. Metab., September 1, 2009; 94(9): 3207 - 3214. [Abstract] [Full Text] [PDF]

				R Hardy and M S Cooper Bone loss in inflammatory disorders J. Endocrinol., June 1, 2009; 201(3): 309 - 320. [Abstract] [Full Text] [PDF]

				L. Tauchmanova, R. Pivonello, M. C. De Martino, A. Rusciano, M. De Leo, C. Ruosi, C. Mainolfi, G. Lombardi, M. Salvatore, and A. Colao Effects of sex steroids on bone in women with subclinical or overt endogenous hypercortisolism Eur. J. Endocrinol., September 1, 2007; 157(3): 359 - 366. [Abstract] [Full Text] [PDF]

				L. Tauchmanova, R. Pivonello, C. Di Somma, R. Rossi, M. C. De Martino, L. Camera, M. Klain, M. Salvatore, G. Lombardi, and A. Colao Bone Demineralization and Vertebral Fractures in Endogenous Cortisol Excess: Role of Disease Etiology and Gonadal Status J. Clin. Endocrinol. Metab., May 1, 2006; 91(5): 1779 - 1784. [Abstract] [Full Text] [PDF]

				C. Kristo, R. Jemtland, T. Ueland, K. Godang, and J. Bollerslev Restoration of the coupling process and normalization of bone mass following successful treatment of endogenous Cushing's syndrome: A prospective, long-term study Eur. J. Endocrinol., January 1, 2006; 154(1): 109 - 118. [Abstract] [Full Text] [PDF]

				J. M. Paterson, J. R. Seckl, and J. J. Mullins Genetic manipulation of 11{beta}-hydroxysteroid dehydrogenases in mice Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2005; 289(3): R642 - R652. [Abstract] [Full Text] [PDF]

				I. Chiodini, G. Guglielmi, C. Battista, V. Carnevale, M. Torlontano, M. Cammisa, V. Trischitta, and A. Scillitani Spinal Volumetric Bone Mineral Density and Vertebral Fractures in Female Patients with Adrenal Incidentalomas: The Effects of Subclinical Hypercortisolism and Gonadal Status J. Clin. Endocrinol. Metab., May 1, 2004; 89(5): 2237 - 2241. [Abstract] [Full Text] [PDF]

				B. Weinstock-Guttman, E. Gallagher, M. Baier, L. Green, J. Feichter, K. Patrick, C. Miller, K. Wrest, and M. Ramanathan Risk of bone loss in men with multiple sclerosis Multiple Sclerosis, April 1, 2004; 10(2): 170 - 175. [Abstract] [PDF]

				J. Justesen, L. Mosekilde, M. Holmes, K. Stenderup, J. Gasser, J. J. Mullins, J. R. Seckl, and M. Kassem Mice Deficient in 11{beta}-Hydroxysteroid Dehydrogenase Type 1 Lack Bone Marrow Adipocytes, but Maintain Normal Bone Formation Endocrinology, April 1, 2004; 145(4): 1916 - 1925. [Abstract] [Full Text] [PDF]

				J. P. Kemp, S. Osur, S. B. Shrewsbury, N. E. Herje, S. P. Duke, S. M. Harding, K. Faulkner, and C. C. Crim Potential Effects of Fluticasone Propionate on Bone Mineral Density in Patients With Asthma: A 2-Year Randomized, Double-Blind, Placebo-Controlled Trial Mayo Clin. Proc., April 1, 2004; 79(4): 458 - 466. [Abstract] [PDF]

				R. A. Adler and M. C. Hochberg Suggested Guidelines for Evaluation and Treatment of Glucocorticoid-Induced Osteoporosis for the Department of Veterans Affairs Arch Intern Med, November 24, 2003; 163(21): 2619 - 2624. [Abstract] [Full Text] [PDF]

				E. Canalis and A. Giustina Glucocorticoid-Induced Osteoporosis: Summary of a Workshop J. Clin. Endocrinol. Metab., December 1, 2001; 86(12): 5681 - 5685. [Full Text] [PDF]

				I. Chiodini, M. Torlontano, V. Carnevale, G. Guglielmi, M. Cammisa, V. Trischitta, and A. Scillitani Bone Loss Rate in Adrenal Incidentalomas: A Longitudinal Study J. Clin. Endocrinol. Metab., November 1, 2001; 86(11): 5337 - 5341. [Abstract] [Full Text] [PDF]

				G. Osella, G. Reimondo, P. Peretti, A. Alì, P. Paccotti, A. Angeli, and M. Terzolo The Patients with Incidentally Discovered Adrenal Adenoma (Incidentaloma) Are Not at Increased Risk of Osteoporosis J. Clin. Endocrinol. Metab., February 1, 2001; 86(2): 604 - 607. [Abstract] [Full Text]

				L. C. Hofbauer and A. E. Heufelder The Role of Receptor Activator of Nuclear Factor-{kappa}B Ligand and Osteoprotegerin in the Pathogenesis and Treatment of Metabolic Bone Diseases J. Clin. Endocrinol. Metab., July 1, 2000; 85(7): 2355 - 2363. [Full Text]

				L. C. Hofbauer, F. Gori, B. L. Riggs, D. L. Lacey, C. R. Dunstan, T. C. Spelsberg, and S. Khosla Stimulation of Osteoprotegerin Ligand and Inhibition of Osteoprotegerin Production by Glucocorticoids in Human Osteoblastic Lineage Cells: Potential Paracrine Mechanisms of Glucocorticoid-Induced Osteoporosis Endocrinology, October 1, 1999; 140(10): 4382 - 4389. [Abstract] [Full Text]

				M. Torlontano, I. Chiodini, M. Pileri, G. Guglielmi, M. Cammisa, S. Modoni, V. Carnevale, V. Trischitta, and A. Scillitani Altered Bone Mass and Turnover in Female Patients with Adrenal Incidentaloma: The Effect of Subclinical Hypercortisolism J. Clin. Endocrinol. Metab., July 1, 1999; 84(7): 2381 - 2385. [Abstract] [Full Text]