This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart 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 Aukrust, P. Articles by Frøland, S. S. Search for Related Content PubMed PubMed Citation Articles by Aukrust, P. Articles by Frøland, S. S.

Decreased Bone Formative and Enhanced Resorptive Markers in Human Immunodeficiency Virus Infection: Indication of Normalization of the Bone-Remodeling Process during Highly Active Antiretroviral Therapy¹

Section of Clinical Immunology and Infectious Diseases and Research Institute for Internal Medicine, Medical Department A (P.A., F.M., S.S.F.), and the Section of Endocrinology, Medical Department B (T.U., J.B.), Rikshospitalet, N-0027 Oslo; and the Institute of Cancer Research and Molecular Biology, The Norwegian University of Science and Technology (E.L., T.E.), 7005 Trondheim, Norway

Address all correspondence and requests for reprints to: Dr. Pål Aukrust, Section of Clinical Immunology and Infectious Diseases, Medical Department A, Rikshospitalet, N-0027 Oslo, Norway. E-mail: pal.aukrust{at}klinmed.uio.no

As cytokines and 1,25-dihydroxyvitamin D [1,25-(OH)₂D] appear to have an important role in bone homeostasis, we examined the possibility that human immunodeficiency virus (HIV)-infected patients, characterized by enhanced levels of proinflammatory cytokines and 1,25-(OH)₂D deficiency, have disturbed bone metabolism by analyzing serum markers of bone formation (osteocalcin) and bone resorption (C-telopeptide) in 73 HIV-infected patients. HIV-infected patients with advanced clinical and immunological disease and high viral load were characterized by increased C-telopeptide and particularly by markedly depressed osteocalcin levels. HIV-infected patients had enhanced activation of the TNF system. Serum concentrations of p55 and p75-TNF receptors were negatively correlated with osteocalcin, and p75-TNF receptor was positively correlated with C-telopeptide. HIV-infected patients with advanced disease also had decreased serum concentrations of 1,25-(OH)₂D, but this parameter was not correlated with osteocalcin or C-telopeptide. During 24 months with highly active antiretroviral therapy there was a marked rise in serum osteolcalcin levels together with a profound fall in viral load and TNF components and a marked rise in CD4⁺ T cell counts. Also, there was a shift from no correlation to a significant correlation between osteocalcin and C-telopeptide levels during such therapy. The present study suggests disturbed bone formation and resorption during HIV infection. Our findings indicating synchronization of bone remodeling during highly active antiretroviral therapy may represent a previously unrecognized beneficial effect of such therapy and expand our knowledge of the interactions between cytokines and bone in the bone-remodeling process.

This article has been cited by other articles:

				S. E. Dolan, J. R. Kanter, and S. Grinspoon Longitudinal Analysis of Bone Density in Human Immunodeficiency Virus-Infected Women J. Clin. Endocrinol. Metab., August 1, 2006; 91(8): 2938 - 2945. [Abstract] [Full Text] [PDF]

				G. PAN, Z. YANG, S. W. BALLINGER, and J. M. MCDONALD Pathogenesis of Osteopenia/Osteoporosis Induced by Highly Active Anti-Retroviral Therapy for AIDS Ann. N.Y. Acad. Sci., April 1, 2006; 1068(1): 297 - 308. [Abstract] [Full Text] [PDF]

				P. Koutkia, B. Canavan, J. Breu, and S. Grinspoon Effects of Growth Hormone-Releasing Hormone on Bone Turnover in Human Immunodeficiency Virus-Infected Men with Fat Accumulation J. Clin. Endocrinol. Metab., April 1, 2005; 90(4): 2154 - 2160. [Abstract] [Full Text] [PDF]

				T. T. Brown, M. D. Ruppe, R. Kassner, P. Kumar, T. Kehoe, A. S. Dobs, and J. Timpone Reduced Bone Mineral Density in Human Immunodeficiency Virus-Infected Patients and Its Association with Increased Central Adiposity and Postload Hyperglycemia J. Clin. Endocrinol. Metab., March 1, 2004; 89(3): 1200 - 1206. [Abstract] [Full Text] [PDF]

				S. Arpadi, M. Horlick, and E. Shane Metabolic Bone Disease in Human Immunodeficiency Virus-Infected Children J. Clin. Endocrinol. Metab., January 1, 2004; 89(1): 21 - 23. [Full Text] [PDF]

				S. Mora, I. Zamproni, S. Beccio, R. Bianchi, V. Giacomet, and A. Vigano Longitudinal Changes of Bone Mineral Density and Metabolism in Antiretroviral-Treated Human Immunodeficiency Virus-Infected Children J. Clin. Endocrinol. Metab., January 1, 2004; 89(1): 24 - 28. [Abstract] [Full Text] [PDF]

				M. Dybul, A. S. Fauci, J. G. Bartlett, J. E. Kaplan, and A. K. Pau Guidelines for Using Antiretroviral Agents among HIV-Infected Adults and Adolescents: The Panel on Clinical Practices for Treatment of HIV Ann Intern Med, September 3, 2002; 137(5_Part_2): 381 - 433. [Abstract] [Full Text] [PDF]

				R. G. Jain and J. M. Lenhard Select HIV Protease Inhibitors Alter Bone and Fat Metabolism ex Vivo J. Biol. Chem., May 24, 2002; 277(22): 19247 - 19250. [Abstract] [Full Text] [PDF]

				D. M. Gaughan, L. M. Mofenson, M. D. Hughes, G. R. Seage III, G. L. Ciupak, and J. M. Oleske Osteonecrosis of the Hip (Legg-Calve-Perthes Disease) in Human Immunodeficiency Virus-Infected Children Pediatrics, May 1, 2002; 109(5): e74 - 74. [Abstract] [Full Text] [PDF]

				A. Y. McDermott, A. Shevitz, T. Knox, R. Roubenoff, J. Kehayias, and S. Gorbach Effect of highly active antiretroviral therapy on fat, lean, and bone mass in HIV-seropositive men and women Am. J. Clinical Nutrition, November 1, 2001; 74(5): 679 - 686. [Abstract] [Full Text] [PDF]

				W. P. Fairfield, J. S. Finkelstein, A. Klibanski, and S. K. Grinspoon Osteopenia in Eugonadal Men with Acquired Immune Deficiency Syndrome Wasting Syndrome J. Clin. Endocrinol. Metab., May 1, 2001; 86(5): 2020 - 2026. [Abstract] [Full Text]

				S. I. Helle, T. Ueland, D. Ekse, S. S. Frøland, J. M. P. Holly, P. E. Lønning, and P. Aukrust The Insulin-Like Growth Factor System in Human Immunodeficiency Virus Infection: Relations to Immunological Parameters, Disease Progression, and Antiretroviral Therapy J. Clin. Endocrinol. Metab., January 1, 2001; 86(1): 227 - 233. [Abstract] [Full Text]