AZT enhances osteoclastogenesis and bone loss

AIDS Research and Human Retroviruses
George PanJay M McDonald

Abstract

A variety of metabolic complications have been reported to be associated with highly active antiretroviral therapy (HAART), including osteopenia and osteoporosis. In this study, we determine the effects of zidovudine (AZT), a nucleoside reverse transcriptase inhibitor, on osteoclastogenesis in a cultured mouse macrophage preosteoclast cell line (RAW264.7), in mouse primary bone marrow macrophage-monocyte precursors, and on bone mineral density in mice. The results indicate that AZT induces an increase in osteoclastogenesis in the mouse preosteoclast cell line and in mouse bone marrow osteoclast precursors in the presence of RANKL. This increased osteoclastogenesis is dependent upon the concentration of AZT. AZT increases the promoter activity of tartrate-resistant acid phosphatase (TRAP) and the binding and function of the nuclear transcription protein, NF-kappaB, in RAW264.7 cells. Therefore, the effect of AZT is mediated, at least in part, by enhancing RANKL-mediated osteoclastogenesis. Bone mineral density (BMD) in AZT-treated mice is decreased and histopathology shows marked osteopenia. These results support an important role of AZT-stimulated osteoclastogenesis in HAART-induced osteopenia.

References

Jan 1, 1994·Annual Review of Immunology·P A Baeuerle, T Henkel
Mar 6, 1997·Nature·M M TondraviS L Teitelbaum
Jul 1, 1997·Calcified Tissue International·N I PatonM Pazianas
Nov 14, 1997·Nature Medicine·V IotsovaR Bravo
Feb 7, 1998·Genes & Development·G FranzosoU Siebenlist
May 1, 1998·The New England Journal of Medicine·C Flexner
Mar 19, 1999·Biochemical and Biophysical Research Communications·N TakahashiT Suda
Jun 17, 1999·Nature Medicine·M S Saag, J M Kilby
Dec 22, 1999·Genes & Development·G Karsenty
Jan 27, 2000·JAMA : the Journal of the American Medical Association·C C CarpenterP A Volberding
Jan 29, 2000·The Journal of Cell Biology·T MiyazakiS Tanaka
Aug 22, 2000·The Journal of Pathology·T J Chambers
Sep 1, 2000·Science·S L Teitelbaum
Jan 10, 2001·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·C A KühneL C Hofbauer
Feb 7, 2001·Sexually Transmitted Infections·S Taylor, A S Pereira
Sep 29, 2001·Oral Diseases·C Scully, P Diz Dios
Nov 20, 2001·Endocrinology·S Khosla
Apr 9, 2002·The Journal of Biological Chemistry·Renu G Jain, James M Lenhard
May 16, 2002·HIV Medicine·R L Murphy, W J Smith
Jun 27, 2002·Biochimica Et Biophysica Acta·Erik De Clercq
Apr 12, 2003·The Journal of Biological Chemistry·Gregory HelbigHarikrishna Nakshatri

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Citations

Mar 10, 2006·Current Infectious Disease Reports·Todd T Brown, Grace A McComsey
Sep 11, 2010·Current Osteoporosis Reports·Shitij AroraJameel Iqbal
Dec 3, 2005·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Valerianna Amorosa, Pablo Tebas
Dec 7, 2006·AIDS Research and Human Retroviruses·George PanJay M McDonald
Jun 18, 2009·AIDS·Birgit GrundUNKNOWN INSIGHT SMART Body Composition Substudy Group
Jun 25, 2009·AIDS·Marco BorderiMaria C Re
Mar 28, 2009·PPAR Research·Eoin J CotterPeter P Doran
Nov 5, 2011·Journal of Clinical Densitometry : the Official Journal of the International Society for Clinical Densitometry·Lauro F S Pinto NetoAngelica E Miranda
Aug 5, 2010·Archives of Biochemistry and Biophysics·Benjamin StoneEugene McCloskey
Oct 28, 2009·Antiviral Research·Trevor Hawkins
Jul 13, 2006·Annals of the New York Academy of Sciences·George PanJay M McDonald
Jul 24, 2008·Journal of Medical Virology·Davide GibelliniMaria Carla Re
Apr 8, 2011·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·George PanJay M McDonald
Jul 22, 2014·Clinical Endocrinology·Susannah O'Sullivan, Andrew Grey
Oct 29, 2008·Infectious Disease Clinics of North America·Helen E Cejtin
Oct 23, 2013·HIV Clinical Trials·Jeannie S HuangUNKNOWN Aids Clinical Trials Group A5142 Study Team
Jun 11, 2009·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Todd T BrownBarbara A da Silva
Sep 19, 2008·Menopause : the Journal of the North American Menopause Society·Délio Marques CondeAarão M Pinto-Neto
Jul 1, 2007·Current Opinion in HIV and AIDS·Nicholas S ChewWilliam G Powderly
Nov 22, 2017·Osteoporosis International : a Journal Established As Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA·S S L GohS Ponnampalavanar

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