BONE COMPLICATIONS IN HIV: Edited by Patrick W.G. Mallon and Todd T. BrownThe protease inhibitors and HIV-associated bone lossMoran, Caitlin A.a,b; Weitzmann, M. Nealec,d; Ofotokun, Ighovwerhaa,bAuthor Information aDepartment of Medicine, Division of Infectious Diseases, Emory University School of Medicine bGrady Healthcare System, Atlanta cDepartment of Medicine, Division of Endocrinology, Metabolism & Lipids, Emory University School of Medicine, Atlanta dAtlanta Department of Veterans Affairs Medical Center, Decatur, Georgia, USA Correspondence to Ighovwerha Ofotokun, Infectious Diseases, Emory University School of Medicine, 49 Jesse Hill Jr Drive, Atlanta, GA 30303, USA. Tel: +1 404 616 0659; fax: +1 404 616 0592; e-mail: [email protected] Current Opinion in HIV and AIDS: May 2016 - Volume 11 - Issue 3 - p 333-342 doi: 10.1097/COH.0000000000000260 Buy Metrics Abstract Purpose of review HIV infection is an established risk factor for osteoporosis and bone fracture. Combination antiretroviral therapy (cART) increases bone resorption leading to an additional 2–6% bone mineral density (BMD) loss within the first 1–2 years of therapy. Although tenofovir disoproxil fumarate is often blamed for antiretroviral drug-associated bone loss, evidence abounds to suggest that other agents, including the protease inhibitors (PIs), have adverse bone effects. In the current review, we examine bone loss associated with protease inhibitor use, describing the relative magnitude of bone loss reported for individual protease inhibitors. We also review the potential mechanisms associated with protease inhibitor-induced bone loss. Recent findings As a class, protease inhibitors contribute to a greater degree of bone loss than other anchor drugs. HIV disease reversal and the associated immune reconstitution following cART initiation play an important role in protease inhibitor-mediated bone loss in addition to plausible direct effects of protease inhibitors on bone cells. Summary Protease inhibitors remain an important component of cART despite their adverse effects on bone. A better understanding of factors that drive HIV/cART-induced bone loss is needed to stem the rising rate of fracture in the HIV-infected population. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.