title: The protease inhibitors and HIV-associated bone loss.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Caitlin A
authors.initials: CA
authors.lastname: Moran
authors.forename: M Neale
authors.initials: MN
authors.lastname: Weitzmann
authors.forename: Ighovwerha
authors.initials: I
authors.lastname: Ofotokun
mesh_terms: D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001851:Bone Diseases, Metabolic / Q000139:chemically induced* / Q000150:complications / Q000453:epidemiology*; D050723:Fractures, Bone / Q000453:epidemiology*; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors