title: Does systemic inflammation and immune activation contribute to fracture risk in HIV?
abstract: OBJECTIVE
  There is increasing evidence pointing toward an important role of heightened immune activation and inflammation in people living with HIV contributing to the development of non-AIDS comorbidities. This review aims to explore low bone mineral density (BMD) in HIV with a focus on the underlying mechanisms and relationships between the immune and skeletal systems.
  
  
  RESULTS
  Baseline immune activation and inflammation negatively impact BMD at antiretroviral therapy (ART) initiation. B- and T-cell alterations in HIV lead to an imbalance in the osteoblastic osteoprotegerin (OPG) and osteoclastic receptor activator of NF-κB ligand (RANKL) cytokines which favours osteoclastogenesis and bone resorption. These findings suggest an important role for immune-mediated mechanisms in the pathogenesis of low BMD in HIV.
  
  
  CONCLUSIONS
  Bone homeostasis is in part regulated by cells of the immune system through complex interactions with the RANK/RANKL/OPG axis. Disturbances in the normal functioning of T, B cells, and monocytes in HIV and the resulting proinflammatory state may contribute to dysregulation of this finely controlled balance leading to increased bone loss. Pre-ART levels of immune activation and inflammation have a consistently negative effect on BMD and further suggest the immunocentric basis of bone loss in HIV alongside supporting the benefits of earlier ART initiation. Further longitudinal studies will help determine the effect this will have on fracture risk in people living with HIV.
authors.affiliation: aHIV Molecular Research Group, School of Medicine, University College Dublin bDepartment of Infectious Diseases, Mater Misericordiae University Hospital, Dublin, Ireland cDepartment of Immunology/Microbiology, Rush University Medical Center, Chicago, Illinois, USA *Tara McGinty and Paria Mirmonsef have contributed equally to the writing of this article.
authors.forename: Tara
authors.initials: T
authors.lastname: McGinty
authors.forename: Paria
authors.initials: P
authors.lastname: Mirmonsef
authors.forename: Patrick W G
authors.initials: PW
authors.lastname: Mallon
authors.forename: Alan L
authors.initials: AL
authors.lastname: Landay
mesh_terms: D001862:Bone Resorption; D050723:Fractures, Bone / Q000209:etiology*; D015658:HIV Infections / Q000150:complications* / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000473:pathology*; D010012:Osteogenesis; D010024:Osteoporosis / Q000150:complications*; D018570:Risk Assessment