title: Relative contribution of HIV infection, demographics and body mass index to bone mineral density.
abstract: BACKGROUND
  Low bone mineral density (BMD) is common in HIV-positive patients, although the role played by HIV infection versus sociodemographic and metabolic factors remains unclear.
  
  
  METHODS
  Understanding the Pathology of Bone Disease in HIV-infected individuals (HIV UPBEAT) is a prospective cohort study, enrolled HIV-positive and HIV-negative participants from similar demographic backgrounds. Dual X-ray absorptiometry at femoral neck, total hip and lumbar spine and blood tests were performed. Associations between BMD and factors of interest were assessed using multivariable linear regression.
  
  
  RESULTS
  A total of 474 participants were recruited. Two hundred and ten were HIV-positive, of whom, 59% were male, 40% African and median (interquartile range) age was 39 (33, 46) years. HIV acquisition risks were heterosexual sex (46.9%), homosexual sex (25.4%) and intravenous drug use (18.7%). Of the HIV-negative participants, 44% were male, 25% were African and median (interquartile range) age was 42 (34-49) years. HIV infection was independently associated with a 0.062 (P < 0.0001), 0.078 (P < 0.0001) and 0.060 g/cm (P =  0.0002) lower BMD at femoral neck, total hip and lumbar spine, respectively, after adjustment for demographic/ lifestyle factors and BMI. After further adjustment for bone biomarkers, HIV remained independently associated with reduced BMD at each site, although effect sizes were reduced. The HIV-positive group had significantly higher bone turnover (all between-group P < 0.0001). Treatment variables and cumulative exposure to antiretroviral therapy were not associated with lower BMD at femoral neck or total hip, but acquisition of HIV infection via intravenous drug use and longer time since HIV diagnosis were independently associated with lower lumbar spine BMD.
  
  
  CONCLUSIONS
  HIV is independently associated with lower BMD, and its effect is likely mediated, in part, by alterations in bone metabolism.
authors.affiliation: aHIV Molecular Research Group, School of Medicine and Medical Science, University College Dublin bDepartment of Infectious Diseases, Mater Misericordiae University Hospital, Dublin, Ireland cResearch Department of Infection & Population Health, UCL, Royal Free Campus, London, UK dDepartment of Radiology eDepartment of Clinical Chemistry and Diagnostic Endocrinology fDepartment of Rheumatology, Mater Misericordiae University Hospital, Dublin, Ireland gDepartment of Medicine, School of Clinical Medicine, Addenbrooke's NHS Trust, University of Cambridge, UK.
authors.forename: Aoife G
authors.initials: AG
authors.lastname: Cotter
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Sabin
authors.forename: Sibongile
authors.initials: S
authors.lastname: Simelane
authors.forename: Alan
authors.initials: A
authors.lastname: Macken
authors.forename: Eoin
authors.initials: E
authors.lastname: Kavanagh
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Brady
authors.forename: Geraldine
authors.initials: G
authors.lastname: McCarthy
authors.forename: Juliet
authors.initials: J
authors.lastname: Compston
authors.forename: Patrick W G
authors.initials: PW
authors.lastname: Mallon
mesh_terms: D015502:Absorptiometry, Photon; D000328:Adult; D015992:Body Mass Index; D015519:Bone Density; D015331:Cohort Studies; D015897:Comorbidity; D003430:Cross-Sectional Studies; D005260:Female; D005272:Femur Neck / Q000473:pathology*; D015658:HIV Infections / Q000150:complications / Q000453:epidemiology / Q000503:physiopathology*; D006615:Hip / Q000473:pathology*; D006801:Humans; D008159:Lumbar Vertebrae / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000453:epidemiology / Q000209:etiology / Q000503:physiopathology*; D011446:Prospective Studies; D012307:Risk Factors; D006113:United Kingdom / Q000453:epidemiology; D019562:Viral Load