title: Decline in Bone Mass With Tenofovir Disoproxil Fumarate/Emtricitabine Is Associated With Hormonal Changes in the Absence of Renal Impairment When Used by HIV-Uninfected Adolescent Boys and Young Men for HIV Preexposure Prophylaxis.
abstract: BACKGROUND
  We aimed to define the relative importance of renal and endocrine changes in tenofovir disoproxil fumarate (TDF)-related bone toxicity.
  
  
  METHODS
  In a study of daily TDF/emtricitabine (FTC) preexposure prophylaxis (PrEP) in human immunodeficiency virus (HIV)-uninfected young men who have sex with men, we measured changes from baseline in blood and urine markers of the parathyroid hormone (PTH)-vitamin D-fibroblast growth factor 23 (FGF23) axis, creatinine, and renal tubular reabsorption of phosphate (TRP). We explored the relationship of those variables to changes in bone mineral density (BMD). Tenofovir-diphosphate (TFV-DP) in red blood cells was used to categorize participants into high and low drug exposure groups.
  
  
  RESULTS
  There were 101 participants, median age 20 years (range 15 to 22). Compared with low drug exposure, high-exposure participants showed increase from baseline in PTH and decline in FGF23 by study week 4, with no differences in creatinine, phosphate, or TRP. At 48 weeks, the median (interquartile range) percent decline in total hip BMD was greater in those with high- compared to low- exposure (-1.59 [2.77] vs +1.54 [3.34] %, respectively; P = .001); in high-exposure participants, this correlated with week 4 TFV-DP (inversely; r = -0.60, P = .002) and FGF23 (directly; r = 0.42; P = .039) but not other variables.
  
  
  CONCLUSIONS
  These findings support the short-term renal safety of TDF/FTC PrEP in HIV-seronegative young men and suggest that endocrine disruption (PTH-FGF23) is a primary contributor to TDF-associated BMD decline in this age group.
  
  
  BACKGROUND
  NCT01769469.
authors.affiliation: Department of Pediatrics, Medical College of Wisconsin/Children's Hospital of Wisconsin, Milwaukee; phavens@mcw.edu.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Havens
authors.affiliation: US Department of Agriculture, Agricultural Research Service, Western Human Nutrition Research Center, and.
authors.forename: Charles B
authors.initials: CB
authors.lastname: Stephensen
authors.affiliation: US Department of Agriculture, Agricultural Research Service, Western Human Nutrition Research Center, and.
authors.forename: Marta D
authors.initials: MD
authors.lastname: Van Loan
authors.affiliation: Department of Nutrition, University of California, Davis.
authors.forename: Gertrud U
authors.initials: GU
authors.lastname: Schuster
authors.affiliation: US Department of Agriculture, Agricultural Research Service, Western Human Nutrition Research Center, and.
authors.forename: Leslie R
authors.initials: LR
authors.lastname: Woodhouse
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Flynn
authors.affiliation: Department of Pediatrics, University of Cincinnati College of Medicine/Cincinnati Children's Hospital Medical Center, Ohio.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Gordon
authors.affiliation: Department of Pediatrics, Medical College of Wisconsin/Children's Hospital of Wisconsin, Milwaukee.
authors.forename: Cynthia G
authors.initials: CG
authors.lastname: Pan
authors.affiliation: Westat, Rockville, Maryland.
authors.forename: Brandy
authors.initials: B
authors.lastname: Rutledge
authors.affiliation: Westat, Rockville, Maryland.
authors.forename: Nancy
authors.initials: N
authors.lastname: Liu
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham.
authors.forename: Craig M
authors.initials: CM
authors.lastname: Wilson
authors.affiliation: Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland.
authors.forename: Rohan
authors.initials: R
authors.lastname: Hazra
authors.affiliation: Department of Psychiatry, Stroger Hospital of Cook County, Chicago, Illinois.
authors.forename: Sybil G
authors.initials: SG
authors.lastname: Hosek
authors.affiliation: Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora; and.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Anderson
authors.affiliation: Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora; and.
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Seifert
authors.affiliation: Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland.
authors.forename: Bill G
authors.initials: BG
authors.lastname: Kapogiannis
authors.affiliation: Department of Medicine, Division of Endocrinology, Zuckerberg San Francisco General Hospital, University of California, San Francisco.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Mulligan
mesh_terms: D000293:Adolescent; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects*; D015519:Bone Density / Q000187:drug effects*; D003404:Creatinine / Q000097:blood / Q000652:urine; D000068679:Emtricitabine / Q000008:administration & dosage / Q000009:adverse effects*; D000089703:Fibroblast Growth Factor-23; D005919:Glomerular Filtration Rate / Q000187:drug effects; D015658:HIV Infections / Q000097:blood / Q000378:metabolism / Q000517:prevention & control* / Q000652:urine; D018451:Homosexuality, Male; D006801:Humans; D007668:Kidney / Q000187:drug effects; D008297:Male; D010281:Parathyroid Hormone / Q000097:blood / Q000652:urine; D065129:Pre-Exposure Prophylaxis; D051437:Renal Insufficiency / Q000139:chemically induced; D000068698:Tenofovir / Q000008:administration & dosage / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; C000717427:FGF23 protein, human; C470125:PTH protein, human; D010281:Parathyroid Hormone; D000089703:Fibroblast Growth Factor-23; D000068698:Tenofovir; D003404:Creatinine; D000068679:Emtricitabine
keywords: HIV pre- exposure prophylaxis.; bone mineral density; fibroblast growth factor 23; parathyroid hormone; tenofovir disoproxil fumarate