title: Impact of tenofovir disoproxil fumarate on bone metabolism and bone mass among perinatally HIV-infected Asian adolescents.
abstract: BACKGROUND
  This study aimed to determine the effect of tenofovir disoproxil fumarate (TDF) on bone metabolism and bone mass in HIV-infected adolescents.
  
  
  METHODS
  This was a sub-study of a cross-sectional multicentre bone health trial that enrolled perinatally HIV-infected Thai and Indonesian adolescents (10-18 years) with viral suppression on antiretroviral therapy. Participants were classified into two groups as TDF users and non-users. Bone metabolism-related markers (25-hydroxyvitamin D [25-OHD], intact parathyroid hormone [iPTH], bone turnover biomarkers), and lumbar spine dual-energy X-ray absorptiometry were assessed. Bone mineral density (BMD)/bone mineral apparent density (BMAD) Z-scores were calculated.
  
  
  RESULTS
  Of 394 adolescents, 136 (34.5%) and 258 (65.5%) were TDF users and non-users, respectively. Among TDF users, median age (IQR) was 16.1 (14.7-17.4) years and TDF treatment duration (IQR) was 2.3 (1.4-3.1) years. Among TDF non-users, median age (IQR) was 14.3 (12.6-16.4) years. BMD and BMAD Z-scores comparing TDF users with non-users were -0.8 and -0.6 (P=0.27), and -0.3 and -0.2 (P=0.58), respectively. The association between TDF use and iPTH elevation was intensified in adolescents with suboptimal vitamin D levels (25-OHD <30 ng/ml; P=0.001). TDF administration was positively associated with bone resorption marker (P=0.04) and negatively associated with bone formation marker (P=0.04). With data up to 4 years, neither association between TDF use and bone mass loss (BMD: P=0.09; BMAD: P=0.22), nor variation of bone mass Z-scores by TDF treatment duration (BMD: P=0.34; BMAD: P=0.58) was demonstrated.
  
  
  CONCLUSIONS
  Recent TDF administration was correlated with PTH elevation and bone turnover dysregulation but not with bone mass reduction in our cohort. A study with extended follow-up to ascertain TDF-associated bone mass deterioration is warranted.
authors: Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.|Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand.
authors: Tavitiya
authors: T
authors: Sudjaritruk
authors: HIV-NAT, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
authors: Torsak
authors: T
authors: Bunupuradah
authors: Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand.
authors: Linda
authors: L
authors: Aurpibul
authors: Department of Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors: Pope
authors: P
authors: Kosalaraksa
authors: Department of Child Health, Cipto Mangunkusumo General Hospital, Jakarta, Indonesia.
authors: Nia
authors: N
authors: Kurniati
authors: HIV-NAT, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
authors: Jiratchaya
authors: J
authors: Sophonphan
authors: HIV-NAT, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.|Present address: The Henry M Jackson Foundation for the Advancement of Military Medicine, the US Military HIV Research Program, Bethesda, MD, USA.
authors: Jintanat
authors: J
authors: Ananworanich
authors: HIV-NAT, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.|Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.|Research Unit in Pediatric Infectious Diseases and Vaccine, Chulalongkorn University, Bangkok, Thailand.
authors: Thanyawee
authors: T
authors: Puthanakit
mesh_terms: D000293:Adolescent; D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers; D015519:Bone Density / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism*; D018791:CD4 Lymphocyte Count; D002648:Child; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012720:Severity of Illness Index; D000068698:Tenofovir / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; D000068698:Tenofovir