PMID- 29623648
OWN - NLM
STAT- MEDLINE
DCOM- 20181106
LR  - 20181114
IS  - 1179-1942 (Electronic)
IS  - 0114-5916 (Print)
IS  - 0114-5916 (Linking)
VI  - 41
IP  - 9
DP  - 2018 Sep
TI  - Osteoporosis-Related Fractures in HIV-Infected Patients Receiving Long-Term 
      Tenofovir Disoproxil Fumarate: An Observational Cohort Study.
PG  - 843-848
LID - 10.1007/s40264-018-0665-z [doi]
AB  - INTRODUCTION: Patients with HIV infection may have a higher prevalence of 
      osteoporosis and osteopenia, as well as an increased risk of bone fracture 
      compared with non-HIV-infected individuals. Antiretroviral therapy is thought to 
      be one of factors associated to osteoporosis-related bone fractures. OBJECTIVE: 
      The aim of this study was to assess the effects of long-term exposure to 
      tenofovir disoproxil fumarate (TDF) on the cumulative risk of 
      osteoporosis-related bone fractures in Japanese patients with HIV infection. 
      DESIGN: This observational cohort study comprised a joint HIV-related drug survey 
      of patients treated with TDF between April 2004 and March 2013. METHODS: 
      Thirty-five healthcare facilities in Japan participated in the survey. The 
      incidence of osteoporosis-related fractures was extracted from all adverse events 
      (AEs) using standardized Medical Dictionary for Regulatory Activities queries, 
      and used to calculate the fracture rate per 10,000 patient-years (PY). 
      Kaplan-Meier analysis was used to estimate the cumulative probability of fracture 
      during the study period. RESULTS: A total of 3251 patients who received TDF or 
      TDF/emtricitabine between April 2004 and March 2013 were analyzed in this study; 
      93.5% of patients were male. The fracture rate was 13.5 per 10,000 PY in males 
      and 42.2 per 10,000 PY in females. The mean age for male patients with 
      osteoporosis-related fracture was 43.2 years, whereas it was 65.7 years in female 
      patients. The cumulative probability of osteoporosis-related fracture increased 
      after >/= 5 years of TDF exposure. The rate of hip fracture (95% confidence 
      interval) was 7.2 (3.1-14.2) per 10,000 PY. CONCLUSIONS: Among HIV-infected 
      patients in Japan, treatment with TDF for >/= 5 years increases the risk of bone 
      fractures in younger men, in addition to that seen in older post-menopausal 
      women.
FAU - Komatsu, Ayami
AU  - Komatsu A
AUID- ORCID: 0000-0002-1673-3490
AD  - Pharmaceutical Division, Drug Safety and Risk Management Department, Japan 
      Tobacco Inc., Tokyo, Japan. ayami.komatsu@jt.com.
FAU - Ikeda, Atsushi
AU  - Ikeda A
AD  - Pharmaceutical Division, Drug Safety and Risk Management Department, Japan 
      Tobacco Inc., Tokyo, Japan.
FAU - Kikuchi, Akio
AU  - Kikuchi A
AD  - Pharmaceutical Division, Drug Safety and Risk Management Department, Japan 
      Tobacco Inc., Tokyo, Japan.
FAU - Minami, Chiaki
AU  - Minami C
AD  - Pharmaceutical Division, Drug Safety and Risk Management Department, Japan 
      Tobacco Inc., Tokyo, Japan.
FAU - Tan, Motomu
AU  - Tan M
AD  - Pharmaceutical Division, Drug Safety and Risk Management Department, Japan 
      Tobacco Inc., Tokyo, Japan.
FAU - Matsushita, Shuzo
AU  - Matsushita S
AD  - Center for AIDS Research, Kumamoto University, Kumamoto, Japan. 
      shuzo@kumamoto-u.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Observational Study
PT  - Research Support, Non-U.S. Gov't
PL  - New Zealand
TA  - Drug Saf
JT  - Drug safety
JID - 9002928
RN  - 0 (Anti-HIV Agents)
RN  - 99YXE507IL (Tenofovir)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Anti-HIV Agents/administration & dosage/*adverse effects
MH  - Cohort Studies
MH  - Drug Administration Schedule
MH  - Female
MH  - Fractures, Bone/*chemically induced/epidemiology
MH  - HIV Infections/*drug therapy/epidemiology
MH  - Humans
MH  - Japan/epidemiology
MH  - Longitudinal Studies
MH  - Male
MH  - Middle Aged
MH  - Osteoporosis/*chemically induced/epidemiology
MH  - Tenofovir/administration & dosage/*adverse effects
PMC - PMC6061259
COIS- FUNDING: This study was fully supported by Japan Tobacco Inc. CONFLICTS OF 
      INTEREST: Ayami Komatsu, Atsushi Ikeda, Akio Kikuchi, Chiaki Minami and Motomu 
      Tan are full-time employee of Japan Tobacco Inc. Shuzo Matsushita has received 
      grants and personal fees from Japan Tobacco Inc., and personal fees from Bayer 
      Yakuhin Ltd, MSD K.K., Janssen Pharmaceuticals K.K., Torii Pharmaceutical Co. 
      Ltd, Shire Japan K.K., Bioverativ Japan Ltd, and Novo Nordisk Pharmaceutical Ltd. 
      ETHICAL APPROVAL: The survey was conducted in accordance with the Good 
      Post-Marketing Study Practice (GPSP) regulations issued by the Ministry of 
      Health, Labour and Welfare of Japan.
EDAT- 2018/04/07 06:00
MHDA- 2018/11/07 06:00
PMCR- 2018/04/05
CRDT- 2018/04/07 06:00
PHST- 2018/04/07 06:00 [pubmed]
PHST- 2018/11/07 06:00 [medline]
PHST- 2018/04/07 06:00 [entrez]
PHST- 2018/04/05 00:00 [pmc-release]
AID - 10.1007/s40264-018-0665-z [pii]
AID - 665 [pii]
AID - 10.1007/s40264-018-0665-z [doi]
PST - ppublish
SO  - Drug Saf. 2018 Sep;41(9):843-848. doi: 10.1007/s40264-018-0665-z.