PMID- 34962571
OWN - NLM
STAT- MEDLINE
DCOM- 20220815
LR  - 20230802
IS  - 1537-6613 (Electronic)
IS  - 0022-1899 (Print)
IS  - 0022-1899 (Linking)
VI  - 226
IP  - 1
DP  - 2022 Aug 12
TI  - Immune Reconstitution Bone Loss Exacerbates Bone Degeneration Due to Natural 
      Aging in a Mouse Model.
PG  - 38-48
LID - 10.1093/infdis/jiab631 [doi]
AB  - BACKGROUND: Immune reconstitution bone loss (IRBL) is a common side-effect of 
      antiretroviral therapy (ART) in people with human immunodeficiency virus (PWH). 
      Immune reconstitution bone loss acts through CD4+ T-cell/immune 
      reconstitution-induced inflammation and is independent of antiviral regimen. 
      Immune reconstitution bone loss may contribute to the high rate of bone fracture 
      in PWH, a cause of significant morbidity and mortality. Although IRBL is 
      transient, it remains unclear whether bone recovers, or whether it is permanently 
      denuded and further compounds bone loss associated with natural aging. METHODS: 
      We used a validated IRBL mouse model involving T-cell reconstitution of 
      immunocompromised mice. Mice underwent cross-sectional bone phenotyping of femur 
      and/or vertebrae between 6 and 20 months of age by microcomputed tomography (microCT) 
      and quantitative bone histomorphometry. CD4+ T cells were purified at 20 months 
      to quantify osteoclastogenic/inflammatory cytokine expression. RESULTS: Although 
      cortical IRBL in young animals recovered with time, trabecular bone loss was 
      permanent and exacerbated skeletal decline associated with natural aging. At 20 
      months of age, reconstituted CD4+ T cells express enhanced osteoclastogenic 
      cytokines including RANKL, interleukin (IL)-1beta, IL-17A, and tumor necrosis 
      factor-alpha, consistent with elevated osteoclast numbers. CONCLUSIONS: Immune 
      reconstitution bone loss in the trabecular compartment is permanent and further 
      exacerbates bone loss due to natural aging. If validated in humans, interventions 
      to limit IRBL may be important to prevent fractures in aging PWH.
CI  - Published by Oxford University Press for the Infectious Diseases Society of 
      America 2021.
FAU - Weitzmann, M Neale
AU  - Weitzmann MN
AUID- ORCID: 0000-0003-3305-5748
AD  - Atlanta Department of Veterans Affairs Medical Center, Decatur, Georgia, USA.
AD  - Division of Endocrinology, Metabolism, and Lipids, Department of Medicine, Emory 
      University School of Medicine, Atlanta, Georgia, USA.
FAU - Weiss, Daiana
AU  - Weiss D
AD  - Division of Endocrinology, Metabolism, and Lipids, Department of Medicine, Emory 
      University School of Medicine, Atlanta, Georgia, USA.
FAU - Vikulina, Tatyana
AU  - Vikulina T
AD  - Atlanta Department of Veterans Affairs Medical Center, Decatur, Georgia, USA.
AD  - Division of Endocrinology, Metabolism, and Lipids, Department of Medicine, Emory 
      University School of Medicine, Atlanta, Georgia, USA.
FAU - Roser-Page, Susanne
AU  - Roser-Page S
AD  - Atlanta Department of Veterans Affairs Medical Center, Decatur, Georgia, USA.
FAU - Yu, Kanglun
AU  - Yu K
AD  - Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta 
      University, Augusta, Georgia, USA.
FAU - McGee-Lawrence, Meghan E
AU  - McGee-Lawrence ME
AD  - Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta 
      University, Augusta, Georgia, USA.
AD  - Department of Orthopaedic Surgery, Medical College of Georgia, Augusta 
      University, Augusta, Georgia, USA.
FAU - Tu, Chia Ling
AU  - Tu CL
AD  - Endocrine Research Unit, San Francisco VA Healthcare System, University of 
      California, San Francisco, California, USA.
FAU - Chang, Wenhan
AU  - Chang W
AD  - Endocrine Research Unit, San Francisco VA Healthcare System, University of 
      California, San Francisco, California, USA.
FAU - Ofotokun, Ighovwerha
AU  - Ofotokun I
AD  - Division of Infectious Diseases, Department of Medicine, Emory University School 
      of Medicine, Atlanta, Georgia, USA.
AD  - Grady Healthcare System, Atlanta, Georgia, USA.
LA  - eng
GR  - IS1 BX004813/BX/BLRD VA/United States
GR  - R01 AR079298/AR/NIAMS NIH HHS/United States
GR  - P01 AG036675/AG/NIA NIH HHS/United States
GR  - I01 BX005851/BX/BLRD VA/United States
GR  - P30 AR066262/AR/NIAMS NIH HHS/United States
GR  - U54 AG062334/AG/NIA NIH HHS/United States
GR  - I01 BX000105/BX/BLRD VA/United States
GR  - IK6 BX004835/BX/BLRD VA/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - J Infect Dis
JT  - The Journal of infectious diseases
JID - 0413675
RN  - 0 (Cytokines)
SB  - IM
MH  - Aging
MH  - Animals
MH  - CD4-Positive T-Lymphocytes
MH  - Cytokines/metabolism
MH  - *HIV Infections/complications
MH  - Humans
MH  - *Immune Reconstitution
MH  - Mice
MH  - X-Ray Microtomography
PMC - PMC9373144
OTO - NOTNLM
OT  - HIV
OT  - T cells
OT  - aging
OT  - antiretroviral therapy
OT  - immune reconstitution bone loss
COIS- Potential conflicts of interest. All authors: No reported conflicts of interest. 
      All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts 
      of Interest.
EDAT- 2021/12/29 06:00
MHDA- 2022/08/16 06:00
PMCR- 2021/12/28
CRDT- 2021/12/28 12:13
PHST- 2021/09/02 00:00 [received]
PHST- 2021/12/23 00:00 [accepted]
PHST- 2021/12/29 06:00 [pubmed]
PHST- 2022/08/16 06:00 [medline]
PHST- 2021/12/28 12:13 [entrez]
PHST- 2021/12/28 00:00 [pmc-release]
AID - 6485936 [pii]
AID - jiab631 [pii]
AID - 10.1093/infdis/jiab631 [doi]
PST - ppublish
SO  - J Infect Dis. 2022 Aug 12;226(1):38-48. doi: 10.1093/infdis/jiab631.