Changes in bone turnover markers with HIV seroconversion and ART initiation.
Osteoporosis is common among HIV-infected persons and contributes to risk of fragility fracture. While ART initiation is associated with decreases in bone mineral density and increases in bone turnover, the impact of HIV on bone metabolism is unclear.



We identified men at the Chicago site of the Multicenter AIDS Cohort Study who HIV seroconverted while under observation. Concentrations of 25-OH vitamin D, bone turnover markers [procollagen type 1 N terminal propeptide (P1NP), osteocalcin (OC), C-telopeptide (CTX)] and sclerostin were measured from stored serum obtained at pre-HIV infection, pre-ART and post-ART initiation timepoints. Mixed models, with each biomarker as an outcome, were fitted. Timepoint, age, CD4 count (cells/mm 3 ), HIV-viral suppression, season and an age by timepoint interaction term were considered as fixed effects.



Data from 52 participants revealed that median duration between HIV seroconversion and ART initiation was 8.7 years (IQR 3.7-11.6). Median CD4 and plasma HIV-RNA concentrations were 445 (IQR 298.5-689) and 20 184 copies/mL (IQR 6237-64 340), respectively, at the pre-ART timepoint. Multivariate analyses demonstrated pre-HIV infection levels of OC that were higher than pre-ART levels (6.8 versus 5.7 ng/mL, P  =   0.04); and pre-ART levels of sclerostin that were higher than post-ART levels (0.033 versus 0.02 ng/mL, P  <0.001). No changes in P1NP, CTX and 25-OH vitamin D levels were detected.



HIV seroconversion was associated with decreased OC levels while ART initiation was associated with decreases in sclerostin, a negative regulator of bone formation. Our results suggest that both HIV infection and ART have an impact on bone metabolism in white men.
Hôpital Hôtel-Dieu, APHP, Service de Thérapeutique en Immuno-Infectiologie, 1 Place du Parvis Notre-Dame, 75181 Paris cedex 04, France.|Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Laurence
L
Slama
Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Susheel
S
Reddy
Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
John
J
Phair
Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Frank J
FJ
Palella
Johns Hopkins University, Baltimore, MD, USA.
Todd T
TT
Brown
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D015519:Bone Density; D019485:Bone Morphogenetic Proteins / Q000097:blood; D016723:Bone Remodeling; D001842:Bone and Bones / Q000187:drug effects / Q000502:physiology; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D024042:Collagen Type I / Q000097:blood; D005819:Genetic Markers; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology*; D006801:Humans; D008297:Male; D015675:Osteocalcin / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000097:blood; D011347:Procollagen / Q000097:blood; D000069078:Seroconversion
D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; D024042:Collagen Type I; D005819:Genetic Markers; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C422903:SOST protein, human; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide; D015675:Osteocalcin