TY - JOUR
T1 - Women have enhanced bone loss associated with phosphaturia and CD4R cell restoration during initial antiretroviral therapy
AU - Kalayjian, Robert C.
AU - Albert, Jeffrey M.
AU - Cremers, Serge
AU - Gupta, Samir K.
AU - McComsey, Grace A.
AU - Klingman, Karin L.
AU - Fichtenbaum, Carl J.
AU - Brown, Todd T.
AU - Taiwo, Babafemi O.
N1 - Publisher Copyright:
Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2018
Y1 - 2018
N2 - Objective: We compared bone mineral density (BMD) changes and their correlates, between men and women participating in two randomized trials of initial [antiretroviral therapy (ART)] regimens, with or without tenofovir disoproxil fumarate (TDF). Methods: Covariates in linear regression models of 48-week hip and spine %BMD changes, by dual energy X-ray absorptiometry, included baseline and 48-week changes in plasma viral load, CD4 cells, plasma C-Terminal telopeptide, procollagen 1 N-Terminal propeptide and glomerular filtration rates, and the 48-week area under the curve of fractional excretion of phosphate. Results: Despite overall hip and spine BMDdeclines of 2.8 and 2.9%, respectively, plasma viral load suppression to less than 50 vs. at least 50 copies/mlwas associated 1.0% (P 0.02) and 0.8% (P 0.01) less BMD decline.Women had lower baseline spine (P 0.04; n 59 women, 418men) and hip BMD(P 0.01) in adjusted models,with 1.7% more hip decline on ART than men (P 0.001). Serum phosphate was positively associated with baseline spine BMD in women (P 0.03) but not men, and area under the curve of fractional excretion of phosphate was negatively associated with spine BMD changes, particularly in women randomized to TDF regimens (P 0.03 and 0.054 for interactions by sex, and randomization to TDF vs. non-TDF regimens, respectively; n 44 women, 326 men). Women also had 0.6%(P 0.004) more hip BMD decline than men associated with each 100 CD4 cells/ml increase on ART (P 0.02; n 49 women, 379 men). Conclusion: Women randomized to TDF-containing ART had accentuated spine loss associated with phosphaturia, and accentuated hip loss associated with CD4 restoration, regardless of TDF exposure. Viral load suppression reduced bone loss.
AB - Objective: We compared bone mineral density (BMD) changes and their correlates, between men and women participating in two randomized trials of initial [antiretroviral therapy (ART)] regimens, with or without tenofovir disoproxil fumarate (TDF). Methods: Covariates in linear regression models of 48-week hip and spine %BMD changes, by dual energy X-ray absorptiometry, included baseline and 48-week changes in plasma viral load, CD4 cells, plasma C-Terminal telopeptide, procollagen 1 N-Terminal propeptide and glomerular filtration rates, and the 48-week area under the curve of fractional excretion of phosphate. Results: Despite overall hip and spine BMDdeclines of 2.8 and 2.9%, respectively, plasma viral load suppression to less than 50 vs. at least 50 copies/mlwas associated 1.0% (P 0.02) and 0.8% (P 0.01) less BMD decline.Women had lower baseline spine (P 0.04; n 59 women, 418men) and hip BMD(P 0.01) in adjusted models,with 1.7% more hip decline on ART than men (P 0.001). Serum phosphate was positively associated with baseline spine BMD in women (P 0.03) but not men, and area under the curve of fractional excretion of phosphate was negatively associated with spine BMD changes, particularly in women randomized to TDF regimens (P 0.03 and 0.054 for interactions by sex, and randomization to TDF vs. non-TDF regimens, respectively; n 44 women, 326 men). Women also had 0.6%(P 0.004) more hip BMD decline than men associated with each 100 CD4 cells/ml increase on ART (P 0.02; n 49 women, 379 men). Conclusion: Women randomized to TDF-containing ART had accentuated spine loss associated with phosphaturia, and accentuated hip loss associated with CD4 restoration, regardless of TDF exposure. Viral load suppression reduced bone loss.
KW - C-Terminal telopeptide
KW - CD4 restoration
KW - N-Terminal propeptide
KW - antiretroviral therapy
KW - bone mineral density
KW - bone turnover
KW - fractional excretion of phosphate
KW - menopause
KW - phosphaturia
KW - tenofovir disoproxil fumarate
UR - http://www.scopus.com/inward/record.url?scp=85055838121&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85055838121&partnerID=8YFLogxK
U2 - 10.1097/QAD.0000000000001995
DO - 10.1097/QAD.0000000000001995
M3 - Article
C2 - 30134291
AN - SCOPUS:85055838121
SN - 0269-9370
VL - 32
SP - 2517
EP - 2524
JO - AIDS
JF - AIDS
IS - 17
ER -