Women have enhanced bone loss associated with phosphaturia and CD4+ cell restoration during initial antiretroviral therapy.

TitleWomen have enhanced bone loss associated with phosphaturia and CD4+ cell restoration during initial antiretroviral therapy.
Publication TypeJournal Article
Year of Publication2018
AuthorsKalayjian RC, Albert JM, Cremers S, Gupta SK, McComsey GA, Klingman KL, Fichtenbaum CJ, Brown TT, Taiwo BO
Corporate AuthorsACTG A5224s, A5303 Teams
JournalAIDS
Volume32
Issue17
Pagination2517-2524
Date Published2018 Nov 13
ISSN1473-5571
Abstract

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 BMD declines of 2.8 and 2.9%, respectively, plasma viral load suppression to less than 50 vs. at least 50 copies/ml was 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, 418 men) 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/μl 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.

DOI10.1097/QAD.0000000000001995
Alternate JournalAIDS
PubMed ID30134291
PubMed Central IDPMC6230267
Grant ListUM1 AI069423 / AI / NIAID NIH HHS / United States
UM1 AI069503 / AI / NIAID NIH HHS / United States
U01 AI069447 / AI / NIAID NIH HHS / United States
UM1 AI069501 / AI / NIAID NIH HHS / United States
UM1 AI069472 / AI / NIAID NIH HHS / United States
P30 AI050409 / AI / NIAID NIH HHS / United States
UL1 TR000445 / TR / NCATS NIH HHS / United States
UL1 TR001111 / TR / NCATS NIH HHS / United States
UM1 AI069424 / AI / NIAID NIH HHS / United States
UL1 TR001079 / TR / NCATS NIH HHS / United States
UM1 AI069432 / AI / NIAID NIH HHS / United States
UL1 RR025780 / RR / NCRR NIH HHS / United States
UM1 AI069471 / AI / NIAID NIH HHS / United States
U01 AI069439 / AI / NIAID NIH HHS / United States
UL1 TR000042 / TR / NCATS NIH HHS / United States
UM1 AI069439 / AI / NIAID NIH HHS / United States
UM1 AI069415 / AI / NIAID NIH HHS / United States
UM1 AI069412 / AI / NIAID NIH HHS / United States
UM1 AI069470 / AI / NIAID NIH HHS / United States
U01 AI069501 / AI / NIAID NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States
P30 AI073961 / AI / NIAID NIH HHS / United States
UL1 TR000454 / TR / NCATS NIH HHS / United States
UM1 AI069452 / AI / NIAID NIH HHS / United States
UM1 AI069496 / AI / NIAID NIH HHS / United States
UL1 RR024160 / RR / NCRR NIH HHS / United States
UL1 TR001082 / TR / NCATS NIH HHS / United States
UM1 AI069465 / AI / NIAID NIH HHS / United States
U01 AI069424 / AI / NIAID NIH HHS / United States
U01 AI069477 / AI / NIAID NIH HHS / United States
UM1 AI069511 / AI / NIAID NIH HHS / United States
P30 AI036219 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States
P30 AI050410 / AI / NIAID NIH HHS / United States
UM1 AI069418 / AI / NIAID NIH HHS / United States