Interruption or deferral of antiretroviral therapy reduces markers of bone turnover compared with continuous therapy: The SMART body composition substudy

Jennifer F Hoy, Birgit Grund, Mollie Roediger, Kristine E Ensrud, Indira Brar, Robert Colebunders, Nathalie De Castro, Margaret Johnson, Anjali Sharma, Andrew Carr

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28 Citations (Scopus)

Abstract

Bone mineral density (BMD) declines significantly in HIV patients on antiretroviral therapy (ART). We compared the effects of intermittent versus continuous ART on markers of bone turnover in the Body Composition substudy of the Strategies for Management of AntiRetroviral Therapy (SMART) trial and determined whether early changes in markers predicted subsequent change in BMD. For 202 participants (median age 44 years, 17 female, 74 on ART) randomized to continuous or intermittent ART, plasma markers of inflammation and bone turnover were evaluated at baseline and months 4 and 12; BMD at the spine (dual-energy X-ray absorptiometry [DXA] and computed tomography) and hip (DXA) was evaluated annually. Compared with the continuous ART group, mean bone-specific alkaline phosphatase (bALP), osteocalcin, procollagen type 1 N-terminal propeptide (P1NP), N-terminal cross-linking telopeptide of type 1 collagen (NTX), and C-terminal cross-linking telopeptide of type 1 collagen (?CTX) decreased significantly in the intermittent ART group, whereas RANKL and the RANKL:osteoprotegerin (OPG) ratio increased (all p = 0.002 at month 4 and month 12). Increases in bALP, osteocalcin, P1NP, NTX, and ?CTX at month 4 predicted decrease in hip BMD at month 12, whereas increases in RANKL and the RANKL:OPG ratio at month 4 predicted increase in hip and spine BMD at month 12. This study has shown that compared with continuous ART, interruption of ART results in a reduction in markers of bone turnover and increase in BMD at hip and spine, and that early changes in markers of bone turnover predict BMD changes at 12 months. Copyright ? 2013 American Society for Bone and Mineral Research.
Original languageEnglish
Pages (from-to)1264 - 1274
Number of pages11
JournalJournal of Bone and Mineral Research
Volume28
Issue number6
DOIs
Publication statusPublished - 2013

Cite this

Hoy, Jennifer F ; Grund, Birgit ; Roediger, Mollie ; Ensrud, Kristine E ; Brar, Indira ; Colebunders, Robert ; De Castro, Nathalie ; Johnson, Margaret ; Sharma, Anjali ; Carr, Andrew. / Interruption or deferral of antiretroviral therapy reduces markers of bone turnover compared with continuous therapy: The SMART body composition substudy. In: Journal of Bone and Mineral Research. 2013 ; Vol. 28, No. 6. pp. 1264 - 1274.
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abstract = "Bone mineral density (BMD) declines significantly in HIV patients on antiretroviral therapy (ART). We compared the effects of intermittent versus continuous ART on markers of bone turnover in the Body Composition substudy of the Strategies for Management of AntiRetroviral Therapy (SMART) trial and determined whether early changes in markers predicted subsequent change in BMD. For 202 participants (median age 44 years, 17 female, 74 on ART) randomized to continuous or intermittent ART, plasma markers of inflammation and bone turnover were evaluated at baseline and months 4 and 12; BMD at the spine (dual-energy X-ray absorptiometry [DXA] and computed tomography) and hip (DXA) was evaluated annually. Compared with the continuous ART group, mean bone-specific alkaline phosphatase (bALP), osteocalcin, procollagen type 1 N-terminal propeptide (P1NP), N-terminal cross-linking telopeptide of type 1 collagen (NTX), and C-terminal cross-linking telopeptide of type 1 collagen (?CTX) decreased significantly in the intermittent ART group, whereas RANKL and the RANKL:osteoprotegerin (OPG) ratio increased (all p = 0.002 at month 4 and month 12). Increases in bALP, osteocalcin, P1NP, NTX, and ?CTX at month 4 predicted decrease in hip BMD at month 12, whereas increases in RANKL and the RANKL:OPG ratio at month 4 predicted increase in hip and spine BMD at month 12. This study has shown that compared with continuous ART, interruption of ART results in a reduction in markers of bone turnover and increase in BMD at hip and spine, and that early changes in markers of bone turnover predict BMD changes at 12 months. Copyright ? 2013 American Society for Bone and Mineral Research.",
author = "Hoy, {Jennifer F} and Birgit Grund and Mollie Roediger and Ensrud, {Kristine E} and Indira Brar and Robert Colebunders and {De Castro}, Nathalie and Margaret Johnson and Anjali Sharma and Andrew Carr",
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Hoy, JF, Grund, B, Roediger, M, Ensrud, KE, Brar, I, Colebunders, R, De Castro, N, Johnson, M, Sharma, A & Carr, A 2013, 'Interruption or deferral of antiretroviral therapy reduces markers of bone turnover compared with continuous therapy: The SMART body composition substudy', Journal of Bone and Mineral Research, vol. 28, no. 6, pp. 1264 - 1274. https://doi.org/10.1002/jbmr.1861

Interruption or deferral of antiretroviral therapy reduces markers of bone turnover compared with continuous therapy: The SMART body composition substudy. / Hoy, Jennifer F; Grund, Birgit; Roediger, Mollie; Ensrud, Kristine E; Brar, Indira; Colebunders, Robert; De Castro, Nathalie; Johnson, Margaret; Sharma, Anjali; Carr, Andrew.

In: Journal of Bone and Mineral Research, Vol. 28, No. 6, 2013, p. 1264 - 1274.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Interruption or deferral of antiretroviral therapy reduces markers of bone turnover compared with continuous therapy: The SMART body composition substudy

AU - Hoy, Jennifer F

AU - Grund, Birgit

AU - Roediger, Mollie

AU - Ensrud, Kristine E

AU - Brar, Indira

AU - Colebunders, Robert

AU - De Castro, Nathalie

AU - Johnson, Margaret

AU - Sharma, Anjali

AU - Carr, Andrew

PY - 2013

Y1 - 2013

N2 - Bone mineral density (BMD) declines significantly in HIV patients on antiretroviral therapy (ART). We compared the effects of intermittent versus continuous ART on markers of bone turnover in the Body Composition substudy of the Strategies for Management of AntiRetroviral Therapy (SMART) trial and determined whether early changes in markers predicted subsequent change in BMD. For 202 participants (median age 44 years, 17 female, 74 on ART) randomized to continuous or intermittent ART, plasma markers of inflammation and bone turnover were evaluated at baseline and months 4 and 12; BMD at the spine (dual-energy X-ray absorptiometry [DXA] and computed tomography) and hip (DXA) was evaluated annually. Compared with the continuous ART group, mean bone-specific alkaline phosphatase (bALP), osteocalcin, procollagen type 1 N-terminal propeptide (P1NP), N-terminal cross-linking telopeptide of type 1 collagen (NTX), and C-terminal cross-linking telopeptide of type 1 collagen (?CTX) decreased significantly in the intermittent ART group, whereas RANKL and the RANKL:osteoprotegerin (OPG) ratio increased (all p = 0.002 at month 4 and month 12). Increases in bALP, osteocalcin, P1NP, NTX, and ?CTX at month 4 predicted decrease in hip BMD at month 12, whereas increases in RANKL and the RANKL:OPG ratio at month 4 predicted increase in hip and spine BMD at month 12. This study has shown that compared with continuous ART, interruption of ART results in a reduction in markers of bone turnover and increase in BMD at hip and spine, and that early changes in markers of bone turnover predict BMD changes at 12 months. Copyright ? 2013 American Society for Bone and Mineral Research.

AB - Bone mineral density (BMD) declines significantly in HIV patients on antiretroviral therapy (ART). We compared the effects of intermittent versus continuous ART on markers of bone turnover in the Body Composition substudy of the Strategies for Management of AntiRetroviral Therapy (SMART) trial and determined whether early changes in markers predicted subsequent change in BMD. For 202 participants (median age 44 years, 17 female, 74 on ART) randomized to continuous or intermittent ART, plasma markers of inflammation and bone turnover were evaluated at baseline and months 4 and 12; BMD at the spine (dual-energy X-ray absorptiometry [DXA] and computed tomography) and hip (DXA) was evaluated annually. Compared with the continuous ART group, mean bone-specific alkaline phosphatase (bALP), osteocalcin, procollagen type 1 N-terminal propeptide (P1NP), N-terminal cross-linking telopeptide of type 1 collagen (NTX), and C-terminal cross-linking telopeptide of type 1 collagen (?CTX) decreased significantly in the intermittent ART group, whereas RANKL and the RANKL:osteoprotegerin (OPG) ratio increased (all p = 0.002 at month 4 and month 12). Increases in bALP, osteocalcin, P1NP, NTX, and ?CTX at month 4 predicted decrease in hip BMD at month 12, whereas increases in RANKL and the RANKL:OPG ratio at month 4 predicted increase in hip and spine BMD at month 12. This study has shown that compared with continuous ART, interruption of ART results in a reduction in markers of bone turnover and increase in BMD at hip and spine, and that early changes in markers of bone turnover predict BMD changes at 12 months. Copyright ? 2013 American Society for Bone and Mineral Research.

UR - http://www.ncbi.nlm.nih.gov/pubmed/23299909

U2 - 10.1002/jbmr.1861

DO - 10.1002/jbmr.1861

M3 - Article

VL - 28

SP - 1264

EP - 1274

JO - Journal of Bone and Mineral Research

JF - Journal of Bone and Mineral Research

SN - 0884-0431

IS - 6

ER -