Changes in bone turnover and bone loss in HIV-infected patients changing treatment to tenofovir-emtricitabine or abacavir-lamivudine

Hila Haskelberg; Jennifer F. Hoy; Janaki Amin; Peter R. Ebeling; Sean Emery; Andrew Carr; Anthony Allworth; Jonathan Anderson; David Baker; Mark Bloch; Mark Boyd; John Chuah; David Cooper; Stephen Davies; Linda Dayan; William Donohue; Nicholas Doong; Dominic Dwyer; John Dyer; Robert Finlayson; Michelle Giles; David Gordon; Mark Kelly; Nicholas Medland; Richard Moore; David Nolan; David Orth; Jeffrey Post; John Quin; Tim Read; Norman Roth; Darren Russell; David Shaw; David Smith; Don Smith; Alan Street; Ban Kiem Tee; Ian Woolley

doi:10.1371/journal.pone.0038377

Changes in bone turnover and bone loss in HIV-infected patients changing treatment to tenofovir-emtricitabine or abacavir-lamivudine

Hila Haskelberg, Jennifer F. Hoy, Janaki Amin, Peter R. Ebeling, Sean Emery, Andrew Carr, Anthony Allworth, Jonathan Anderson, David Baker, Mark Bloch, Mark Boyd, John Chuah, David Cooper, Stephen Davies, Linda Dayan, William Donohue, Nicholas Doong, Dominic Dwyer, John Dyer, Robert FinlaysonMichelle Giles, David Gordon, Mark Kelly, Nicholas Medland, Richard Moore, David Nolan, David Orth, Jeffrey Post, John Quin, Tim Read, Norman Roth, Darren Russell, David Shaw, David Smith, Don Smith, Alan Street, Ban Kiem Tee, Ian Woolley

Research output: Contribution to journal › Article › peer-review

Abstract

Background: Those receiving tenofovir/emtricitabine (TDF-FTC) had greater bone loss compared with abacavir/lamivudine (ABC-3TC) in a randomized simplification trial (STEAL study). Previous studies associated increased bone turnover and bone loss with initiation of antiretroviral treatment, however it is unclear whether change in bone mineral density (BMD) was a result of specific drugs, from immune reconstitution or from suppression of HIV replication. This analysis determined predictors of BMD change in the hip and spine by dual-energy x-ray absorptiometry in virologically suppressed participants through week 96. Methodology/Principal Findings: Bone turnover markers (BTMs) tested were: formation [bone alkaline phosphatase, procollagen type 1 N-terminal propeptide (P1NP)]; resorption (C-terminal cross-linking telopeptide of type 1 collagen [CTx]); and bone cytokine-signalling (osteoprotegerin, RANK ligand). Independent predictors of BMD change were determined using forward, stepwise, linear regression. BTM changes and fracture risk (FRAX®) at week 96 were compared by t-test. Baseline characteristics (n = 301) were: 98% male, mean age 45 years, current protease-inhibitor (PI) 23%, tenofovir/abacavir-naïve 52%. Independent baseline predictors of greater hip and spine bone loss were TDF-FTC randomisation (p≤0.013), lower fat mass (p-trend≤0.009), lower P1NP (p = 0.015), and higher hip T score/spine BMD (p-trend≤0.006). Baseline PI use was associated with greater spine bone loss (p = 0.004). TDF-FTC increased P1NP and CTx through Wk96 (p<0.01). Early changes in BTM did not predict bone loss at week 96. No significant between-group difference was found in fracture risk. Conclusions/Significance: Tenofovir/emtricitabine treatment, lower bone formation and lower fat mass predicted subsequent bone loss. There was no association between TDF-FTC and fracture risk.

Original language	English (US)
Article number	e38377
Journal	PloS one
Volume	7
Issue number	6
DOIs	https://doi.org/10.1371/journal.pone.0038377
State	Published - Jun 15 2012
Externally published	Yes

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)
Agricultural and Biological Sciences(all)
General

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Haskelberg, H., Hoy, J. F., Amin, J., Ebeling, P. R., Emery, S., Carr, A., Allworth, A., Anderson, J., Baker, D., Bloch, M., Boyd, M., Chuah, J., Cooper, D., Davies, S., Dayan, L., Donohue, W., Doong, N., Dwyer, D., Dyer, J., ... Woolley, I. (2012). Changes in bone turnover and bone loss in HIV-infected patients changing treatment to tenofovir-emtricitabine or abacavir-lamivudine. PloS one, 7(6), [e38377]. https://doi.org/10.1371/journal.pone.0038377

Changes in bone turnover and bone loss in HIV-infected patients changing treatment to tenofovir-emtricitabine or abacavir-lamivudine. / Haskelberg, Hila; Hoy, Jennifer F.; Amin, Janaki; Ebeling, Peter R.; Emery, Sean; Carr, Andrew; Allworth, Anthony; Anderson, Jonathan; Baker, David; Bloch, Mark; Boyd, Mark; Chuah, John; Cooper, David; Davies, Stephen; Dayan, Linda; Donohue, William; Doong, Nicholas; Dwyer, Dominic; Dyer, John; Finlayson, Robert; Giles, Michelle; Gordon, David; Kelly, Mark; Medland, Nicholas; Moore, Richard; Nolan, David; Orth, David; Post, Jeffrey; Quin, John; Read, Tim; Roth, Norman; Russell, Darren; Shaw, David; Smith, David; Smith, Don; Street, Alan; Tee, Ban Kiem; Woolley, Ian.

In: PloS one, Vol. 7, No. 6, e38377, 15.06.2012.

Research output: Contribution to journal › Article › peer-review

Haskelberg, H, Hoy, JF, Amin, J, Ebeling, PR, Emery, S, Carr, A, Allworth, A, Anderson, J, Baker, D, Bloch, M, Boyd, M, Chuah, J, Cooper, D, Davies, S, Dayan, L, Donohue, W, Doong, N, Dwyer, D, Dyer, J, Finlayson, R, Giles, M, Gordon, D, Kelly, M, Medland, N, Moore, R, Nolan, D, Orth, D, Post, J, Quin, J, Read, T, Roth, N, Russell, D, Shaw, D, Smith, D, Smith, D, Street, A, Tee, BK & Woolley, I 2012, 'Changes in bone turnover and bone loss in HIV-infected patients changing treatment to tenofovir-emtricitabine or abacavir-lamivudine', PloS one, vol. 7, no. 6, e38377. https://doi.org/10.1371/journal.pone.0038377

Haskelberg, Hila ; Hoy, Jennifer F. ; Amin, Janaki ; Ebeling, Peter R. ; Emery, Sean ; Carr, Andrew ; Allworth, Anthony ; Anderson, Jonathan ; Baker, David ; Bloch, Mark ; Boyd, Mark ; Chuah, John ; Cooper, David ; Davies, Stephen ; Dayan, Linda ; Donohue, William ; Doong, Nicholas ; Dwyer, Dominic ; Dyer, John ; Finlayson, Robert ; Giles, Michelle ; Gordon, David ; Kelly, Mark ; Medland, Nicholas ; Moore, Richard ; Nolan, David ; Orth, David ; Post, Jeffrey ; Quin, John ; Read, Tim ; Roth, Norman ; Russell, Darren ; Shaw, David ; Smith, David ; Smith, Don ; Street, Alan ; Tee, Ban Kiem ; Woolley, Ian. / Changes in bone turnover and bone loss in HIV-infected patients changing treatment to tenofovir-emtricitabine or abacavir-lamivudine. In: PloS one. 2012 ; Vol. 7, No. 6.

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title = "Changes in bone turnover and bone loss in HIV-infected patients changing treatment to tenofovir-emtricitabine or abacavir-lamivudine",

abstract = "Background: Those receiving tenofovir/emtricitabine (TDF-FTC) had greater bone loss compared with abacavir/lamivudine (ABC-3TC) in a randomized simplification trial (STEAL study). Previous studies associated increased bone turnover and bone loss with initiation of antiretroviral treatment, however it is unclear whether change in bone mineral density (BMD) was a result of specific drugs, from immune reconstitution or from suppression of HIV replication. This analysis determined predictors of BMD change in the hip and spine by dual-energy x-ray absorptiometry in virologically suppressed participants through week 96. Methodology/Principal Findings: Bone turnover markers (BTMs) tested were: formation [bone alkaline phosphatase, procollagen type 1 N-terminal propeptide (P1NP)]; resorption (C-terminal cross-linking telopeptide of type 1 collagen [CTx]); and bone cytokine-signalling (osteoprotegerin, RANK ligand). Independent predictors of BMD change were determined using forward, stepwise, linear regression. BTM changes and fracture risk (FRAX{\textregistered}) at week 96 were compared by t-test. Baseline characteristics (n = 301) were: 98% male, mean age 45 years, current protease-inhibitor (PI) 23%, tenofovir/abacavir-na{\"i}ve 52%. Independent baseline predictors of greater hip and spine bone loss were TDF-FTC randomisation (p≤0.013), lower fat mass (p-trend≤0.009), lower P1NP (p = 0.015), and higher hip T score/spine BMD (p-trend≤0.006). Baseline PI use was associated with greater spine bone loss (p = 0.004). TDF-FTC increased P1NP and CTx through Wk96 (p<0.01). Early changes in BTM did not predict bone loss at week 96. No significant between-group difference was found in fracture risk. Conclusions/Significance: Tenofovir/emtricitabine treatment, lower bone formation and lower fat mass predicted subsequent bone loss. There was no association between TDF-FTC and fracture risk.",

author = "Hila Haskelberg and Hoy, {Jennifer F.} and Janaki Amin and Ebeling, {Peter R.} and Sean Emery and Andrew Carr and Anthony Allworth and Jonathan Anderson and David Baker and Mark Bloch and Mark Boyd and John Chuah and David Cooper and Stephen Davies and Linda Dayan and William Donohue and Nicholas Doong and Dominic Dwyer and John Dyer and Robert Finlayson and Michelle Giles and David Gordon and Mark Kelly and Nicholas Medland and Richard Moore and David Nolan and David Orth and Jeffrey Post and John Quin and Tim Read and Norman Roth and Darren Russell and David Shaw and David Smith and Don Smith and Alan Street and Tee, {Ban Kiem} and Ian Woolley",

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doi = "10.1371/journal.pone.0038377",

language = "English (US)",

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T1 - Changes in bone turnover and bone loss in HIV-infected patients changing treatment to tenofovir-emtricitabine or abacavir-lamivudine

AU - Haskelberg, Hila

AU - Hoy, Jennifer F.

AU - Amin, Janaki

AU - Ebeling, Peter R.

AU - Emery, Sean

AU - Carr, Andrew

AU - Allworth, Anthony

AU - Anderson, Jonathan

AU - Baker, David

AU - Bloch, Mark

AU - Boyd, Mark

AU - Chuah, John

AU - Cooper, David

AU - Davies, Stephen

AU - Dayan, Linda

AU - Donohue, William

AU - Doong, Nicholas

AU - Dwyer, Dominic

AU - Dyer, John

AU - Finlayson, Robert

AU - Giles, Michelle

AU - Gordon, David

AU - Kelly, Mark

AU - Medland, Nicholas

AU - Moore, Richard

AU - Nolan, David

AU - Orth, David

AU - Post, Jeffrey

AU - Quin, John

AU - Read, Tim

AU - Roth, Norman

AU - Russell, Darren

AU - Shaw, David

AU - Smith, David

AU - Smith, Don

AU - Street, Alan

AU - Tee, Ban Kiem

AU - Woolley, Ian

PY - 2012/6/15

Y1 - 2012/6/15

N2 - Background: Those receiving tenofovir/emtricitabine (TDF-FTC) had greater bone loss compared with abacavir/lamivudine (ABC-3TC) in a randomized simplification trial (STEAL study). Previous studies associated increased bone turnover and bone loss with initiation of antiretroviral treatment, however it is unclear whether change in bone mineral density (BMD) was a result of specific drugs, from immune reconstitution or from suppression of HIV replication. This analysis determined predictors of BMD change in the hip and spine by dual-energy x-ray absorptiometry in virologically suppressed participants through week 96. Methodology/Principal Findings: Bone turnover markers (BTMs) tested were: formation [bone alkaline phosphatase, procollagen type 1 N-terminal propeptide (P1NP)]; resorption (C-terminal cross-linking telopeptide of type 1 collagen [CTx]); and bone cytokine-signalling (osteoprotegerin, RANK ligand). Independent predictors of BMD change were determined using forward, stepwise, linear regression. BTM changes and fracture risk (FRAX®) at week 96 were compared by t-test. Baseline characteristics (n = 301) were: 98% male, mean age 45 years, current protease-inhibitor (PI) 23%, tenofovir/abacavir-naïve 52%. Independent baseline predictors of greater hip and spine bone loss were TDF-FTC randomisation (p≤0.013), lower fat mass (p-trend≤0.009), lower P1NP (p = 0.015), and higher hip T score/spine BMD (p-trend≤0.006). Baseline PI use was associated with greater spine bone loss (p = 0.004). TDF-FTC increased P1NP and CTx through Wk96 (p<0.01). Early changes in BTM did not predict bone loss at week 96. No significant between-group difference was found in fracture risk. Conclusions/Significance: Tenofovir/emtricitabine treatment, lower bone formation and lower fat mass predicted subsequent bone loss. There was no association between TDF-FTC and fracture risk.

AB - Background: Those receiving tenofovir/emtricitabine (TDF-FTC) had greater bone loss compared with abacavir/lamivudine (ABC-3TC) in a randomized simplification trial (STEAL study). Previous studies associated increased bone turnover and bone loss with initiation of antiretroviral treatment, however it is unclear whether change in bone mineral density (BMD) was a result of specific drugs, from immune reconstitution or from suppression of HIV replication. This analysis determined predictors of BMD change in the hip and spine by dual-energy x-ray absorptiometry in virologically suppressed participants through week 96. Methodology/Principal Findings: Bone turnover markers (BTMs) tested were: formation [bone alkaline phosphatase, procollagen type 1 N-terminal propeptide (P1NP)]; resorption (C-terminal cross-linking telopeptide of type 1 collagen [CTx]); and bone cytokine-signalling (osteoprotegerin, RANK ligand). Independent predictors of BMD change were determined using forward, stepwise, linear regression. BTM changes and fracture risk (FRAX®) at week 96 were compared by t-test. Baseline characteristics (n = 301) were: 98% male, mean age 45 years, current protease-inhibitor (PI) 23%, tenofovir/abacavir-naïve 52%. Independent baseline predictors of greater hip and spine bone loss were TDF-FTC randomisation (p≤0.013), lower fat mass (p-trend≤0.009), lower P1NP (p = 0.015), and higher hip T score/spine BMD (p-trend≤0.006). Baseline PI use was associated with greater spine bone loss (p = 0.004). TDF-FTC increased P1NP and CTx through Wk96 (p<0.01). Early changes in BTM did not predict bone loss at week 96. No significant between-group difference was found in fracture risk. Conclusions/Significance: Tenofovir/emtricitabine treatment, lower bone formation and lower fat mass predicted subsequent bone loss. There was no association between TDF-FTC and fracture risk.

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Changes in bone turnover and bone loss in HIV-infected patients changing treatment to tenofovir-emtricitabine or abacavir-lamivudine

Abstract

ASJC Scopus subject areas

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