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

Haskelberg H, Hoy JF, Amin J, Ebeling PR, Emery S, Carr A - PLoS ONE (2012)

Bottom Line: BTM changes and fracture risk (FRAX®) at week 96 were compared by t-test.No significant between-group difference was found in fracture risk.There was no association between TDF-FTC and fracture risk.

View Article: PubMed Central - PubMed

Affiliation: The Kirby Institute, University of New South Wales, Sydney, Australia. hhaskelberg@kirby.unsw.edu.au

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.

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Mean change from baseline to week 96 in right hip (A,B) and lumbar spine bone mineral density (C,D) by study population and randomised arm (abacavir-lamivudine vs. tenofovir-emtricitabine).The right hand side of each graph shows the mean percent change in BMD at weeks 48 and 96. Note. p values from t-test comparing mean change from baseline to study week of interest in randomized arms. Error bars represent 1 standard deviation from the mean.Abbreviations: ABC/3TC, abacavir/lamivudine; TDF/FTC, tenofovir/emtricitabine.
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pone-0038377-g001: Mean change from baseline to week 96 in right hip (A,B) and lumbar spine bone mineral density (C,D) by study population and randomised arm (abacavir-lamivudine vs. tenofovir-emtricitabine).The right hand side of each graph shows the mean percent change in BMD at weeks 48 and 96. Note. p values from t-test comparing mean change from baseline to study week of interest in randomized arms. Error bars represent 1 standard deviation from the mean.Abbreviations: ABC/3TC, abacavir/lamivudine; TDF/FTC, tenofovir/emtricitabine.

Mentions: At week 96, the absolute change from baseline in hip BMD in the ABC-3TC group was 0.004 g/cm2 versus −0.007 g/cm2 in the TDF-FTC group (treatment difference 0.01 g/cm2 (95% confidence interval [CI] 0.003 to 0.018; p = 0.006). For lumbar spine, the absolute BMD change over 96 weeks in ABC-3TC group was 0.008 g/cm2 and −0.005 g/cm2 in the TDF-FTC group (treatment difference 0.01 g/cm2 (95% CI 0.002 to 0.024; p = 0.016). BMD changes in the ‘TDF/ABC-naïve’ subpopulation, were of similar magnitude (Table 2, Figure 1).


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

Haskelberg H, Hoy JF, Amin J, Ebeling PR, Emery S, Carr A - PLoS ONE (2012)

Mean change from baseline to week 96 in right hip (A,B) and lumbar spine bone mineral density (C,D) by study population and randomised arm (abacavir-lamivudine vs. tenofovir-emtricitabine).The right hand side of each graph shows the mean percent change in BMD at weeks 48 and 96. Note. p values from t-test comparing mean change from baseline to study week of interest in randomized arms. Error bars represent 1 standard deviation from the mean.Abbreviations: ABC/3TC, abacavir/lamivudine; TDF/FTC, tenofovir/emtricitabine.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3376146&req=5

pone-0038377-g001: Mean change from baseline to week 96 in right hip (A,B) and lumbar spine bone mineral density (C,D) by study population and randomised arm (abacavir-lamivudine vs. tenofovir-emtricitabine).The right hand side of each graph shows the mean percent change in BMD at weeks 48 and 96. Note. p values from t-test comparing mean change from baseline to study week of interest in randomized arms. Error bars represent 1 standard deviation from the mean.Abbreviations: ABC/3TC, abacavir/lamivudine; TDF/FTC, tenofovir/emtricitabine.
Mentions: At week 96, the absolute change from baseline in hip BMD in the ABC-3TC group was 0.004 g/cm2 versus −0.007 g/cm2 in the TDF-FTC group (treatment difference 0.01 g/cm2 (95% confidence interval [CI] 0.003 to 0.018; p = 0.006). For lumbar spine, the absolute BMD change over 96 weeks in ABC-3TC group was 0.008 g/cm2 and −0.005 g/cm2 in the TDF-FTC group (treatment difference 0.01 g/cm2 (95% CI 0.002 to 0.024; p = 0.016). BMD changes in the ‘TDF/ABC-naïve’ subpopulation, were of similar magnitude (Table 2, Figure 1).

Bottom Line: BTM changes and fracture risk (FRAX®) at week 96 were compared by t-test.No significant between-group difference was found in fracture risk.There was no association between TDF-FTC and fracture risk.

View Article: PubMed Central - PubMed

Affiliation: The Kirby Institute, University of New South Wales, Sydney, Australia. hhaskelberg@kirby.unsw.edu.au

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.

Show MeSH
Related in: MedlinePlus