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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 bone turnover markers by randomised arm (abacavir-lamivudine vs. tenofovir-emtricitabine).Note. Error bars represent 1 standard deviation from the mean (a) BALP, bone-specific alkaline phosphatase; (b) P1NP, procollagen type 1 N-terminal propeptide; (c) βCTx, C-terminal cross-linking telopeptide of type 1 collagen; (d) OPG, osteoprotegerin; ABC/3TC, abacavir/lamivudine; TDF/FTC, tenofovir/emtricitabine. There was no significant between-group difference at any time point for RANK.
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pone-0038377-g002: Mean change from baseline to week 96 in bone turnover markers by randomised arm (abacavir-lamivudine vs. tenofovir-emtricitabine).Note. Error bars represent 1 standard deviation from the mean (a) BALP, bone-specific alkaline phosphatase; (b) P1NP, procollagen type 1 N-terminal propeptide; (c) βCTx, C-terminal cross-linking telopeptide of type 1 collagen; (d) OPG, osteoprotegerin; ABC/3TC, abacavir/lamivudine; TDF/FTC, tenofovir/emtricitabine. There was no significant between-group difference at any time point for RANK.

Mentions: Significant differences in absolute changes in bone resorption and formation markers were seen after baseline between treatment groups. In the PP population, βCTx (bone resorption marker) increased significantly at week 12 in TDF-FTC compared to ABC-3TC arm (treatment difference 71.8 ng/L (95% CI 40.2 to 103.4; p<0.001)) and then remained stable through week 96. Similarly, increases in bone formation markers were greater with TDF-FTC than with ABC-3TC arm; P1NP was increased at week 12 (difference 8.79 µg/L [95% CI 5.48 to 12.10; p<0.001]) and remained stable thereafter. Another formation marker, BALP, was significantly different from week 24 onwards with greater increases with TDF-FTC than with ABC-3TC (difference 2.83 µg/L [95% CI 0.59 to 5.07; p = 0.014]) (Table 3, Figure 2). There was no significant, between-group difference in OPG or RANKL. Similar results were found in the ABC/TDF-naive subpopulation (data not shown). Changes in the bone resorption marker, βCTx, were correlated at all time points with changes in P1NP, a formation marker (r>0.30, p<0.001). Changes in BALP were correlated with changes in βCTx from week 24 onwards (r>0.15, p<0.014) except at week 48.


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 bone turnover markers by randomised arm (abacavir-lamivudine vs. tenofovir-emtricitabine).Note. Error bars represent 1 standard deviation from the mean (a) BALP, bone-specific alkaline phosphatase; (b) P1NP, procollagen type 1 N-terminal propeptide; (c) βCTx, C-terminal cross-linking telopeptide of type 1 collagen; (d) OPG, osteoprotegerin; ABC/3TC, abacavir/lamivudine; TDF/FTC, tenofovir/emtricitabine. There was no significant between-group difference at any time point for RANK.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0038377-g002: Mean change from baseline to week 96 in bone turnover markers by randomised arm (abacavir-lamivudine vs. tenofovir-emtricitabine).Note. Error bars represent 1 standard deviation from the mean (a) BALP, bone-specific alkaline phosphatase; (b) P1NP, procollagen type 1 N-terminal propeptide; (c) βCTx, C-terminal cross-linking telopeptide of type 1 collagen; (d) OPG, osteoprotegerin; ABC/3TC, abacavir/lamivudine; TDF/FTC, tenofovir/emtricitabine. There was no significant between-group difference at any time point for RANK.
Mentions: Significant differences in absolute changes in bone resorption and formation markers were seen after baseline between treatment groups. In the PP population, βCTx (bone resorption marker) increased significantly at week 12 in TDF-FTC compared to ABC-3TC arm (treatment difference 71.8 ng/L (95% CI 40.2 to 103.4; p<0.001)) and then remained stable through week 96. Similarly, increases in bone formation markers were greater with TDF-FTC than with ABC-3TC arm; P1NP was increased at week 12 (difference 8.79 µg/L [95% CI 5.48 to 12.10; p<0.001]) and remained stable thereafter. Another formation marker, BALP, was significantly different from week 24 onwards with greater increases with TDF-FTC than with ABC-3TC (difference 2.83 µg/L [95% CI 0.59 to 5.07; p = 0.014]) (Table 3, Figure 2). There was no significant, between-group difference in OPG or RANKL. Similar results were found in the ABC/TDF-naive subpopulation (data not shown). Changes in the bone resorption marker, βCTx, were correlated at all time points with changes in P1NP, a formation marker (r>0.30, p<0.001). Changes in BALP were correlated with changes in βCTx from week 24 onwards (r>0.15, p<0.014) except at week 48.

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