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Tenofovir May Speed Bone Mineral Loss in First Years After Menopause
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3rd International Workshop on HIV and Aging, November 5-6, 2012, Baltimore
Mark Mascolini
Tenofovir use correlated with declining lumbar spine bone mineral density (BMD) in the 2 years after menopause in a prospective study of 55 women in Italy [1]. After that, however, tenofovir was not associated with continuing lumbar spine BMD loss in these same women.
Ample research links tenofovir use to swifter BMD drops [2-4], while other work shows that postmenopausal HIV-positive women lose BMD faster than postmenopausal HIV-negative women [5]. But premenopausal HIV-positive and negative women do not lose BMD at significantly different rates [6]. Until this new analysis of 55 women by researchers at the University of Modena and other institutions, the impact of tenofovir on BMD had not been studied prospectively as women passed the menopause.
The 55 study participants had at least one DEXA scan of the lumbar spine (L1-L4) and femoral neck before and after the menopause. The study excluded women taking bisphosphonates. Researchers divided the observation period into four windows: reproductive period (more than 2 years before menopause), menopause transition period (0 to 2 years before menopause), early menopause period (1 to 2 years after menopause), and late menopause period (more than 2 years after menopause). There were 11 observations in the reproductive period, 56 in the menopause transition period, 125 in the early menopause period, and 63 in the late menopause period.
Median age stood at 46 years when women enrolled in the study (interquartile range [IQR] 44 to 49). Median observation time stretched from 16 months (IQR 8 to 23) before the menopause and to 33 months (IQR 23 to 72) after the menopause. CD4 count averaged 471 at enrollment, nadir CD4 count averaged 161, and three quarters of women taking antiretrovirals (77.5%) had an undetectable viral load. Six women were not taking antiretrovirals. Among those who were, 47% were taking tenofovir/emtricitabine, 20% abacavir/lamivudine, and 8% zidovudine/lamivudine. Women taking tenofovir did not differ in osteoporosis risk factors from women not taking tenofovir. And women did not stop tenofovir when they reached menopause.
When women entered the cohort, 60% had osteopenia and 4% had osteoporosis. At the last DEXA scan, 78% had osteopenia and 36% had osteoporosis. Lumbar spine BMD was largely stable in the premenopausal period, began declining in the menopause transition period, and continued falling after the menopause.
Treatment-specific analysis of lumbar spine BMD showed similar levels with tenofovir and nontenofovir regimens during the reproductive period and the transition period. But in the early menopause period, lumbar spine BMD began dropping in the tenofovir group while remaining more stable in the nontenofovir group. In the early menopause period, estimated annual decline in lumbar spine BMD measured 3.4% among women not taking tenofovir and 4.7% among women taking tenofovir. In the late menopause period, there was almost no difference in estimated annual lumbar spine BMD decline (1.4% without tenofovir and 1.5% with tenofovir).
Multivariate regression analysis including classic risk factors and antiretroviral exposure determined that tenofovir was independently associated with lower BMD in the early menopause period (beta -0.028, P < 0.05) but not in the late menopause period. A model including classic risk factors and nucleoside/protease inhibitor combinations found that taking tenofovir with atazanavir (beta -0.049, P < 0.001) or lopinavir (beta -0.106, P < 0.001) heightened the impact of tenofovir on declining lumbar spine BMD in the early menopause period. In contrast, abacavir plus lopinavir was not independently associated with lumbar spine BMD loss in the early menopause period. Traditional risk factors including body mass index and years from menopause also contributed to BMD change in the postmenopausal period.
The association between current tenofovir and lower BMD in the early but not the late menopause period suggested to the investigators that a mechanism compensating for tenofovir-associated bone loss takes hold in the third year after the menopause.
References
1. Guaraldi G, Garlassi E, Stentarelli C, et al. Tenofovir accelerates bone mass loss of the lumbar spine in the first years of menopause in HIV infected women. 3rd International Workshop on HIV and Aging. November 5-6, 2012, Baltimore. Abstract O_08.
2. Jacobson DL, Spiegelman D, Knox TK, Wilson IB. Evolution and predictors of change in total bone mineral density over time in HIV-infected men and women in the Nutrition for Healthy Living Study. J Acquir Immune Defic Syndr. 2008;49:298-308.
3. Bonjoch A, Figueras M, Estany C, et al. High prevalence of and progression to low bone mineral density in HIV-infected patients: a longitudinal cohort study. AIDS. 2010;24:2827-2833.
4. McComsey GA, Kitch D, Daar ES, et al. Bone mineral density and fractures in antiretroviral-naive persons randomized to receive abacavir-lamivudine or tenofovir disoproxil fumarate-emtricitabine along with efavirenz or atazanavir-ritonavir: AIDS Clinical Trials Group A5224s, a substudy of ACTG A5202. J Infect Dis. 2011;203:1791-1801.
http://jid.oxfordjournals.org/content/203/12/1791.long
5. Yin MT, McMahon DJ, Ferris DC, et al. Low bone mass and high bone turnover in postmenopausal human immunodeficiency virus-infected women. J Clin Endocrinol Metab. 2010;95:620-629. http://jcem.endojournals.org/content/95/2/620.long.
6. Yin MT, Lu D, Cremers S, et al. Short-term bone loss in HIV-infected premenopausal women. J Acquir Immune Defic Syndr. 2010;53:202-208. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2813405/
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