title: Effects of 96 Weeks of Rosuvastatin on Bone, Muscle, and Fat in HIV-Infected Adults on Effective Antiretroviral Therapy.
abstract: Heightened inflammation and immune activation are associated with lower bone mineral density (BMD) and lean body mass (LBM) among HIV-infected persons. We hypothesized that a reduction in inflammation with rosuvastatin would be associated with improvements in BMD and LBM. HIV-infected participants on stable antiretroviral therapy without statin indication and with heightened immune activation (≥19% CD8(+)CD38(+)HLA-DR(+) T cells) or inflammation (hsCRP ≥2 mg/liter) were randomized to rosuvastatin 10 mg daily or placebo for 96 weeks. Among 72 participants randomized to rosuvastatin and 75 to placebo, there were no significant differences in the relative changes in BMD (p > 0.29) or in fat (p ≥ 0.19). A trend toward increased LBM (p = 0.059) was seen in the rosuvastatin arm without differences in creatinine kinase or self-reported physical activity (p ≥ 0.10). In a multivariable regression model, rosuvastatin was associated with a significant positive effect on LBM after adjusting for age, sex, race, smoking status, and detectable HIV-1 viral load. Higher baseline sCD163 correlated with increases in LBM from weeks 0 to 96 (p = 0.023); greater changes in total and leg lean mass were seen among statin users with higher compared to lower baseline IP-10 levels (LBM 1.8 vs. -0.3%; p = 0.028 and leg lean mass 2.9 vs. -1.7%; p = 0.012). Rosuvastatin is associated with an absence of toxicity on BMD and a potential benefit on LBM over 96 weeks of therapy. The preservation of LBM in the rosuvastatin arm over the 2 years of the study is of major clinical relevance in delaying loss of muscle mass with aging.
authors.affiliation: 1 Department of Medicine, Divisions of Infectious Diseases and Geriatric Medicine, University of Colorado , Aurora, Colorado.
authors.forename: Kristine M
authors.initials: KM
authors.lastname: Erlandson
authors.affiliation: 2 Department of Epidemiology and Biostatistics, Case Western Reserve University , Cleveland, Ohio.
authors.forename: Ying
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: 2 Department of Epidemiology and Biostatistics, Case Western Reserve University , Cleveland, Ohio.
authors.forename: Sara M
authors.initials: SM
authors.lastname: Debanne
authors.affiliation: 3 Department of Medicine and Pediatrics, Division of Pediatric Infectious Diseases and Rheumatology, Case Western Reserve University , Cleveland, Ohio.
authors.forename: Grace A
authors.initials: GA
authors.lastname: McComsey
mesh_terms: D000273:Adipose Tissue / Q000473:pathology; D000293:Adolescent; D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001842:Bone and Bones / Q000473:pathology; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000473:pathology; D010919:Placebos / Q000008:administration & dosage; D000068718:Rosuvastatin Calcium / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D044966:Anti-Retroviral Agents; D000924:Anticholesteremic Agents; D010919:Placebos; D000068718:Rosuvastatin Calcium